Assessment of In vitro activity of Levonadifloxacin against clinical bacterial isolates in patients admitted in ICU in a tertiary care hospital

Assessment of In vitro activity of Levonadifloxacin against clinical bacterial isolates in patients admitted in ICU in a tertiary care hospital | 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 Assessment of In vitro activity of Levonadifloxacin against clinical bacterial isolates in patients admitted in ICU in a tertiary care hospital Nida Fatima, Nidhi Tejan, Anju Dinkar, Awadhesh Kumar, Sangram Singh Patel, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7029796/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Background: Levonadifloxacin, a benzoquinolizine subclass of fluoroquinolones, has demonstrated potent activity against methicillin-resistant Staphylococcus aureus (MRSA), quinolone-resistant S. aureus (QRSA), vancomycin-intermediate and vancomycin-resistant S. aureus . Its mechanism—preferential inhibition of DNA gyrase with high affinity for topoisomerase IV—enhances its efficacy against resistant Gram-positive bacteria. Despite its approval in India for treating skin and soft tissue infections, data on its activity against Gram-negative organisms remains limited. This study aimed to assess the in vitro activity of levonadifloxacin against clinical bacterial isolates from ICU patients using broth microdilution. Material and Method: This descriptive study was conducted at Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, between March 27 and May 25, 2025. A total of 135 non-duplicate clinical isolates from ICU patients (blood, pus, urine, catheter tips, and sterile fluids) were analysed. Isolates were identified via Gram stain, biochemical tests, and MALDI-TOF MS. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method. Minimum inhibitory concentrations (MICs) for levonadifloxacin were determined using the broth microdilution method as per CLSI 2025 guidelines, with interpretation based on proposed pharmacokinetic/pharmacodynamic breakpoints (≤ 4 µg/ml). Result: Among 135 isolates, 85 (62.96%) were Gram-negative bacilli and 50 (37.04%) were Gram-positive cocci. The most frequent isolates were K. pneumoniae (21.28%), E. coli (17.77%), CONS (17.77%), and P. aeruginosa (15.55%). Methicillin resistance was observed in 47% of S. aureus and 79.16% of CONS. A total of 76.29% of isolates were resistant to levofloxacin; however, all Gram-positive isolates (including MRSA, MRCONS, and vancomycin resistant E. faecalis ) were susceptible to levonadifloxacin. Among Gram-negative bacilli, levonadifloxacin showed limited efficacy and was active only against strains that were already susceptible to levofloxacin. Conclusion: Levonadifloxacin exhibited excellent in vitro activity against Gram-positive cocci, including multidrug-resistant MRSA and VRE, supporting its role in treating ICU-acquired infections. Its oral and IV availability and lack of renal/hepatic dose adjustments make it a valuable therapeutic option. However, its limited efficacy against Gram-negative bacilli highlights the need for further studies and resistance mechanism evaluation. Levonadifloxacin MRSA ICU infections antimicrobial resistance Gram-positive cocci Gram-negative bacilli broth microdilution MIC Figures Figure 1 Figure 2 Highlights Levonadifloxacin exhibited excellent activity against Gram-positive cocci, including MRSA, MRCONS and VRE. We evaluated the efficacy of levonadifloxacin against Gram-negative bacilli also and found it to be effective against isolates that are sensitive to levofloxacin. Introduction Levonadifloxacin is benzoquinolizine subclass of fluoroquinolone antibiotic with potent activity against both methicillin-resistant (MRSA) and quinolone resistant S.aureus (QRSA), vancomycin intermediate S. aureus (VISA), and vancomycinresistant S. aureus (VRSA). Its intravenous formulation, levonadifloxacin, and its oral prodrug, ala-levonadifloxacin, have been recently approved in India for treating acute bacterial skin and skin structure infections (ABSSI), including cases with concomitant bacteraemia and diabetic foot infections [1]. The strong effectiveness of levonadifloxacin against MRSA, QRSA, and heterogenous vancomycin intermediate S. aureus (hVISA) is due to unique mechanism: it primarily inhibits DNA gyrase while still retaining high affinity for topoisomerase IV. This dual targeted action enhances its potency against resistant strains [2]. Methicillin resistant Staphylococcus infections, especially in ICUs, pose serious treatment challenges. The most commonly used drugs vancomycin and linezolid each have notable drawbacks: like vancomycin is considered as a suboptimal option in critically ill patients due to its weak bactericidal activity, poor penetration into tissues (such as lung), renal toxicity and risk of clinical failure due to Minimum Inhibitory Concentration (MIC) creep [ 3 , 4 , 5 ]. Linezolid is a bacteriostatic agent and therefore, not recommended to be used in Blood Stream Infections (BSI). Can suppress bone marrow, cause thrombocytopenia, and requires shorter courses with safety monitoring [ 6 ]. Clinicians need better antibiotics ideally bactericidal agents with strong tissue penetration and acceptable safety for longer treatment durations. Methicillin resistant Staphylococcus aureus (MRSA) is a significant contributor to healthcare associated infections (HAI) [ 7 ]. The World Health Organization (WHO) has reported that MRSA infections are linked to a higher risk of mortality compared to infections caused by methicillin susceptible Staphylococcus aureus (MSSA) [ 8 ]. Most of epidemiological studies are confined to levonadifloxacin susceptibility in Gram positive isolates using the diskdiffusion method. Levonadifloxacin’s activity against Gram negative bacilli has been explored very minimally to date. This study was conducted to produce antimicrobial susceptibility data by determining MIC values. The objective of the present study was to assess the in vitro activity of levonadifloxacin against clinical bacterial isolates in patients admitted in ICU. Material and methods Study setting The present descriptive study was conducted in Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India, between March 27, 2025, to May 25, 2025 duration. The study was conducted after obtaining Ethical Committee approval with Letter number- PGI/BE/1561/2021. A total of 135 clinical bacterial isolates collected from all ICUs of the hospital were analyzed. The samples were obtained from patients of all age group and both sexes. Demographic information and clinical details of the patient included in the study were recorded [Table 2 ]. Table 1 Susceptibility test interpretative criteria for Levonadifloxacin Microorganism MIC µg/ml Susceptible Intermediate Resistant S. aureus (methicillin-resistant, methicillin-susceptible, quinolone resistant, quinolone-susceptible isolates) ≤ 2 4 ≥ 8 E. faecalis ≤ 8 - ≥ 16 E. faecalis: Enterococcus faecalis, S. aureus: Staph aureus Table 2 Clinical profile of study participants (n = 135) Patient clinical profile Total no. of isolates (%) n = 135 Gender Male 85(62.97%) Female 50(37.03%) 1. Age group ≤ 20yrs 21(15.55%) 21-40yrs 34(17.77%) 41-60yrs 54(40%) ≥ 61yrs 26(19.25%) 2. Underlying clinical condition Hematological malignancy 28(20.74%) Respiratory disease 28(20.74%) Renal disease 26(19.25%) Trauma 18(13.33%) Solid organ malignancy 18(13.33%) Liver disease 8(5.92%) Gastrointestinal disease 6(4.44%) Neurological disease 3(2.22%) Inclusion criteria : All consecutive, non-duplicate isolates from blood, sterile body fluids, catheter tips, skin and soft tissue, pus and urine samples collected from ICUs considered clinically significant were included in the study. Exclusion criteria : Duplicate isolates were excluded from study. Sample collection and culture processing Pus and sputum samples were cultured on Blood, MacConkey, and Chocolate agar, while urine samples were cultured on HI Chrome agar according to standard microbiological methods. All culture plates were incubated aerobically at 37°C for 24 hours. Blood and sterile body fluids were inoculated into BACTEC FX blood culture bottles (BD, USA) and incubated at 35°C for 5 days. Upon a positive signal, Gram staining was done, and broths were sub-cultured on Blood and MacConkey agar, followed by 24-hour aerobic incubation at 37°C. Identification of bacterial isolates Isolates were identified using Gram staining, standard biochemical tests and automated MALDI TOF-MS system according to manufacturer recommendations (VITEK MS, bioMérieux, USA). The zone diameter obtained with a 30 µg cefoxitin disk was used to determine methicillin resistance in Staphylococci. Antibiotic susceptibility tests (AST) Routine antibiotic susceptibility tests were performed by Kirby Bauer disk diffusion method and evaluated by recommendations of Clinical Laboratory Standards Institute (CLSI) guideline [ 9 ], using commercially available antibiotic discs procured from HI Media (Mumbai, India). Broth microdilution tests (BMD) Minimal inhibitory concentrations (MIC) for Levonadifloxacin were detected by the broth microdilution method. While preparing drug stock solution, the weighed quantity of levonadifloxacin dry powder has to be dissolved in L-arginine solution (27.5 mg/L L-arginine in water) [ 10 ] The MIC of Levonadifloxacin was determined using cation-adjusted Muller-Hinton broth (CAMHB) according to CLSI guidelines (CLSI, 2025). In 96-well microtiter plates (Genetix Inc., India) containing CAMHB, range of concentrations of Levonadifloxacin (EMROK, WOCKHARDT, India) was between (0.5–512 µg/ml) were added at two-fold serial dilutions. Test organism was added to each well to obtain an approximate density of 1.5 X 10 5 CFU/ml in 150 µl of CAMHB and incubated overnight at 37°C in ambient air. One well with only inoculum was used as a positive growth control and one well with neither inoculum nor antibiotics was used as negative control on each plate. The plates were read for visual turbidity and MIC was defined as the well in the microtiter plate with lowest drug concentration at which no visible bacterial growth was observed. Strains showing MIC values ≥ 4µg/ml reference value were interpreted resistant based on proposed pharmacokinetic/ pharmacodynamic breakpoint (13). Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 were used as standard control strains. Interpretation of MIC of levonadifloxacin for S. aureus and E. faecalis were done as per MIC ranges [Table 1 ] based on population pharmacokinetic model and Monte Carlo simulation enabled probability of pharmacodynamic target attainment analysis [ 11 , 12 ]. As there are no breakpoints for interpretation of levonadifloxacin in case of CoNS so breakpoints of S. aureus were used for its interpretation. For interpretation of MIC of Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii. Since the final breakpoints have yet to be assigned, the proportions of strains inhibited by levonadifloxacin at 4 mg/L (proposed pharmacokinetic/pharmacodynamic breakpoint) have been reported. (13) Statistical analysis Data analysis was performed using SPSS software, version 25.0 for descriptive statistics. Categorical data were described using numbers and percentages. Results In this study, a total of 135 clinical bacterial isolates were evaluated. Patient ages ranged from under 20 to over 60 years, with a median age of 43 years. Of those enrolled, 85 were male and 50 were female, yielding a male-to-female ratio of approximately 1.7:1. Detailed clinical profile of the patients is illustrated in [Table-2]. Distribution of clinical sample is shown in [Figure-1]. In this study, out of total clinical bacterial isolates analysed, 85 were identified as Gramnegative bacilli, while the remaining 50 belonged to Grampositive cocci. The most common clinical isolate was K. pneumoniae 21.28% (n = 29/135) followed by E. coli 17.77% (n = 24/135), P. aeruginosa 15.55% (21/135) [Figure 2 ]. Amongst Gram positive cocci, most common isolates were CONS 17.77% (24/135). Out of 24 CoNS isolated most common were S. hemolyticus 50% (12/24), S. epidermidis 33.33% (8/24) and S. hominis 16.66% (4/24) [Figure 2 ]. Antibiotic susceptibility profile of clinical bacterial isolates Amongst the 50 Gram positive isolates of the study Methicillin resistance in S. aureus and CONS was seen in 8 (47%) out of 17 and 19 (79.16%) out of 24, respectively. Overall, a total of 103 bacterial isolates (76.29%) exhibited resistance to levofloxacin, among these 35 isolates (33.98%) were identified as Gram positive cocci (GPC), while the remaining 68 isolates (66%) were Gram-negative bacilli(GNB). All the isolates of S. aureus were sensitive to vancomycin and teicoplanin. Susceptibility of other comparator antibiotics tested in Gram positive cocci is shown in [Table 3 ]. Table 3 Susceptibility profile of comparator antibiotics against Gram positive isolates. Antimicrobial agent No. of isolates (n = 50) MSSA (n = 9) MRSA (n = 8) MSCONS (n = 5) MRCONS (n = 19) VSE (n = 4) VRE (n = 5) Ampicillin 5 8 4 19 3 5 Ampicillin + sulbactum 4 8 3 19 2 5 Amikacin 1 1 0 7 NT NT Gentamicin 2 3 1 `12 2 4 Clindamycin 2 4 2 14 NT NT Erythromycin 5 8 3 17 NT NT Doxycycline 0 1 0 9 1 2 Levofloxacin 8 5 2 14 1 5 Linezolid 0 0 0 0 0 5 Vancomycin 0 0 0 0 0 5 Teicoplanin 0 0 0 0 0 5 MSSA: Methicillin sensitive Staphylococcus aureus, MRSA: Methicillin resistant Staphylococcus aureus, MS-CONS: Methicillin sensitive coagulase negative Staphylococcus, MR-CONS: Methicillin resistant coagulase negative Staphylococcus, NT: Not Tested Based on the MIC of Levonadifloxacin, by employing the interpretive criteria provided in [Table-1], all the isolates including MRSA and MRCONS and VRE were susceptible to levonadifloxacin. Additionally, all the levofloxacin resistant S. aureus, CoNS and E. faecalis isolates were susceptible to levonadifloxacin [Table-5]. Amongst 85 Gram negative isolates of the study, all the isolates were sensitive to colistin and minocycline except one isolate of K. pneumoniae which was resistant to colistin. Susceptibility of other comparator antibiotics tested in Gram negative bacilli is shown in [Table 4 ]. Five isolates of S. maltophilia were identified, all of which were sensitive to ceftriaxone, levofloxacin, minocycline, cotrimoxazole, chloramphenicol, and ticarcillin-clavulanic acid. Two isolates of A. baumannii were identified, both of which were sensitive only to colistin and minocycline and resistant to levofloxacin. Additionally, two isolates of C. freundii were identified, all sensitive to colistin, minocycline, and levofloxacin. One isolate of P. rettgeri was identified, which was pan-drug resistant. One isolate of Proteus was identified, which was sensitive to levofloxacin, imipenem, meropenem, and minocycline. Table 4 Susceptibility profile of comparator antibiotics against Gram-negative isolates Antimicrobial agent No. of isolates (n = 85) K. Pneumoniae (n = 29) E. Coli (n = 24) P. aeruginosa (n = 21) Amikacin 21 16 8 Ceftazidime 24 19 9 Ceftriaxone 23 18 NT Ciprofloxacin 28 22 NT Levofloxacin 28 22 13 Cefoperazone + sulbactam 25 20 11 Imipenem 26 21 12 Meropenem 26 21 12 Colistin 1 0 0 Minocycline 1 0 0 Aztreonam NT NT 2 Tazobactum + piperacillin NT NT 2 NT-Not Tested. Table 5 In vitro activity of levonadifloxacin against Gram-positive and Gram-negative clinical isolates Microorganism MIC range (µg/ml) MIC 50 (µg/ml) MIC 90 (µg/ml) MSSA (n = 9) 0.25-8 0.5 1 MRSA(n = 8) 0.25-16 0.5 1 MS-CONS(n = 5) 0.25-8 0.5 1 MR-CONS(n = 19) 0.25-8 0.5 1 VSE(n = 4) 0.25-1 0.25 0.5 VRE(n = 5) 0.25-1 0.25 0.5 K. pneumonie (n = 29) 0.5–512 32 64 E. coli (n = 24) 0.5–128 64 128 P. aeruginosa (n = 21) 0.5–512 0.5 1 S. maltophilia (n = 5) 0.25-2 1 2 C. freundii (n = 2) 1–4 1 4 A. baumannii (n = 2) 4–16 4 16 Based on MIC of Levonadifloxacin, Since the official breakpoints have not yet been established, the percentage of strains inhibited by levonadifloxacin at a concentration of ≤ 4 µg/ml (proposed PK/PD breakpoint) is considered as susceptible. Additionally, only 20 isolates were susceptible to Levonadifloxacin [Table-5]. For a single P. mirabilis isolate, the minimum inhibitory concentration (MIC) of levonadifloxacin was 2 µg/mL, while for a single P. rettgeri isolate, MIC was 16 µg/ml. Discussion In the present study most, common isolates were K pneumoniae (21.28%) followed by E. coli (17.77%), CoNS (17.77%) and P. aeruginosa (15.55%). Amongst 24 CoNS isolated, most common were S. haemolyticus (50%) followed by S. epidermidis and S. hominis which was similar to other studies [ 14 , 15 ]. A methicillin resistance rate of 38% was observed in S. aureus which was consistent with other studies [ 16 , 17 ]. We found 79.16.% of methicillin resistance CoNS which is consistent with other studies [ 18 , 19 ]. Levofloxacin resistance was noted in 76.3% of isolates. Among these, 33.0% were Gram positive cocci (GPC) and 66.0% were Gram negative bacilli(GNB). All isolates of S. aureus and CoNS were sensitive to Vancomycin, teicoplanin and linezolid. However, 55% of the E. faecalis isolates exhibited resistance to these three antibiotics. The findings were consistent with previously reported data from India [ 20 ]. he activity of levonadifloxacin against Gram-positive isolates observed in this study was consistent with various previous studies [ 21 , 22 , 23 , 24 ]. DNA gyrase and topoisomerase IV are two essential bacterial enzymes involved in DNA replication. Most quinolone antibiotics used against Gram positive bacteria primarily target topoisomerase IV rather than DNA gyrase. Hence, their effectiveness is often reduced against S. aureus strains that carry mutations in topoisomerase IV. In contrast, levonadifloxacin overcomes resistance to ciprofloxacin and levofloxacin in S. aureus by preferentially targeting DNA gyrase [ 25 ]. To the best of our knowledge, this is the first study in which the efficacy of levonadifloxacin has been analyzed not only against gram positive but also against gram negative bacterial isolates. In this study, levonadifloxacin was found to be effective against all gram-positive isolates, regardless of whether they were sensitive or resistant to levofloxacin. It may also serve well as an empirical treatment. Although vancomycin and linezolid both exhibit high activity against Gram-positive bacteria, vancomycin often causes nephrotoxicity and prolonged linezolid therapy can lead to myelosuppression. In contrast, levonadifloxacin does not require dosage adjustments in patients with renal or hepatic impairment. Although enterococci often show high level resistance to most antibiotic classes, in this study all Enterococcus isolates including those resistant to levofloxacin remained susceptible to levonadifloxacin. Most authors have used disc diffusion for testing levonadifloxacin. However, in this study, we used the reference broth microdilution method, which improves the accuracy of the results. In our study, levonadifloxacin showed limited efficacy against gram-negative bacilli. It was effective only against those gram-negative isolates that were also susceptible to levofloxacin. However, since levonadifloxacin is available in both oral and IV formulations, it presents a good option for IV-to-oral switch therapy in ICU patients. For gram-negative bacilli that were resistant to levofloxacin, the MIC of levonadifloxacin was significantly high. Limitation A study involving a larger number of Enterococcal and Gram negative isolates is required to better establish the efficacy of