A Strategic Combat Against Antimicrobial Resistance: A Cross-sectional Evaluation of Levofloxacin’s Efficacy against Multidrug-resistant Bacterial Isolates in Nigeria

A Strategic Combat Against Antimicrobial Resistance: A Cross-sectional Evaluation of Levofloxacin’s Efficacy against Multidrug-resistant Bacterial Isolates in Nigeria | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A Strategic Combat Against Antimicrobial Resistance: A Cross-sectional Evaluation of Levofloxacin’s Efficacy against Multidrug-resistant Bacterial Isolates in Nigeria Abubakar Sadiq Abdullahi, Gloria Abiodun Ayoola, Adebowale O. Adeluola, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6693557/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Background: Key mechanisms of antimicrobial resistance (AMR) include the presence of efflux pumps and the production of drug-degrading enzymes upon exposure to antimicrobial drugs. Levofloxacin, a widely prescribed fluoroquinolone, has marked antimicrobial activity against Gram-positive pathogens like Streptococcus pneumoniae and Gram-negative pathogens like Pseudomonas aeruginosa . However, additional multidrug resistance (MDR) mechanisms in microbes, such as mutations in DNA gyrase and topoisomerase IV or altered efflux pump activity (EPA), threaten its clinical efficacy. To the best of our knowledge, no study has reported the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of levofloxacin against genetically validated MDR isolates in Nigeria. Methods: A cross-sectional study assessing levofloxacin’s potency, MIC and MBC was conducted against 20 validated bacterial isolates with resistance mechanisms such as efflux pump activity, oxacillin resistance, ESBL, and carbapenemase production, following CLSI guidelines. The American Type Culture Collection (ATCC 25922) Escherichia coli reference isolate was used as the standard drug-susceptible control and all assays were performed in triplicate to ensure reproducibility and minimise observer bias. All data were expressed as mean ± standard deviation (S.D.). Significant differences among the groups were determined by one-way analysis of variance (ANOVA), and Graphs were plotted using Microsoft Excel. Results were considered to be significant at p ≤ 0.05. Results: Three MDR Klebsiella pneumoniae strains exhibited non-susceptibility and intermediate resistance to levofloxacin. MICs ranged from 0.0625–8.00 µg/ml for Gram-positive and 0.015625–1.00 µg/ml for Gram-negative organisms. Levofloxacin demonstrated greater inhibitory activity against Gram-negative (72.73% susceptible) than Gram-positive (55.56% susceptible) organisms. MBCs ranged from 0.125–8.00 µg/ml (Gram-positive) and 0.015625–8.00 µg/ml (Gram-negative), with Micrococcus spp. showing marked susceptibility (IZD 50 µg/ml: 37.33 mm ± 0.58; MIC: 0.125 µg/ml). Conclusion: Our study findings underscore the need for continuous surveillance, molecular characterisation of resistance mechanisms, and MIC-guided antimicrobial stewardship. While levofloxacin remains effective for many infections, emerging resistance among previously susceptible organisms highlights the urgent need for informed prescribing practices and the development of novel antimicrobials to combat MDR. Levofloxacin Minimum Inhibitory Concentration Minimum bacterial concentration Multidrug-resistant bacteria antimicrobial resistance Figures Figure 1 Figure 2 Figure 3 INTRODUCTION BACKGROUND The United Nations Environmental Programme has projected that by 2050, antimicrobial resistance (AMR) would claim annually over ten million lives, mirroring the staggering global cancer death toll of 2020 1 . Recent studies rank AMR among the leading causes of death worldwide, with the highest mortality rates in low-resource settings 2 . The widespread use of antimicrobial drugs has significantly driven resistance among various bacterial strains, posing a critical threat to global health 2–4 . Multidrug resistance (MDR) refers to a microorganism’s insensitivity to multiple, structurally unrelated antimicrobial agents, despite demonstrating prior susceptibility 5 . MDR infections severely limit therapeutic options 6 , undermining optimal patient care and escalating global health risks 7 . In 2019, bacterial AMR directly caused 1.27 million deaths and contributed to 4.95 million deaths globally 8 . Key bacterial pathogens implicated in AMR include Methicillin-resistant Staphylococcus aureus (MRSA) 9 ; and Staphylococcus xylosus , which harbours resistance genes and causes opportunistic infections 10 . Enterobacteriaceae species such as Escherichia coli , Klebsiella pneumoniae , and Enterobacter spp. produce extended-spectrum β-lactamases (ESBLs) that confer resistance to antibiotics like penicillins, third-generation cephalosporins, and even carbapenems. These resistance mechanisms exacerbate the global AMR crisis, necessitating the development of targeted therapeutic strategies 11–13 . Previous studies by Adeluola et al 2017 and 2018 10,11 have linked phenotypic antibiotic drug-resistance and detectable genetic markers in 28 clinical isolates of Klebsiella pneumonia , 3 isolates of Escherichia coli , 1 isolate of E. aerogenes, 14 isolates of Staphylococcus aureus , 2 isolates of S. lentus , 1 isolate of S. xylosus and 1 Micrococcus spp. o btained from medical microbiology laboratories of the University of Lagos Teaching Hospital (LUTH) and screened for (i) antibiotic-susceptibility over a range of 11 classes of antibiotics, (ii) β-lactamase production, (iii) Extended Spectrum β-Lactamase(ESBL) production and (iv) Efflux pump activity (EPA) 10,11 . Analysis of the Gram-negative isolates revealed that the isolates were mostly resistant to ampicillin, most susceptible to neomycin and ciprofloxacin and specifically constituted of nine MDR strains, twenty inducible β-lactamase producers and seven intrinsic β-lactamase producers. In addition, AcrA and AcrB genes were detected in six isolates (confirming EPA in four K. pneumonia strains , one Enterobacter aerogenes and one E. coli strain), and blaCTX-M was detected as the gene conferring characteristics in three Klebsiella pneumoniae strains, one E. aerogenes strain, blaTEM was detected as the gene conferring ESBL characteristics in K. pneumonia isolates and a positive correlation between ESBL production and fluoroquinolones resistance was reported. Studies on the Gram-positive isolates showed that twelve (12) isolates were MDR, 10 isolates were inducible β-lactamase producers, 3 isolates were intrinsic β-lactamase producers, seven were resistant to oxacillin and also produced carbapenemase enzyme, with 5 S. aureus isolates and one S. lentus found as an Oxacillin Resistant S. aureus (ORSA) and carbapenemase producers. The understudied Micrococcus spp . was MDR, ORSA, and a carbapenemase producer 10,11 . Levofloxacin, a third-generation and widely prescribed fluoroquinolone 14 , plays a pivotal role in combating bacterial infections, including community-acquired pneumonia, urinary tract infections, and Pseudomonas -mediated diseases 15 . Approved by the U.S. FDA in 1996, levofloxacin demonstrates superior antimicrobial activity against Gram-positive ( Streptococcus pneumoniae ) and Gram-negative ( Pseudomonas aeruginosa ) pathogens 16 , surpassing other fluoroquinolones in potency 17–19 . Chemically, levofloxacin is a chiral fluorinated carboxyquinolone and the optically active (−)-(S)-enantiomer of ofloxacin racemate, exhibiting 8- to 128-fold greater activity against bacterial pathogens 16,20 Chemical structure of Levofloxacin is shown in Figure I below 15 ; Levofloxacin functions by inhibiting DNA gyrase and topoisomerase IV, which play important roles in DNA replication, recombination and transcription 19,21,22 . In bacteria, topoisomerase IV, a tetramer of two ParC and two ParE subunits, unlinks daughter chromosomes before cell division, whereas the related enzyme gyrase, a GyrA2GyrB2 tetramer, supercoils DNA and helps unwind DNA at replication forks 21 . Both enzymes act via a double-strand DNA break involving a cleavage complex and are targets for quinolone antimicrobials that act by trapping these enzymes at the DNA-cleavage stage and preventing strand re-joining 19,21 . The three-dimensional X-ray structure of a K. pneumoniae topoisomerase IV ParC/ParE cleavage complex with DNA stabilised by levofloxacin is shown in Figure 2a and 2b below; Resistance to levofloxacin may generally develop due to mutations in DNA gyrase or topoisomerase IV, or via efflux pump overexpression and production of β-Lactamases, thus limiting intracellular drug accumulation 22 . Cross-resistance with other fluoroquinolones is common, although resistance between levofloxacin and structurally distinct antibiotic classes is rare due to significant differences in chemical structure and mechanism of action 23 . While numerous studies have documented levofloxacin-resistance rates 24–26 , the minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) for levofloxacin among MDR bacterial isolates in Nigeria remain largely unexplored. The MIC value is a critical parameter for optimising antibiotic therapy, offering a quantitative measure of bacterial susceptibility 27 . Unlike qualitative methods, MIC determination provides insights into the degree of resistance and informs clinical decision-making 27,28 . Previous studies, including investigations in Iraq 12 and India 13 , report high resistance rates to levofloxacin among E. coli and K. pneumoniae . Similarly, Ghanaian investigations revealed significant resistance in Staphylococcus aureus isolates 18 and Nigerian studies indicated 18% resistance among S. aureus isolates 29 . However, the absence of MIC and MBC data limits in these studies necessitates further studies to achieve a comprehensive understanding and targeted intervention strategies against these multidrug-resistant pathogens. Objectives Previous studies have linked phenotypic antibiotic drug-resistance and detectable genetic markers in 50 clinical isolates o btained from a tertiary hospital in Nigeria 10,11 . Here we aimed to evaluate the changes in antimicrobial susceptibility, minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of 20 validated bacterial isolates to levofloxacin. Rationale These findings will provide a critical foundation for optimising therapeutic regimens, revising clinical breakpoints, and advancing antimicrobial stewardship programs, particularly in Nigeria, where MDR infections remain a significant public health concern. From our literature search and to the best of our knowledge, no previous studies have been conducted on the minimum inhibitory and bactericidal concentration of levofloxacin on genetically validated multidrug-resistant bacteria isolates in Nigeria. METHODS Study Design, Setting and Test Organisms Bacterial Isolates Eighteen clinical isolates from infections of the urinary tract, upper respiratory tract, ear and eye swabs, and blood cultures from medical microbiology laboratories of the University of Lagos Teaching Hospital (LUTH) that had been previously profiled and validated for identity and antimicrobial susceptibility in earlier studies 10 , 11 , were obtained from the Department of Pharmaceutical Microbiology, University of Lagos. All bacterial isolates used in this cross-sectional study were calibrated to 0.5 McFarland’s standard (0.05 ml of 1.0% barium chloride in 9.95 ml of 1.0% sulphuric acid) using sterile normal saline as diluent to yield an approximate cell density of 1x10 8 CFU/ ml. Gram-negative Bacteria Isolates : The study utilised seven strains of Extended β-lactamase producing Klebsiella pneumoniae : Oga, N3, N24, OG 1(4), N19, Med 1(2) and N14; One strain of AmpC β-lactamase producing Klebsiella pneumoniae Med 5(1); one strain of Klebsiella pneumonia with efflux pump activity (EPA) OG 1(3) and a clinical isolate, Pseudomonas aeruginosa PA 24 were used for this study. The American Type Culture Collection (ATCC 25922) Escherichia coli reference isolate was used as the standard drug-susceptible control against potential sources of bias, as recommended by the Clinical Laboratory Standards Institute 35 . Gram-positive Bacteria Isolates The study utilised three isolates of Oxacillin-Resistant and carbapenemase-producing strains of Staphylococcus aureus (ES 21, ES 44, MED4 (2)); one isolate of carbapenemase-producing strains of Staphylococcus aureus (ML 10). One strain of Oxacillin-resistant Staphylococcus lentus (ES 14), one strain of Oxacillin-resistant and carbapenemase-producing Micrococcus spp. with efflux pump activity (ES 7), a strain of Oxacillin-resistant Staphylococcus xylosus (ES 16) and a strain of Enterococcus faecalis EF 24 were used for the study. The American Type Culture Collection (ATCC 25923) Staphylococcus aureus reference isolate was used as the standard drug-susceptible control against potential sources of bias. Variables Outcomes were defined as the zones of inhibition (mm), minimum inhibitory concentrations (MIC), and minimum bactericidal concentrations (MBC) of levofloxacin against MDR isolates. Exposure was defined as in vitro treatment with standardised concentrations of levofloxacin. Predictors included bacterial species and resistance mechanisms (e.g., ESBL, AmpC). No known confounders or effect modifiers were introduced in this controlled in vitro study. MDR status was determined in a previous study by Adeluola et al, based on phenotypic antibiotic drug-resistance and detectable genetic markers in clinical isolates o btained from a tertiary hospital in Nigeria 10 , 11 . Data Sources / Measurement Bacterial isolates were sourced from previously characterised clinical collections. Zone diameters, MIC, and MBC values were measured using standardised procedures, as per Bauer et al 48 and CLSI 35 recommendations, to ensure comparability across all bacterial groups. Bias Validated multidrug-resistant (MDR) isolates of Klebsiella pneumoniae , Staphylococcus aureus , and Pseudomonas aeruginosa were chosen for this study to minimise selection and measurement bias. Standardised protocols were followed for sample handling, antimicrobial susceptibility testing, and MIC/MBC determination based on Bauer et al 48 and CLSI 35 guidelines. All assays were performed in triplicate to ensure reproducibility and minimise observer bias. Study Size The study analysed 20 MDR bacterial isolates chosen based on the presence of specific resistance phenotypes (e.g., ESBL, AmpC, carbapenemase production). This size was determined to provide sufficient representation across key MDR profiles within logistical and resource constraints while allowing meaningful comparison of susceptibility and bactericidal thresholds. Quantitative Variables Quantitative variables such as zone of inhibition, MIC, and MBC values were recorded in millimetres (mm) and micrograms per millilitre (µg/ml), respectively. Groupings were based on bacterial species and resistance profiles to enable comparative evaluation of levofloxacin efficacy across different MDR phenotypes. Preparation of Working Concentrations : A stock solution of Levofloxacin with a concentration of 5 mg/ ml, equivalent to 5000 µg/ ml, was prepared and labelled as Sample I. From sample I, a series of 1:10 dilutions was carried out to yield a 500 µg/ ml concentration and a 50 µg/ ml concentration. From this, a series of double dilutions was done using sterile distilled water as diluent to yield a 25 µg/ ml, 12.5 µg/ ml and 6.25 µg/ml concentration for susceptibility testing. Antibiotic Susceptibility Testing Similar to Bauer et al. 48 , calibrated cultures of the isolates were seeded into 25 ml Mueller-Hinton agar (MHA), which was poured and allowed to solidify on petri dishes. Each plate appropriately labelled with the identity of the seeded isolate was marked out in four segments, with each segment assigned to a particular test concentration of levofloxacin being used. Plates were allowed to dry on the bench for 3–5 minutes, and a cork borer of 10 mm in diameter was used to bore wells in the marked-out segments of the MHA Petri dishes. In each of the segments, 150 µL of levofloxacin (50µg/ ml, 25 µg / ml, and 6.25 µg/ ml) was aseptically dispensed into their assigned bored holes in the labelled quadrants. The plates were allowed to stand for 2 hrs on the bench, incubated at 37 ℃ ± 2 for 24 hrs and observed for zones of inhibition. Determination of Minimum Inhibitory Concentration (MIC) A combination of the Agar dilution technique recommended by Hugo and Russell 49 and the Clinical and Laboratory Standards Institute 35 , were used to determine the minimum concentration and interpretative breakpoints of the levofloxacin that inhibited each assay organism. CLSI Interpretative breakpoints and categories are as shown in Table 1 below; Table 1 CLSI Interpretative Categories and MIC Breakpoints (µg/ml) for Levofloxacin 35 Isolates Susceptible (S) Intermediate (I) Resistant ( R ) Enterobacterales ≤ 0.5 1.00 ≥ 2.00 Pseudomonas aeruginosa ≤ 1.00 