Molecular characterization of Plasmid-Mediated Quinolone Resistance (PMQR) and Extended-Spectrum β-Lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolated from Urinary Tract Infections (UTIs) among patients living with Sickle Cell Diseases (SCD) in Yaoundé, Cameroon

Molecular characterization of Plasmid-Mediated Quinolone Resistance (PMQR) and Extended-Spectrum β-Lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolated from Urinary Tract Infections (UTIs) among patients living with Sickle Cell Diseases (SCD) in Yaoundé, Cameroon | 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 Molecular characterization of Plasmid-Mediated Quinolone Resistance (PMQR) and Extended-Spectrum β-Lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolated from Urinary Tract Infections (UTIs) among patients living with Sickle Cell Diseases (SCD) in Yaoundé, Cameroon Roxane Belvine Mamwo, Valentina Josiane Ngo Bitoungui, Symphorien Ewodo, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7696682/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 15 You are reading this latest preprint version Abstract Background Extended-spectrum β-lactamase producing- E. coli (ESBL- Ec ) and K. pneumoniae (ESBL- Kp ) are pathogens of critical priority that urgently required research and development of new antibiotics. Fluoroquinolones are broad-spectrum antibiotics commonly used to treat urinary tract infections (UTIs) among patients living with sickle cell disease (SCD). This study aims at determining the prevalence, phenotypic and genotypic characterizatics of plasmid-mediated quinolone resistance genes among ESBL- Ec and ESBL- Kp isolated from SCD patients with UTIs in Yaoundé, Cameroon. Methods A cross-sectional study was conducted in two healthcare facilities from February to June, 2024. Mid-stream urine samples were collected from UTI patients living with SCD. ESBL- Ec and ESBL- Kp isolates were biochemical identified using API20E following the manufacturer’s instructions. The antimicrobial susceptibility test was performed using the Kirby-Bauer disk diffusion method. ESBL-phenotype was screened using the double-disk synergy test and confirm by plating onto ChromAgar™ ESBL medium. Antimicrobial resistance genes were detected using polymerase chain reaction methods. The data analysis was performed using Excel 2016 and IBM SPSS version 20. Results A total of 90 urine samples were collected and analysed during the study period. The prevalences of Escherichia coli and Klebsiella pneumoniae were 7,7% (7/90) and 10% (10/90) respectively. Among these, the rate of ESBL production was 57,14% (4/7) for E. coli and 60% (6/10) for Klebsiella pneumoniae . The prevalences of ciprofloxacin non-susceptible among ESBL- Ec and ESBL- Kp were 12,5% (1/8) and 87,5% (7/8) respectively. High antimicrobial resistance rate was observed for amoxicillin, amoxicillin + clavulanic acid, ceftazidime, thrimethoprim, pefloxacin. The most common resistance genes detected encoding for β-lactam and fluoroquinolone resistance were bla CTX−M , oqx A, bla TEM , qnr S respectively. Conclusion The findings revealed a high burden of fluoroquinolone resistance in ESBL- Ec and ESBL- Kp among SCD patients with UTIs. This study emphasizes the necessity for monitoring and surveillance of resistant strains against β-lactam and fluoroquinolone antibiotics among this vulnerable population. It is thus crucial to implement antimicrobial stewardship programs at the local and national levels and develop the appropriate protocols for antibiotic usage in these healthcare facilities to curb the emergence and escalation of these growing resistant bacteria. UTIs Escherichia coli K. pneumoniae ESBL Sikcle cell Cameroon Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Sickle cell disease (SCD) is a group of genetic disorders commonly characterized by the abnormal haemoglobin, leading to sickle-shaped red blood and various health issus ( 1 ). The primary genetic mutation in SCD is a single nucleotide change (GTG for GAG) in the β-globin gene on chromosome 11, resulting in a valine substitution for glutamic acid in the haemoglobin protein (HbS) ( 1 ). Approximately 75% of individuals with SCD reside in sub-Saharan Africa (sSA), where infectious diseases are prevalent ( 1 ). Globally, there are over 300,000 new cases of SCD each year including nearly two thirds in sSA ( 2 ). SCD is characterize by frequent vaso-occlusive crisis (VOCs), chronic anaemia and susceptibility to infections ( 3 ). Urinary tract infections (UTIs) are a common complication in SCD patients often leading to significant morbidity and mortality ( 3 ). The treatment of these infections coupled the antibiotic prophylaxis is increasingly complicated by the emergence of antibiotic resistance, particularly among uropathogens Enterobacteriaceae like Escherichia coli and Klebsiella pneumoniae ( 3 ). Escherichia coli and Klebsiella pneumoniae belonging to the Enterobacteriaceae family remain indicators for increasing antimicrobial resistance in clinical samples. To escape the activities of numerous antibiotics, these pathogens commonly produce extended-spectrum β-lactamase ezymes, which confer resistance to all β-lactam antibiotics except cephamycins, carbapenems and monobactams ( 4 ). Extended-spectrum β-lactamase (ESBL)-producing E. coli (ESLB- Ec ) and K. pneumoniae (ESBL- Kp ) have been listed by the World Health Organization (WHO) as critical priority pathogens for which new antibiotics need to be developed (WHO., 2017). Several studies in Uganda, Ghana and Cameroon shown that ESBL- Ec and ESBL- Kp are always found to be high among patients with SCDs due to the fact that, there are often subjected to long-term antibiotic prophylaxis ( 1 , 5 – 7 ). To treat ESBL- Ec and ESBL- Kp UTIs among SCD patients, the broad-spectrum antibiotics including fluoroquinolone are commonly used ( 1 , 5 – 7 ). Fluoroquinolones (FQs) are widely used and effective against numerous infectious diseases caused by ESBL- Ec and ESBL- Kp including UTIs ( 8 ). The primary mechanisms of FQ resistance among these pathogens involve chromosomal mutations in the Quinolone Resistance Determining Region (QRDR) of gyr A and par C genes, affecting DNA gyrase and topoisomerase IV by reducing the affinity of these enzymes to FQs ( 9 ). The second mechanism commonly used is plasmid-mediated quinolone resistance (PMQR) conferring resistance to fluoroquinolones, even without prior exposure to antibiotics included in this family ( 9 ). Ciprofloxacin non-susceptible E. coli and K. pneumoniae represent the most common pathogens involved in UTIs and were associated with numerous risk factors such as age, poor economic status, poor hygiene measures, hospitalization, catheterization, sexual activities, pregnancy, diabetes mellitus and SCDs as illustrated in sSA ( 10 ). It is therefore crucial to investigate the prevalence and characterize genotypically plasmid-mediated quinolone resistance genes among ESBL- Ec and ESBL- Kp isolated from UTI patients living with SCDs in Yaoundé Central Hospital and the Mother-Child Centre of the Chantal Biya Foundation, Yaoundé, Cameroon. MATERIALS AND METHODS 1. Study design and settings This study was a cross-sectional study conducted over a five-month periods, from February to June 2024 in two healthcare facilities including Yaoundé Central Hospital (YCH) and Yaoundé Mother-Child Centre of the Chantal Biya Foundation which are tertiary and referral hospitals in Yaoundé, Cameroon. All urine samples from patients attending these two hospital settings presenting signs and symptoms of hospital- acquired urinary tract infections (HA-UTI) and/or community acquired urinary tract infection (CA-UTI) were collected at the medical laboratories of these structures. In addition, demographic data of each patient were recorded after filling to the questionnaire. All participants were recruited in compliance upon obtaining individual or parental informed consent with the ethical approval for human research in force in hospitals (N°117/24/AP/MINSANTE/SG/DHCY/CM/SM). More specifically, participants and/or legal guardian who were contacted, signed informed consent, and accepted to fill out the questionnaire and provide a sample were included in the study. This data collection included demographic details, antibiotic use history, and other relevant information from participants. 