levonadifloxacin against Enterococcus species and Gram negative isolates. We did not explore the additional resistance mechanisms present in the gram-negative isolates with high MICs for levonadifloxacin. The role of levonadifloxacin against gram-negative bacilli remains an area that requires further investigation. Conclusion This study demonstrates strong activity of levonadifloxacin against gram positive isolates, including challenging methicillin-resistant staphylococcal strains. The observed 100% susceptibility of these isolates to levonadifloxacin highlights its potential clinical utility in treating infections, especially those caused by methicillin-resistant Staphylococcus and other gram-positive pathogens. Levonadifloxacin showed limited efficacy against gram-negative bacilli. Its MIC values fell within the susceptible range only for those isolates that were sensitive to levofloxacin. Abbreviations MSSA Methicillin Susceptible Staphylococcus. aureus MRSA Methicillin Resistant Staphylococcus aureus VSSA Vancomycin Sensitive Staphylococcus. aureus VISA Vancomycin Intermediate Staphylococcus. aureus VRSA Vancomycin Resistant Staphylococcus. aureus QRSA quinolone Resistan t Staphylococcus. aureus QSSA quinolone Susceptible Staphylococcus. aureus MSCONS Methicillin susceptible Coagulase Negative Staphylococcus MRCONS Methicillin Resistant Coagulase Negative Staphylococcus VRE Vancomycin Resistant Enterococci VSE Vancomycin Sensitive Enterococci GPC Gram positive cocci GNB Gram negative bacilli ABSSI Acute bacterial skin and skin structure infections AMR Antimicrobial resistance BMD Broth Microdilution ICU Intensive Care Unit MIC Minimum Inhibitory Concentration WHO World Health Organization BSI Blood Stream Infections MALDI TOFMS-Matrix Assisted Laser Desorption Ionization Time Of Flight Mass Spectrometry CAMHB Cation Adjusted Muller Hinton Broth CFU Colony Forming Unit CLSI Clinical & Laboratory Standards Institute ATCC American Type Culture Collection SPSS Statistical Product and Service Solutions PK/PD Pharmacokinetic/Pharmacodynamic breakpoint Declarations Acknowledgements The authors thank Indian Council of Medical Research ( ICMR), New Delhi for part funding of the study ( Project 2020-2703). The authors thank Wockhardt, India for supplying the antibiotics. Author contribution Nidhi Yaduvanshi:NY; Chinmoy Sahu:CS; Nidhi Tejan:NT; Nida Fatima:NF ; Sangram Singh Patel: SSP ; Anju Dinkar: AD ; Awadesh Kumar: AK NY, CS: Protocol development NY, CS :Methodology used to collect isolates NT, NF:Data collection CS, SSP :Data analysis ,Data curation CS:Supervision NY:Writing original draft CS, SSP, NF, AD, AK :Writing review and editing NY, CS contributed to the drafting of the manuscript and all authors read and approved the final manuscript for submission Funding Declaration Not applicable Availability of data and materials The data presented in this study are available on request from the corresponding author Ethics approval and Consent to participate The study was conducted after obtaining Institutional Ethical Committee, SGPGIMS (IEC, SGPGIMS ) approval with Letter number- PGI/BE/1561/2021. Bacterial strains were collected as part of the routine clinical management of patients, according to the national guidelines in India (Clinical trial number: not applicable). Therefore, informed consent was not sought, and informed consent waiver was approved by the institutional ethical committee of Sanjay Gandhi Postgraduate Institute, Lucknow, UP, India, 226014. The study was conducted in compliance with the Helsinki Declaration of 1964 and all of its amendments. All patient data was kept confidential and secured. The collected patient information was used only for research purposes. Consent for publication Not applicable Trial registration number This was a laboratory based study. It was not a clinical trial. So, trial registration number is not applicable Conflicts of interest There are no conflicts of interest Competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript. Author details 1 Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh – 226014, India. 2 Department of Microbiology, Uttar Pradesh University of Medical Sciences, Saifai, Etawah Uttar Pradesh, 206130, India . References India’s First New Discovery Antibiotics from Wockhardt Granted Indian Regulatory Approval. Assessed at http://www.wockhardt.com/pdfs/Press-Release-16-01-2020.pdf Bhagwat SS, Mundkur LA, Gupte SV, Patel MV, Khorakiwala HF. 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Determination of disk diffusion zone and broth dilution MIC correlations and broth dilution versus agar dilution MICs for WCK 771. F-1195, Poster presented at the Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC. San Diego, California; 17–21 September, 2015. Bhagwat SS, Mundkur LA, Gupte SV, Patel MV, Khorakiwala HF. The anti-methicillin-resistant Staphylococcus aureus quinolone WCK 771 has potent activity against sequentially selected mutants, has a narrow mutant selection window against quinolone-resistant Staphylococcus aureus , and preferentially targets DNA gyrase. Antimicrobe Agents Chemother. 2006;50(11):3568–79. Additional Declarations No competing interests reported. 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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-7029796","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":504635759,"identity":"9caa4750-bbdd-471c-b6dd-2a10ecd43bb9","order_by":0,"name":"Nida Fatima","email":"","orcid":"","institution":"Sanjay Gandhi Post Graduate Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Nida","middleName":"","lastName":"Fatima","suffix":""},{"id":504635760,"identity":"5818c15c-b12b-4144-9ea8-9fe0c8546508","order_by":1,"name":"Nidhi Tejan","email":"","orcid":"","institution":"Sanjay Gandhi Post Graduate Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Nidhi","middleName":"","lastName":"Tejan","suffix":""},{"id":504635761,"identity":"90096634-b039-4285-8270-468c0c6f9d59","order_by":2,"name":"Anju Dinkar","email":"","orcid":"","institution":"Sanjay Gandhi Post Graduate Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Anju","middleName":"","lastName":"Dinkar","suffix":""},{"id":504635762,"identity":"d9b176b1-698d-461c-b94c-303aba37cb65","order_by":3,"name":"Awadhesh Kumar","email":"","orcid":"","institution":"Sanjay Gandhi Post Graduate Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Awadhesh","middleName":"","lastName":"Kumar","suffix":""},{"id":504635763,"identity":"441d2f2f-1e19-46a8-a4e7-695d0ec5b62d","order_by":4,"name":"Sangram Singh Patel","email":"","orcid":"","institution":"Sanjay Gandhi Post Graduate Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Sangram","middleName":"Singh","lastName":"Patel","suffix":""},{"id":504635764,"identity":"290470ce-b66c-43d5-b453-b4deafe37507","order_by":5,"name":"Nidhi Yaduvanshi","email":"","orcid":"","institution":"Uttar Pradesh University of Medical Sciences, Saifai","correspondingAuthor":false,"prefix":"","firstName":"Nidhi","middleName":"","lastName":"Yaduvanshi","suffix":""},{"id":504635765,"identity":"10400fb9-d724-4334-b6c1-f7939a44ac2d","order_by":6,"name":"Chinmoy Sahu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5ElEQVRIiWNgGAWjYFACHhBxAEwyfABiNnZStDDOAGlhJlILmMkMZhPSIt9+9pgEQ80dGXOxw8ekbX5tk+djZmD88DEHtxaDM3lpEgzHnvFYzk5Lk87tu23YxszALDlzGx4tDDlmEowNh3kMbueYSef23GYEamFj5sWjRb7/DZIWy57b9gS1MNxAtoXhx+1EgloMbrwxtkg4BtKSlmzZ23A7uY2ZsRmvX+T7cwxvfKg5bG9wO/ngjR9/btvOb28++OEjPoeBQAKEYpFgbAPRjA0E1CMA8weGP0QrHgWjYBSMghEEACfETXAF21XYAAAAAElFTkSuQmCC","orcid":"","institution":"Sanjay Gandhi Post Graduate Institute of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Chinmoy","middleName":"","lastName":"Sahu","suffix":""}],"badges":[],"createdAt":"2025-07-02 13:23:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7029796/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7029796/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89980932,"identity":"ed0b1afd-6126-408c-80cf-e4f11bcc2af4","added_by":"auto","created_at":"2025-08-27 06:23:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":95931,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDistribution of Clinical Bacterial Isolates by Sample Type\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7029796/v1/62537429054923f333b6c38d.png"},{"id":89980930,"identity":"9e21bb46-fa00-449b-8924-2ec5ad825f01","added_by":"auto","created_at":"2025-08-27 06:23:54","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":112617,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDistribution of Clinical Bacterial Isolates by Microorganism\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7029796/v1/a8c2771db45e727245e1f6b1.png"},{"id":89981123,"identity":"b970c4cc-fd65-4c67-b721-f476319a917e","added_by":"auto","created_at":"2025-08-27 06:24:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1504324,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7029796/v1/305eac67-7eb3-46d9-8915-4f437c03268d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Assessment of In vitro activity of Levonadifloxacin against clinical bacterial isolates in patients admitted in ICU in a tertiary care hospital","fulltext":[{"header":"Highlights","content":"\u003cp\u003eLevonadifloxacin exhibited excellent activity against Gram-positive cocci, including MRSA, MRCONS and VRE.\u003c/p\u003e\u003cp\u003eWe evaluated the efficacy of levonadifloxacin against Gram-negative bacilli also and found it to be effective against isolates that are sensitive to levofloxacin.