2.00 ≥ 4.00 Staphylococcus spp. ≤ 1.00 2.00 ≥ 4.00 Enterococcus spp. ≤ 2.00 4.00 ≥ 8.00 ATCC 25922 Escherichia coli 0.008–0.06 Eight (8) concentrations of 2500, 250, 25, 2.5, 1.25, 0.625, 0.0625 and 0.00625 ug/ ml were prepared, four (4) concentrations – 25, 0.625, 0.0625 and 0.00625 ug/ ml were used as stock concentrations and thirteen (13) working concentrations were used- 0.001953125, 0.00390625, 0.0078125, 0.015625, 0.03125, 0.0625, 0.125, 0.25, 0.50, 1.00, 2.00, 4.00 and 8.00 ug/ ml as highlighted in Table 2 below. Working concentrations for MIC determination were prepared by measuring specified volumes of agar into universal glass bottles labelled A-M measured agar was sterilised in the autoclave at 121°C for 15 mins. The required volumes of levofloxacin test solutions were added to the required volume of molten MHA, thoroughly mixed and transferred into labelled Petri dishes (150 mm x 15 mm). Each test organism was spotted twice, with the aid of an inoculating loop, on its respective assigned sites on the MHA plates, in an aseptic zone. All test organisms used were standardised to 0.5 McFarland’s Standard. Inoculated plates were incubated at 37°C for 24 hrs, and the MICs were recorded as the lowest concentration of Levofloxacin with no apparent growth of the test isolates on the MHA plates. Table 2 Constitution of Muller Hinton Agar (MHA) Plates for Determination of Minimum Inhibitory Concentration (MIC) of Levofloxacin Bottle / Plate Label Stock Concentration of Levofloxacin (ug/ ml) Volume of Levofloxacin withdrawn from Stock (ml) Volume of MHA used (ml) Concentration of Levofloxacin in MHA (ug/ ml) A 0.00625 6.25 13.75 0.001953125 B 0.062500 1.25 18.75 0.003906250 C 0.062500 2.50 17.50 0.007812500 D 0.062500 5.00 15.00 0.015625000 E 0.625000 1.00 19.00 0.031250000 F 0.625000 2.00 18.00 0.062500000 G 0.625000 4.00 16.00 0.125000000 H 25.00000 0.20 19.80 0.250000000 I 25.00000 0.40 19.60 0.500000000 J 25.00000 0.80 19.20 1.000000000 K 25.00000 1.60 18.40 2.000000000 L 25.00000 3.20 16.80 4.000000000 M 25.00000 6.40 13.60 8.000000000 Determination of Minimum Bactericidal Concentration (MBC ) In universal glass bottles, 20 ml of single-strength MHA with 0.1% Tween 80 (MHA-Tween 80 agar) was autoclaved at 121 o C. for 15 minutes. Molten MHA - Tween 80 agar was aseptically transferred into labelled Petri dishes and allowed to solidify and dry for about 30 minutes. All MIC plates that showed no growth were selected for sub-culturing onto blank MHA–Tween 80 agar plates. Using a flame-sterilised inoculating loop, the spots where there was no bacterial growth, on the selected MIC plates, were rubbed and streaked onto the blank MHA-Tween 80 agar plates. The fresh plates were incubated at 37°C for 24 hrs. For each test isolate, the lowest concentration that still did not show any growth at this stage was taken as the MBC. Statistical Methods A. All data were expressed as mean ± standard deviation (S.D.). Significant differences among the groups were determined by one-way analysis of variance (ANOVA), and Graphs were plotted using Microsoft Excel. Results were considered to be significant at p ≤ 0.05. B. Missing Data: There were no missing data; all isolates were successfully profiled, and all experimental replicates were completed. RESULTS Bacterial Isolates flow (numbers at each stage) Out of 50 originally profiled isolates, 20 genetically validated MDR strains were selected based on previously confirmed resistance mechanisms and susceptibility profiles 10 , 11 . Reasons for non-participation All selected isolates met the inclusion criteria; no exclusions were made. Antimicrobial Susceptibility The results, as shown in Fig. 1 reveal the dose dependent antibacterial susceptibility of MDR bacteria isolates to levofloxacin across four concentrations. Table 1 shows that 15% (3/20) of MDR K. pneumoniae strains with EPA and ESBL-producing activity demonstrated no susceptibility to levofloxacin. Table 1 Zones of Inhibition (mm) From Different Concentrations of Levofloxacin (µg/ml) against Bacterial isolates S/N ORGANISM CODE ( Organism Phenotype) Key: ESBL- Extended Spectrum β-Lactamase EPA: Efflux Pump Activity ORSA: Oxacillin-resistant Staphylococcus aureus *MEAN ZONES OF INHIBITION (mm) FROM DIFFERENT CONCENTRATIONS (µg/ml) [Mean ± S.D] 50.00 ug /ml 25.00 ug /ml 12.50 ug /ml 6.25 ug /ml 1. N 19 : Klebsiella pneumoniae ESBL producer 28.67 ± 1.15 27.67 ± 0.58 26.33 ± 0.58 15.67 ± 0.58 2. N 24 : Klebsiella pneumoniae ESBL producer 34.00 ± 0.00 31.00 ± 1.00 29.00 ± 0.00 23.67 ± 0.58 3. Med 1(2) : Klebsiella pneumoniae EPA; ESBL producer 27.33 ± 0.58 25.67 ± 0.58 22.00 ± 1.00 20.33 ± 0.58 4. OG 1(3) : Klebsiella pneumoniae EPA 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 5. OG 1(4) : Klebsiella pneumoniae EPA; ESBL producer 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 6. Oga : Klebsiella pneumoniae ESBL producer 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 7. Med 5(1) : Klebsiella pneumoniae AmpC β-lactamase producer 30.67 ± 1.15 24.33 ± 0.58 21.67 ± 0.58 21.33 ± 1.15 8. N 14 : Enterobacter aerogenes ESBL producer 26.00 ± 1.00 22.33 ± 0.58 21.67 ± 0.58 20.33 ± 0.58 9. N 3 : Klebsiella pneumoniae ESBL producer 37.67 ± 0.58 33.33 ± 0.58 28.33 ± 1.53 26.33 ± 1.15 10. PA 24 : Pseudomonas aeruginosa 28.33 ± 0.58 22.00 ± 1.00 20.33 ± 0.58 16.33 ± 1.15 11. ATCC 25922 : Escherichia coli 34.00 ± 1.00 29.67 ± 0.58 24.00 ± 1.00 21.67 ± 0.58 12. ES 44 : Staphylococcus aureus, EPA, ORSA, Carbapenemase 42.33 ± 0.58 42.67 ± 0.58 35.00 ± 1.00 33.67 ± 0.58 13. Med 4 (2) : Staphylococcus aureus, EPA, ORSA, Carbapenemase 36.67 ± 0.58 32.33 ± 0.58 29.67 ± 0.58 28.67 ± 0.58 14. ES 14 : Staphylococcus lentus ORSA 36.00 ± 0.00 32.33 ± 0.58 26.00 ± 1.00 0.00 ± 0.00 15. ES 16 : Staphylococcus xylosus, ORSA 13.33 ± 0.58 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 16. ES 21 : Staphylococcus aureus, ORSA, Carbapenemase 35.33 ± 0.58 34.33 ± 1.15 28.00 ± 0.00 21.33 ± 0.58 17. ML 10 : Staphylococcus aureus , Carbapenemase 40.00 ± 0.00 36.00 ± 1.00 23.33 ± 0.58 0.00 ± 0.00 18. ES 7 : Micrococcus species EPA, ORSA, Carbapenemase 37.33 ± 0.58 37.00 ± 1.00 34.00 ± 0.00 32.33 ± 0.58 19. EF 24 : Enterococcus faecalis 31.67 ± 0.58 29.00 ± 1.00 23.33 ± 0.58 15.33 ± 0.58 20. ATCC 25923 : Staphylococcus aureus 31.33 ± 0.58 25.67 ± 0.58 21.00 ± 1.00 0.00 ± 0.00 *p < 0.05 when values are greater than 0.00 Minimum Inhibitory Concentration (MIC) and Interpretative Breakpoints As shown in Table 2 , the MIC of levofloxacin against Escherichia coli (ATCC 25922) was 0.03125 µg/ml, within the CLSI QC range (0.008–0.06 µg/ml) 35 confirming the reproducibility of this study. Levofloxacin exhibited higher inhibitory activity against Gram-negative (72.73% susceptible) than Gram-positive (55.56% susceptible) organisms. MICs ranged from 0.0625–8.00 µg/ml for Gram-positive and 0.015625–1.00 µg/ml for Gram-negative organisms. Our findings also reveal the marked susceptibility of Micrococci to levofloxacin across all studied concentrations (IZD 50ug/ml: 37.33 mm ± 0.58, MIC: 0.125 µg/ml). Table 2 Minimum Inhibitory Concentration (MICs) and Minimum Bactericidal Concentrations of Levofloxacin against Gram-positive Bacterial Isolates S/N ORGANISM CODE ( Organism Phenotype; Genus and Species ) MIC VALUE (µg/ml) CLSI Interpretative Category / QC range 35 MBC VALUE (µg/ml) GRAM-POSITIVE ORGANISMS 1 Es 44 : Staphylococcus aureus , (EPA, ORSA, Carbapenemase producer) 8.00 R 8.00 2 Med 4 (2) : Staphylococcus aureus, (EPA, ORSA, Carbapenemase producer) 0.0625 S 2.00 3 Es 14 : Staphylococcus lentus (ORSA) 0.25 S 4.00 4 Es 16 : Staphylococcus xylosus (ORSA) 0.0625 S 2.00 5 Es 21 : Staphylococcus aureus, (ORSA, Carbapenemase producer) 1.00 S 2.00 6 ML 10 Staphylococcus aureus (Carbapenemase producer) 1.00 S 2.00 7 Es 7 : Micrococcus species (EPA, ORSA, Carbapenemase producer) 0.125 - 0.125 8 EF 24 : Enterococcus faecalis (clinical isolate) 4.00 I 4.00 9 ATCC 25923 : Staphylococcus aureus (standard strain) 2.00 - 2.00 Lowest Concentration: 0.06 0.125 Highest Concentration: 8.00 8.00 Total Number of Resistant isolates (R): 1 (11.11%) Total Number of Intermediate isolates (I): 1 (11.11%) Total Number of Susceptible isolates (U): 5 (55.56%) Total Number of Unclassified isolates (-): 2 (22.22%) Table 3 Minimum Inhibitory Concentration (MICs) and Minimum Bactericidal Concentrations of Levofloxacin against Gram-Negative Bacterial Isolates S/N ORGANISM CODE ( Organism Phenotype; Genus and Species ) MIC VALUE (µg/ml) CLSI Interpretative Category / QC range 35 MBC VALUE (µg/ml) GRAM NEGATIVE ORGANISMS 10 N 19 : Klebsiella pneumoniae (ESBL producer) 0.015625 S 0.015625 11 N 24 : Klebsiella pneumoniae (ESBL producer) 0.5 S 8.00 12 Med 1(2) : Klebsiella pneumoniae (EPA; ESBL producer) 0.25 S 2.00 13 OG 1(3) Klebsiella pneumoniae (EPA) 0.25 S 0.50 14 OG 1(4) : Klebsiella pneumoniae (EPA; ESBL producer) 1.00 I 2.00 15 Oga : Klebsiella pneumoniae (ESBL producer) 1.00 I 2.00 16 Med 5(1) Klebsiella pneumoniae (AmpC β-lactamase producer) 0.50 S 0.50 17 N 14 : Enterobacter aerogenes (ESBL producer) 0.50 S 2.00 18 N 3 : Klebsiella pneumoniae (ESBL producer) 0.50 S 2.00 19 PA 24 : Pseudomonas aeruginosa (Clinical isolate) 0.125 S 0.125 20 ATCC 25922 : Escherichia coli (Standard Strain) 0.03125 Complies 0.25 Lowest Concentration : 0.015625 0.015625 Highest Concentration : 1.00 8.00 Total Number of Resistant isolates (R): 0 (0.00%) Total Number of Intermediate isolates (S): 2 (18.18%) Total Number of Susceptible isolates (S): 8 (72.73%) Total Number of Unclassified isolates (-): 1 (9.09%) Minimum Bactericidal Concentration (MBC) In this study, MBCs ranged from 0.125–8.00 µg/ml for Gram-positive and 0.015625–8.00 µg/ml for Gram-negative organisms, as shown in Tables 2 and 3 above. These results show a 50% increase in the lower limit MIC concentration for Gram-positive organisms and a 12.5% increase in the upper limit MBC concentration for Gram-negative organisms. The success of antimicrobial therapy is determined by the interaction of drug administration, the state of the host and the causative agent of infection 47 . DISCUSSION Antimicrobial Susceptibility Klebsiella pneumoniae remains a leading nosocomial pathogen 30 , implicated in urinary tract infection and rising multidrug resistance rates 12 , 13 , 21 , 30 , 31 . The non-susceptibility of 15% of MDR K. pneumoniae strains with EPA and ESBL-producing activity to Levofloxacin is consistent with Geetha et al .'s findings, who reported levofloxacin resistance in 110 K. pneumoniae isolates 13 . Dehnamaki et al. also identified 57%, 56%, and 21% molecular distribution of oqxA, oqxB and qepa genes, respectively, in K. pneumoniae isolates from urine samples, conferring 68% levofloxacin resistance 31 . These findings emphasise the need for research into efflux pump characterisation and the development of targeted inhibitors to combat MDR. Coagulase-negative staphylococci (CoNS), such as Staphylococcus xylosus , S. hominis , and S. saprophyticus , are common nosocomial pathogens causing deep organ infections 32 , 33 . In the antimicrobial susceptibility study, levofloxacin exhibited the lowest inhibition against an oxacillin-resistant S. xylosus strain, with activity only at 50.00 µg/ml. In contrast, the same concentration markedly inhibited two carbapenemase-producing S. aureus strains. This aligns with Garbacz et al.'s findings, which reported higher resistance in CoNS compared to S. aureus 34 . Despite its commensal nature, S. xylosus has been linked to opportunistic infections, necessitating re-evaluation of infection management protocols. Minimum Inhibitory Concentration (MIC) and Interpretative Breakpoints Levofloxacin, a broad-spectrum fluoroquinolone, treats infections in the respiratory tract, skin, urinary tract, and prostate, among others 23 . In this study, Levofloxacin exhibited higher inhibitory activity against Gram-negative than Gram-positive organisms, which corroborates Grillon et al. 's findings, which showed higher levofloxacin susceptibility in Gram-negative isolates such as K. pneumoniae (75%) compared to Gram-positive strains like S. maltophilia (35%) 36 . Since the primary target of Levofloxacin in Gram-negative bacteria is DNA gyrase, whereas Topoisomerase IV enzyme is their preferential target in Gram-positive bacteria 37 , Levofloxacin’s higher inhibitory activity against Gram- Negative bacteria suggests its higher inhibition of DNA gyrase relative to Topoisomerase enzymes. Ultimately, these findings underscore the role of DNA gyrase as an ideal target for future antibacterial discovery efforts. Regional molecular profiling of clinical isolates is essential to validate MIC breakpoints and guide empirical therapy, minimizing resistance risks. Conversely, studies in Italy, Sweden, and India reported higher levofloxacin activity against Gram-positive organisms 38 – 40 , which may reflect regional differences in prescribing patterns, pathogen characteristics, or heteroresistance, which has been described for the bacteria isolates investigated in this study, such as S. aureus, Klebsiella pneumoniae, E. coli , and P. aeruginosa 27 . Nonetheless, results from this study reinforce the need for novel antimicrobial chemotherapy, especially in the face of levofloxacin-resistant pathogens and the borderline susceptibility of most isolates, which pose higher tendencies for therapy failure and antimicrobial resistance 27 , 28 . Additionally, periodic molecular profiling of clinical isolates is recommended to ascertain the validity of the set clinical MIC breakpoints for various antibiotics. Resistance mechanisms, including efflux pumps (e.g., norA, norB in S. aureus ), highlight the critical need for MIC tests to inform therapeutic decisions and strongly suggest a rationale for the notable levofloxacin-resistance of a carbapenemase-producing oxacillin-resistant strain of S. aureus – ‘ES 44’ with efflux pump activity (MIC: 8.00 µg/ml). Notably, two of the three MDR Klebsiella pneumoniae strains, which earlier demonstrated non-susceptibility to levofloxacin, exhibited intermediate resistance to levofloxacin during the MIC determinations. The intermediate category is defined as uncertain therapeutic success for the individual species/drug combination and is intended for compounds for which dosing can be increased 41 . CLSI defines the intermediate category as a lower response rate than for susceptible isolates, but clinical efficacy if the drug accumulates at the site of infection 35 . The intermediate category thus represents the ‘grey zone’ for which high potential for therapy failure and antimicrobial resistance exists at standard dosage regimens 41 . Additionally, intermediate resistance among these strains reduces the tendency of achieving the threshold antibiotic therapeutic concentration for effective eradication of the pathogen using the standard dosage, hence increasing the likelihood of antimicrobial resistance. Micrococcus spp., though often regarded as non-pathogenic, can be opportunistic pathogens for the immunocompromised 42 and have occasionally been reported as a causative pathogen in pneumonia, septic arthritis, bacteremia, catheter-associated bloodstream infection and endocarditis 10 , 43 , 44 . A study with 188 micrococci, identified only to the genus level, demonstrated MICs at achievable concentrations for most β-lactams, aminoglycosides, glycopeptides and clindamycin 45 . Generally, clinical data on Micrococcus spp. infections and treatment reports with levofloxacin are sparse, hence the current lack of clear therapeutic recommendations 42 , 45 . Our findings reveal the marked susceptibility of Micrococci to levofloxacin across all studied concentrations, thus highlighting levofloxacin’s importance in the management of infections mediated by Micrococcus spp. and informing the need for further studies to validate levofloxacin’s breakpoints for usage in clinical medicine. Minimum Bactericidal Concentration (MBC) Fluoroquinolones exhibit concentration-dependent bactericidal activity 46 . Relative to the MIC results, the MBCs show a 50% increase in the lower limit MIC concentration for Gram-positive organisms and a 12.5% increase in the upper limit MBC concentration for Gram-negative organisms. The success of antimicrobial therapy is determined by the interaction of drug administration, the state of the host and the causative agent of infection 47 . Findings from this study extensively highlight the necessity for correlating MIC values with pharmacokinetic (PK) and pharmacodynamic (PD) parameters, such as volume of distribution and clearance, in designing dosage regimens. Levofloxacin maintained a consistent MIC in exhibiting bactericidal activity against Pseudomonas aeruginosa (MBC: 0.125 µg/ml), indicating its potent antibacterial activity against Pseudomonas aeruginosa. These results align with the findings of Sihotang et al , whose study on the time-kill curve and effect of Levofloxacin on Pseudomonas aeruginosa showed marked bactericidal