2. Culture, Identification and Phenotypic screening Clean catch mid-stream urines were cultured on Eosine Methylene Bleue (EMB) medium (Oxoid Ltd., Basingstoke, UK) and incubated at 37°C for 18-24h. In addition, the urinary strip was used to screen many parameters involved in the bacteriuria including pH, nitrites and leukocyte rate. All growing colonies were counted and leukocytes were enumerated with a Malassez cell. UTI was defined based on pyuria (≥ 10 4 leukocyte/mL of urine) and positive culture (≥ 10 5 colony-forming units) diffusion method. Identification was performed based on the biochemical characteristics using API 20E according to the manufacturer’s instructions. The production of ESBL enzymes was double screened using a Double Disc synergy Test (DDT) combining ceftazidime and clavulanic acid and confirm by plating onto CHROMagar™ ESBL (CHROMagar, Paris - France). The samples were then stored at -20°C in cryotubes containing trypticase soya broth supplemented with 20% glycerol for future uses. 3. Antimicrobial Susceptibility Testing (AST) Antimicrobial susceptibility testing (AST) was performed using Kirby-Baueur disc diffusion method on Muller Hinton agar and interpretation was done as recommended by the Committee of the Antibiogram Committee of the French Society of Microbiology (CA-SFM) guidelines (2023). A panel of 19 antibiotics including ticarcillin (TIC; 75 µg), amoxicillin (AMC; 30 µg), piperacillin (PRL; 75 µg), aztreonam (ATM; 30 µg), amoxicillin clavulanic (AMX; 30 µg), ceftazidime (CAZ; 30 µg), cefotaxime (CTX; 30 µg), ceftriaxone (CRO; 30 µg), pefloxacin (PEF; 30µg), ciprofloxacin (CIP; 5µg), levofloxacin (LEV; 5µg), Thrimethoprime + sufalmethoxasole (SXT; 25/125µg), nitrofurantoin (NIT; 300 µg), meropenem (MEM; 30 µg), gentamicin (10 µg), chloramphenicol (30 µg), and colistin (30 µg) (Oxoid Ltd., Basingstoke, UK) have been tested. All isolates were classified as multidrug-resistant (MDR) if they were resistant to at least three or more antimicrobial classes as previously defined ( 4 ). 4. DNA genomic extraction and amplification Briefly the genomic DNA of ESBL- Kp and ESBL- Ec were extracted using a modified boiling method. Globally, a pure colony of Klebseilla pneumoniae and Escherichia coli were suspended in 300 µL of Tris-EDTA (10 mMTris, 0.1 mMEDTA), then the mixture was vortexed during five seconds. The suspension was then incubated for 25 min at 95°C in a digital dry bath (MIULab DKT200-1, Lasec International Ltd., Johannesburg, South Africa). After incubation, the suspension was centrifuged for 5 minutes at 9500 rpm. The supernatant containing DNA (200 µl) was then transferred to a new Eppendorf tube and stored at -20°C for later analysis. Detection of resistance genes including bl a CTX−M, bla TEM and bla SHV, qnr A, qnr B, qnr S, oqx A, oqx B and qep A genes were carried out by multiplex-PCR method using a thermal cycler T100 (Bio-Rad Laboratories, Mames-la coquette, France). The reaction was carried out in a 10 µL reaction mixture consisting of 5 µL of Dream Taq green Polymerase Master Mix 2x (New England Biolabs, Ipswich, MA, USA); 2.6 µL of nuclease-free water, 0.1 µL of each forward and reverse primers (10 µM) and 2 µL of DNA. Thermal cycler program was included initial denaturation (95°C for 3min), 30 cycles of denaturation at 95°C for 4s, annealing at 46.9°C for 40s, elongation at 72°C for 50s and final elongation at 72°C for 5 min. In addition, amplification of bla SHV gene occurs in a 10 µL reaction mixture consisting of 5 µL Dream Taq Green Polymerase Master Mix 2x (ThermoFisher Scientic, Vilnius, Lithuania), 2.8 µL nuclease-free water, 0.1 µL each primer direct and reverse [10 µM] and 2 µl of DNA with approximately the same condition. 5. PCR products and visualization PCR products were subjected to electrophoresis analysis carried out on a 1.5% (w/v) agarose gel running at 90v during 45 minutes along with a 100 bp molecular ladder (New England Biolabs, MA, USA). After electrophoresis, the gel was stained in an ethidium bromide solution (0.5 µg/mL) for 20 min and unstained with water. the visualization was done under UV light using a G-BOX Chemi-XL gel documentation system (Syngene, Cambridge, UK). 6. Data analysis Sociodemographic and biological data were captured and analysed using the Excel 2013 and IBM SPSS Statistics 22 sofware. The Ficher exact and chi-square tests were used to compare variables as appropriate and the estimation of risk factors was assessed by determining the Odds ratio value. All the results with p-value < 0.05 was considered to be statistically significant. 7. Quality control To ensure the quality of the results the American Type Culture Collection (ATCC) of Escherichia coli (ATCC25922) and K. pneumoniae (ATCC700603) were used to assess the quality of the media and antibiotic discs. In addition, all previously whole-genome sequenced Enterobacterales harboring PMQR genes found (unpublished data) at the Global Health Research Unit in Nigeria (GHRU), were used as positive controls. RESULTS 1. Demographic characteristics of the study population A total of 120 patients were contacted and 90 SCD patients were enrolled, comprising 46 men and 44 women, for a male-to-female sex ratio of 1.04. The mean age the population was 11.51+/- 6.181 years. The majority of participants were between 10 and 14 years representing 32.22% of the population survey. Clinical features presented 62% (n = 56) patients under antibiotic prophylaxis with 21.1% (n = 19) under amoxicillin and 41.1% (n = 37) under penicillin V. These findings revealed that 68.8% (n = 62), 55.5% (n = 50) and 57.7% (n = 52) of patients had less than three hospitalization, three seizures and four consultations each per year with a standard deviation of 2.68, 3.27 and 3.42 respectively. undefined 2. Prevalence of ESBL- Ec and ESBL- Kp isolates This study identified 17.8% (n = 16) E. coli and 20% (n = 18) K. pneumoniae . The overall prevalence of ESBL- Ec and ESBL- Kp in UTIs were 14% (4/7) and 60% (6/10) respectively, as illustrated in (Fig. 1 ). High prevalence of MDR- Ec and MDR- Kp with 85,71% (n = 6/7) and 100% (n = 10/10) were observed respectively. 4. Multidrug resistant 4. Multidrug resistant E. coli and K. pneumoniae Majority of these isolates exhibiting ESBL enzyme were multi-drug resistant (15/16; 93,75%) with ESBL- Ec (n = 6/7; 85,71%) and ESBL- Kp (n = 10/10; 100%), respectively. The most prevalent phenotypic profile was AMC-ATM-AX-CTX-CXN-CRO-CAZ-CN-C-CIP-MEM-LEV-F-PEF-SXT-TIC-PRL including 17 antibiotics from 6 different family. 5. Molecular characterisation of resistance genes The prevalence of genes encoding resistance to β-lactam were mostly represented by bla CTX−M (9/13; 69.2%), bla TEM (7/13; 53.8%) and bla SHV (3/13; 23.1%). The global prevalence of PQMR genes were 62.5%, 37.5%, 25%, 25% for oqx A, qnr S, qnr B and aac ( 6 )-Ib respectively (Fig. 3 ). High prevalence of bla CTX−M was observed among ESBL- Ec (3/3;100%) and ESBL- Kp (6/10; 60%). The most prevalent gene encoding fluoroquinolone resistance observed among ESBL- Ec and ESBL- Kp was oqx A with (5/8; 62,5%) respectively. DISCUSSION Antimicrobial resistance remains a significant public health threat worldwide ( 11 ). The immunocompromised patients especially those living with HIV and SCDs are among the most vulnerable populations ( 7 ). Several studies conducted in African countries revealed a high burden of ESBL- Ec and ESBL- Kp isolated from UTIs ( 3 , 5 , 7 ). A study conducted in Cameroon, in 2021, reported a high prevalence of MDR and ESBL-producing E. coli and K. pneumoniae isolated from UTIs among SCDs in Cameroon ( 7 ). There is a paucity of data regarding the resistance level of fluoroquinolone in ESBL- Kp and ESBL- Ec from SCDs with UTIs. This study thus, aimed to investigate the prevalence, phenotypic and genotypic characterization of ESBL and fluoroquinolone resistance genes among SCD patients in Yaoundé, Cameroon. Among all patients contacted and enrolled in this study, SS homozygous patients (n = 86/90 95.6%) were most represented. This observation is attributable to the high prevalence of SCD within the population. Epidemiological studies have documented a significant frequency and burden of SCD in this region. Specifically, in Cameroon, it is estimated that approximately 20–30% of the population carry the sickle cell trait, while the prevalence of SCD ranges from about 0.6% to 2% in the general population ( 12 ). This high prevalence significantly influences the regional population health dynamics and constitutes a major public health concern in Cameroon ( 12 ). The results revealed that the most participants affected being male and the ages ranged between 10 and 14 years. These results are similar with those obtained in Tanzania who shown than half of his study population living with SCDs and having UTIs were boys and the age group of this population ranged between 12 to 15 years ( 15 ). The observed variation in bacterial isolates among females may be attributed to anatomical configuration, including the shorter urethra's proximity to the anal and vaginal orifices, which predispose to ascending infections, as well as suboptimal hygiene practices. These findings reflect a lower prevalence compared to reports from Tanzania and Nigeria, where UTI prevalence rates among SCD patients were documented at 21.1% and 22.4%, respectively ( 13 – 15 ). This gender disparity in UTI incidence aligns with established knowledge that females generally exhibit higher susceptibility to UTIs due to anatomical and behavioural factors. After bacteriological analysis of urine samples from SCD patients with UTI symptoms, the prevalence was 3.3% among this study population. This prevalence is lower than those reported in the studies conducted by Sangeda et al., Mava et al., and Asinobi et al., which documented UTI prevalence rates of 21.1%, 26%, and 22.4%, respectively ( 13 – 15 ). The predominant uropathogens identified in healthcare settings in Yaoundé, Cameroon, were