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eLevonadifloxacin is benzoquinolizine subclass of fluoroquinolone antibiotic with potent activity against both methicillin-resistant (MRSA) and quinolone resistant \u003cem\u003eS.aureus\u003c/em\u003e (QRSA), vancomycin intermediate \u003cem\u003eS. aureus\u003c/em\u003e (VISA), and vancomycinresistant \u003cem\u003eS. aureus\u003c/em\u003e(VRSA). Its intravenous formulation, levonadifloxacin, and its oral prodrug, ala-levonadifloxacin, have been recently approved in India for treating acute bacterial skin and skin structure infections (ABSSI), including cases with concomitant bacteraemia and diabetic foot infections [1]. The strong effectiveness of levonadifloxacin against MRSA, QRSA, and heterogenous vancomycin intermediate \u003cem\u003eS. aureus\u003c/em\u003e (hVISA) is due to unique mechanism: it primarily inhibits DNA gyrase while still retaining high affinity for topoisomerase IV. This dual targeted action enhances its potency against resistant strains [2].\u003c/p\u003e\u003cp\u003eMethicillin resistant \u003cem\u003eStaphylococcus\u003c/em\u003e infections, especially in ICUs, pose serious treatment challenges. The most commonly used drugs vancomycin and linezolid each have notable drawbacks: like vancomycin is considered as a suboptimal option in critically ill patients due to its weak bactericidal activity, poor penetration into tissues (such as lung), renal toxicity and risk of clinical failure due to Minimum Inhibitory Concentration (MIC) creep [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Linezolid is a bacteriostatic agent and therefore, not recommended to be used in Blood Stream Infections (BSI). Can suppress bone marrow, cause thrombocytopenia, and requires shorter courses with safety monitoring [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Clinicians need better antibiotics ideally bactericidal agents with strong tissue penetration and acceptable safety for longer treatment durations.\u003c/p\u003e\u003cp\u003eMethicillin resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (MRSA) is a significant contributor to healthcare associated infections (HAI) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The World Health Organization (WHO) has reported that MRSA infections are linked to a higher risk of mortality compared to infections caused by methicillin susceptible \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (MSSA) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMost of epidemiological studies are confined to levonadifloxacin susceptibility in Gram positive isolates using the diskdiffusion method. Levonadifloxacin\u0026rsquo;s activity against Gram negative bacilli has been explored very minimally to date. This study was conducted to produce antimicrobial susceptibility data by determining MIC values. The objective of the present study was to assess the in vitro activity of levonadifloxacin against clinical bacterial isolates in patients admitted in ICU.\u003c/p\u003e"},{"header":"Material and methods","content":"\u003cp\u003e\u003cb\u003eStudy setting\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe present descriptive study was conducted in Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India, between March 27, 2025, to May 25, 2025 duration. The study was conducted after obtaining Ethical Committee approval with Letter number- PGI/BE/1561/2021. A total of 135 clinical bacterial isolates collected from all ICUs of the hospital were analyzed. The samples were obtained from patients of all age group and both sexes. Demographic information and clinical details of the patient included in the study were recorded [Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSusceptibility test interpretative criteria for Levonadifloxacin\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eMicroorganism\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eMIC \u0026micro;g/ml\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSusceptible\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIntermediate\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eResistant\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eS.\u003c/b\u003e \u003cb\u003eaureus\u003c/b\u003e \u003cb\u003e(methicillin-resistant, methicillin-susceptible, quinolone resistant, quinolone-susceptible isolates)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eE. faecalis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;16\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eE. \u003cem\u003efaecalis: Enterococcus faecalis, S. aureus: Staph aureus\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eClinical profile of study participants (n\u0026thinsp;=\u0026thinsp;135)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatient clinical profile\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal no. of isolates (%) n\u0026thinsp;=\u0026thinsp;135\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eGender\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMale\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e85(62.97%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFemale\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50(37.03%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e1. \u003cb\u003eAge group\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e\u0026le;\u0026thinsp;20yrs\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21(15.55%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e21-40yrs\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34(17.77%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e41-60yrs\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e54(40%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e\u0026ge;\u0026thinsp;61yrs\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26(19.25%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e2. \u003cb\u003eUnderlying clinical condition\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHematological malignancy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28(20.74%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRespiratory disease\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28(20.74%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRenal disease\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26(19.25%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTrauma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18(13.33%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSolid organ malignancy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18(13.33%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLiver disease\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8(5.92%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGastrointestinal disease\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6(4.44%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNeurological disease\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3(2.22%)\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\u003cb\u003eInclusion criteria\u003c/b\u003e: All consecutive, non-duplicate isolates from blood, sterile body fluids, catheter tips, skin and soft tissue, pus and urine samples collected from ICUs considered clinically significant were included in the study. \u003cb\u003eExclusion criteria\u003c/b\u003e: Duplicate isolates were excluded from study.\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e\u003cb\u003eSample collection and culture processing\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e Pus and sputum samples were cultured on Blood, MacConkey, and Chocolate agar, while urine samples were cultured on HI Chrome agar according to standard microbiological methods. All culture plates were incubated aerobically at 37\u0026deg;C for 24 hours. Blood and sterile body fluids were inoculated into BACTEC FX blood culture bottles (BD, USA) and incubated at 35\u0026deg;C for 5 days. Upon a positive signal, Gram staining was done, and broths were sub-cultured on Blood and MacConkey agar, followed by 24-hour aerobic incubation at 37\u0026deg;C.\u003c/p\u003e\u003cp\u003e\u003cb\u003eIdentification of bacterial isolates\u003c/b\u003e\u003c/p\u003e\u003cp\u003eIsolates were identified using Gram staining, standard biochemical tests and automated MALDI TOF-MS system according to manufacturer recommendations (VITEK MS, bioM\u0026eacute;rieux, USA). The zone diameter obtained with a 30 \u0026micro;g cefoxitin disk was used to determine methicillin resistance in Staphylococci.\u003c/p\u003e\u003cp\u003e\u003cb\u003eAntibiotic susceptibility tests (AST)\u003c/b\u003e\u003c/p\u003e\u003cp\u003eRoutine antibiotic susceptibility tests were performed by Kirby Bauer disk diffusion method and evaluated by recommendations of Clinical Laboratory Standards Institute (CLSI) guideline [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], using commercially available antibiotic discs procured from HI Media (Mumbai, India).\u003c/p\u003e\u003cp\u003e\u003cb\u003eBroth microdilution tests (BMD)\u003c/b\u003e\u003c/p\u003e\u003cp\u003eMinimal inhibitory concentrations (MIC) for Levonadifloxacin were detected by the broth microdilution method. While preparing drug stock solution, the weighed quantity of levonadifloxacin dry powder has to be dissolved in L-arginine solution (27.5 mg/L L-arginine in water) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] The MIC of Levonadifloxacin was determined using cation-adjusted Muller-Hinton broth (CAMHB) according to CLSI guidelines (CLSI, 2025). In 96-well microtiter plates (Genetix Inc., India) containing CAMHB, range of concentrations of Levonadifloxacin (EMROK, WOCKHARDT, India) was between (0.5\u0026ndash;512 \u0026micro;g/ml) were added at two-fold serial dilutions. Test organism was added to each well to obtain an approximate density of 1.5 X 10\u003csup\u003e5\u003c/sup\u003e CFU/ml in 150 \u0026micro;l of CAMHB and incubated overnight at 37\u0026deg;C in ambient air. One well with only inoculum was used as a positive growth control and one well with neither inoculum nor antibiotics was used as negative control on each plate. The plates were read for visual turbidity and MIC was defined as the well in the microtiter plate with lowest drug concentration at which no visible bacterial growth was observed. Strains showing MIC values\u0026thinsp;\u0026ge;\u0026thinsp;4\u0026micro;g/ml reference value were interpreted resistant based on proposed pharmacokinetic/ pharmacodynamic breakpoint (13). \u003cem\u003eStaphylococcus aureus\u003c/em\u003e ATCC 29213, \u003cem\u003eEnterococcus faecalis\u003c/em\u003e ATCC 29212, \u003cem\u003eEscherichia coli\u003c/em\u003e ATCC 25922 and \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e ATCC 27853 were used as standard control strains.