activity in all assay concentrations 47 . Remarkably, Sihotang et al findings also showed levofloxacin’s superior bactericidal effect against Pseudomonas aeruginosa relative to ciprofloxacin and ofloxacin. Overall, these studies underscore the urgent need for innovative antimicrobial agents and enhanced stewardship to combat MDR. Limitations Study limitations include the limited sample size of isolates and a focus on a single antimicrobial agent. Rationale for variations in susceptibility among similar resistance phenotypes was not further determined via molecular mechanisms, which may impact the interpretation of resistance. Generalisability These findings may be generalisable to similar tertiary care settings in low-resource regions where MDR infections are prevalent. However, broader surveillance studies are needed to confirm external validity. CONCLUSION This study represents the first to report levofloxacin MIC and MBC values for genetically validated MDR isolates in Nigeria. The findings emphasise the critical need for further research into microbial efflux pump mechanisms and the molecular characterisation of DNA gyrase and topoisomerase enzymes to develop novel targeted therapies. Periodic molecular profiling of clinical isolates is essential to validate and refine clinical MIC breakpoints for antibiotics. Additionally, MIC-data-driven antimicrobial stewardship can improve therapeutic outcomes and guide rational antibiotic classification for empiric treatment. Levofloxacin demonstrated significant inhibitory activity, across all studied concentrations, against Micrococcus spp ., bringing to light its importance in managing infections mediated by Micrococcus spp. Furthermore, levofloxacin maintained consistent inhibitory and bactericidal activity against Pseudomonas aeruginosa (MIC/MBC: 0.125 µg/ml), corroborating its potent efficacy as reported in previous studies. Despite these promising results, the study reveals emerging levofloxacin resistance in previously susceptible organisms, underscoring the necessity for ongoing surveillance, targeted antimicrobial design, and comprehensive sensitivity testing to combat the global challenge of antimicrobial resistance (AMR). Abbreviations MDR: Multidrug resistance, AMR: Antimicrobial resistance, IZD: Inhibition Zone Diameter, MIC: Minimum Inhibitory Concentration, MBC: Minimum Bactericidal Concentration. Declarations Ethics approval and consent to participate: Ethical clearance was obtained from the Research Ethics Committee of the University of Lagos. (REG NO: UNILAGREC/22/06/005 ) Consent for publication: Not Applicable Availability of data and material: All data generated or analysed during this study are included in this published article. The data that support the findings of this study are available from https://www.ajol.info/index.php/tjpr/article/view/164273/153790 and https://www.researchgate.net/publication/325538114_Detection_inhibition_and_molecular_analysis_of_multidrug_resistant_aerobic_gram-negative_clinical_isolates_from_a_tertiary_hospital_in_Nigeria 10,11 . Competing interests: The authors declare that they have no competing interests Funding : This project was funded by the Tertiary Education Trust Fund (TETfund), registration number TETF/ES/DR&D-CE/NRF2021/SETHi/HSW/00290/VOL.1 with Gloria A. Ayoola as the Principal Investigator, and the department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Lagos as the hosting laboratory. Authors' contributions: The manuscript was written through the contributions of all authors. All authors have approved the final version of the manuscript. Specific author contributions are as follows: A.S.A. developed the research concept and design, collected, analysed, and interpreted data, and prepared and reviewed the manuscript; GAA is the Principal Investigator. She developed the research concept and design, analysed and interpreted data, and reviewed and approved the manuscript; AOA developed the research concept and design, analysed and interpreted data, and reviewed and approved the manuscript; DBO developed the research concept and design, collected, analysed, and interpreted data, and approved the manuscript; OSN analysed and interpreted data, and reviewed and approved the manuscript; DKA critically reviewed and approved the manuscript; MOO critically reviewed and approved the manuscript; OOJ critically reviewed and approved the manuscript; UA analysed and interpreted data, and reviewed and approved the manuscript. Acknowledgements: We acknowledge the numerous authors whose works are referenced in this study for laying the foundation and inspiring our research. Authors' information: Corresponding Author: Abubakar Sadiq Abdullahi- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Lagos College of Medicine Campus, Idi-araba, Lagos, Nigeria. Email: [email protected] , Contact: +2348137501119, ORCID ID: https://orcid.org/0000-0002-3896-3844 Authors: Gloria Abiodun Ayoola, David Blessing Orojuekun, David K. Adeyemi and Oluwatosin O. Johnson - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Lagos College of Medicine Campus, Idi-araba, Lagos, Nigeria. Email contacts: [email protected] , [email protected] , [email protected] , and [email protected] respectively. Adebowale O. Adeluola and Usman Abdulrahman - Department of Pharmaceutical Microbiology & Biotechnology, Faculty of Pharmacy, University of Lagos College of Medicine Campus, Idi-araba, Lagos, Nigeria. Email: [email protected] and [email protected] , respectively. Okafor Sunday N - Department of Pharmaceutical and Medicinal Chemistry, University of Nigeria Nsukka, Enugu State Nigeria. ORCID: https://orcid.org/0000-0002-7476-3292 , Email [email protected] Modupe O. Ologunagba - Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Lagos College of Medicine Campus, Idi-araba, Lagos, Nigeria . Email: [email protected] References UN Environment Programme. Bracing for Superbugs : Strengthening Environmental Action in the One Health Response to Antimicrobial Resistance ; United Nations Environment Programme, 2023. World Health Organisation (WHO). Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report 2022 ; World Health Organization, 2022. Prestinaci, F.; Pezzotti, P.; Pantosti, A. Antimicrobial Resistance: A Global Multifaceted Phenomenon. Pathogens and Global Health . Maney Publishing October 1, 2015, pp 309–318. https://doi.org/10.1179/2047773215Y.0000000030. Nkansa-Gyamfi, N. A.; Kazibwe, J.; Traore, D. A. K.; Nji, E. Prevalence of Multidrug-, Extensive Drug-, and Pandrug-Resistant Commensal Escherichia Coli Isolated from Healthy Humans in Community Settings in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis. Global Health Action . Taylor and Francis Ltd. December 13, 2019. https://doi.org/10.1080/16549716.2020.1815272. Tanwar, J.; Das, S.; Fatima, Z.; Hameed, S. Multidrug Resistance: An Emerging Crisis. Interdisciplinary Perspectives on Infectious Diseases . Hindawi Limited 2014. https://doi.org/10.1155/2014/541340. Berry, L.; Domalaon, R.; Brizuela, M.; Zhanel, G. G.; Schweizer, F. Polybasic Peptide-Levofloxacin Conjugates Potentiate Fluoroquinolones and Other Classes of Antibiotics against Multidrug-Resistant Gram-Negative Bacteria. Medchemcomm 2019 , 10 (4), 517–527. https://doi.org/10.1039/c9md00051h. O.B. Makanjuola; S.A. Fayemiwo; A.O. Okesola; A. Gbaja; V.A. Ogunleye; A.O. Kehinde; R.A. Bakare. Pattern of Multidrug Resistant Bacteria Associated with Intensive Care Unit Infections in Ibadan Nigeria. Ann Ib Postgrad Med 2018 , 16 (2). World Health Organisation. Antimicrobial Resistance ; 2023. https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance (accessed 2024-08-19). Sajid, M. I.; Lohan, S.; Kato, S.; Tiwari, R. K. Combination of Amphiphilic Cyclic Peptide [R4W4] and Levofloxacin against Multidrug-Resistant Bacteria. Antibiotics 2022 , 11 (3). https://doi.org/10.3390/antibiotics11030416. Adeluola, A. O.; Oyedeji, K. S.; Mendie, U. E.; Johnson, J. R.; Porter, J. R. Detection of Efflux Pump Activity among Clinical Isolates of Staphylococcus and Micrococcus Species. Tropical Journal of Pharmaceutical Research 2017 , 16 (11), 2697–2704. https://doi.org/10.4314/tjpr.v16i11.18. Adeluola A.O; Oyedeji K.S; Mendie U. E; Johnson J.R; Porter J.R. Detection, Inhibition and Molecular Analysis of Multidrug Resistant Aerobic Gram-Negative Clinical Isolates from a Tertiary Hospital in Nigeria. Afr. J. Biomed. Res 2018 , 21 , 15–21. Jalil, M. B.; Al Atbee, M. Y. N. The Prevalence of Multiple Drug Resistance Escherichia Coli and Klebsiella Pneumoniae Isolated from Patients with Urinary Tract Infections. J Clin Lab Anal 2022 , 36 (9). https://doi.org/10.1002/jcla.24619. Geetha, P. V.; Aishwarya, K. V. L.; Mariappan, S.; Sekar, U. Fluoroquinolone Resistance in Clinical Isolates of Klebsiella Pneumoniae. J Lab Physicians 2020 , 12 (02), 121–125. https://doi.org/10.1055/s-0040-1716478. Veličković-Radovanović, R.; Stefanović, N.; Damnjanović, I.; Kocić, B.; Mladenović-Antić, S.; Dinić, M.; Petrović, J.; Mitić, R.; Catić-Đorđević, A. Antibiotic Utility and Susceptibility Changes of Multidrug-Resistant Escherichia Coli and Klebsiella Spp: 5-Year Experience in a Tertiary Healthcare Centre. European Journal of Hospital Pharmacy 2022 , 29 (2), 84–89. https://doi.org/10.1136/ejhpharm-2021-002758. National Center for Biotechnology Information. PubChem Compound Summary for CID 149096, Levofloxacin . https://pubchem.ncbi.nlm.nih.gov/compound/Levofloxacin (accessed 2024-12-07). Croom, K. F.; Goa, K. L. Levofloxacin A Review of Its Use in the Treatment of Bacterial Infections in the United States. Adis Drug Evaluation 2003 , 63 (24), 2769–2802. Sihotang, T. S. U.; Widodo, A. D. W.; Endraswari, P. D. Effect of Ciprofloxacin, Levofloxacin, and Ofloxacin on Pseudomonas Aeruginosa: A Case Control Study with Time Kill Curve Analysis. Annals of Medicine and Surgery 2022 , 82 . https://doi.org/10.1016/j.amsu.2022.104674. Daniel Kwame Afriyie; Linda Brakowaah Adu; Marc Dzradosi; Seth Kwabena Amponsah; Prince Ohene-Manu; Francis Manu-Ofei. Comparative in Vitro Activity of Ciprofloxacin and Levofloxacin against Isolated Uropathogens in Ghana: A Pilot Study. Pan Africa Medical Journal 2018 , 30 (194). https://doi.org/10.11604/pamj.2018.30.194.15457. Croom, K. F.; Goa, K. L. Levofloxacin A Review of Its Use in the Treatment of Bacterial Infections in the United States. Adis Drug Evaluation 2003 , 63 (24), 2769–2802. Alves, D. A.; Machado, D.; Melo, A.; Pereira, R. F. C.; Severino, P.; Hollanda, L. M. De; Araújo, D. R.; Lancellotti, M. Preparation of Thermosensitive Gel for Controlled Release of Levofloxacin and Their Application in the Treatment of Multidrug-Resistant Bacteria. Biomed Res Int 2016 , 2016 . https://doi.org/10.1155/2016/9702129. Veselkov, D. A.; Laponogov, I.; Pan, X. S.; Selvarajah, J.; Skamrova, G. B.; Branstrom, A.; Narasimhan, J.; Prasad, J. V. N. V.; Fisher, L. M.; Sanderson, M. R. Structure of a Quinolone-Stabilized Cleavage Complex of Topoisomerase IV from Klebsiella Pneumoniae and Comparison with a Related Streptococcus Pneumoniae Complex. Acta Crystallogr D Struct Biol 2016 , 72 (4), 488–496. https://doi.org/10.1107/S2059798316001212. National Center for Biotechnology Information. PubChem Compound Summary for CID 149096, Levofloxacin. https://pubchem.ncbi.nlm.nih.gov/compound/Levofloxacin. DrugBank Online. Levofloxacin . https://go.drugbank.com/drugs/DB01137. Izadi, E.; Afshan, G.; Patel, R. P.; Rao, V. M.; Liew, K. Bin; Affandi, M. M. R. M. M.; Kifli, N.; Suleiman, A.; Lee, K. S.; Sarker, M. M. R.; Zaidi, S. T.; Ming, L. C. Levofloxacin: Insights into Antibiotic Resistance and Product Quality. Front Pharmacol 2019 , 10 (August). https://doi.org/10.3389/fphar.2019.00881. Geetha, P. V.; Aishwarya, K. V. L.; Mariappan, S.; Sekar, U. Fluoroquinolone Resistance in Clinical Isolates of Klebsiella Pneumoniae. J Lab Physicians 2020 , 12 (02), 121–125. https://doi.org/10.1055/s-0040-1716478. Saad Latteef, N.; Salih, W. Y.; Aziz Abdulhassan, A.; Jasim Obeed, R. Evaluation of Gene Expression of NorA and NorB Gene in Ciproflaxin and Levofloxacin Resistant Staphylococcus Aureus. Arch Razi Inst 2022 , 77 (5), 1987–1993. https://doi.org/10.22092/ARI.2022.358335.2197. Kowalska-Krochmal, B.; Dudek-Wicher, R. The Minimum Inhibitory Concentration of Antibiotics: Methods, Interpretation, Clinical Relevance. Pathogens . MDPI AG February 1, 2021, pp 1–21. https://doi.org/10.3390/pathogens10020165. Magréault, S.; Jauréguy, F.; Carbonnelle, E.; Zahar, J. R. When and How to Use MIC in Clinical Practice? Antibiotics . MDPI December 1, 2022. https://doi.org/10.3390/antibiotics11121748. O’Malley, S. M.; Emele, F. E.; Nwaokorie, F. O.; Idika, N.; Umeizudike, A. K.; Emeka-Nwabunnia, I.; Hanson, B. M.; Nair, R.; Wardyn, S. E.; Smith, T. C. Molecular Typing of Antibiotic-Resistant Staphylococcus Aureus in Nigeria. J Infect Public Health 2015 , 8 (2), 187–193. https://doi.org/10.1016/j.jiph.2014.08.001. Innocent, I. G.; Gowon, A. G.; Ademah, C.; Agbese, J. B.; Kuleve, M. I.; Jonah, O. I. Isolation and Antibiotic Sensitivity of Klebsiella Pneumoniae among Urinary Tract Infected Patients in Dalhatu Araf Specialist Hospital Lafia, Nasarawa State Nigeria. J Adv Microbiol 2023 , 23 (7), 1–6. https://doi.org/10.9734/jamb/2023/v23i7731. Dehnamaki, M.; Ghane, M.; Babaeekhou, L. Detection of OqxAB and QepA Efflux Pumps and Their Association with Antibiotic Resistance in Klebsiella Pneumoniae Isolated From Urinary Tract Infection. International Journal of Infection 2020 , 7 (4). https://doi.org/10.5812/iji.107397. Michalik, M.; Samet, A.; Podbielska‑Kubera, A.; Savini, V.; Międzobrodzki, J.; Kosecka‑Strojek, M. Coagulase-Negative Staphylococci (CoNS) as a Significant Etiological Factor of Laryngological Infections: A Review. Annals of Clinical Microbiology and Antimicrobials . BioMed Central Ltd June 4, 2020. https://doi.org/10.1186/s12941-020-00367-x. Azih, A.; Enabulele, I. Species Distribution and Virulence Factors of Coagulase Negative Staphylococci Isolated From Clinical Samples From the University of Benin Teaching Hospital, Edo State, Nigeria. Journal of Natural Sciences Research 2013 , 3 (9). Garbacz, K.; Wierzbowska, M.; Kwapisz, E.; Kosecka-Strojek, M.; Bronk, M.; Saki, M.; Międzobrodzki, J. Distribution and Antibiotic-Resistance of Different Staphylococcus Species Identified by Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) Isolated from the Oral Cavity. J Oral Microbiol 2021 , 13 (1). https://doi.org/10.1080/20002297.2021.1983322. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing. In CLSI supplement M100 ; CLINICAL AND LABORATORY, 2024; Vol. 34th ed. Grillon, A.; Schramm, F.; Kleinberg, M.; Jehl, F. Comparative Activity of Ciprofloxacin, Levofloxacin and Moxifloxacin against Klebsiella Pneumoniae, Pseudomonas Aeruginosa and Stenotrophomonas Maltophilia Assessed by Minimum Inhibitory Concentrations and Time-Kill Studies. PLoS One 2016 , 11 (6). https://doi.org/10.1371/journal.pone.0156690. Spencer, A. C.; Panda, S. S. DNA Gyrase as a Target for Quinolones. Biomedicines . MDPI February 1, 2023. https://doi.org/10.3390/biomedicines11020371. L. Drago; E. De Vecchi; B. Mombelli; L. Nicola; M.Valli; M.R. Gismondo. Activity of Levofloxacin and Ciprofloxacin against Urinary Pathogens. Journal of Antimicrobial Chemotherapy 2001 , 48 , 37–45. Duggirala, A.; Joseph, J.; Sharma, S.; Nutheti, R.; Garg, P.; Das, T. Activity of Newer Fluoroquinolones against Gram-Positive and Gram-Negative Bacteria Isolated from Ocular Infections: An in Vitro Comparison. Indian J Ophthalmol 2007 , 55 (1), 15–19. https://doi.org/10.4103/0301-4738.29489. Odenholt, I.; Lowdin, E.; Cars, O. Bactericidal Effects of Levofloxacin in Comparison with Those of Ciprofloxacin and Sparfloxacin. Clinical Microbiology and Infection 1998 , 4 (5), 264–270. Hombach, M.; Böttger, E. C.; Roos, M. The Critical Influence of the Intermediate Category on Interpretation Errors in Revised EUCAST and CLSI Antimicrobial Susceptibility Testing Guidelines. Clinical Microbiology and Infection 2013 , 19 (2). https://doi.org/10.1111/1469-0691.12090. Pathogen Regulation Directorate, P. H. A. of C. Pathogen Safety Data Sheets: Infectious Substances-Micrococcus Spp. ; 2010. https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/micrococcus.html. Shi, X.; Qiu, S.; Ji, L.; Lu, H.; Wu, S.; Chen, Q.; Zou, X.; Hu, Q.; Feng, T.; Chen, S.; Cui, W.; Xu, S.; Jiang, M.; Cai, R.; Geng, Y.; Bai, Q.; Huang, D.; Liu, P. Pathogenetic Characterization of a Micrococcus Luteus Strain Isolated from an Infant. Front Pediatr 2023 , 11 . https://doi.org/10.3389/fped.2023.1303040. Zhu, M.; Zhu, Q.; Yang, Z.; Liang, Z. Clinical Characteristics of Patients with Micrococcus Luteus Bloodstream Infection in a Chinese Tertiary-Care Hospital. Pol J Microbiol 2021 , 70 (3), 321–326. https://doi.org/10.33073/PJM-2021-030. Miquel B.Ekkelenkamp; Suzan H.M.Rooijakkers; Marc J.M.Bonten. Staphylococci and Micrococci. In Infectious Diseases ; 2010; Vol. 2. Wispelwey, B. Clinical Implications of Pharmacokinetics and Pharmacodynamics of Fluoroquinolones. Clinical Infectious Diseases 2005 , 41 (Supplement 2), S127–S135. https://doi.org/10.1086/428053. Sihotang, T. S. U.; Widodo, A. D. W.; Endraswari, P. D. Effect of Ciprofloxacin, Levofloxacin, and Ofloxacin on Pseudomonas Aeruginosa: A Case Control Study with Time Kill Curve Analysis. Annals of Medicine and Surgery 2022 , 82 . https://doi.org/10.1016/j.amsu.2022.104674. A.W. Bauer; W.M. Kirby; J.C. Sherris; M. Turck. Antibiotic Susceptibility Testing by a Standardized Single Disk Method. Am J Clin Pathol 1966 , 45 (4), 493–496. https://doi.org/https://doi.org/10.1093/ajcp/45.4_ts.493. Hugo and Russell’s. Pharmaceutical Microbiology , Seventh Edition.; Denyer, S. P., Norman A Hodges, Sean P. Gorman, Eds.; Blackwell Science, 2004. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 26 May, 2025 Editor assigned by journal 24 May, 2025 Submission checks completed at journal 19 May, 2025 First submitted to journal 18 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6693557","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":458979174,"identity":"4fcecae4-4568-4e86-b634-a6cee27b3421","order_by":0,"name":"Abubakar Sadiq Abdullahi","email":"data:image/png;base64,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","orcid":"","institution":"University of Lagos","correspondingAuthor":true,"prefix":"","firstName":"Abubakar","middleName":"Sadiq","lastName":"Abdullahi","suffix":""},{"id":458979176,"identity":"250ae584-979c-446c-a924-dccedaadafe4","order_by":1,"name":"Gloria Abiodun Ayoola","email":"","orcid":"","institution":"University of Lagos","correspondingAuthor":false,"prefix":"","firstName":"Gloria","middleName":"Abiodun","lastName":"Ayoola","suffix":""},{"id":458979179,"identity":"c6c9300b-aed0-4d2d-acdc-39e17422e3ed","order_by":2,"name":"Adebowale O. 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Okafor","email":"","orcid":"","institution":"University of Nigeria","correspondingAuthor":false,"prefix":"","firstName":"Sunday","middleName":"N.","lastName":"Okafor","suffix":""},{"id":458979186,"identity":"99e9fd3b-2512-4670-8037-a417ab5b6f49","order_by":5,"name":"David Kehinde Adeyemi","email":"","orcid":"","institution":"University of Lagos","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"Kehinde","lastName":"Adeyemi","suffix":""},{"id":458979187,"identity":"0e2c8ce5-95df-40f3-ae7b-76cf696c1fde","order_by":6,"name":"Modupe O. Ologunagba","email":"","orcid":"","institution":"University of Lagos","correspondingAuthor":false,"prefix":"","firstName":"Modupe","middleName":"O.","lastName":"Ologunagba","suffix":""},{"id":458979188,"identity":"f8bd0646-5069-4b6d-98dd-c6277a58ee1f","order_by":7,"name":"Oluwatosin O. Johnson","email":"","orcid":"","institution":"University of Lagos","correspondingAuthor":false,"prefix":"","firstName":"Oluwatosin","middleName":"O.","lastName":"Johnson","suffix":""},{"id":458979189,"identity":"d95480d0-5100-476a-be2e-0a6631ab300c","order_by":8,"name":"Usman Abdulrahman","email":"","orcid":"","institution":"University of Lagos","correspondingAuthor":false,"prefix":"","firstName":"Usman","middleName":"","lastName":"Abdulrahman","suffix":""}],"badges":[],"createdAt":"2025-05-18 20:23:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6693557/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6693557/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":83194632,"identity":"2beeb336-2c05-40d9-8ea9-40cfb0d1afb6","added_by":"auto","created_at":"2025-05-21 04:53:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":45254,"visible":true,"origin":"","legend":"\u003cp\u003e3D Conformer of Levofloxacin. \u003cem\u003eSource: National Centre for Biotechnology Information\u003c/em\u003e. \u003cem\u003ePubChem Compound Summary on Levofloxacin\u003c/em\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6693557/v1/1fa03630b959ea8eb9a3cf30.png"},{"id":83195229,"identity":"2232f20f-bab4-4d65-9e69-7263cbc4dafd","added_by":"auto","created_at":"2025-05-21 05:09:55","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":219794,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e(a)\u003c/em\u003e Orthogonal view of the cleavage complex of topoisomerase IV from \u003cem\u003eK. pneumoniae \u003c/em\u003ein cartoon representations. \u003cem\u003eThe ParC subunit is in blue, ParE is in yellow and DNA is in cyan. The bound quinolone molecules (levofloxacin) are in red and are shown using van der Waals representation.\u003c/em\u003e \u003cem\u003e(b) \u003c/em\u003eChemical structure of levofloxacin observed within the active sites of \u003cem\u003eK. pneumoniae\u003c/em\u003etopoisomerase IV\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6693557/v1/073848338ccbbe412fd693ba.png"},{"id":83194633,"identity":"39ceb7d3-2bbc-44a9-81af-e6d625abaa63","added_by":"auto","created_at":"2025-05-21 04:53:55","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":59898,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 1: \u003c/strong\u003eMean Zone of inhibition (mm) from different concentrations of Levofloxacin (µg/ml) on bacteria isolates\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6693557/v1/ceabbc133b1dbf0bf620d939.png"},{"id":83195232,"identity":"bcca0589-f459-4cfb-9a77-517a1e28ea55","added_by":"auto","created_at":"2025-05-21 05:10:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2279693,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6693557/v1/dfa4ddc5-5268-498e-af07-f2e62de26b08.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Strategic Combat Against Antimicrobial Resistance: A Cross-sectional Evaluation of Levofloxacin’s Efficacy against Multidrug-resistant Bacterial Isolates in Nigeria","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003e\u003cstrong\u003eBACKGROUND\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe United Nations Environmental Programme has projected that by 2050, antimicrobial resistance (AMR) would claim annually over ten million lives, mirroring the staggering global cancer death toll of 2020\u0026nbsp;\u003csup\u003e1\u003c/sup\u003e. Recent studies rank AMR among the leading causes of death worldwide, with the highest mortality rates in low-resource settings\u003csup\u003e2\u003c/sup\u003e. The widespread use of antimicrobial drugs has significantly driven resistance among various bacterial strains, posing a critical threat to global health\u003csup\u003e2\u0026ndash;4\u003c/sup\u003e . Multidrug resistance (MDR) refers to a microorganism\u0026rsquo;s insensitivity to multiple, structurally unrelated antimicrobial agents, despite demonstrating prior susceptibility\u003csup\u003e5\u003c/sup\u003e. MDR infections severely limit therapeutic options\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003csup\u003e6\u003c/sup\u003e, undermining optimal patient care and escalating global health risks\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003csup\u003e7\u003c/sup\u003e. In 2019, bacterial AMR directly caused 1.27 million deaths and contributed to 4.95 million deaths globally\u003csup\u003e8\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eKey bacterial pathogens implicated in AMR include Methicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (MRSA)\u003csup\u003e9\u003c/sup\u003e; and \u003cem\u003eStaphylococcus xylosus\u003c/em\u003e, which harbours resistance genes and causes opportunistic infections\u003csup\u003e10\u003c/sup\u003e. \u003cem\u003eEnterobacteriaceae\u003c/em\u003e species such as \u003cem\u003eEscherichia coli\u003c/em\u003e, \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e, and \u003cem\u003eEnterobacter\u003c/em\u003e spp. produce extended-spectrum \u0026beta;-lactamases (ESBLs) that confer resistance to antibiotics like penicillins, third-generation cephalosporins, and even carbapenems. These resistance mechanisms exacerbate the global AMR crisis, necessitating the development of targeted therapeutic strategies\u003csup\u003e11\u0026ndash;13\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePrevious studies by Adeluola \u003cem\u003eet al\u0026nbsp;\u003c/em\u003e2017 and 2018\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003csup\u003e10,11\u003c/sup\u003e have linked phenotypic antibiotic drug-resistance and detectable genetic markers in 28 clinical isolates of \u003cem\u003eKlebsiella pneumonia\u003c/em\u003e, 3 isolates of \u003cem\u003eEscherichia coli\u003c/em\u003e, 1 isolate of \u003cem\u003eE. aerogenes,\u0026nbsp;\u003c/em\u003e14 isolates of \u003cem\u003eStaphylococcus aureus\u003c/em\u003e, 2 isolates of \u003cem\u003eS. lentus\u003c/em\u003e, 1 isolate of \u003cem\u003eS. xylosus\u003c/em\u003e and 1 \u003cem\u003eMicrococcus spp. o\u003c/em\u003ebtained from medical microbiology laboratories of the University of Lagos Teaching Hospital (LUTH)\u003cem\u003eand\u0026nbsp;\u003c/em\u003escreened for (i) antibiotic-susceptibility over a range of 11 classes of antibiotics, (ii) \u0026beta;-lactamase production, (iii) Extended Spectrum \u0026beta;-Lactamase(ESBL) production and (iv) Efflux pump activity (EPA)\u0026nbsp;\u003csup\u003e10,11\u003c/sup\u003e. Analysis of the Gram-negative isolates revealed that the isolates were mostly resistant to ampicillin, most susceptible to neomycin and ciprofloxacin and specifically constituted of nine MDR strains, twenty inducible \u0026beta;-lactamase producers and seven intrinsic \u0026beta;-lactamase producers. In addition, \u003cem\u003eAcrA\u003c/em\u003e and \u003cem\u003eAcrB\u0026nbsp;\u003c/em\u003egenes were detected in six isolates (confirming EPA in four \u003cem\u003eK. pneumonia strains\u003c/em\u003e, one \u003cem\u003eEnterobacter aerogenes\u003c/em\u003e and one \u003cem\u003eE. coli\u003c/em\u003e strain), \u003cem\u003eand blaCTX-M\u0026nbsp;\u003c/em\u003ewas detected as the gene conferring characteristics in three\u003cem\u003e\u0026nbsp;Klebsiella pneumoniae\u0026nbsp;\u003c/em\u003estrains, one \u003cem\u003eE. aerogenes\u003c/em\u003e strain, \u003cem\u003eblaTEM\u0026nbsp;\u003c/em\u003ewas detected as the gene conferring ESBL characteristics in \u003cem\u003eK. pneumonia isolates and a\u0026nbsp;\u003c/em\u003epositive correlation between ESBL production and fluoroquinolones resistance was reported. Studies on the Gram-positive isolates showed that twelve (12) isolates were MDR, 10 isolates were inducible \u0026beta;-lactamase producers, 3 isolates were intrinsic \u0026beta;-lactamase producers, seven were resistant to oxacillin and also produced carbapenemase enzyme, with 5 \u003cem\u003eS. aureus\u003c/em\u003e isolates and one \u003cem\u003eS. lentus\u0026nbsp;\u003c/em\u003efound as an Oxacillin Resistant \u003cem\u003eS. aureus\u003c/em\u003e (ORSA) and carbapenemase producers. The understudied \u003cem\u003eMicrococcus spp\u003c/em\u003e. was MDR, ORSA, and a carbapenemase producer\u003csup\u003e10,11\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eLevofloxacin, a third-generation and widely prescribed fluoroquinolone\u003csup\u003e14\u003c/sup\u003e, plays a pivotal role in combating bacterial infections, including community-acquired pneumonia, urinary tract infections, and \u003cem\u003ePseudomonas\u003c/em\u003e-mediated diseases\u003csup\u003e15\u003c/sup\u003e. Approved by the U.S. FDA in 1996, levofloxacin demonstrates superior antimicrobial activity against Gram-positive (\u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e) and Gram-negative (\u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e) pathogens\u003csup\u003e16\u003c/sup\u003e, surpassing other fluoroquinolones in potency\u003csup\u003e17\u0026ndash;19\u003c/sup\u003e. Chemically, levofloxacin is a chiral fluorinated carboxyquinolone and the optically active (\u0026minus;)-(S)-enantiomer of ofloxacin racemate, exhibiting 8- to 128-fold greater activity against bacterial pathogens\u003csup\u003e16,20\u003c/sup\u003e Chemical structure of Levofloxacin is shown in Figure I below\u003csup\u003e15\u003c/sup\u003e;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Levofloxacin functions by inhibiting DNA gyrase and topoisomerase IV, which play important roles in DNA replication, recombination and transcription\u003csup\u003e19,21,22\u003c/sup\u003e. In bacteria, topoisomerase IV, a tetramer of two ParC and two ParE subunits, unlinks daughter chromosomes before cell division, whereas the related enzyme gyrase, a GyrA2GyrB2 tetramer, supercoils DNA and helps unwind DNA at replication forks\u003csup\u003e21\u003c/sup\u003e. Both enzymes act via a double-strand DNA break involving a cleavage complex and are targets for quinolone antimicrobials that act by trapping these enzymes at the DNA-cleavage stage and preventing strand re-joining\u003csup\u003e19,21\u003c/sup\u003e. The three-dimensional X-ray structure of a \u003cem\u003eK. pneumoniae\u003c/em\u003e topoisomerase IV ParC/ParE cleavage complex with DNA stabilised by levofloxacin is shown in Figure 2a and 2b below; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eResistance to levofloxacin may generally develop due to mutations in DNA gyrase or topoisomerase IV,\u0026nbsp;or via efflux pump overexpression and production of \u0026beta;-Lactamases, thus limiting intracellular drug accumulation\u003csup\u003e22\u003c/sup\u003e. \u0026nbsp;Cross-resistance with other fluoroquinolones is common, although resistance between levofloxacin and structurally distinct antibiotic classes is rare due to significant differences in chemical structure and mechanism of action\u003csup\u003e23\u003c/sup\u003e. While numerous studies have documented levofloxacin-resistance rates\u003csup\u003e24\u0026ndash;26\u003c/sup\u003e, the minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) for levofloxacin among MDR bacterial isolates in Nigeria remain largely unexplored.\u003c/p\u003e\n\u003cp\u003eThe MIC value is a critical parameter for optimising antibiotic therapy, offering a quantitative measure of bacterial susceptibility\u003csup\u003e27\u003c/sup\u003e. Unlike qualitative methods, MIC determination provides insights into the degree of resistance and informs clinical decision-making\u003csup\u003e27,28\u003c/sup\u003e. Previous studies, including investigations in Iraq\u003csup\u003e12\u003c/sup\u003e and India\u003csup\u003e13\u003c/sup\u003e, report high resistance rates to levofloxacin among \u003cem\u003eE. coli\u003c/em\u003e and \u003cem\u003eK. pneumoniae\u003c/em\u003e. Similarly, Ghanaian investigations revealed significant resistance in \u003cem\u003eStaphylococcus aureus\u003c/em\u003e isolates\u003csup\u003e18\u0026nbsp;\u003c/sup\u003eand Nigerian studies indicated 18% resistance among \u003cem\u003eS. aureus\u003c/em\u003e isolates\u003csup\u003e29\u003c/sup\u003e. However, the absence of MIC and MBC data limits in these studies necessitates further studies to achieve a comprehensive understanding and targeted intervention strategies against these multidrug-resistant pathogens.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePrevious studies have linked phenotypic antibiotic drug-resistance and detectable genetic markers in 50 clinical isolates \u003cem\u003eo\u003c/em\u003ebtained from a tertiary hospital in Nigeria\u003csup\u003e10,11\u003c/sup\u003e. Here we aimed to evaluate the changes in antimicrobial susceptibility, minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of 20 validated bacterial isolates to levofloxacin.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRationale\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThese findings will provide a critical foundation for optimising therapeutic regimens, revising clinical breakpoints, and advancing antimicrobial stewardship programs, particularly in Nigeria, where MDR infections remain a significant public health concern. From our literature search and to the best of our knowledge, no previous studies have been conducted on the minimum inhibitory and bactericidal concentration of levofloxacin on genetically validated multidrug-resistant bacteria isolates in Nigeria.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003eStudy Design, Setting and Test Organisms\u003c/h2\u003e\n \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e\n \u003ch2\u003eBacterial Isolates\u003c/h2\u003e\n \u003cp\u003eEighteen clinical isolates from infections of the urinary tract, upper respiratory tract, ear and eye swabs, and blood cultures from medical microbiology laboratories of the University of Lagos Teaching Hospital (LUTH) that had been previously profiled and validated for identity and antimicrobial susceptibility in earlier studies\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e, were obtained from the Department of Pharmaceutical Microbiology, University of Lagos. All bacterial isolates used in this cross-sectional study were calibrated to 0.5 McFarland\u0026rsquo;s standard (0.05 ml of 1.0% barium chloride in 9.95 ml of 1.0% sulphuric acid) using sterile normal saline as diluent to yield an approximate cell density of 1x10\u003csup\u003e8\u003c/sup\u003e CFU/ ml.