Klebsiella pneumoniae (10%) and Escherichia coli (7.77%). These findings differ from studies conducted in Tanzania, where Escherichia coli consistently emerged as the dominant causative agent of UTIs in SCD patients ( 15 ). Such regional variations underscore the importance of localized epidemiological surveillance to inform effective management and antimicrobial stewardship in this vulnerable population. The resistance profiles observed in this study are consistent with prior report from Nigeria and the USA, where high resistance rates to multiple antibiotic classes were documented among ESBL-producing pathogens ( 14 , 16 ). In contrast, low resistance levels were identified against gentamicin, chloramphenicol, and meropenem, indicating these antibiotics retain relative efficacy. Additionally, nitrofurantoin exhibited low resistance, suggesting its potential use in specific clinical scenarios. Moderate resistance to fosfomycin (~ 50%) suggests a possible therapeutic consideration depending on AST. Notably, colistin, often reserved as a last-resort antibiotic for MDR- Kp and MDR- Ec UTI infections, demonstrated no resistance among all isolates. Most isolates exhibited multidrug resistance, defined as non-susceptibility to at least one agent in three or more antimicrobial classes, highlighting the therapeutic challenges in managing infections caused by these ESBL- Kp and ESBL- Ec . The most common resistant patterns in our study was related to eleven and fifteen antibiotics including AMC-ATM-AX-CTX-CXN-CRO-CAZ-CN-C-CIP-MEM-LEV-F-PEF-SXT-TIC-PRL and AMC-ATM-AX-CAZ-C-CIP-LEV-F-PEF-SXT-TIC-PRL for ESBL- Kp and ESBL- Ec respectively. These data underscore the critical need for continuous antimicrobial resistance surveillance and tailored stewardship programs to optimize treatment outcomes for infections caused by ESBL- Kp and ESBL- Ec in Cameroon ( 6 , 15 – 17 ). The overall prevalence of ESBL- Ec and ESBL- Kp exhibiting resistance to antibiotics including amoxicillin, amoxicillin-clavulanic acid (amoxypenicillin), piperacillin, ticarcillin (carboxypenicillin), ceftazidime, pefloxacin, and trimethoprim was notably high. These resistance patterns align with findings reported in Tanzania and Nigeria, underscoring the widespread dissemination of MDR- Enterobacteriaceae in sSA among vulnerable populations such as SCD patients ( 13 – 15 ). Similarly, a Cameroonian study by Alima Yanda et al. (2017) reported similar resistance profiles among SCD patients within the same healthcare facilities, affirming consistent regional trends in antimicrobial resistance among these pathogens ( 7 ). Furthermore, moderate resistance rates to third-generation cephalosporins and fluoroquinolone including cefotaxime, ceftriaxone, levofloxacin and ciprofloxacin were observed, with high resistance levels to cephalosporins and fluoroquinolone reaching 83.33% and 50%, respectively. These findings highlight the therapeutic challenges posed by ESBL-producing isolates in managing infections within SCD patients and emphasize the urgent need for antimicrobial stewardship implementation and interventions tailored to local resistance profiles in Cameroon and comparable sub-Saharan settings. The high resistance prevalence of cephalosporins and fluoroquinolone reflects likely factors including prior antibiotic exposure and the plasmid-mediated dissemination of ESBL and fluoroquinolone resistance genes, as already documented in studies from Cameroon and neighbouring regions ( 5 , 15 ). This data is critical for guiding empirical therapy and public health policies targeting bacterial infections in SCD patients. Among the different ESBL resistance genes tested, bla CTX−M and bla TEM were the most frequently detected with the prevalence being 69.2% (9/13) and 53.8% (7/13) respectively. This result is an agreement with the previous studies showing that bla CTX − M was the most common ESBL genes carried among ESBL- Enterobacterales responsible for UTIs in Cameroon ( 4 , 17 , 18 ). The prevalence rates of bla CTX−M and bla TEM observed in this study differ from those reported in Nepal, Cameroon and Egypt ( 4 , 19 , 20 ).The predominance of the bla CTX−M is consistent with numerous reports highlighting its broad hydrolytic activity against various β-lactam antibiotics, which explains its frequent selection in countries of intensive antibiotic pressure, particularly the empirical use of third-generation cephalosporins such as ceftriaxone in managing SCD patients. In contrast, the comparatively lower prevalence of bla CTX−M and bla TEM genes in your study relative to larger cohorts such as those in Nigeria can be reasonably attributed to your smaller sample size, which limits the overall number of ESBL strains available for genotypic analysis ( 14 ). The relative low frequency of the bla SHV gene in your study is also consistent with findings from Cameroon and Egypt, where bla SHV was found at low or undetectable levels ( 4 , 19 ). Globally, bla SHV prevalence frequently varies by region and appears generally lower than bla CTX−M and bla TEM in many clinical isolates. The literature confirms that the coexistence of bla CTX−M , bla TEM , and bla SHV genes is common given their plasmid-mediated horizontal gene transfer among Enterobacteriaceae, contributing to genetic diversity and multidrug resistance, not only for cephalosporins but also for fluoroquinolone. Fluoroquinolone antibiotics like a ciprofloxacin, are a group of effective drugs for the treatment of ESBL- E. coli and ESBL- Klebsiella pneumoniae responsible for a various infections ( 21 ). The molecular analysis revealed that all ciprofloxacin resistant ESBL- Ec and ESBL- Kp harboured at least one PMQR gene and the global prevalence of fluoroquinolone and aminoglycoside resistance genes detected were oqx A (62.5%), qnr S (37.5%), qnr B (25%) and aac(6')-Ib (25%). These findings are similar to the study conducted in Ghana and Iran by Sah et al., (2022) and Razaeil et al., (2024), where the widespread carriage and clinical PMQR genes including oqx A, qnr S and aac (6')-Ib-cr among quinolone-resistant gram-negative E. coli and K. pneumonia have been observed, emphasizing their role in community and clinical resistance ( 21 ). In addition, the frequencies of qnr B and qnr S detected in this study is close to the rates reported by Gomaa et al., (2024) in Egypt ( 22 ). These findings were also noted in a study conducted in Ghana, where Klebsiella pneumoniae isolates showed a high frequency of qnr S (17.9%), compared to Escherichia coli (4.4%). CONCLUSION This study has described the clinical and genotypic characterization of PMQR and ESBL isolates from UTIs among SCDs in Cameroon. High prevalence of PMQR and ESBL-producing E.coli and K. pneumoniae were evidenced. Meropenem, colistin, fosfomycin and gentamycin remain the most effective antibiotics with good activities against PMQR and ESBL- E. coli and K. pneumoniae . The PMQR were associated with ESBL-producing E. coli and K. pneumoniae contributing to the spread of multidrug resistance and may lead for life-threating infections among these vulnerable populations. The observed widespread resistance across multiple antibiotic classes warrants improving empiric therapy within these facilities. It is thus crucial to implement antimicrobial stewardship programs at the local and national in order to curb the emergence and escalation of antimicrobial resistance. LIMITS This study was limited to two structures in the Yaoundé, it would be interested to expand this research to all sickle cell disease management Centers in Yaoundé and across Cameroon as far as possible to obtain more comprehensive and relevant findings. Additionally, a further limitation was the undetected mutations occurring within the quinolone-determining region contributing to fluoroquinolone resistance. Abbreviations MDR Multidrug resistance SCDs Sickle Cell Diseases UTI Urinary Tract Infection CAUTI Community Acquired Urinary Tract Infections HAUTI Hospital Acquired Urinary Tract Infections ESBL-E Extended Spectrum β-lactamase producing- Enterobacterales Declarations Ethics approval and consent to participate This research was approved by the Regional Ethics Committee for Research in Human Health, Centre region, Cameroon N°0098/19/02/2024/CE/CRERSHC/VP. In addition, it was approved by the Research institute of the Centre of Expertise and Biological Diagnostic of Cameroon (CEDBCAM-RI) under the number (N° 002/02/24/LA/CEDBCAM-RI/DG). All participants or the legal guardian/nearest relative for minor were recruited in compliance upon obtaining individual or parental informed consent with the ethical approval for human research in force in hospitals under the number of (117/24/AP/MINSANTE/SG/DHCY/CM/SM). The study was conducted in accordance with the declaration of Helsinki. All methods and protocols used were approved by the CEDBCAM-RI in accordance with the relevant national and international guidelines and regulations for research laboratory ethics. Data availability The data are available upon request in accordance with confidentiality and privacy regulations from the corresponding author. Consent for publication Not applicable Competing of interest The authors declare no conflict of interest. Clinical trial number Not applicable. Funding Dr Raspail Carrel Founou received funding from the Mérieux Institute, Lyon France for the CAREFOOD project. CAREFOOD project had supported all the molecular aspects of this study. This work was also supported by the Research Institute of Centre of Expertise and Biological Diagnostic of Cameroon (CEDBCAM-RI). The funders had no role in the study design, nor the decision to submit the work for publication. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the organizations or agencies that provided support for the project. Author information Authors and affiliations Department of Microbiology-Haematology and Immunology, Faculty of Medicine and Pharmaceutical Sciences, University of Dschang, Dschang, Cameroon; Antimicrobial Research Unit, School of Health Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa; Antimicrobial Resistance and Infectious Disease (ARID) Research Unit, Research Institute of Centre of Expertise and Biological Diagnostic of Cameroon (CEDBCAM-RI), Yaoundé, Cameroon; Reproductive, Maternal, Newborn and Child Health (ReMARCH) Research Unit, Research Institute of the Centre of Expertise and Biological Diagnostic of Cameroon (CEDBCAM-RI); Yaoundé, Cameroon; Bioinformatics & Applied Machine Learning Research Unit, EDEN Biosciences Research Institute (EBRI), EDEN Foundation, Yaoundé Cameroon; National Blood Transfusion Service (NBTS), Yaoundé Cameroon; Mother and Child Center of Chantal Biya Foundation, Yaoundé, Cameroon; Department of Microbiology-Haematology and Immunology, Faculty of Medicine and Biomedical Sciences, University of Yaoundé 1, Yaoundé, Cameroon; National Public Health Laboratory (NPHL), Yaoundé, Cameroon Author contributions Conceptualizatio n: RBM, RCF and VJBG; Methodology : RCF, LLF, VJGB, RGE, RBM; Software : RBM, JNN; Validation : RCF, LLF, VJGB, RGE, SE, BC and EW; Formal analysis : RBM, VJGB and RCF; Investigation : RCF, LLF, VJGB, RGE, RBM; Resources : RCF, LLF, VJGB and RGE; Writing original draft : RBM, LLF, VJGB, RGE, SE and RCF; Review and editing : RCF, LLF, VJGB, RGE, SE, BC and EW; Visualization : RBM, RCF and VJGB; Supervision : RCF and VJGB; Project administration : RCF, LLF, VJGB and RGE. All authors have read and agreed to the published version of the manuscript. Acknowledgements We thank all staff members of two healthcare structures and all participants who agreed to participate to this study. References Donkor ES, Osei JA, Anim-Baidoo I, Darkwah S. Risk of Asymptomatic Bacteriuria among People with Sickle Cell Disease in Accra, Ghana. Diseases . 2017; 5(1). Available from: https://mdpi-res.com/d_attachment/diseases/diseases-05-00004/article_deploy/diseases-05-00004.pdf?version=1487137639 Piel FB, Rees DC, DeBaun MR, Nnodu O, Ranque B, Thompson AA, et al. Defining global strategies to improve outcomes in sickle cell disease: a Lancet Haematology Commission. Lancet Haematol. 2023;10(8):e633–86. Brim H, Taylor J, Abbas M, Vilmenay K, Daremipouran M, Varma S, et al. The gut microbiome in sickle cell disease: Characterization and potential implications. PLoS ONE. 2021;16(8):e0255956. Nkengkana OA, Founou RC, Founou LL, Dimani BD, Koudoum PL, Zemtsa JR, et al. Phenotypic and genotypic characterization of multidrug resistant and extended-spectrum β-lactamase-producing Enterobacterales isolated from clinical samples in the western region in Cameroon. BMC Infect Dis. 2023;23(1):819. Said MM, Msanga DR, Mtemisika CI, Silago V, Mirambo MM, Mshana SE. Extended Spectrum β-Lactamase Producing Lactose Fermenting Bacteria Colonizing Children with Human Immunodeficiency Virus, Sickle Cell Disease and Diabetes Mellitus in Mwanza City, Tanzania: A Cross-Sectional Study. Trop Med Infect Dis . 2022; 7(8). Available from: https://mdpi-res.com/d_attachment/tropicalmed/tropicalmed-07-00144/article_deploy/tropicalmed-07-00144.pdf?version=1658477495 Maghembe RS, Magulye MAK, Eilu E, Sekyanzi S, Mwesigwa S, Katagirya E. Chromosomal and plasmid-encoded virulence and multidrug resistance of Escherichia coli ST58/24 infecting a 2-year-old sickle cell patient with sepsis in Kampala Uganda, East Africa. Heliyon. 2024;10(9):e30187. Alima Yanda AN, Nansseu JRN, Mbassi Awa HD, Tatah SA, Seungue J, Eposse C, et al. Burden and spectrum of bacterial infections among sickle cell disease children living in Cameroon. BMC Infect Dis. 2017;17(1):211. Araújo MRB, Sant'Anna LO, Santos N, Seabra LF, Santos LSD. Monitoring fluoroquinolone resistance among ESBL-positive and ESBL-negative Escherichia coli strains isolated from urinary tract infections: An alert for empirical treatment. Rev Soc Bras Med Trop. 2023;56:e0513. Aldred KJ, Kerns RJ, Osheroff N. Mechanism of quinolone action and resistance. Biochem. 2014;53(10):1565–74. Bayaba S, Founou RC, Tchouangueu FT, Dimani BD, Mafo LD, Nkengkana OA, et al. High prevalence of multidrug resistant and extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolated from urinary tract infections in the West region, Cameroon. BMC Infect Dis. 2025;25(1):115. Founou RC, Founou LL, Essack SY. Clinical and economic impact of antibiotic resistance in developing countries: A systematic review and meta-analysis. PLoS ONE. 2017;12(12):e0189621. Saidu Y, Masong MC, Francoise N, Ngenge BM, Ndansi E, Foma MK. Sickle cell disease in Cameroon: Taking out the neglect and highlighting key opportunities for sustainable control. PLOS Glob Pub Health. 2024;4(10):e0003668. Asinobi AO, Fatunde OJ, Brown BJ, Osinusi K, Fasina NA. Urinary tract infection in febrile children with sickle cell anaemia in Ibadan, Nigeria. Ann Trop Paed. 2003;23(2):129–34. Mava Y, Bello M, Ambe JP, Zailani SB. Antimicrobial sensitivity pattern of organisms causing urinary tract infection in children with sickle cell anemia in Maiduguri, Nigeria. Niger J Clin Pract. 2012;15(4):420–3. Sangeda RZ, Yohana J, Jonathan A, Manyanga VP, Soka D, Makani J. Prevalence of Urinary Tract Infections and Antibiogram of Bacteria Isolated From Children With Sickle Cell Disease in Tanzania. Cureus. 2024;16(4):e58786. Srisuwananukorn A, Han J, Raslan R, Gowhari M, Hussain F, Njoku F, et al. Antimicrobial resistance is a risk factor for mortality in adults with sickle cell disease. Haematologica. 2021;106(6):1745–8. Said MM, Msanga DR, Mtemisika CI, Silago V, Mirambo MM, Mshana SE. Extended Spectrum β-Lactamase Producing Lactose Fermenting Bacteria Colonizing Children with Human Immunodeficiency Virus, Sickle Cell Disease and Diabetes Mellitus in Mwanza City, Tanzania: A Cross-Sectional Study. Trop Med Infect Dis. 2022;7(8). Djim-Adjim-Ngana K, Mbiakop BW, Oumar LA, Munshili Njifon HL, Tchinda Fossi C, Enyegue ELE, et al. Phenotypic characterization and epidemiology of extended-spectrum β-lactamase-producing Enterobacteriaceae strains from urinary tract infections in Garoua, Cameroon. Front Public Health. 2023;11:1187934. Ouchar Mahamat O, Lounnas M, Hide M, Dumont Y, Tidjani A, Kamougam K, et al. High prevalence and characterization of extended-spectrum ß-lactamase producing Enterobacteriaceae in Chadian hospitals. BMC Infect Dis. 2019;19(1):205. Koirala S, Khadka S, Sapkota S, Sharma S, Khanal S, Thapa A, et al. Prevalence of CTX-M β-Lactamases Producing Multidrug Resistant Escherichia coli and Klebsiella pneumoniae among Patients Attending Bir Hospital, Nepal. Biomed Res Int. 2021;2021:9958294. Rezaei S, Tajbakhsh S, Naeimi B, Yousefi F. Investigation of gyrA and parC mutations and the prevalence of plasmid-mediated quinolone resistance genes in Klebsiella pneumoniae clinical isolates. BMC Microbiol. 2024;24(1):265. Gomaa EA, Ehab MF, Abdellatif AM, Ahmed ME, El Sayed ZM, Mofreh MM. Study of plasmid mediated quinolone resistance genes among Escherichia coli and Klebsiella pneumoniae isolated from pediatric patients with sepsis. Sci Rep. 2024;14(1):11849. Additional Declarations No competing interests reported. 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01:54:09","extension":"html","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":108120,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7696682/v1/1de56bbfbbfb062431a82f3c.html"},{"id":93637685,"identity":"8e3f3dbd-67e5-48e3-963f-fe5099d082bd","added_by":"auto","created_at":"2025-10-16 01:54:08","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":129370,"visible":true,"origin":"","legend":"\u003cp\u003ePrevalence of ESBL-\u003cem\u003eE.coli\u003c/em\u003e and \u003cem\u003eK. pneumoniae\u003c/em\u003e among UTI patients\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7696682/v1/da5432b84352d1ce95ff158f.jpg"},{"id":93637691,"identity":"06b88df1-8491-4102-bd12-c85bd1a745df","added_by":"auto","created_at":"2025-10-16 01:54:09","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":240041,"visible":true,"origin":"","legend":"\u003cp\u003eAntibiotic resistance profiles of \u003cem\u003eE. coli\u003c/em\u003e and \u003cem\u003eK. pneumoniae \u003c/em\u003eisolated from UTIs patients with SCDs\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7696682/v1/758046231c2cb51e76987b2a.jpg"},{"id":93637687,"identity":"b3d7f09c-351c-45c2-8be0-a8965e0e463a","added_by":"auto","created_at":"2025-10-16 01:54:08","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":165798,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of β-lactam and fluoroquinolone resistance genes\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7696682/v1/a51517dfe3e050cb613a62a1.jpg"},{"id":93638896,"identity":"dc251798-2975-4d3a-924d-09fd2d36e784","added_by":"auto","created_at":"2025-10-16 02:02:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1503472,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7696682/v1/ef89920a-70a8-4be0-9f97-ac33893245ec.