\u003c/p\u003e\u003cp\u003eInterpretation of MIC of levonadifloxacin for \u003cem\u003eS. aureus\u003c/em\u003e and \u003cem\u003eE. faecalis\u003c/em\u003e were done as per MIC ranges [Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e] based on population pharmacokinetic model and Monte Carlo simulation enabled probability of pharmacodynamic target attainment analysis [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. As there are no breakpoints for interpretation of levonadifloxacin in case of CoNS so breakpoints of \u003cem\u003eS. aureus\u003c/em\u003e were used for its interpretation.\u003c/p\u003e\u003cp\u003eFor interpretation of MIC of \u003cem\u003eEscherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii.\u003c/em\u003e Since the final breakpoints have yet to be assigned, the proportions of strains inhibited by levonadifloxacin at 4 mg/L (proposed pharmacokinetic/pharmacodynamic breakpoint) have been reported. (13)\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eData analysis was performed using SPSS software, version 25.0 for descriptive statistics. Categorical data were described using numbers and percentages.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eIn this study, a total of 135 clinical bacterial isolates were evaluated. Patient ages ranged from under 20 to over 60 years, with a median age of 43 years. Of those enrolled, 85 were male and 50 were female, yielding a male-to-female ratio of approximately 1.7:1. Detailed clinical profile of the patients is illustrated in [Table-2]. Distribution of clinical sample is shown in [Figure-1].\u003c/p\u003e\u003cp\u003eIn this study, out of total clinical bacterial isolates analysed, 85 were identified as Gramnegative bacilli, while the remaining 50 belonged to Grampositive cocci. The most common clinical isolate was \u003cem\u003eK. pneumoniae\u003c/em\u003e 21.28% (n\u0026thinsp;=\u0026thinsp;29/135) followed by \u003cem\u003eE. coli\u003c/em\u003e 17.77% (n\u0026thinsp;=\u0026thinsp;24/135), \u003cem\u003eP. aeruginosa\u003c/em\u003e 15.55% (21/135) [Figure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e]. Amongst Gram positive cocci, most common isolates were CONS 17.77% (24/135). Out of 24 CoNS isolated most common were \u003cem\u003eS. hemolyticus\u003c/em\u003e 50% (12/24), \u003cem\u003eS. epidermidis\u003c/em\u003e 33.33% (8/24) and \u003cem\u003eS. hominis\u003c/em\u003e 16.66% (4/24) [Figure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eAntibiotic susceptibility profile of clinical bacterial isolates\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAmongst the 50 Gram positive isolates of the study Methicillin resistance in \u003cem\u003eS. aureus\u003c/em\u003e and CONS was seen in 8 (47%) out of 17 and 19 (79.16%) out of 24, respectively. Overall, a total of 103 bacterial isolates (76.29%) exhibited resistance to levofloxacin, among these 35 isolates (33.98%) were identified as Gram positive cocci (GPC), while the remaining 68 isolates (66%) were Gram-negative bacilli(GNB). All the isolates of S. aureus were sensitive to vancomycin and teicoplanin. Susceptibility of other comparator antibiotics tested in Gram positive cocci is shown in [Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\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 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSusceptibility profile of comparator antibiotics against Gram positive isolates.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\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\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAntimicrobial agent\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"6\" nameend=\"c7\" namest=\"c2\"\u003e\u003cp\u003eNo. of isolates (n\u0026thinsp;=\u0026thinsp;50)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMSSA\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMRSA\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMSCONS\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eMRCONS\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eVSE\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eVRE\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAmpicillin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAmpicillin\u0026thinsp;+\u0026thinsp;sulbactum\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAmikacin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGentamicin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e`12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eClindamycin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eErythromycin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDoxycycline\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLevofloxacin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c8\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLinezolid\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVancomycin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTeicoplanin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003eMSSA: Methicillin sensitive Staphylococcus aureus, MRSA: Methicillin resistant Staphylococcus aureus, MS-CONS: Methicillin sensitive coagulase negative Staphylococcus, MR-CONS: Methicillin resistant coagulase negative Staphylococcus, NT: Not Tested\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eBased on the MIC of Levonadifloxacin, by employing the interpretive criteria provided in [Table-1], all the isolates including MRSA and MRCONS and VRE were susceptible to levonadifloxacin. Additionally, all the levofloxacin resistant \u003cem\u003eS. aureus, CoNS\u003c/em\u003e and \u003cem\u003eE. faecalis\u003c/em\u003e isolates were susceptible to levonadifloxacin [Table-5].\u003c/p\u003e\u003cp\u003eAmongst 85 Gram negative isolates of the study, all the isolates were sensitive to colistin and minocycline except one isolate of \u003cem\u003eK. pneumoniae\u003c/em\u003e which was resistant to colistin. Susceptibility of other comparator antibiotics tested in Gram negative bacilli is shown in [Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e]. Five isolates of \u003cem\u003eS. maltophilia\u003c/em\u003e were identified, all of which were sensitive to ceftriaxone, levofloxacin, minocycline, cotrimoxazole, chloramphenicol, and ticarcillin-clavulanic acid. Two isolates of \u003cem\u003eA. baumannii\u003c/em\u003e were identified, both of which were sensitive only to colistin and minocycline and resistant to levofloxacin. Additionally, two isolates of \u003cem\u003eC. freundii\u003c/em\u003e were identified, all sensitive to colistin, minocycline, and levofloxacin. One isolate of \u003cem\u003eP. rettgeri\u003c/em\u003e was identified, which was pan-drug resistant. One isolate of \u003cem\u003eProteus\u003c/em\u003e was identified, which was sensitive to levofloxacin, imipenem, meropenem, and minocycline.\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 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSusceptibility profile of comparator antibiotics against Gram-negative isolates\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAntimicrobial agent\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eNo. of isolates (n\u0026thinsp;=\u0026thinsp;85)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eK. \u003cem\u003ePneumoniae\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003e(n\u0026thinsp;=\u0026thinsp;29)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eE. \u003cem\u003eColi\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003e(n\u0026thinsp;=\u0026thinsp;24)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP. aeruginosa\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003e(n\u0026thinsp;=\u0026thinsp;21)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAmikacin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCeftazidime\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCeftriaxone\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNT\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCiprofloxacin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNT\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLevofloxacin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCefoperazone\u0026thinsp;+\u0026thinsp;sulbactam\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eImipenem\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMeropenem\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eColistin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMinocycline\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAztreonam\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTazobactum\u0026thinsp;+\u0026thinsp;piperacillin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eNT-Not Tested.