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eGram-negative Bacteria Isolates\u003c/strong\u003e: The study utilised seven strains of Extended \u0026beta;-lactamase producing \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e: Oga, N3, N24, OG 1(4), N19, Med 1(2) and N14; One strain of AmpC \u0026beta;-lactamase producing \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e Med 5(1); one strain of \u003cem\u003eKlebsiella pneumonia with\u003c/em\u003e efflux pump activity (EPA) OG 1(3) and a clinical isolate, \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e PA 24 were used for this study.\u003c/p\u003e\n \u003cp\u003eThe American Type Culture Collection (ATCC 25922) \u003cem\u003eEscherichia coli\u003c/em\u003e reference isolate was used as the standard drug-susceptible control against potential sources of bias, as recommended by the Clinical Laboratory Standards Institute\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eGram-positive Bacteria Isolates\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe study utilised three isolates of Oxacillin-Resistant and carbapenemase-producing strains of \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (ES 21, ES 44, MED4 (2)); one isolate of carbapenemase-producing strains of \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (ML 10). One strain of Oxacillin-resistant \u003cem\u003eStaphylococcus lentus\u003c/em\u003e (ES 14), one strain of Oxacillin-resistant and carbapenemase-producing Micrococcus \u003cem\u003espp.\u003c/em\u003e with efflux pump activity (ES 7), a strain of Oxacillin-resistant \u003cem\u003eStaphylococcus xylosus\u003c/em\u003e (ES 16) and a strain of \u003cem\u003eEnterococcus faecalis\u003c/em\u003e EF 24 were used for the study. The American Type Culture Collection (ATCC 25923) \u003cem\u003eStaphylococcus aureus reference\u003c/em\u003e isolate was used as the standard drug-susceptible control against potential sources of bias.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eVariables\u003c/h2\u003e\n \u003cp\u003eOutcomes were defined as the zones of inhibition (mm), minimum inhibitory concentrations (MIC), and minimum bactericidal concentrations (MBC) of levofloxacin against MDR isolates. Exposure was defined as in vitro treatment with standardised concentrations of levofloxacin. Predictors included bacterial species and resistance mechanisms (e.g., ESBL, AmpC). No known confounders or effect modifiers were introduced in this controlled in vitro study. MDR status was determined in a previous study by Adeluola et al, based on phenotypic antibiotic drug-resistance and detectable genetic markers in clinical isolates \u003cem\u003eo\u003c/em\u003ebtained from a tertiary hospital in Nigeria\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eData Sources / Measurement\u003c/h3\u003e\n\u003cp\u003eBacterial isolates were sourced from previously characterised clinical collections. Zone diameters, MIC, and MBC values were measured using standardised procedures, as per Bauer \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e and CLSI\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e recommendations, to ensure comparability across all bacterial groups.\u003c/p\u003e\n\u003ch3\u003eBias\u003c/h3\u003e\n\u003cp\u003eValidated multidrug-resistant (MDR) isolates of \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e, \u003cem\u003eStaphylococcus aureus\u003c/em\u003e, and \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e were chosen for this study to minimise selection and measurement bias. Standardised protocols were followed for sample handling, antimicrobial susceptibility testing, and MIC/MBC determination based on Bauer \u003cem\u003eet al\u003c/em\u003e\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e and CLSI\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e guidelines. All assays were performed in triplicate to ensure reproducibility and minimise observer bias.\u003c/p\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eStudy Size\u003c/h2\u003e\n \u003cp\u003eThe study analysed 20 MDR bacterial isolates chosen based on the presence of specific resistance phenotypes (e.g., ESBL, AmpC, carbapenemase production). This size was determined to provide sufficient representation across key MDR profiles within logistical and resource constraints while allowing meaningful comparison of susceptibility and bactericidal thresholds.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003eQuantitative Variables\u003c/h2\u003e\n \u003cp\u003eQuantitative variables such as zone of inhibition, MIC, and MBC values were recorded in millimetres (mm) and micrograms per millilitre (\u0026micro;g/ml), respectively. Groupings were based on bacterial species and resistance profiles to enable comparative evaluation of levofloxacin efficacy across different MDR phenotypes.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePreparation of Working Concentrations\u003c/strong\u003e: A stock solution of Levofloxacin with a concentration of 5 mg/ ml, equivalent to 5000 \u0026micro;g/ ml, was prepared and labelled as Sample I. From sample I, a series of 1:10 dilutions was carried out to yield a 500 \u0026micro;g/ ml concentration and a 50 \u0026micro;g/ ml concentration. From this, a series of double dilutions was done using sterile distilled water as diluent to yield a 25 \u0026micro;g/ ml, 12.5 \u0026micro;g/ ml and 6.25 \u0026micro;g/ml concentration for susceptibility testing.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAntibiotic Susceptibility Testing\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eSimilar to Bauer \u003cem\u003eet al.\u003c/em\u003e \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e, calibrated cultures of the isolates were seeded into 25 ml Mueller-Hinton agar (MHA), which was poured and allowed to solidify on petri dishes. Each plate appropriately labelled with the identity of the seeded isolate was marked out in four segments, with each segment assigned to a particular test concentration of levofloxacin being used. Plates were allowed to dry on the bench for 3\u0026ndash;5 minutes, and a cork borer of 10 mm in diameter was used to bore wells in the marked-out segments of the MHA Petri dishes. In each of the segments, 150 \u0026micro;L of levofloxacin (50\u0026micro;g/ ml, 25 \u0026micro;g / ml, and 6.25 \u0026micro;g/ ml) was aseptically dispensed into their assigned bored holes in the labelled quadrants. The plates were allowed to stand for 2 hrs on the bench, incubated at 37 ℃ \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e 2 for 24 hrs and observed for zones of inhibition.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eDetermination of Minimum Inhibitory Concentration (MIC)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eA combination of the Agar dilution technique recommended by Hugo and Russell\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e and the Clinical and Laboratory Standards Institute\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e, were used to determine the minimum concentration and interpretative breakpoints of the levofloxacin that inhibited each assay organism. CLSI Interpretative breakpoints and categories are as shown in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e below;\u0026nbsp;\u003c/p\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003e\u003cstrong\u003eCLSI Interpretative Categories and MIC Breakpoints (\u0026micro;g/ml) for Levofloxacin\u003c/strong\u003e\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIsolates\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSusceptible (S)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIntermediate (I)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eResistant ( R )\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eEnterobacterales\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;\u0026thinsp;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;2.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;\u0026thinsp;1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;4.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eStaphylococcus spp.\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;\u0026thinsp;1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;4.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eEnterococcus spp.\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;\u0026thinsp;2.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;8.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eATCC 25922\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eEscherichia coli\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e0.008\u0026ndash;0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003eEight (8) concentrations of 2500, 250, 25, 2.5, 1.25, 0.625, 0.0625 and 0.00625 ug/ ml were prepared, four (4) concentrations \u0026ndash; 25, 0.625, 0.0625 and 0.00625 ug/ ml were used as stock concentrations and thirteen (13) working concentrations were used- 0.001953125, 0.00390625, 0.0078125, 0.015625, 0.03125, 0.0625, 0.125, 0.25, 0.50, 1.00, 2.00, 4.00 and 8.00 ug/ ml as highlighted in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e below. Working concentrations for MIC determination were prepared by measuring specified volumes of agar into universal glass bottles labelled A-M measured agar was sterilised in the autoclave at 121\u0026deg;C for 15 mins. The required volumes of levofloxacin test solutions were added to the required volume of molten MHA, thoroughly mixed and transferred into labelled Petri dishes (150 mm x 15 mm). Each test organism was spotted twice, with the aid of an inoculating loop, on its respective assigned sites on the MHA plates, in an aseptic zone. All test organisms used were standardised to 0.5 McFarland\u0026rsquo;s Standard. Inoculated plates were incubated at 37\u0026deg;C for 24 hrs, and the MICs were recorded as the lowest concentration of Levofloxacin with no apparent growth of the test isolates on the MHA plates.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eConstitution of Muller Hinton Agar (MHA) Plates for Determination of Minimum Inhibitory Concentration (MIC) of Levofloxacin\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBottle / Plate Label\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eStock Concentration of Levofloxacin (ug/ ml)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVolume of Levofloxacin withdrawn from Stock (ml)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVolume of MHA used (ml)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eConcentration of Levofloxacin in MHA (ug/ ml)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.00625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.001953125\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.062500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.003906250\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.062500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.007812500\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.062500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.015625000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.625000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.031250000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.625000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.062500000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.625000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.125000000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.00000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.250000000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.00000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.500000000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eJ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.00000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000000000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.00000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.000000000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.00000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.000000000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.00000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.000000000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cstrong\u003eDetermination of Minimum Bactericidal Concentration (MBC\u003c/strong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eIn universal glass bottles, 20 ml of single-strength MHA with 0.1% Tween 80 (MHA-Tween 80 agar) was autoclaved at 121 \u003csup\u003eo\u003c/sup\u003eC. for 15 minutes. Molten MHA - Tween 80 agar was aseptically transferred into labelled Petri dishes and allowed to solidify and dry for about 30 minutes. All MIC plates that showed no growth were selected for sub-culturing onto blank MHA\u0026ndash;Tween 80 agar plates. Using a flame-sterilised inoculating loop, the spots where there was no bacterial growth, on the selected MIC plates, were rubbed and streaked onto the blank MHA-Tween 80 agar plates. The fresh plates were incubated at 37\u0026deg;C for 24 hrs. For each test isolate, the lowest concentration that still did not show any growth at this stage was taken as the MBC.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eStatistical Methods\u003c/strong\u003e\u003c/p\u003e\u003cspan\u003e\n \u003cp\u003eA. All data were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (S.D.). Significant differences among the groups were determined by one-way analysis of variance (ANOVA), and Graphs were plotted using Microsoft Excel. Results were considered to be significant at \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.05.\u003c/p\u003e\n \u003c/span\u003e \u003cspan\u003e\n \u003cp\u003eB. Missing Data: There were no missing data; all isolates were successfully profiled, and all experimental replicates were completed.\u003c/p\u003e\n \u003c/span\u003e\n\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eBacterial Isolates flow (numbers at each stage)\u003c/h2\u003e \u003cp\u003eOut of 50 originally profiled isolates, 20 genetically validated MDR strains were selected based on previously confirmed resistance mechanisms and susceptibility profiles\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eReasons for non-participation\u003c/h2\u003e \u003cp\u003eAll selected isolates met the inclusion criteria; no exclusions were made.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eAntimicrobial Susceptibility\u003c/h2\u003e \u003cp\u003eThe results, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e reveal the dose dependent antibacterial susceptibility of MDR bacteria isolates to levofloxacin across four concentrations. Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows that 15% (3/20) of MDR \u003cem\u003eK. pneumoniae\u003c/em\u003e strains with EPA and ESBL-producing activity demonstrated no susceptibility to levofloxacin.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eZones of Inhibition (mm) From Different Concentrations of Levofloxacin (\u0026micro;g/ml) against Bacterial isolates\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eS/N\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eORGANISM CODE (\u003cem\u003eOrganism Phenotype)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003eKey: ESBL- Extended Spectrum β-Lactamase\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003eEPA: Efflux Pump Activity\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003eORSA: Oxacillin-resistant Staphylococcus aureus\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003e*MEAN ZONES OF INHIBITION (mm) FROM DIFFERENT CONCENTRATIONS (\u0026micro;g/ml)\u003c/p\u003e \u003cp\u003e[Mean\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;S.D]\u003c/p\u003e\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.00 ug /ml\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.00 ug /ml\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.50 ug /ml\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.25 ug /ml\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eN 19\u003c/b\u003e: \u003cem\u003eKlebsiella pneumoniae ESBL producer\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.67\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.67\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15.67\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eN 24\u003c/b\u003e: \u003cem\u003eKlebsiella pneumoniae ESBL producer\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23.67\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMed 1(2)\u003c/b\u003e: \u003cem\u003eKlebsiella pneumoniae EPA; ESBL producer\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.67\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eOG 1(3)\u003c/b\u003e: \u003cem\u003eKlebsiella pneumoniae EPA\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eOG 1(4)\u003c/b\u003e: \u003cem\u003eKlebsiella pneumoniae EPA; ESBL producer\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eOga\u003c/b\u003e: \u003cem\u003eKlebsiella pneumoniae ESBL producer\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMed 5(1)\u003c/b\u003e: \u003cem\u003eKlebsiella pneumoniae AmpC β-lactamase producer\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.67\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21.67\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eN 14\u003c/b\u003e: \u003cem\u003eEnterobacter aerogenes ESBL producer\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21.67\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eN 3\u003c/b\u003e: \u003cem\u003eKlebsiella pneumoniae ESBL producer\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.67\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e26.