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Molecular characterization of Plasmid-Mediated Quinolone Resistance (PMQR) and Extended-Spectrum β-Lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolated from Urinary Tract Infections (UTIs) among patients living with Sickle Cell Diseases (SCD) in Yaoundé, Cameroon","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eSickle cell disease (SCD) is a group of genetic disorders commonly characterized by the abnormal haemoglobin, leading to sickle-shaped red blood and various health issus (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The primary genetic mutation in SCD is a single nucleotide change (GTG for GAG) in the β-globin gene on chromosome 11, resulting in a valine substitution for glutamic acid in the haemoglobin protein (HbS) (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Approximately 75% of individuals with SCD reside in sub-Saharan Africa (sSA), where infectious diseases are prevalent (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Globally, there are over 300,000 new cases of SCD each year including nearly two thirds in sSA (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). SCD is characterize by frequent vaso-occlusive crisis (VOCs), chronic anaemia and susceptibility to infections (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Urinary tract infections (UTIs) are a common complication in SCD patients often leading to significant morbidity and mortality (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). The treatment of these infections coupled the antibiotic prophylaxis is increasingly complicated by the emergence of antibiotic resistance, particularly among uropathogens \u003cem\u003eEnterobacteriaceae\u003c/em\u003e like \u003cem\u003eEscherichia coli\u003c/em\u003e and \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cem\u003eEscherichia coli\u003c/em\u003e and \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e belonging to the \u003cem\u003eEnterobacteriaceae\u003c/em\u003e family remain indicators for increasing antimicrobial resistance in clinical samples. To escape the activities of numerous antibiotics, these pathogens commonly produce extended-spectrum β-lactamase ezymes, which confer resistance to all β-lactam antibiotics except cephamycins, carbapenems and monobactams (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Extended-spectrum β-lactamase (ESBL)-producing \u003cem\u003eE. coli\u003c/em\u003e (ESLB-\u003cem\u003eEc\u003c/em\u003e) and \u003cem\u003eK. pneumoniae\u003c/em\u003e (ESBL-\u003cem\u003eKp\u003c/em\u003e) have been listed by the World Health Organization (WHO) as critical priority pathogens for which new antibiotics need to be developed (WHO., 2017). Several studies in Uganda, Ghana and Cameroon shown that ESBL-\u003cem\u003eEc\u003c/em\u003e and ESBL-\u003cem\u003eKp\u003c/em\u003e are always found to be high among patients with SCDs due to the fact that, there are often subjected to long-term antibiotic prophylaxis (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). To treat ESBL-\u003cem\u003eEc\u003c/em\u003e and ESBL-\u003cem\u003eKp\u003c/em\u003e UTIs among SCD patients, the broad-spectrum antibiotics including fluoroquinolone are commonly used (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eFluoroquinolones (FQs) are widely used and effective against numerous infectious diseases caused by ESBL-\u003cem\u003eEc\u003c/em\u003e and ESBL-\u003cem\u003eKp\u003c/em\u003e including UTIs (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). The primary mechanisms of FQ resistance among these pathogens involve chromosomal mutations in the Quinolone Resistance Determining Region (QRDR) of \u003cem\u003egyr\u003c/em\u003eA and \u003cem\u003epar\u003c/em\u003eC genes, affecting DNA gyrase and topoisomerase IV by reducing the affinity of these enzymes to FQs (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). The second mechanism commonly used is plasmid-mediated quinolone resistance (PMQR) conferring resistance to fluoroquinolones, even without prior exposure to antibiotics included in this family (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eCiprofloxacin non-susceptible \u003cem\u003eE. coli\u003c/em\u003e and \u003cem\u003eK. pneumoniae\u003c/em\u003e represent the most common pathogens involved in UTIs and were associated with numerous risk factors such as age, poor economic status, poor hygiene measures, hospitalization, catheterization, sexual activities, pregnancy, diabetes mellitus and SCDs as illustrated in sSA (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). It is therefore crucial to investigate the prevalence and characterize genotypically plasmid-mediated quinolone resistance genes among ESBL-\u003cem\u003eEc\u003c/em\u003e and ESBL-\u003cem\u003eKp\u003c/em\u003e isolated from UTI patients living with SCDs in Yaound\u0026eacute; Central Hospital and the Mother-Child Centre of the Chantal Biya Foundation, Yaound\u0026eacute;, Cameroon.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\n\u003ch3\u003e1. Study design and settings\u003c/h3\u003e\n\u003cp\u003eThis study was a cross-sectional study conducted over a five-month periods, from February to June 2024 in two healthcare facilities including Yaound\u0026eacute; Central Hospital (YCH) and Yaound\u0026eacute; Mother-Child Centre of the Chantal Biya Foundation which are tertiary and referral hospitals in Yaound\u0026eacute;, Cameroon. All urine samples from patients attending these two hospital settings presenting signs and symptoms of hospital- acquired urinary tract infections (HA-UTI) and/or community acquired urinary tract infection (CA-UTI) were collected at the medical laboratories of these structures. In addition, demographic data of each patient were recorded after filling to the questionnaire. All participants were recruited in compliance upon obtaining individual or parental informed consent with the ethical approval for human research in force in hospitals (N\u0026deg;117/24/AP/MINSANTE/SG/DHCY/CM/SM). More specifically, participants and/or legal guardian who were contacted, signed informed consent, and accepted to fill out the questionnaire and provide a sample were included in the study. This data collection included demographic details, antibiotic use history, and other relevant information from participants.\u003c/p\u003e\n\u003ch3\u003e2. Culture, Identification and Phenotypic screening\u003c/h3\u003e\n\u003cp\u003eClean catch mid-stream urines were cultured on Eosine Methylene Bleue (EMB) medium (Oxoid Ltd., Basingstoke, UK) and incubated at 37\u0026deg;C for 18-24h. In addition, the urinary strip was used to screen many parameters involved in the bacteriuria including pH, nitrites and leukocyte rate. All growing colonies were counted and leukocytes were enumerated with a Malassez cell. UTI was defined based on pyuria (\u0026ge;\u0026thinsp;10\u003csup\u003e4\u003c/sup\u003e leukocyte/mL of urine) and positive culture (\u0026ge;\u0026thinsp;10\u003csup\u003e5\u003c/sup\u003e colony-forming units) diffusion method. Identification was performed based on the biochemical characteristics using API 20E according to the manufacturer\u0026rsquo;s instructions.\u003c/p\u003e\u003cp\u003eThe production of ESBL enzymes was double screened using a Double Disc synergy Test (DDT) combining ceftazidime and clavulanic acid and confirm by plating onto CHROMagar\u0026trade; ESBL (CHROMagar, Paris - France). The samples were then stored at -20\u0026deg;C in cryotubes containing trypticase soya broth supplemented with 20% glycerol for future uses.