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\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 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eIn vitro activity of levonadifloxacin against Gram-positive and Gram-negative clinical isolates\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMicroorganism\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMIC range (\u0026micro;g/ml)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMIC\u003csub\u003e50\u003c/sub\u003e (\u0026micro;g/ml)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMIC\u003csub\u003e90\u003c/sub\u003e (\u0026micro;g/ml)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMSSA (n\u0026thinsp;=\u0026thinsp;9)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.25-8\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\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMRSA(n\u0026thinsp;=\u0026thinsp;8)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.25-16\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\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMS-CONS(n\u0026thinsp;=\u0026thinsp;5)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.25-8\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\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMR-CONS(n\u0026thinsp;=\u0026thinsp;19)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.25-8\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\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVSE(n\u0026thinsp;=\u0026thinsp;4)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.25-1\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\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVRE(n\u0026thinsp;=\u0026thinsp;5)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.25-1\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\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eK. pneumonie\u003c/b\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;29)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.5\u0026ndash;512\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e64\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eE. coli\u003c/b\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;24)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.5\u0026ndash;128\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e128\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eP. aeruginosa\u003c/b\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;21)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.5\u0026ndash;512\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\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eS. maltophilia\u003c/b\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;5)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.25-2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eC. freundii\u003c/b\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;2)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u0026ndash;4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eA. baumannii\u003c/b\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;2)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u0026ndash;16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16\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\u003eBased on MIC of Levonadifloxacin, Since the official breakpoints have not yet been established, the percentage of strains inhibited by levonadifloxacin at a concentration of \u0026le;\u0026thinsp;4 \u0026micro;g/ml (proposed PK/PD breakpoint) is considered as susceptible. Additionally, only 20 isolates were susceptible to Levonadifloxacin [Table-5]. For a single \u003cem\u003eP. mirabilis\u003c/em\u003e isolate, the minimum inhibitory concentration (MIC) of levonadifloxacin was 2 \u0026micro;g/mL, while for a single \u003cem\u003eP. rettgeri\u003c/em\u003e isolate, MIC was 16 \u0026micro;g/ml.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the present study most, common isolates were \u003cem\u003eK pneumoniae\u003c/em\u003e (21.28%) followed by \u003cem\u003eE. coli\u003c/em\u003e (17.77%), CoNS (17.77%) and \u003cem\u003eP. aeruginosa\u003c/em\u003e (15.55%). Amongst 24 CoNS isolated, most common were \u003cem\u003eS. haemolyticus\u003c/em\u003e (50%) followed by \u003cem\u003eS. epidermidis\u003c/em\u003e and \u003cem\u003eS. hominis\u003c/em\u003e which was similar to other studies [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. A methicillin resistance rate of 38% was observed in \u003cem\u003eS. aureus\u003c/em\u003e which was consistent with other studies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. We found 79.16.% of methicillin resistance CoNS which is consistent with other studies [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Levofloxacin resistance was noted in 76.3% of isolates. Among these, 33.0% were Gram positive cocci (GPC) and 66.0% were Gram negative bacilli(GNB).\u003c/p\u003e\u003cp\u003eAll isolates of S. aureus and CoNS were sensitive to Vancomycin, teicoplanin and linezolid. However, 55% of the \u003cem\u003eE. faecalis\u003c/em\u003e isolates exhibited resistance to these three antibiotics. The findings were consistent with previously reported data from India [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. he activity of levonadifloxacin against Gram-positive isolates observed in this study was consistent with various previous studies [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDNA gyrase and topoisomerase IV are two essential bacterial enzymes involved in DNA replication. Most quinolone antibiotics used against Gram positive bacteria primarily target topoisomerase IV rather than DNA gyrase. Hence, their effectiveness is often reduced against \u003cem\u003eS. aureus\u003c/em\u003e strains that carry mutations in topoisomerase IV. In contrast, levonadifloxacin overcomes resistance to ciprofloxacin and levofloxacin in \u003cem\u003eS. aureus\u003c/em\u003e by preferentially targeting DNA gyrase [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTo the best of our knowledge, this is the first study in which the efficacy of levonadifloxacin has been analyzed not only against gram positive but also against gram negative bacterial isolates. In this study, levonadifloxacin was found to be effective against all gram-positive isolates, regardless of whether they were sensitive or resistant to levofloxacin. It may also serve well as an empirical treatment. Although vancomycin and linezolid both exhibit high activity against Gram-positive bacteria, vancomycin often causes nephrotoxicity and prolonged linezolid therapy can lead to myelosuppression. In contrast, levonadifloxacin does not require dosage adjustments in patients with renal or hepatic impairment. Although enterococci often show high level resistance to most antibiotic classes, in this study all Enterococcus isolates including those resistant to levofloxacin remained susceptible to levonadifloxacin. Most authors have used disc diffusion for testing levonadifloxacin. However, in this study, we used the reference broth microdilution method, which improves the accuracy of the results.\u003c/p\u003e\u003cp\u003eIn our study, levonadifloxacin showed limited efficacy against gram-negative bacilli. It was effective only against those gram-negative isolates that were also susceptible to levofloxacin. However, since levonadifloxacin is available in both oral and IV formulations, it presents a good option for IV-to-oral switch therapy in ICU patients. For gram-negative bacilli that were resistant to levofloxacin, the MIC of levonadifloxacin was significantly high.\u003c/p\u003e\u003cp\u003e\u003cb\u003eLimitation\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA study involving a larger number of Enterococcal and Gram negative isolates is required to better establish the efficacy of levonadifloxacin against Enterococcus species and Gram negative isolates. We did not explore the additional resistance mechanisms present in the gram-negative isolates with high MICs for levonadifloxacin. The role of levonadifloxacin against gram-negative bacilli remains an area that requires further investigation.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study demonstrates strong activity of levonadifloxacin against gram positive isolates, including challenging methicillin-resistant staphylococcal strains. The observed 100% susceptibility of these isolates to levonadifloxacin highlights its potential clinical utility in treating infections, especially those caused by methicillin-resistant Staphylococcus and other gram-positive pathogens. Levonadifloxacin showed limited efficacy against gram-negative bacilli. Its MIC values fell within the susceptible range only for those isolates that were sensitive to levofloxacin.