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003ePA 24\u003c/b\u003e: \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eATCC 25922\u003c/b\u003e: \u003cem\u003eEscherichia coli\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.67\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21.67\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eES 44\u003c/b\u003e: \u003cem\u003eStaphylococcus aureus, EPA, ORSA, Carbapenemase\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42.67\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e33.67\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMed 4 (2)\u003c/b\u003e: \u003cem\u003eStaphylococcus aureus, EPA, ORSA, Carbapenemase\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.67\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29.67\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e28.67\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eES 14\u003c/b\u003e: \u003cem\u003eStaphylococcus lentus ORSA\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eES 16\u003c/b\u003e: \u003cem\u003eStaphylococcus xylosus, ORSA\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eES 21\u003c/b\u003e: \u003cem\u003eStaphylococcus aureus, ORSA, Carbapenemase\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eML 10\u003c/b\u003e\u003c/p\u003e \u003cp\u003e: \u003cem\u003eStaphylococcus aureus\u003c/em\u003e,\u003c/p\u003e \u003cp\u003e\u003cem\u003eCarbapenemase\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eES 7\u003c/b\u003e: \u003cem\u003eMicrococcus species\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003eEPA, ORSA, Carbapenemase\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e34.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e32.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e19.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eEF 24\u003c/b\u003e: \u003cem\u003eEnterococcus faecalis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.67\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eATCC 25923\u003c/b\u003e: \u003cem\u003eStaphylococcus aureus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.33\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.67\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e*p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 when values are greater than 0.00\u003c/h2\u003e \u003cdiv id=\"Sec18\" class=\"Section3\"\u003e \u003ch2\u003eMinimum Inhibitory Concentration (MIC) and Interpretative Breakpoints\u003c/h2\u003e \u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e2\u003c/span\u003e, the MIC of levofloxacin against \u003cem\u003eEscherichia coli\u003c/em\u003e (ATCC 25922) was 0.03125 \u0026micro;g/ml, within the CLSI QC range (0.008\u0026ndash;0.06 \u0026micro;g/ml)\u003csup\u003e35\u003c/sup\u003e confirming the reproducibility of this study.\u003c/p\u003e \u003cp\u003eLevofloxacin exhibited higher inhibitory activity against Gram-negative (72.73% susceptible) than Gram-positive (55.56% susceptible) organisms. MICs ranged from 0.0625\u0026ndash;8.00 \u0026micro;g/ml for Gram-positive and 0.015625\u0026ndash;1.00 \u0026micro;g/ml for Gram-negative organisms. Our findings also reveal the marked susceptibility of \u003cem\u003eMicrococci\u003c/em\u003e to levofloxacin across all studied concentrations (IZD 50ug/ml: 37.33 mm\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.58, MIC: 0.125 \u0026micro;g/ml).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMinimum Inhibitory Concentration (MICs) and Minimum Bactericidal Concentrations of Levofloxacin against Gram-positive Bacterial Isolates\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eS/N\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eORGANISM CODE\u003c/p\u003e \u003cp\u003e(\u003cem\u003eOrganism Phenotype; Genus and Species\u003c/em\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMIC VALUE\u003c/p\u003e \u003cp\u003e(\u0026micro;g/ml)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCLSI Interpretative Category / QC range\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMBC VALUE\u003c/p\u003e \u003cp\u003e(\u0026micro;g/ml)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eGRAM-POSITIVE ORGANISMS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eEs 44\u003c/b\u003e: \u003cem\u003eStaphylococcus aureus\u003c/em\u003e,\u003c/p\u003e \u003cp\u003e\u003cem\u003e(EPA, ORSA, Carbapenemase producer)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMed 4 (2)\u003c/b\u003e: \u003cem\u003eStaphylococcus aureus, \u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(EPA, ORSA, Carbapenemase producer)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0625\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eEs 14\u003c/b\u003e: \u003cem\u003eStaphylococcus lentus (ORSA)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eEs 16\u003c/b\u003e: \u003cem\u003eStaphylococcus xylosus (ORSA)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0625\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eEs 21\u003c/b\u003e: \u003cem\u003eStaphylococcus aureus,\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(ORSA, Carbapenemase producer)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eML 10\u003c/b\u003e \u003cem\u003eStaphylococcus aureus\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(Carbapenemase producer)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eEs 7\u003c/b\u003e: \u003cem\u003eMicrococcus species\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(EPA, ORSA, Carbapenemase producer)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.125\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eEF 24\u003c/b\u003e: \u003cem\u003eEnterococcus faecalis (clinical isolate)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eATCC 25923\u003c/b\u003e: \u003cem\u003eStaphylococcus aureus\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(standard strain)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLowest Concentration:\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.125\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHighest Concentration:\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTotal Number of Resistant isolates (R):\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1 (11.11%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTotal Number of Intermediate isolates (I):\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1 (11.11%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTotal Number of Susceptible isolates (U):\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e5 (55.56%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTotal Number of Unclassified isolates (-):\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e2 (22.22%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMinimum Inhibitory Concentration (MICs) and Minimum Bactericidal Concentrations of Levofloxacin against Gram-Negative Bacterial Isolates\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eS/N\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eORGANISM CODE\u003c/p\u003e \u003cp\u003e(\u003cem\u003eOrganism Phenotype; Genus and Species\u003c/em\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMIC VALUE\u003c/p\u003e \u003cp\u003e(\u0026micro;g/ml)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCLSI Interpretative Category / QC range\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMBC VALUE\u003c/p\u003e \u003cp\u003e(\u0026micro;g/ml)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eGRAM NEGATIVE ORGANISMS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eN 19\u003c/b\u003e: \u003cem\u003eKlebsiella pneumoniae \u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(ESBL producer)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.015625\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.015625\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eN 24\u003c/b\u003e: \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(ESBL producer)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMed 1(2)\u003c/b\u003e: \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(EPA; ESBL producer)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eOG 1(3)\u003c/b\u003e \u003cem\u003eKlebsiella pneumoniae (EPA)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eOG 1(4)\u003c/b\u003e: \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(EPA; ESBL producer)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eOga\u003c/b\u003e: \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(ESBL producer)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMed 5(1)\u003c/b\u003e \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(AmpC β-lactamase producer)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eN 14\u003c/b\u003e: \u003cem\u003eEnterobacter aerogenes\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(ESBL producer)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eN 3\u003c/b\u003e: \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(ESBL producer)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003ePA 24\u003c/b\u003e: \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(Clinical isolate)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.125\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eATCC 25922\u003c/b\u003e: \u003cem\u003eEscherichia coli\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(Standard Strain)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.03125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eComplies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eLowest Concentration\u003c/b\u003e:\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.015625\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.015625\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eHighest Concentration\u003c/b\u003e:\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTotal Number of Resistant isolates (R):\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0 (0.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTotal Number of Intermediate isolates (S):\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e2 (18.18%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTotal Number of Susceptible isolates (S):\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e8 (72.73%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTotal Number of Unclassified isolates (-):\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1 (9.09%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eMinimum Bactericidal Concentration (MBC)\u003c/h2\u003e \u003cp\u003eIn this study, MBCs ranged from 0.125\u0026ndash;8.00 \u0026micro;g/ml for Gram-positive and 0.015625\u0026ndash;8.00 \u0026micro;g/ml for Gram-negative organisms, as shown in Tables\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e3\u003c/span\u003e above. These results show a 50% increase in the lower limit MIC concentration for Gram-positive organisms and a 12.5% increase in the upper limit MBC concentration for Gram-negative organisms. The success of antimicrobial therapy is determined by the interaction of drug administration, the state of the host and the causative agent of infection\u003csup\u003e\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eAntimicrobial Susceptibility\u003c/h2\u003e \u003cp\u003e \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e remains a leading nosocomial pathogen\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e, implicated in urinary tract infection and rising multidrug resistance rates\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. The non-susceptibility of 15% of MDR \u003cem\u003eK. pneumoniae\u003c/em\u003e strains with EPA and ESBL-producing activity to Levofloxacin is consistent with Geetha \u003cem\u003eet al\u003c/em\u003e.'s findings, who reported levofloxacin resistance in 110 \u003cem\u003eK. pneumoniae\u003c/em\u003e isolates\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Dehnamaki \u003cem\u003eet al.\u003c/em\u003e also identified 57%, 56%, and 21% molecular distribution of \u003cem\u003eoqxA, oqxB\u003c/em\u003e and \u003cem\u003eqepa\u003c/em\u003e genes, respectively, in \u003cem\u003eK. pneumoniae\u003c/em\u003e isolates from urine samples, conferring 68% levofloxacin resistance\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. These findings emphasise the need for research into efflux pump characterisation and the development of targeted inhibitors to combat MDR.\u003c/p\u003e \u003cp\u003eCoagulase-negative staphylococci (CoNS), such as \u003cem\u003eStaphylococcus xylosus\u003c/em\u003e, \u003cem\u003eS. hominis\u003c/em\u003e, and \u003cem\u003eS. saprophyticus\u003c/em\u003e, are common nosocomial pathogens causing deep organ infections \u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e. In the antimicrobial susceptibility study, levofloxacin exhibited the lowest inhibition against an oxacillin-resistant \u003cem\u003eS. xylosus\u003c/em\u003e strain, with activity only at 50.00 \u0026micro;g/ml. In contrast, the same concentration markedly inhibited two carbapenemase-producing \u003cem\u003eS. aureus\u003c/em\u003e strains.\u003c/p\u003e \u003cp\u003eThis aligns with Garbacz et al.'s findings, which reported higher resistance in CoNS compared to \u003cem\u003eS. aureus\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. Despite its commensal nature, \u003cem\u003eS. xylosus\u003c/em\u003e has been linked to opportunistic infections, necessitating re-evaluation of infection management protocols.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eMinimum Inhibitory Concentration (MIC) and Interpretative Breakpoints\u003c/h2\u003e \u003cp\u003eLevofloxacin, a broad-spectrum fluoroquinolone, treats infections in the respiratory tract, skin, urinary tract, and prostate, among others \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. In this study, Levofloxacin exhibited higher inhibitory activity against Gram-negative than Gram-positive organisms, which corroborates Grillon \u003cem\u003eet al.\u003c/em\u003e's findings, which showed higher levofloxacin susceptibility in Gram-negative isolates such as \u003cem\u003eK. pneumoniae\u003c/em\u003e (75%) compared to Gram-positive strains like \u003cem\u003eS. maltophilia\u003c/em\u003e (35%)\u003csup\u003e36\u003c/sup\u003e. Since the primary target of Levofloxacin in Gram-negative bacteria is DNA gyrase, whereas Topoisomerase IV enzyme is their preferential target in Gram-positive bacteria \u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e, Levofloxacin\u0026rsquo;s higher inhibitory activity against Gram- Negative bacteria suggests its higher inhibition of DNA gyrase relative to Topoisomerase enzymes. Ultimately, these findings underscore the role of DNA gyrase as an ideal target for future antibacterial discovery efforts. Regional molecular profiling of clinical isolates is essential to validate MIC breakpoints and guide empirical therapy, minimizing resistance risks.\u003c/p\u003e \u003cp\u003eConversely, studies in Italy, Sweden, and India reported higher levofloxacin activity against Gram-positive organisms\u003csup\u003e\u003cspan additionalcitationids=\"CR39\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e, which may reflect regional differences in prescribing patterns, pathogen characteristics, or heteroresistance, which has been described for the bacteria isolates investigated in this study, such as \u003cem\u003eS. aureus, Klebsiella pneumoniae, E. coli\u003c/em\u003e, and \u003cem\u003eP. aeruginosa\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. Nonetheless, results from this study reinforce the need for novel antimicrobial chemotherapy, especially in the face of levofloxacin-resistant pathogens and the borderline susceptibility of most isolates, which pose higher tendencies for therapy failure and antimicrobial resistance\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. Additionally, periodic molecular profiling of clinical isolates is recommended to ascertain the validity of the set clinical MIC breakpoints for various antibiotics.