\u003c/p\u003e\n\u003ch3\u003e3. Antimicrobial Susceptibility Testing (AST)\u003c/h3\u003e\n\u003cp\u003e Antimicrobial susceptibility testing (AST) was performed using Kirby-Baueur disc diffusion method on Muller Hinton agar and interpretation was done as recommended by the Committee of the Antibiogram Committee of the French Society of Microbiology (CA-SFM) guidelines (2023). A panel of 19 antibiotics including ticarcillin (TIC; 75 \u0026micro;g), amoxicillin (AMC; 30 \u0026micro;g), piperacillin (PRL; 75 \u0026micro;g), aztreonam (ATM; 30 \u0026micro;g), amoxicillin clavulanic (AMX; 30 \u0026micro;g), ceftazidime (CAZ; 30 \u0026micro;g), cefotaxime (CTX; 30 \u0026micro;g), ceftriaxone (CRO; 30 \u0026micro;g), pefloxacin (PEF; 30\u0026micro;g), ciprofloxacin (CIP; 5\u0026micro;g), levofloxacin (LEV; 5\u0026micro;g), Thrimethoprime\u0026thinsp;+\u0026thinsp;sufalmethoxasole (SXT; 25/125\u0026micro;g), nitrofurantoin (NIT; 300 \u0026micro;g), meropenem (MEM; 30 \u0026micro;g), gentamicin (10 \u0026micro;g), chloramphenicol (30 \u0026micro;g), and colistin (30 \u0026micro;g) (Oxoid Ltd., Basingstoke, UK) have been tested. All isolates were classified as multidrug-resistant (MDR) if they were resistant to at least three or more antimicrobial classes as previously defined (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003e4. DNA genomic extraction and amplification\u003c/h3\u003e\n\u003cp\u003eBriefly the genomic DNA of ESBL-\u003cem\u003eKp\u003c/em\u003e and ESBL-\u003cem\u003eEc\u003c/em\u003e were extracted using a modified boiling method. Globally, a pure colony of \u003cem\u003eKlebseilla pneumoniae\u003c/em\u003e and \u003cem\u003eEscherichia coli\u003c/em\u003e were suspended in 300 \u0026micro;L of Tris-EDTA (10 mMTris, 0.1 mMEDTA), then the mixture was vortexed during five seconds. The suspension was then incubated for 25 min at 95\u0026deg;C in a digital dry bath (MIULab DKT200-1, Lasec International Ltd., Johannesburg, South Africa). After incubation, the suspension was centrifuged for 5 minutes at 9500 rpm. The supernatant containing DNA (200 \u0026micro;l) was then transferred to a new Eppendorf tube and stored at -20\u0026deg;C for later analysis. Detection of resistance genes including \u003cem\u003ebl\u003c/em\u003ea\u003csub\u003eCTX\u0026minus;M,\u003c/sub\u003e \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eTEM\u003c/sub\u003e and \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eSHV,\u003c/sub\u003e \u003cem\u003eqnr\u003c/em\u003eA, \u003cem\u003eqnr\u003c/em\u003eB, \u003cem\u003eqnr\u003c/em\u003eS, \u003cem\u003eoqx\u003c/em\u003eA, \u003cem\u003eoqx\u003c/em\u003eB and \u003cem\u003eqep\u003c/em\u003eA genes were carried out by multiplex-PCR method using a thermal cycler T100 (Bio-Rad Laboratories, Mames-la coquette, France). The reaction was carried out in a 10 \u0026micro;L reaction mixture consisting of 5 \u0026micro;L of Dream Taq green Polymerase Master Mix 2x (New England Biolabs, Ipswich, MA, USA); 2.6 \u0026micro;L of nuclease-free water, 0.1 \u0026micro;L of each forward and reverse primers (10 \u0026micro;M) and 2 \u0026micro;L of DNA. Thermal cycler program was included initial denaturation (95\u0026deg;C for 3min), 30 cycles of denaturation at 95\u0026deg;C for 4s, annealing at 46.9\u0026deg;C for 40s, elongation at 72\u0026deg;C for 50s and final elongation at 72\u0026deg;C for 5 min. In addition, amplification of \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eSHV\u003c/sub\u003e gene occurs in a 10 \u0026micro;L reaction mixture consisting of 5 \u0026micro;L Dream Taq Green Polymerase Master Mix 2x (ThermoFisher Scientic, Vilnius, Lithuania), 2.8 \u0026micro;L nuclease-free water, 0.1 \u0026micro;L each primer direct and reverse [10 \u0026micro;M] and 2 \u0026micro;l of DNA with approximately the same condition.\u003c/p\u003e\n\u003ch3\u003e5. PCR products and visualization\u003c/h3\u003e\n\u003cp\u003ePCR products were subjected to electrophoresis analysis carried out on a 1.5% (w/v) agarose gel running at 90v during 45 minutes along with a 100 bp molecular ladder (New England Biolabs, MA, USA). After electrophoresis, the gel was stained in an ethidium bromide solution (0.5 \u0026micro;g/mL) for 20 min and unstained with water. the visualization was done under UV light using a G-BOX Chemi-XL gel documentation system (Syngene, Cambridge, UK).\u003c/p\u003e\n\u003ch3\u003e6. Data analysis\u003c/h3\u003e\n\u003cp\u003eSociodemographic and biological data were captured and analysed using the Excel 2013 and IBM SPSS Statistics 22 sofware. The Ficher exact and chi-square tests were used to compare variables as appropriate and the estimation of risk factors was assessed by determining the Odds ratio value. All the results with p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered to be statistically significant.\u003c/p\u003e\n\u003ch3\u003e7. Quality control\u003c/h3\u003e\n\u003cp\u003eTo ensure the quality of the results the American Type Culture Collection (ATCC) of \u003cem\u003eEscherichia coli\u003c/em\u003e (ATCC25922) and \u003cem\u003eK. pneumoniae\u003c/em\u003e (ATCC700603) were used to assess the quality of the media and antibiotic discs. In addition, all previously whole-genome sequenced \u003cem\u003eEnterobacterales\u003c/em\u003e harboring PMQR genes found (unpublished data) at the Global Health Research Unit in Nigeria (GHRU), were used as positive controls.\u003c/p\u003e"},{"header":"RESULTS","content":"\n\u003ch3\u003e1. Demographic characteristics of the study population\u003c/h3\u003e\n\u003cp\u003eA total of 120 patients were contacted and 90 SCD patients were enrolled, comprising 46 men and 44 women, for a male-to-female sex ratio of 1.04. The mean age the population was 11.51+/- 6.181 years. The majority of participants were between 10 and 14 years representing 32.22% of the population survey. Clinical features presented 62% (n\u0026thinsp;=\u0026thinsp;56) patients under antibiotic prophylaxis with 21.1% (n\u0026thinsp;=\u0026thinsp;19) under amoxicillin and 41.1% (n\u0026thinsp;=\u0026thinsp;37) under penicillin V. These findings revealed that 68.8% (n\u0026thinsp;=\u0026thinsp;62), 55.5% (n\u0026thinsp;=\u0026thinsp;50) and 57.7% (n\u0026thinsp;=\u0026thinsp;52) of patients had less than three hospitalization, three seizures and four consultations each per year with a standard deviation of 2.68, 3.27 and 3.42 respectively.\u003c/p\u003e\n\u003ch3\u003eundefined\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003e2. \u003cb\u003ePrevalence of ESBL-\u003c/b\u003e\u003cb\u003eEc\u003c/b\u003e \u003cb\u003eand ESBL-\u003c/b\u003e\u003cb\u003eKp\u003c/b\u003e \u003cb\u003eisolates\u003c/b\u003e\u003c/div\u003e\u003cp\u003eThis study identified 17.8% (n\u0026thinsp;=\u0026thinsp;16) \u003cem\u003eE. coli\u003c/em\u003e and 20% (n\u0026thinsp;=\u0026thinsp;18) \u003cem\u003eK. pneumoniae\u003c/em\u003e. The overall prevalence of ESBL-\u003cem\u003eEc\u003c/em\u003e and ESBL-\u003cem\u003eKp\u003c/em\u003e in UTIs were 14% (4/7) and 60% (6/10) respectively, as illustrated in (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). High prevalence of MDR-\u003cem\u003eEc\u003c/em\u003e and MDR-\u003cem\u003eKp\u003c/em\u003e with 85,71% (n\u0026thinsp;=\u0026thinsp;6/7) and 100% (n\u0026thinsp;=\u0026thinsp;10/10) were observed respectively.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\n\u003ch3\u003e4. Multidrug resistant \u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003e4. Multidrug resistant \u003cem\u003eE. coli and K. pneumoniae\u003c/em\u003e\u003c/div\u003e\u003cp\u003eMajority of these isolates exhibiting ESBL enzyme were multi-drug resistant (15/16; 93,75%) with ESBL-\u003cem\u003eEc\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;6/7; 85,71%) and ESBL-\u003cem\u003eKp\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;10/10; 100%), respectively. The most prevalent phenotypic profile was \u003cb\u003eAMC-ATM-AX-CTX-CXN-CRO-CAZ-CN-C-CIP-MEM-LEV-F-PEF-SXT-TIC-PRL\u003c/b\u003e including 17 antibiotics from 6 different family.\u003c/p\u003e\n\u003ch3\u003e5. Molecular characterisation of resistance genes\u003c/h3\u003e\n\u003cp\u003eThe prevalence of genes encoding resistance to β-lactam were mostly represented by \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eCTX\u0026minus;M\u003c/sub\u003e (9/13; 69.2%), \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eTEM\u003c/sub\u003e (7/13; 53.8%) and \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eSHV\u003c/sub\u003e (3/13; 23.1%). The global prevalence of PQMR genes were 62.5%, 37.5%, 25%, 25% for \u003cem\u003eoqx\u003c/em\u003eA, \u003cem\u003eqnr\u003c/em\u003eS, \u003cem\u003eqnr\u003c/em\u003eB and \u003cem\u003eaac\u003c/em\u003e(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)-Ib respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). High prevalence of \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eCTX\u0026minus;M\u003c/sub\u003e was observed among ESBL-\u003cem\u003eEc\u003c/em\u003e (3/3;100%) and ESBL-\u003cem\u003eKp\u003c/em\u003e (6/10; 60%). The most prevalent gene encoding fluoroquinolone resistance observed among ESBL-\u003cem\u003eEc\u003c/em\u003e and ESBL-\u003cem\u003eKp\u003c/em\u003e was \u003cem\u003eoqx\u003c/em\u003eA with (5/8; 62,5%) respectively.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eAntimicrobial resistance remains a significant public health threat worldwide (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). The immunocompromised patients especially those living with HIV and SCDs are among the most vulnerable populations (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Several studies conducted in African countries revealed a high burden of ESBL-\u003cem\u003eEc\u003c/em\u003e and ESBL-\u003cem\u003eKp\u003c/em\u003e isolated from UTIs (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). A study conducted in Cameroon, in 2021, reported a high prevalence of MDR and ESBL-producing \u003cem\u003eE. coli\u003c/em\u003e and \u003cem\u003eK. pneumoniae\u003c/em\u003e isolated from UTIs among SCDs in Cameroon (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). There is a paucity of data regarding the resistance level of fluoroquinolone in ESBL-\u003cem\u003eKp\u003c/em\u003e and ESBL-\u003cem\u003eEc\u003c/em\u003e from SCDs with UTIs. This study thus, aimed to investigate the prevalence, phenotypic and genotypic characterization of ESBL and fluoroquinolone resistance genes among SCD patients in Yaound\u0026eacute;, Cameroon.