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMSSA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMethicillin Susceptible \u003cem\u003eStaphylococcus. aureus\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMRSA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMethicillin Resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eVSSA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eVancomycin Sensitive \u003cem\u003eStaphylococcus. aureus\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eVISA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eVancomycin Intermediate \u003cem\u003eStaphylococcus. aureus\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eVRSA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eVancomycin Resistant \u003cem\u003eStaphylococcus. aureus\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eQRSA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003equinolone Resistan\u003cem\u003et Staphylococcus. aureus\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eQSSA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003equinolone Susceptible \u003cem\u003eStaphylococcus. aureus\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMSCONS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMethicillin susceptible Coagulase Negative Staphylococcus\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMRCONS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMethicillin Resistant Coagulase Negative Staphylococcus\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eVRE\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eVancomycin Resistant \u003cem\u003eEnterococci\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eVSE\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eVancomycin Sensitive \u003cem\u003eEnterococci\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eGPC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eGram positive cocci\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eGNB\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eGram negative bacilli\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eABSSI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAcute bacterial skin and skin structure infections\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAMR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAntimicrobial resistance\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eBMD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eBroth Microdilution\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eICU\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eIntensive Care Unit\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMIC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMinimum Inhibitory Concentration\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eWHO\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eWorld Health Organization\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eBSI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eBlood Stream Infections\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMALDI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eTOFMS-Matrix Assisted Laser Desorption Ionization Time Of Flight Mass Spectrometry\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCAMHB\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCation Adjusted Muller Hinton Broth\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCFU\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eColony Forming Unit\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCLSI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eClinical \u0026amp; Laboratory Standards Institute\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eATCC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAmerican Type Culture Collection\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSPSS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eStatistical Product and Service Solutions\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePK/PD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePharmacokinetic/Pharmacodynamic breakpoint\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank Indian Council of Medical Research ( ICMR), New Delhi for part funding of the study ( Project 2020-2703).\u003c/p\u003e\n\u003cp\u003eThe authors thank Wockhardt, India for supplying the antibiotics.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contribution\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNidhi Yaduvanshi:NY; Chinmoy Sahu:CS; Nidhi Tejan:NT; Nida Fatima:NF ; Sangram Singh Patel: SSP ; \u0026nbsp;Anju Dinkar: AD ; Awadesh Kumar: AK\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;NY, CS: Protocol development\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNY, CS :Methodology used to collect isolates\u003c/p\u003e\n\u003cp\u003eNT, NF:Data collection\u003c/p\u003e\n\u003cp\u003eCS, SSP :Data analysis ,Data curation\u003c/p\u003e\n\u003cp\u003eCS:Supervision\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;NY:Writing original draft\u003c/p\u003e\n\u003cp\u003eCS, SSP, NF, AD, AK :Writing \u0026nbsp;review and editing\u003c/p\u003e\n\u003cp\u003eNY, CS contributed to the drafting of the manuscript and all authors read and approved the final manuscript for submission\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Declaration\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data presented in this study are available on request from the corresponding author\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eand\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted after obtaining Institutional Ethical Committee, SGPGIMS (IEC, SGPGIMS ) approval with Letter number- PGI/BE/1561/2021.\u0026nbsp;Bacterial strains were collected as part of the routine clinical management of patients, according to the national guidelines in India (Clinical trial number: not applicable). Therefore, informed consent was not sought, and informed consent waiver was approved by the institutional ethical committee of Sanjay Gandhi Postgraduate Institute, Lucknow, UP, India, 226014. The study was conducted in compliance with the Helsinki Declaration of 1964 and all of its amendments. All patient data was kept confidential and secured. The collected patient information was used only for research purposes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis was a laboratory based study. It was not a clinical trial. So, trial registration number is not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are no conflicts of interest\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u0026nbsp;\u003c/sup\u003eDepartment of Microbiology,\u0026nbsp;Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh \u0026ndash; 226014, India.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003eDepartment of Microbiology, Uttar Pradesh University of Medical Sciences, Saifai, Etawah\u003c/p\u003e\n\u003cp\u003eUttar Pradesh, 206130, India .\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eIndia\u0026rsquo;s First New Discovery Antibiotics from Wockhardt Granted Indian Regulatory Approval. Assessed at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.wockhardt.com/pdfs/Press-Release-16-01-2020.pdf\u003c/span\u003e\u003cspan address=\"http://www.wockhardt.com/pdfs/Press-Release-16-01-2020.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBhagwat SS, Mundkur LA, Gupte SV, Patel MV, Khorakiwala HF. The anti-methicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e quinolone WCK 771 has potent activity against sequentially selected mutants, has a narrow mutant selection window against quinolone-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e, and preferentially targets DNA gyrase. Antimicrobe Agents Chemother. 2006;50(11):3568\u0026ndash;79.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChang W, Ma X, Gao P, Lv X, Lu H, Chen F. Vancomycin MIC creep in methicillin resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (MRSA) isolates from 2006 to 2010 in a hospital in China. Indian J Med Microbiol. 2015;33(2):262\u0026ndash;66.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEstes KS, Derendorf H. Comparison of the pharmacokinetic properties of vancomycin, linezolid, tigecyclin, and daptomycin. Eur J Med Res. 2010;15(12):533\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMiyazaki M, Takata T, Yoshimura H, Matsunaga A, Ohta D, Ishikura H, et al. Vancomycin bactericidal activity as a predictor of 30-day mortality in patients with methicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e bacteremia. Antimicrob Agents Chemother. 2011;55(4):1819\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eParlak E, Tan H. Pancytopenia due to linezolid treatment. Turk Pediatri Ars. 2015;50(3):185\u0026ndash;88.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSievert DM, Ricks P, Edwards JR, Schneider A, Patel J, Srinivasan A, et al. National Healthcare Safety Network (NHSN) Team and Participating NHSN Facilities Antimicrobial-resistant pathogens associated with health care associated infections: Summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention 2009\u0026ndash;2010. Infect Control Hosp Epidemiol. 2013;34(1):01\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWorld Health Organization. Antimicrobial resistance: Global report on surveillance. World Health Organization; 2014.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eClinical Laboratory Standards. Institute (CLSI) guideline: Performance Standards for Antimicrobial Susceptibility Testing. 35th edition. CLSI M100.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTeppler H, Gesser RM, Friedland IR, Woods GL, Meibohm A, Herman G, Mistry G, Isaacs R. Safety and tolerability of ertapenem. J Antimicrob Chemother. 2004;53(Suppl 2):ii75\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBhagwat S, Ivaturi V, Gobburu J, Takalkar S, Periasamy H, Chavan R, et al. Pharmacokinetic/Pharmacodynamic (PK/PD) Target Attainment (TA) Analyses to Support WCK 771 (INN: Levonadifloxacin) Clinical Dose Selection. P-1941, Poster Presented at the 29th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID. Amsterdam: Netherlands; April, 2019. pp. 13\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHackel M, Bhagwat S, Palwe S, Patel M, Sahm D. Determination of disk diffusion zone and broth dilution MIC correaltions and broth dilution versus agar dilution MICs for WCK 771. F-1195, Poster presented at the Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC. San Diego, California; 17\u0026ndash;21 September, 2015.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAppalaraju B, Baveja S, Baliga S, Shenoy S, Bhardwaj R, et al. In vitro activity of a novel antibacterial agent, levonadifloxacin, against clinical isolates collected in a prospective, multicentre surveillance study in India during 2016-18. J Antimicrob Chemother. 2020;75:600\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSingh S, Dhawan B, Kapil A, Kabra SK, Suri A, Sreenivas V, et al. Coagulase negative staphylococci causing blood stream infection at an Indian tertiary care hospital: Prevalence, antimicrobial resistance and molecular characterisation. Indian J Med Microbiol. 