\u003c/p\u003e \u003cp\u003eResistance mechanisms, including efflux pumps (e.g., norA, norB in \u003cem\u003eS. aureus\u003c/em\u003e), highlight the critical need for MIC tests to inform therapeutic decisions and strongly suggest a rationale for the notable levofloxacin-resistance of a carbapenemase-producing oxacillin-resistant strain of \u003cem\u003eS. aureus\u003c/em\u003e \u0026ndash; \u0026lsquo;ES 44\u0026rsquo; with efflux pump activity (MIC: 8.00 \u0026micro;g/ml). Notably, two of the three MDR \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e strains, which earlier demonstrated non-susceptibility to levofloxacin, exhibited intermediate resistance to levofloxacin during the MIC determinations. The intermediate category is defined as uncertain therapeutic success for the individual species/drug combination and is intended for compounds for which dosing can be increased\u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. CLSI defines the intermediate category as a lower response rate than for susceptible isolates, but clinical efficacy if the drug accumulates at the site of infection\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe intermediate category thus represents the \u0026lsquo;grey zone\u0026rsquo; for which high potential for therapy failure and antimicrobial resistance exists at standard dosage regimens\u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. Additionally, intermediate resistance among these strains reduces the tendency of achieving the threshold antibiotic therapeutic concentration for effective eradication of the pathogen using the standard dosage, hence increasing the likelihood of antimicrobial resistance.\u003c/p\u003e \u003cp\u003e \u003cem\u003eMicrococcus\u003c/em\u003e spp., though often regarded as non-pathogenic, can be opportunistic pathogens for the immunocompromised\u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e and have occasionally been reported as a causative pathogen in pneumonia, septic arthritis, bacteremia, catheter-associated bloodstream infection and endocarditis\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e,\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e. A study with 188 micrococci, identified only to the genus level, demonstrated MICs at achievable concentrations for most β-lactams, aminoglycosides, glycopeptides and clindamycin\u003csup\u003e\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e. Generally, clinical data on \u003cem\u003eMicrococcus spp.\u003c/em\u003e infections and treatment reports with levofloxacin are sparse, hence the current lack of clear therapeutic recommendations\u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e,\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur findings reveal the marked susceptibility of \u003cem\u003eMicrococci\u003c/em\u003e to levofloxacin across all studied concentrations, thus highlighting levofloxacin\u0026rsquo;s importance in the management of infections mediated by \u003cem\u003eMicrococcus spp.\u003c/em\u003e and informing the need for further studies to validate levofloxacin\u0026rsquo;s breakpoints for usage in clinical medicine.\u003c/p\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003ch2\u003eMinimum Bactericidal Concentration (MBC)\u003c/h2\u003e \u003cp\u003eFluoroquinolones exhibit concentration-dependent bactericidal activity\u003csup\u003e\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e. Relative to the MIC results, the MBCs show a 50% increase in the lower limit MIC concentration for Gram-positive organisms and a 12.5% increase in the upper limit MBC concentration for Gram-negative organisms. The success of antimicrobial therapy is determined by the interaction of drug administration, the state of the host and the causative agent of infection\u003csup\u003e\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u003c/sup\u003e. Findings from this study extensively highlight the necessity for correlating MIC values with pharmacokinetic (PK) and pharmacodynamic (PD) parameters, such as volume of distribution and clearance, in designing dosage regimens.\u003c/p\u003e \u003cp\u003eLevofloxacin maintained a consistent MIC in exhibiting bactericidal activity against \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e (MBC: 0.125 \u0026micro;g/ml), indicating its potent antibacterial activity against \u003cem\u003ePseudomonas aeruginosa.\u003c/em\u003e These results align with the findings of Sihotang \u003cem\u003eet al\u003c/em\u003e, whose study on the time-kill curve and effect of Levofloxacin on \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e showed marked bactericidal activity in all assay concentrations\u003csup\u003e\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u003c/sup\u003e. Remarkably, Sihotang \u003cem\u003eet al\u003c/em\u003e findings also showed levofloxacin\u0026rsquo;s superior bactericidal effect against \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e relative to ciprofloxacin and ofloxacin. Overall, these studies underscore the urgent need for innovative antimicrobial agents and enhanced stewardship to combat MDR.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec24\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eStudy limitations include the limited sample size of isolates and a focus on a single antimicrobial agent. Rationale for variations in susceptibility among similar resistance phenotypes was not further determined via molecular mechanisms, which may impact the interpretation of resistance.\u003c/p\u003e \u003cdiv id=\"Sec25\" class=\"Section3\"\u003e \u003ch2\u003eGeneralisability\u003c/h2\u003e \u003cp\u003eThese findings may be generalisable to similar tertiary care settings in low-resource regions where MDR infections are prevalent. However, broader surveillance studies are needed to confirm external validity.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThis study represents the first to report levofloxacin MIC and MBC values for genetically validated MDR isolates in Nigeria. The findings emphasise the critical need for further research into microbial efflux pump mechanisms and the molecular characterisation of DNA gyrase and topoisomerase enzymes to develop novel targeted therapies. Periodic molecular profiling of clinical isolates is essential to validate and refine clinical MIC breakpoints for antibiotics. Additionally, MIC-data-driven antimicrobial stewardship can improve therapeutic outcomes and guide rational antibiotic classification for empiric treatment. Levofloxacin demonstrated significant inhibitory activity, across all studied concentrations, against \u003cem\u003eMicrococcus spp\u003c/em\u003e., bringing to light its importance in managing infections mediated by Micrococcus spp. Furthermore, levofloxacin maintained consistent inhibitory and bactericidal activity against \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e (MIC/MBC: 0.125 \u0026micro;g/ml), corroborating its potent efficacy as reported in previous studies. Despite these promising results, the study reveals emerging levofloxacin resistance in previously susceptible organisms, underscoring the necessity for ongoing surveillance, targeted antimicrobial design, and comprehensive sensitivity testing to combat the global challenge of antimicrobial resistance (AMR).\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eMDR: Multidrug resistance, AMR: Antimicrobial resistance, IZD: Inhibition Zone Diameter, MIC: Minimum Inhibitory Concentration, MBC: Minimum Bactericidal Concentration.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eEthical clearance was obtained from the Research Ethics Committee of the University of Lagos. \u003cem\u003e(REG NO:\u0026nbsp;\u003c/em\u003e\u003cem\u003eUNILAGREC/22/06/005\u003cem\u003e)\u003c/em\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eNot Applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material:\u0026nbsp;\u003c/strong\u003eAll data generated or analysed during this study are included in this published article. The data that support the findings of this study are available from https://www.ajol.info/index.php/tjpr/article/view/164273/153790 and https://www.researchgate.net/publication/325538114_Detection_inhibition_and_molecular_analysis_of_multidrug_resistant_aerobic_gram-negative_clinical_isolates_from_a_tertiary_hospital_in_Nigeria\u003csup\u003e10,11\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: This project was funded by the Tertiary Education Trust Fund (TETfund), registration number TETF/ES/DR\u0026amp;D-CE/NRF2021/SETHi/HSW/00290/VOL.1 with Gloria A. Ayoola as the Principal Investigator, and the department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Lagos as the hosting laboratory.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u0026nbsp;\u003c/strong\u003eThe manuscript was written through the contributions of all authors. All authors have approved the final version of the manuscript. Specific author contributions are as follows: A.S.A. developed the research concept and design, collected, analysed, and interpreted data, and prepared and reviewed the manuscript; GAA is the Principal Investigator. She developed the research concept and design, analysed and interpreted data, and reviewed and approved the manuscript; AOA developed the research concept and design, analysed and interpreted data, and reviewed and approved the manuscript; DBO developed the research concept and design, collected, analysed, and interpreted data, and approved the manuscript; OSN analysed and interpreted data, and reviewed and approved the manuscript; DKA critically reviewed and approved the manuscript; MOO critically reviewed and approved the manuscript; OOJ critically reviewed and approved the manuscript; UA analysed and interpreted data, and reviewed and approved the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eWe acknowledge the numerous authors whose works are referenced in this study for laying the foundation and inspiring our research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; information:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding Author:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbubakar Sadiq Abdullahi-\u0026nbsp;\u003c/strong\u003e\u003cem\u003eDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Lagos College of Medicine Campus, Idi-araba, Lagos, Nigeria.\u0026nbsp;\u003c/em\u003eEmail: [email protected], Contact: +2348137501119, ORCID ID: https://orcid.org/0000-0002-3896-3844\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGloria Abiodun Ayoola, David Blessing Orojuekun, David K. Adeyemi and Oluwatosin O. Johnson\u003c/strong\u003e- \u003cem\u003eDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Lagos College of Medicine Campus, Idi-araba, Lagos, Nigeria.\u0026nbsp;\u003c/em\u003eEmail contacts: [email protected] , [email protected] , [email protected] , and [email protected] respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdebowale O. Adeluola and Usman Abdulrahman\u003c/strong\u003e- \u003cem\u003eDepartment of Pharmaceutical Microbiology \u0026amp; Biotechnology, Faculty of Pharmacy, University of Lagos College of Medicine Campus, Idi-araba, Lagos, Nigeria.\u0026nbsp;\u003c/em\u003eEmail: [email protected] and [email protected], respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOkafor Sunday N\u003c/strong\u003e- \u003cem\u003eDepartment of Pharmaceutical and Medicinal Chemistry, University of Nigeria Nsukka, Enugu State Nigeria. ORCID:\u0026nbsp;\u003c/em\u003e\u003cem\u003ehttps://orcid.org/0000-0002-7476-3292\u003c/em\u003e\u003cem\u003e\u0026nbsp;,\u0026nbsp;\u003c/em\u003eEmail [email protected]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eModupe O. Ologunagba\u003c/strong\u003e- \u003cem\u003eDepartment of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Lagos College of Medicine Campus, Idi-araba, Lagos, Nigeria\u003c/em\u003e. Email: [email protected]\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eUN Environment Programme. \u003cem\u003eBracing for Superbugs : Strengthening Environmental Action in the One Health Response to Antimicrobial Resistance\u003c/em\u003e; United Nations Environment Programme, 2023.\u003c/li\u003e\n\u003cli\u003eWorld Health Organisation (WHO). \u003cem\u003eGlobal Antimicrobial Resistance and Use Surveillance System (GLASS) Report 2022\u003c/em\u003e; World Health Organization, 2022.\u003c/li\u003e\n\u003cli\u003ePrestinaci, F.; Pezzotti, P.; Pantosti, A. Antimicrobial Resistance: A Global Multifaceted Phenomenon. \u003cem\u003ePathogens and Global Health\u003c/em\u003e. Maney Publishing October 1, 2015, pp 309\u0026ndash;318. https://doi.org/10.1179/2047773215Y.0000000030.\u003c/li\u003e\n\u003cli\u003eNkansa-Gyamfi, N. A.; Kazibwe, J.; Traore, D. A. K.; Nji, E. Prevalence of Multidrug-, Extensive Drug-, and Pandrug-Resistant Commensal Escherichia Coli Isolated from Healthy Humans in Community Settings in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis. \u003cem\u003eGlobal Health Action\u003c/em\u003e. Taylor and Francis Ltd. December 13, 2019. https://doi.org/10.1080/16549716.2020.1815272.\u003c/li\u003e\n\u003cli\u003eTanwar, J.; Das, S.; Fatima, Z.; Hameed, S. Multidrug Resistance: An Emerging Crisis. \u003cem\u003eInterdisciplinary Perspectives on Infectious Diseases\u003c/em\u003e. Hindawi Limited 2014. https://doi.org/10.1155/2014/541340.\u003c/li\u003e\n\u003cli\u003eBerry, L.; Domalaon, R.; Brizuela, M.; Zhanel, G. G.; Schweizer, F. Polybasic Peptide-Levofloxacin Conjugates Potentiate Fluoroquinolones and Other Classes of Antibiotics against Multidrug-Resistant Gram-Negative Bacteria. \u003cem\u003eMedchemcomm\u003c/em\u003e \u003cstrong\u003e2019\u003c/strong\u003e, \u003cem\u003e10\u003c/em\u003e (4), 517\u0026ndash;527. https://doi.org/10.1039/c9md00051h.\u003c/li\u003e\n\u003cli\u003eO.B. Makanjuola; S.A. Fayemiwo; A.O. Okesola; A. Gbaja; V.A. Ogunleye; A.O. Kehinde; R.A. Bakare. Pattern of Multidrug Resistant Bacteria Associated with Intensive Care Unit Infections in Ibadan Nigeria. \u003cem\u003eAnn Ib Postgrad Med\u003c/em\u003e \u003cstrong\u003e2018\u003c/strong\u003e, \u003cem\u003e16\u003c/em\u003e (2).\u003c/li\u003e\n\u003cli\u003eWorld Health Organisation. \u003cem\u003eAntimicrobial Resistance\u003c/em\u003e; 2023. https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance (accessed 2024-08-19).\u003c/li\u003e\n\u003cli\u003eSajid, M. I.; Lohan, S.; Kato, S.; Tiwari, R. K. Combination of Amphiphilic Cyclic Peptide [R4W4] and Levofloxacin against Multidrug-Resistant Bacteria. \u003cem\u003eAntibiotics\u003c/em\u003e \u003cstrong\u003e2022\u003c/strong\u003e, \u003cem\u003e11\u003c/em\u003e (3). https://doi.org/10.3390/antibiotics11030416.\u003c/li\u003e\n\u003cli\u003eAdeluola, A. O.; Oyedeji, K. S.; Mendie, U. E.; Johnson, J. R.; Porter, J. R. Detection of Efflux Pump Activity among Clinical Isolates of Staphylococcus and Micrococcus Species. \u003cem\u003eTropical Journal of Pharmaceutical Research\u003c/em\u003e \u003cstrong\u003e2017\u003c/strong\u003e, \u003cem\u003e16\u003c/em\u003e (11), 2697\u0026ndash;2704. https://doi.org/10.4314/tjpr.v16i11.18.\u003c/li\u003e\n\u003cli\u003eAdeluola A.O; Oyedeji K.S; Mendie U. E; Johnson J.R; Porter J.R. Detection, Inhibition and Molecular Analysis of Multidrug Resistant Aerobic Gram-Negative Clinical Isolates from a Tertiary Hospital in Nigeria. \u003cem\u003eAfr. J. Biomed. Res\u003c/em\u003e \u003cstrong\u003e2018\u003c/strong\u003e, \u003cem\u003e21\u003c/em\u003e, 15\u0026ndash;21.\u003c/li\u003e\n\u003cli\u003eJalil, M. B.; Al Atbee, M. Y. N. The Prevalence of Multiple Drug Resistance Escherichia Coli and Klebsiella Pneumoniae Isolated from Patients with Urinary Tract Infections. \u003cem\u003eJ Clin Lab Anal\u003c/em\u003e \u003cstrong\u003e2022\u003c/strong\u003e, \u003cem\u003e36\u003c/em\u003e (9). https://doi.org/10.1002/jcla.24619.\u003c/li\u003e\n\u003cli\u003eGeetha, P. V.; Aishwarya, K. V. L.; Mariappan, S.; Sekar, U. Fluoroquinolone Resistance in Clinical Isolates of Klebsiella Pneumoniae. \u003cem\u003eJ Lab Physicians\u003c/em\u003e \u003cstrong\u003e2020\u003c/strong\u003e, \u003cem\u003e12\u003c/em\u003e (02), 121\u0026ndash;125. https://doi.org/10.1055/s-0040-1716478.\u003c/li\u003e\n\u003cli\u003eVeličković-Radovanović, R.; Stefanović, N.; Damnjanović, I.; Kocić, B.; Mladenović-Antić, S.; Dinić, M.; Petrović, J.; Mitić, R.; Catić-Đorđević, A. Antibiotic Utility and Susceptibility Changes of Multidrug-Resistant Escherichia Coli and Klebsiella Spp: 5-Year Experience in a Tertiary Healthcare Centre. \u003cem\u003eEuropean Journal of Hospital Pharmacy\u003c/em\u003e \u003cstrong\u003e2022\u003c/strong\u003e, \u003cem\u003e29\u003c/em\u003e (2), 84\u0026ndash;89. https://doi.org/10.1136/ejhpharm-2021-002758.\u003c/li\u003e\n\u003cli\u003eNational Center for Biotechnology Information. \u003cem\u003ePubChem Compound Summary for CID 149096, Levofloxacin\u003c/em\u003e. https://pubchem.ncbi.nlm.nih.gov/compound/Levofloxacin (accessed 2024-12-07).