\u003c/p\u003e\u003cp\u003eAmong all patients contacted and enrolled in this study, SS homozygous patients (n\u0026thinsp;=\u0026thinsp;86/90 95.6%) were most represented. This observation is attributable to the high prevalence of SCD within the population. Epidemiological studies have documented a significant frequency and burden of SCD in this region. Specifically, in Cameroon, it is estimated that approximately 20\u0026ndash;30% of the population carry the sickle cell trait, while the prevalence of SCD ranges from about 0.6% to 2% in the general population (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). This high prevalence significantly influences the regional population health dynamics and constitutes a major public health concern in Cameroon (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). The results revealed that the most participants affected being male and the ages ranged between 10 and 14 years. These results are similar with those obtained in Tanzania who shown than half of his study population living with SCDs and having UTIs were boys and the age group of this population ranged between 12 to 15 years (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The observed variation in bacterial isolates among females may be attributed to anatomical configuration, including the shorter urethra's proximity to the anal and vaginal orifices, which predispose to ascending infections, as well as suboptimal hygiene practices. These findings reflect a lower prevalence compared to reports from Tanzania and Nigeria, where UTI prevalence rates among SCD patients were documented at 21.1% and 22.4%, respectively (\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). This gender disparity in UTI incidence aligns with established knowledge that females generally exhibit higher susceptibility to UTIs due to anatomical and behavioural factors.\u003c/p\u003e\u003cp\u003eAfter bacteriological analysis of urine samples from SCD patients with UTI symptoms, the prevalence was 3.3% among this study population. This prevalence is lower than those reported in the studies conducted by Sangeda et al., Mava et al., and Asinobi et al., which documented UTI prevalence rates of 21.1%, 26%, and 22.4%, respectively (\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The predominant uropathogens identified in healthcare settings in Yaound\u0026eacute;, Cameroon, were \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e (10%) and \u003cem\u003eEscherichia coli\u003c/em\u003e (7.77%). These findings differ from studies conducted in Tanzania, where \u003cem\u003eEscherichia coli\u003c/em\u003e consistently emerged as the dominant causative agent of UTIs in SCD patients (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Such regional variations underscore the importance of localized epidemiological surveillance to inform effective management and antimicrobial stewardship in this vulnerable population.\u003c/p\u003e\u003cp\u003eThe resistance profiles observed in this study are consistent with prior report from Nigeria and the USA, where high resistance rates to multiple antibiotic classes were documented among ESBL-producing pathogens (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). In contrast, low resistance levels were identified against gentamicin, chloramphenicol, and meropenem, indicating these antibiotics retain relative efficacy. Additionally, nitrofurantoin exhibited low resistance, suggesting its potential use in specific clinical scenarios. Moderate resistance to fosfomycin (~\u0026thinsp;50%) suggests a possible therapeutic consideration depending on AST. Notably, colistin, often reserved as a last-resort antibiotic for MDR-\u003cem\u003eKp\u003c/em\u003e and MDR-\u003cem\u003eEc\u003c/em\u003e UTI infections, demonstrated no resistance among all isolates. Most isolates exhibited multidrug resistance, defined as non-susceptibility to at least one agent in three or more antimicrobial classes, highlighting the therapeutic challenges in managing infections caused by these ESBL-\u003cem\u003eKp\u003c/em\u003e and ESBL-\u003cem\u003eEc\u003c/em\u003e. The most common resistant patterns in our study was related to eleven and fifteen antibiotics including \u003cb\u003eAMC-ATM-AX-CTX-CXN-CRO-CAZ-CN-C-CIP-MEM-LEV-F-PEF-SXT-TIC-PRL\u003c/b\u003e and \u003cb\u003eAMC-ATM-AX-CAZ-C-CIP-LEV-F-PEF-SXT-TIC-PRL\u003c/b\u003e for ESBL-\u003cem\u003eKp\u003c/em\u003e and ESBL-\u003cem\u003eEc\u003c/em\u003e respectively. These data underscore the critical need for continuous antimicrobial resistance surveillance and tailored stewardship programs to optimize treatment outcomes for infections caused by ESBL-\u003cem\u003eKp\u003c/em\u003e and ESBL-\u003cem\u003eEc\u003c/em\u003e in Cameroon (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe overall prevalence of ESBL-\u003cem\u003eEc\u003c/em\u003e and ESBL-\u003cem\u003eKp\u003c/em\u003e exhibiting resistance to antibiotics including amoxicillin, amoxicillin-clavulanic acid (amoxypenicillin), piperacillin, ticarcillin (carboxypenicillin), ceftazidime, pefloxacin, and trimethoprim was notably high. These resistance patterns align with findings reported in Tanzania and Nigeria, underscoring the widespread dissemination of MDR-\u003cem\u003eEnterobacteriaceae\u003c/em\u003e in sSA among vulnerable populations such as SCD patients (\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Similarly, a Cameroonian study by Alima Yanda et al. (2017) reported similar resistance profiles among SCD patients within the same healthcare facilities, affirming consistent regional trends in antimicrobial resistance among these pathogens (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Furthermore, moderate resistance rates to third-generation cephalosporins and fluoroquinolone including cefotaxime, ceftriaxone, levofloxacin and ciprofloxacin were observed, with high resistance levels to cephalosporins and fluoroquinolone reaching 83.33% and 50%, respectively. These findings highlight the therapeutic challenges posed by ESBL-producing isolates in managing infections within SCD patients and emphasize the urgent need for antimicrobial stewardship implementation and interventions tailored to local resistance profiles in Cameroon and comparable sub-Saharan settings. The high resistance prevalence of cephalosporins and fluoroquinolone reflects likely factors including prior antibiotic exposure and the plasmid-mediated dissemination of ESBL and fluoroquinolone resistance genes, as already documented in studies from Cameroon and neighbouring regions (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). This data is critical for guiding empirical therapy and public health policies targeting bacterial infections in SCD patients.\u003c/p\u003e\u003cp\u003eAmong the different ESBL resistance genes tested, \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eCTX\u0026minus;M\u003c/sub\u003e and \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eTEM\u003c/sub\u003e were the most frequently detected with the prevalence being 69.2% (9/13) and 53.8% (7/13) respectively. This result is an agreement with the previous studies showing that \u003cem\u003ebla\u003c/em\u003eCTX\u0026thinsp;\u0026minus;\u0026thinsp;M was the most common ESBL genes carried among ESBL-\u003cem\u003eEnterobacterales\u003c/em\u003e responsible for UTIs in Cameroon (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). The prevalence rates of \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eCTX\u0026minus;M\u003c/sub\u003e and \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eTEM\u003c/sub\u003e observed in this study differ from those reported in Nepal, Cameroon and Egypt (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).The predominance of the \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eCTX\u0026minus;M\u003c/sub\u003e is consistent with numerous reports highlighting its broad hydrolytic activity against various β-lactam antibiotics, which explains its frequent selection in countries of intensive antibiotic pressure, particularly the empirical use of third-generation cephalosporins such as ceftriaxone in managing SCD patients. In contrast, the comparatively lower prevalence of \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eCTX\u0026minus;M\u003c/sub\u003e and \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eTEM\u003c/sub\u003e genes in your study relative to larger cohorts such as those in Nigeria can be reasonably attributed to your smaller sample size, which limits the overall number of ESBL strains available for genotypic analysis (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). The relative low frequency of the \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eSHV\u003c/sub\u003e gene in your study is also consistent with findings from Cameroon and Egypt, where \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eSHV\u003c/sub\u003e was found at low or undetectable levels (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Globally, \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eSHV\u003c/sub\u003e prevalence frequently varies by region and appears generally lower than \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eCTX\u0026minus;M\u003c/sub\u003e and \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eTEM\u003c/sub\u003e in many clinical isolates. The literature confirms that the coexistence of \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eCTX\u0026minus;M\u003c/sub\u003e, \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eTEM\u003c/sub\u003e, and \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eSHV\u003c/sub\u003e genes is common given their plasmid-mediated horizontal gene transfer among Enterobacteriaceae, contributing to genetic diversity and multidrug resistance, not only for cephalosporins but also for fluoroquinolone.