2016;34(4):500\u0026ndash;05.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCui J, Liang Z, Mo Z, Zhang J. The species distribution, antimicrobial resistance and risk factors for poor outcome of coagulase-negative staphylococci bacteraemia in China. Antimicrob Resist Infect Control. 2019;8:65.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJoshi S, Ray P, Manchanda V, Bajaj J, Chitnis DS, Gautam V. Methicillin resistant Staphylococcus aureus (MRSA) in India: Prevalence \u0026amp; susceptibility pattern. Indian J Med Res. 2013;137(2):363\u0026ndash;69.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMehta Y, Hegde A, Pande R, Zirpe KG, Gupta V, Ahdal J, et al. Methicillin resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e in intensive care unit setting of India: A review of clinical burden, patterns of prevalence, preventive measures, and future strategies. Indian J Crit Care Med. 2020;24(1):55\u0026ndash;62. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.5005/jp-journals-\u003c/span\u003e\u003cspan address=\"10.5005/jp-journals-\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 32148350; PMCID: PMC7050173.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEhsan MM, Memon Z, Ismail MO, Fatima G. Identification and antibiotic susceptibility pattern of coagulase-negative staphylococci in various clinical specimens. Pak J Med Sci. 2013;29(6):1420\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eUstulin D, Cunha M. Methods for detection of oxacillin resistance among coagulase- negative staphylococci recovered from patients with bloodstream infections at the University Hospital in Brazil. J Virol Microbiol. 2012; 2012:164822.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBhatia A, Mastim M, Shah M, Gutte R, Joshi P, Kumbhar D, et al. Efficacy and safety of a novel broad-spectrum anti-MRSA agent levonadifloxacin compared with linezolid for acute bacterial skin and skin structure infections: A phase 3, Openlabel, randomized study. J Assoc Physicians India. 2020;68(8):30\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBakthavatchalam YD, Shankar A, Muniyasamy R, Peter JV, Marcus Z, Triplicane Dwarakanathan H, et al. Levonadifloxacin, a recently approved benzo quinolizine fluoroquinolone, exhibits potent \u003cem\u003ein vitro\u003c/em\u003e activity against contemporary \u003cem\u003eStaphylococcus aureus\u003c/em\u003e isolates and Bengal Bay clone isolates collected from a large Indian tertiary care hospital. J Antimicrob Chemother. 2020;75(8):2156\u0026ndash;59.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCLSI. Performance Standards for Antimicrobial Susceptibility Testing. 26th ed. Wayne, PA: Clinical and Laboratory Standards Institute. 2016. Pp. 100. Wayne, PA: Clinical and Laboratory Standards Institute; 2020.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBhagwat S, Ivaturi V, Gobburu J, Takalkar S, Periasamy H, Chavan R, et al. Pharmacokinetic/Pharmacodynamic (PK/PD) Target Attainment (TA) Analyses to Support WCK 771 (INN: Levonadifloxacin) Clinical Dose Selection. P-1941, Poster Presented at the 29th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID. Amsterdam: Netherlands; April, 2019. pp. 13\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHackel M, Bhagwat S, Palwe S, Patel M, Sahm D. Determination of disk diffusion zone and broth dilution MIC correlations and broth dilution versus agar dilution MICs for WCK 771. F-1195, Poster presented at the Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC. San Diego, California; 17\u0026ndash;21 September, 2015.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBhagwat SS, Mundkur LA, Gupte SV, Patel MV, Khorakiwala HF. The anti-methicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e quinolone WCK 771 has potent activity against sequentially selected mutants, has a narrow mutant selection window against quinolone-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e, and preferentially targets DNA gyrase. Antimicrobe Agents Chemother. 2006;50(11):3568\u0026ndash;79.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"bmc-microbiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mcro","sideBox":"Learn more about [BMC Microbiology](http://bmcmicrobiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/mcro","title":"BMC Microbiology","twitterHandle":"#bmcmicrobiology","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Levonadifloxacin, MRSA, ICU infections, antimicrobial resistance, Gram-positive cocci, Gram-negative bacilli, broth microdilution, MIC","lastPublishedDoi":"10.21203/rs.3.rs-7029796/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7029796/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e\u003cp\u003eLevonadifloxacin, a benzoquinolizine subclass of fluoroquinolones, has demonstrated potent activity against methicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (MRSA), quinolone-resistant \u003cem\u003eS. aureus\u003c/em\u003e (QRSA), vancomycin-intermediate and vancomycin-resistant \u003cem\u003eS. aureus\u003c/em\u003e. Its mechanism\u0026mdash;preferential inhibition of DNA gyrase with high affinity for topoisomerase IV\u0026mdash;enhances its efficacy against resistant Gram-positive bacteria. Despite its approval in India for treating skin and soft tissue infections, data on its activity against Gram-negative organisms remains limited. This study aimed to assess the in vitro activity of levonadifloxacin against clinical bacterial isolates from ICU patients using broth microdilution.\u003c/p\u003e\u003ch2\u003eMaterial and Method:\u003c/h2\u003e\u003cp\u003eThis descriptive study was conducted at Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, between March 27 and May 25, 2025. A total of 135 non-duplicate clinical isolates from ICU patients (blood, pus, urine, catheter tips, and sterile fluids) were analysed. Isolates were identified via Gram stain, biochemical tests, and MALDI-TOF MS. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method. Minimum inhibitory concentrations (MICs) for levonadifloxacin were determined using the broth microdilution method as per CLSI 2025 guidelines, with interpretation based on proposed pharmacokinetic/pharmacodynamic breakpoints (\u0026le;\u0026thinsp;4 \u0026micro;g/ml).\u003c/p\u003e\u003ch2\u003eResult:\u003c/h2\u003e\u003cp\u003eAmong 135 isolates, 85 (62.96%) were Gram-negative bacilli and 50 (37.04%) were Gram-positive cocci. The most frequent isolates were \u003cem\u003eK. pneumoniae\u003c/em\u003e (21.28%), \u003cem\u003eE. coli\u003c/em\u003e (17.77%), CONS (17.77%), and \u003cem\u003eP. aeruginosa\u003c/em\u003e (15.55%). Methicillin resistance was observed in 47% of \u003cem\u003eS. aureus\u003c/em\u003e and 79.16% of CONS. A total of 76.29% of isolates were resistant to levofloxacin; however, all Gram-positive isolates (including MRSA, MRCONS, and vancomycin resistant \u003cem\u003eE. faecalis\u003c/em\u003e) were susceptible to levonadifloxacin. Among Gram-negative bacilli, levonadifloxacin showed limited efficacy and was active only against strains that were already susceptible to levofloxacin.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e\u003cp\u003eLevonadifloxacin exhibited excellent in vitro activity against Gram-positive cocci, including multidrug-resistant MRSA and VRE, supporting its role in treating ICU-acquired infections. Its oral and IV availability and lack of renal/hepatic dose adjustments make it a valuable therapeutic option. However, its limited efficacy against Gram-negative bacilli highlights the need for further studies and resistance mechanism evaluation.\u003c/p\u003e","manuscriptTitle":"Assessment of In vitro activity of Levonadifloxacin against clinical bacterial isolates in patients admitted in ICU in a tertiary care hospital","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-27 06:23:16","doi":"10.21203/rs.3.rs-7029796/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-01T12:34:11+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-24T10:53:26+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-18T11:34:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"40226216430725036010059804673064935178","date":"2025-09-03T20:53:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"92367706721793119339864632587477820678","date":"2025-08-31T06:32:39+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-17T12:59:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"116608680436315092734808757072003101723","date":"2025-08-17T12:38:01+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-17T11:22:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-12T10:40:51+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-07-22T21:35:32+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-21T17:14:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Microbiology","date":"2025-07-21T17:11:38+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-microbiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mcro","sideBox":"Learn more about [BMC Microbiology](http://bmcmicrobiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/mcro","title":"BMC Microbiology","twitterHandle":"#bmcmicrobiology","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"962d5841-b3e1-486c-928d-68595adc3efc","owner":[],"postedDate":"August 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-14T04:08:56+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-27 06:23:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7029796","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7029796","identity":"rs-7029796","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}