\u003c/li\u003e\n\u003cli\u003eCroom, K. F.; Goa, K. L. Levofloxacin A Review of Its Use in the Treatment of Bacterial Infections in the United States. \u003cem\u003eAdis Drug Evaluation\u003c/em\u003e \u003cstrong\u003e2003\u003c/strong\u003e, \u003cem\u003e63\u003c/em\u003e (24), 2769\u0026ndash;2802.\u003c/li\u003e\n\u003cli\u003eSihotang, T. S. U.; Widodo, A. D. W.; Endraswari, P. D. Effect of Ciprofloxacin, Levofloxacin, and Ofloxacin on Pseudomonas Aeruginosa: A Case Control Study with Time Kill Curve Analysis. \u003cem\u003eAnnals of Medicine and Surgery\u003c/em\u003e \u003cstrong\u003e2022\u003c/strong\u003e, \u003cem\u003e82\u003c/em\u003e. https://doi.org/10.1016/j.amsu.2022.104674.\u003c/li\u003e\n\u003cli\u003eDaniel Kwame Afriyie; Linda Brakowaah Adu; Marc Dzradosi; Seth Kwabena Amponsah; Prince Ohene-Manu; Francis Manu-Ofei. Comparative in Vitro Activity of Ciprofloxacin and Levofloxacin against Isolated Uropathogens in Ghana: A Pilot Study. \u003cem\u003ePan Africa Medical Journal\u003c/em\u003e \u003cstrong\u003e2018\u003c/strong\u003e, \u003cem\u003e30\u003c/em\u003e (194). https://doi.org/10.11604/pamj.2018.30.194.15457.\u003c/li\u003e\n\u003cli\u003eCroom, K. F.; Goa, K. L. Levofloxacin A Review of Its Use in the Treatment of Bacterial Infections in the United States. \u003cem\u003eAdis Drug Evaluation\u003c/em\u003e \u003cstrong\u003e2003\u003c/strong\u003e, \u003cem\u003e63\u003c/em\u003e (24), 2769\u0026ndash;2802.\u003c/li\u003e\n\u003cli\u003eAlves, D. A.; Machado, D.; Melo, A.; Pereira, R. F. C.; Severino, P.; Hollanda, L. M. De; Ara\u0026uacute;jo, D. R.; Lancellotti, M. Preparation of Thermosensitive Gel for Controlled Release of Levofloxacin and Their Application in the Treatment of Multidrug-Resistant Bacteria. \u003cem\u003eBiomed Res Int\u003c/em\u003e \u003cstrong\u003e2016\u003c/strong\u003e, \u003cem\u003e2016\u003c/em\u003e. https://doi.org/10.1155/2016/9702129.\u003c/li\u003e\n\u003cli\u003eVeselkov, D. A.; Laponogov, I.; Pan, X. S.; Selvarajah, J.; Skamrova, G. B.; Branstrom, A.; Narasimhan, J.; Prasad, J. V. N. V.; Fisher, L. M.; Sanderson, M. R. Structure of a Quinolone-Stabilized Cleavage Complex of Topoisomerase IV from Klebsiella Pneumoniae and Comparison with a Related Streptococcus Pneumoniae Complex. \u003cem\u003eActa Crystallogr D Struct Biol\u003c/em\u003e \u003cstrong\u003e2016\u003c/strong\u003e, \u003cem\u003e72\u003c/em\u003e (4), 488\u0026ndash;496. https://doi.org/10.1107/S2059798316001212.\u003c/li\u003e\n\u003cli\u003eNational Center for Biotechnology Information. \u003cem\u003ePubChem Compound Summary for CID 149096, Levofloxacin.\u003c/em\u003e https://pubchem.ncbi.nlm.nih.gov/compound/Levofloxacin.\u003c/li\u003e\n\u003cli\u003eDrugBank Online. \u003cem\u003eLevofloxacin\u003c/em\u003e. https://go.drugbank.com/drugs/DB01137.\u003c/li\u003e\n\u003cli\u003eIzadi, E.; Afshan, G.; Patel, R. P.; Rao, V. M.; Liew, K. Bin; Affandi, M. M. R. M. M.; Kifli, N.; Suleiman, A.; Lee, K. S.; Sarker, M. M. R.; Zaidi, S. T.; Ming, L. C. Levofloxacin: Insights into Antibiotic Resistance and Product Quality. \u003cem\u003eFront Pharmacol\u003c/em\u003e \u003cstrong\u003e2019\u003c/strong\u003e, \u003cem\u003e10\u003c/em\u003e (August). https://doi.org/10.3389/fphar.2019.00881.\u003c/li\u003e\n\u003cli\u003eGeetha, P. V.; Aishwarya, K. V. L.; Mariappan, S.; Sekar, U. Fluoroquinolone Resistance in Clinical Isolates of Klebsiella Pneumoniae. \u003cem\u003eJ Lab Physicians\u003c/em\u003e \u003cstrong\u003e2020\u003c/strong\u003e, \u003cem\u003e12\u003c/em\u003e (02), 121\u0026ndash;125. https://doi.org/10.1055/s-0040-1716478.\u003c/li\u003e\n\u003cli\u003eSaad Latteef, N.; Salih, W. Y.; Aziz Abdulhassan, A.; Jasim Obeed, R. Evaluation of Gene Expression of NorA and NorB Gene in Ciproflaxin and Levofloxacin Resistant Staphylococcus Aureus. \u003cem\u003eArch Razi Inst\u003c/em\u003e \u003cstrong\u003e2022\u003c/strong\u003e, \u003cem\u003e77\u003c/em\u003e (5), 1987\u0026ndash;1993. https://doi.org/10.22092/ARI.2022.358335.2197.\u003c/li\u003e\n\u003cli\u003eKowalska-Krochmal, B.; Dudek-Wicher, R. The Minimum Inhibitory Concentration of Antibiotics: Methods, Interpretation, Clinical Relevance. \u003cem\u003ePathogens\u003c/em\u003e. MDPI AG February 1, 2021, pp 1\u0026ndash;21. https://doi.org/10.3390/pathogens10020165.\u003c/li\u003e\n\u003cli\u003eMagr\u0026eacute;ault, S.; Jaur\u0026eacute;guy, F.; Carbonnelle, E.; Zahar, J. R. When and How to Use MIC in Clinical Practice? \u003cem\u003eAntibiotics\u003c/em\u003e. MDPI December 1, 2022. https://doi.org/10.3390/antibiotics11121748.\u003c/li\u003e\n\u003cli\u003eO\u0026rsquo;Malley, S. M.; Emele, F. E.; Nwaokorie, F. O.; Idika, N.; Umeizudike, A. K.; Emeka-Nwabunnia, I.; Hanson, B. M.; Nair, R.; Wardyn, S. E.; Smith, T. C. Molecular Typing of Antibiotic-Resistant Staphylococcus Aureus in Nigeria. \u003cem\u003eJ Infect Public Health\u003c/em\u003e \u003cstrong\u003e2015\u003c/strong\u003e, \u003cem\u003e8\u003c/em\u003e (2), 187\u0026ndash;193. https://doi.org/10.1016/j.jiph.2014.08.001.\u003c/li\u003e\n\u003cli\u003eInnocent, I. G.; Gowon, A. G.; Ademah, C.; Agbese, J. B.; Kuleve, M. I.; Jonah, O. I. Isolation and Antibiotic Sensitivity of Klebsiella Pneumoniae among Urinary Tract Infected Patients in Dalhatu Araf Specialist Hospital Lafia, Nasarawa State Nigeria. \u003cem\u003eJ Adv Microbiol\u003c/em\u003e \u003cstrong\u003e2023\u003c/strong\u003e, \u003cem\u003e23\u003c/em\u003e (7), 1\u0026ndash;6. https://doi.org/10.9734/jamb/2023/v23i7731.\u003c/li\u003e\n\u003cli\u003eDehnamaki, M.; Ghane, M.; Babaeekhou, L. Detection of OqxAB and QepA Efflux Pumps and Their Association with Antibiotic Resistance in Klebsiella Pneumoniae Isolated From Urinary Tract Infection. \u003cem\u003eInternational Journal of Infection\u003c/em\u003e \u003cstrong\u003e2020\u003c/strong\u003e, \u003cem\u003e7\u003c/em\u003e (4). https://doi.org/10.5812/iji.107397.\u003c/li\u003e\n\u003cli\u003eMichalik, M.; Samet, A.; Podbielska‑Kubera, A.; Savini, V.; Międzobrodzki, J.; Kosecka‑Strojek, M. Coagulase-Negative Staphylococci (CoNS) as a Significant Etiological Factor of Laryngological Infections: A Review. \u003cem\u003eAnnals of Clinical Microbiology and Antimicrobials\u003c/em\u003e. BioMed Central Ltd June 4, 2020. https://doi.org/10.1186/s12941-020-00367-x.\u003c/li\u003e\n\u003cli\u003eAzih, A.; Enabulele, I. Species Distribution and Virulence Factors of Coagulase Negative Staphylococci Isolated From Clinical Samples From the University of Benin Teaching Hospital, Edo State, Nigeria. \u003cem\u003eJournal of Natural Sciences Research\u003c/em\u003e \u003cstrong\u003e2013\u003c/strong\u003e, \u003cem\u003e3\u003c/em\u003e (9).\u003c/li\u003e\n\u003cli\u003eGarbacz, K.; Wierzbowska, M.; Kwapisz, E.; Kosecka-Strojek, M.; Bronk, M.; Saki, M.; Międzobrodzki, J. Distribution and Antibiotic-Resistance of Different Staphylococcus Species Identified by Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) Isolated from the Oral Cavity. \u003cem\u003eJ Oral Microbiol\u003c/em\u003e \u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e13\u003c/em\u003e (1). https://doi.org/10.1080/20002297.2021.1983322.\u003c/li\u003e\n\u003cli\u003eClinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing. In \u003cem\u003eCLSI supplement M100\u003c/em\u003e; CLINICAL AND LABORATORY, 2024; Vol. 34th ed.\u003c/li\u003e\n\u003cli\u003eGrillon, A.; Schramm, F.; Kleinberg, M.; Jehl, F. Comparative Activity of Ciprofloxacin, Levofloxacin and Moxifloxacin against Klebsiella Pneumoniae, Pseudomonas Aeruginosa and Stenotrophomonas Maltophilia Assessed by Minimum Inhibitory Concentrations and Time-Kill Studies. \u003cem\u003ePLoS One\u003c/em\u003e \u003cstrong\u003e2016\u003c/strong\u003e, \u003cem\u003e11\u003c/em\u003e (6). https://doi.org/10.1371/journal.pone.0156690.\u003c/li\u003e\n\u003cli\u003eSpencer, A. C.; Panda, S. S. DNA Gyrase as a Target for Quinolones. \u003cem\u003eBiomedicines\u003c/em\u003e. MDPI February 1, 2023. https://doi.org/10.3390/biomedicines11020371.\u003c/li\u003e\n\u003cli\u003eL. Drago; E. De Vecchi; B. Mombelli; L. Nicola; M.Valli; M.R. Gismondo. Activity of Levofloxacin and Ciprofloxacin against Urinary Pathogens. \u003cem\u003eJournal of Antimicrobial Chemotherapy\u003c/em\u003e \u003cstrong\u003e2001\u003c/strong\u003e, \u003cem\u003e48\u003c/em\u003e, 37\u0026ndash;45.\u003c/li\u003e\n\u003cli\u003eDuggirala, A.; Joseph, J.; Sharma, S.; Nutheti, R.; Garg, P.; Das, T. Activity of Newer Fluoroquinolones against Gram-Positive and Gram-Negative Bacteria Isolated from Ocular Infections: An in Vitro Comparison. \u003cem\u003eIndian J Ophthalmol\u003c/em\u003e \u003cstrong\u003e2007\u003c/strong\u003e, \u003cem\u003e55\u003c/em\u003e (1), 15\u0026ndash;19. https://doi.org/10.4103/0301-4738.29489.\u003c/li\u003e\n\u003cli\u003eOdenholt, I.; Lowdin, E.; Cars, O. Bactericidal Effects of Levofloxacin in Comparison with Those of Ciprofloxacin and Sparfloxacin. \u003cem\u003eClinical Microbiology and Infection\u003c/em\u003e \u003cstrong\u003e1998\u003c/strong\u003e, \u003cem\u003e4\u003c/em\u003e (5), 264\u0026ndash;270.\u003c/li\u003e\n\u003cli\u003eHombach, M.; B\u0026ouml;ttger, E. C.; Roos, M. The Critical Influence of the Intermediate Category on Interpretation Errors in Revised EUCAST and CLSI Antimicrobial Susceptibility Testing Guidelines. \u003cem\u003eClinical Microbiology and Infection\u003c/em\u003e \u003cstrong\u003e2013\u003c/strong\u003e, \u003cem\u003e19\u003c/em\u003e (2). https://doi.org/10.1111/1469-0691.12090.\u003c/li\u003e\n\u003cli\u003ePathogen Regulation Directorate, P. H. A. of C. \u003cem\u003ePathogen Safety Data Sheets: Infectious Substances-Micrococcus Spp.\u003c/em\u003e; 2010. https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/micrococcus.html.\u003c/li\u003e\n\u003cli\u003eShi, X.; Qiu, S.; Ji, L.; Lu, H.; Wu, S.; Chen, Q.; Zou, X.; Hu, Q.; Feng, T.; Chen, S.; Cui, W.; Xu, S.; Jiang, M.; Cai, R.; Geng, Y.; Bai, Q.; Huang, D.; Liu, P. Pathogenetic Characterization of a Micrococcus Luteus Strain Isolated from an Infant. \u003cem\u003eFront Pediatr\u003c/em\u003e \u003cstrong\u003e2023\u003c/strong\u003e, \u003cem\u003e11\u003c/em\u003e. https://doi.org/10.3389/fped.2023.1303040.\u003c/li\u003e\n\u003cli\u003eZhu, M.; Zhu, Q.; Yang, Z.; Liang, Z. Clinical Characteristics of Patients with Micrococcus Luteus Bloodstream Infection in a Chinese Tertiary-Care Hospital. \u003cem\u003ePol J Microbiol\u003c/em\u003e \u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e70\u003c/em\u003e (3), 321\u0026ndash;326. https://doi.org/10.33073/PJM-2021-030.\u003c/li\u003e\n\u003cli\u003eMiquel B.Ekkelenkamp; Suzan H.M.Rooijakkers; Marc J.M.Bonten. Staphylococci and Micrococci. In \u003cem\u003eInfectious Diseases\u003c/em\u003e; 2010; Vol. 2.\u003c/li\u003e\n\u003cli\u003eWispelwey, B. Clinical Implications of Pharmacokinetics and Pharmacodynamics of Fluoroquinolones. \u003cem\u003eClinical Infectious Diseases\u003c/em\u003e \u003cstrong\u003e2005\u003c/strong\u003e, \u003cem\u003e41\u003c/em\u003e (Supplement 2), S127\u0026ndash;S135. https://doi.org/10.1086/428053.\u003c/li\u003e\n\u003cli\u003eSihotang, T. S. U.; Widodo, A. D. W.; Endraswari, P. D. Effect of Ciprofloxacin, Levofloxacin, and Ofloxacin on Pseudomonas Aeruginosa: A Case Control Study with Time Kill Curve Analysis. \u003cem\u003eAnnals of Medicine and Surgery\u003c/em\u003e \u003cstrong\u003e2022\u003c/strong\u003e, \u003cem\u003e82\u003c/em\u003e. https://doi.org/10.1016/j.amsu.2022.104674.\u003c/li\u003e\n\u003cli\u003eA.W. Bauer; W.M. Kirby; J.C. Sherris; M. Turck. Antibiotic Susceptibility Testing by a Standardized Single Disk Method. \u003cem\u003eAm J Clin Pathol\u003c/em\u003e \u003cstrong\u003e1966\u003c/strong\u003e, \u003cem\u003e45\u003c/em\u003e (4), 493\u0026ndash;496. https://doi.org/https://doi.org/10.1093/ajcp/45.4_ts.493.\u003c/li\u003e\n\u003cli\u003eHugo and Russell\u0026rsquo;s. \u003cem\u003ePharmaceutical Microbiology\u003c/em\u003e, Seventh Edition.; Denyer, S. P., Norman A Hodges, Sean P. Gorman, Eds.; Blackwell Science, 2004.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bulletin-of-the-national-research-centre","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnrc","sideBox":"Learn more about [Bulletin of the National Research Centre](https://BNRC.springeropen.com)","snPcode":"42269","submissionUrl":"https://submission.springernature.com/new-submission/42269/3","title":"Bulletin of the National Research Centre","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Levofloxacin, Minimum Inhibitory Concentration, Minimum bacterial concentration, Multidrug-resistant bacteria, antimicrobial resistance","lastPublishedDoi":"10.21203/rs.3.rs-6693557/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6693557/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eKey mechanisms of antimicrobial resistance (AMR) include the presence of efflux pumps and the production of drug-degrading enzymes upon exposure to antimicrobial drugs. Levofloxacin, a widely prescribed fluoroquinolone, has marked antimicrobial activity against Gram-positive pathogens like \u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e and Gram-negative pathogens like \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e. However, additional multidrug resistance (MDR) mechanisms in microbes, such as mutations in DNA gyrase and topoisomerase IV or altered efflux pump activity (EPA), threaten its clinical efficacy. To the best of our knowledge, no study has reported the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of levofloxacin against genetically validated MDR isolates in Nigeria.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA cross-sectional study assessing levofloxacin’s potency, MIC and MBC was conducted against 20 validated bacterial isolates with resistance mechanisms such as efflux pump activity, oxacillin resistance, ESBL, and carbapenemase production, following CLSI guidelines.\u003c/p\u003e\n\u003cp\u003eThe American Type Culture Collection (ATCC 25922) \u003cem\u003eEscherichia coli \u003c/em\u003ereference isolate was used as the standard drug-susceptible control and all assays were performed in triplicate to ensure reproducibility and minimise observer bias. All data were expressed as mean ± standard deviation (S.D.). Significant differences among the groups were determined by one-way analysis of variance (ANOVA), and Graphs were plotted using Microsoft Excel. Results were considered to be significant at \u003cem\u003ep\u003c/em\u003e ≤ 0.05.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThree MDR \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e strains exhibited non-susceptibility and intermediate resistance to levofloxacin. MICs ranged from 0.0625–8.00 µg/ml for Gram-positive and 0.015625–1.00 µg/ml for Gram-negative organisms. Levofloxacin demonstrated greater inhibitory activity against Gram-negative (72.73% susceptible) than Gram-positive (55.56% susceptible) organisms. MBCs ranged from 0.125–8.00 µg/ml (Gram-positive) and 0.015625–8.00 µg/ml (Gram-negative), with \u003cem\u003eMicrococcus spp.\u003c/em\u003e showing marked susceptibility (IZD 50 µg/ml: 37.33 mm ± 0.58; MIC: 0.125 µg/ml).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eOur study findings underscore the need for continuous surveillance, molecular characterisation of resistance mechanisms, and MIC-guided antimicrobial stewardship. While levofloxacin remains effective for many infections, emerging resistance among previously susceptible organisms highlights the urgent need for informed prescribing practices and the development of novel antimicrobials to combat MDR.\u003c/p\u003e","manuscriptTitle":"A Strategic Combat Against Antimicrobial Resistance: A Cross-sectional Evaluation of Levofloxacin’s Efficacy against Multidrug-resistant Bacterial Isolates in Nigeria","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-21 04:53:50","doi":"10.21203/rs.3.rs-6693557/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-26T09:44:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-24T16:48:30+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-19T23:00:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"Bulletin of the National Research Centre","date":"2025-05-18T20:17:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bulletin-of-the-national-research-centre","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnrc","sideBox":"Learn more about [Bulletin of the National Research Centre](https://BNRC.springeropen.com)","snPcode":"42269","submissionUrl":"https://submission.springernature.com/new-submission/42269/3","title":"Bulletin of the National Research Centre","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6fa6ac22-78b5-4ac5-909c-4341745ab924","owner":[],"postedDate":"May 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-17T17:08:22+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-21 04:53:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6693557","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6693557","identity":"rs-6693557","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}