\u003c/p\u003e\u003cp\u003eFluoroquinolone antibiotics like a ciprofloxacin, are a group of effective drugs for the treatment of ESBL-\u003cem\u003eE. coli\u003c/em\u003e and ESBL-\u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e responsible for a various infections (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). The molecular analysis revealed that all ciprofloxacin resistant ESBL-\u003cem\u003eEc\u003c/em\u003e and ESBL-\u003cem\u003eKp\u003c/em\u003e harboured at least one PMQR gene and the global prevalence of fluoroquinolone and aminoglycoside resistance genes detected were \u003cem\u003eoqx\u003c/em\u003eA (62.5%), \u003cem\u003eqnr\u003c/em\u003eS (37.5%), \u003cem\u003eqnr\u003c/em\u003eB (25%) and \u003cem\u003eaac(6')-Ib\u003c/em\u003e (25%). These findings are similar to the study conducted in Ghana and Iran by Sah et al., (2022) and Razaeil et al., (2024), where the widespread carriage and clinical PMQR genes including \u003cem\u003eoqx\u003c/em\u003eA, \u003cem\u003eqnr\u003c/em\u003eS and \u003cem\u003eaac\u003c/em\u003e(6')-Ib-cr among quinolone-resistant gram-negative \u003cem\u003eE. coli\u003c/em\u003e and \u003cem\u003eK. pneumonia\u003c/em\u003e have been observed, emphasizing their role in community and clinical resistance (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). In addition, the frequencies of \u003cem\u003eqnr\u003c/em\u003eB and \u003cem\u003eqnr\u003c/em\u003eS detected in this study is close to the rates reported by Gomaa et al., (2024) in Egypt (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). These findings were also noted in a study conducted in Ghana, where \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e isolates showed a high frequency of \u003cem\u003eqnr\u003c/em\u003eS (17.9%), compared to \u003cem\u003eEscherichia coli\u003c/em\u003e (4.4%).\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThis study has described the clinical and genotypic characterization of PMQR and ESBL isolates from UTIs among SCDs in Cameroon. High prevalence of PMQR and ESBL-producing \u003cem\u003eE.coli\u003c/em\u003e and \u003cem\u003eK. pneumoniae\u003c/em\u003e were evidenced. Meropenem, colistin, fosfomycin and gentamycin remain the most effective antibiotics with good activities against PMQR and ESBL-\u003cem\u003eE. coli\u003c/em\u003e and \u003cem\u003eK. pneumoniae\u003c/em\u003e. The PMQR were associated with ESBL-producing \u003cem\u003eE. coli\u003c/em\u003e and \u003cem\u003eK. pneumoniae\u003c/em\u003e contributing to the spread of multidrug resistance and may lead for life-threating infections among these vulnerable populations. The observed widespread resistance across multiple antibiotic classes warrants improving empiric therapy within these facilities. It is thus crucial to implement antimicrobial stewardship programs at the local and national in order to curb the emergence and escalation of antimicrobial resistance.\u003c/p\u003e\n\u003ch3\u003eLIMITS\u003c/h3\u003e\n\u003cp\u003eThis study was limited to two structures in the Yaound\u0026eacute;, it would be interested to expand this research to all sickle cell disease management Centers in Yaound\u0026eacute; and across Cameroon as far as possible to obtain more comprehensive and relevant findings. Additionally, a further limitation was the undetected mutations occurring within the quinolone-determining region contributing to fluoroquinolone resistance.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMDR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMultidrug resistance\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSCDs\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eSickle Cell Diseases\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eUTI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eUrinary Tract Infection\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCAUTI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCommunity Acquired Urinary Tract Infections\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHAUTI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eHospital Acquired Urinary Tract Infections\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eESBL-E\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eExtended Spectrum β-lactamase producing-\u003cem\u003eEnterobacterales\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was approved by the Regional Ethics Committee for Research in Human Health, Centre region, Cameroon N\u0026deg;0098/19/02/2024/CE/CRERSHC/VP. In addition, it was approved by the Research institute of the Centre of Expertise and Biological Diagnostic of Cameroon (CEDBCAM-RI) under the number (N\u0026deg; 002/02/24/LA/CEDBCAM-RI/DG). All participants or the legal guardian/nearest relative for minor were recruited in compliance upon obtaining individual or parental informed consent with the ethical approval for human research in force in hospitals under the number of (117/24/AP/MINSANTE/SG/DHCY/CM/SM). The study was conducted in accordance with the declaration of Helsinki. All methods and protocols used were approved by the CEDBCAM-RI in accordance with the relevant national and international guidelines and regulations for research laboratory ethics.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data are available upon request in accordance with confidentiality and privacy regulations from the corresponding author.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDr Raspail Carrel Founou received funding from the M\u0026eacute;rieux Institute, Lyon France for the CAREFOOD project. CAREFOOD project had supported all the molecular aspects of this study. This work was also supported by the Research Institute of Centre of Expertise and Biological Diagnostic of Cameroon (CEDBCAM-RI). The funders had no role in the study design, nor the decision to submit the work for publication. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the organizations or agencies that provided support for the project.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors and affiliations \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDepartment of Microbiology-Haematology and Immunology, Faculty of Medicine and Pharmaceutical Sciences, University of Dschang, Dschang, Cameroon;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAntimicrobial Research Unit, School of Health Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa;\u003c/p\u003e\n\u003cp\u003eAntimicrobial Resistance and Infectious Disease (ARID) Research Unit, Research Institute of Centre of Expertise and Biological Diagnostic of Cameroon (CEDBCAM-RI), Yaound\u0026eacute;, Cameroon;\u003c/p\u003e\n\u003cp\u003eReproductive, Maternal, Newborn and Child Health (ReMARCH) Research Unit, Research\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInstitute of the Centre of Expertise and Biological Diagnostic of Cameroon (CEDBCAM-RI); Yaound\u0026eacute;, Cameroon;\u003c/p\u003e\n\u003cp\u003eBioinformatics \u0026amp; Applied Machine Learning Research Unit, EDEN Biosciences Research Institute (EBRI), EDEN Foundation, Yaound\u0026eacute; Cameroon;\u003c/p\u003e\n\u003cp\u003eNational Blood Transfusion Service (NBTS), Yaound\u0026eacute; Cameroon;\u003c/p\u003e\n\u003cp\u003eMother and Child Center of Chantal Biya Foundation, Yaound\u0026eacute;, Cameroon;\u003c/p\u003e\n\u003cp\u003eDepartment of Microbiology-Haematology and Immunology, Faculty of Medicine and Biomedical Sciences, University of Yaound\u0026eacute; 1, Yaound\u0026eacute;, Cameroon;\u003c/p\u003e\n\u003cp\u003eNational Public Health Laboratory (NPHL), Yaound\u0026eacute;, Cameroon\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConceptualizatio\u003c/strong\u003en: RBM, RCF and VJBG; \u003cstrong\u003eMethodology\u003c/strong\u003e: RCF, LLF, VJGB, RGE, RBM; \u003cstrong\u003eSoftware\u003c/strong\u003e: RBM, JNN; \u003cstrong\u003eValidation\u003c/strong\u003e: RCF, LLF, VJGB, RGE, SE, BC and EW; \u003cstrong\u003eFormal analysis\u003c/strong\u003e: RBM, VJGB and RCF; \u003cstrong\u003eInvestigation\u003c/strong\u003e: RCF, LLF, VJGB, RGE, RBM; \u003cstrong\u003eResources\u003c/strong\u003e: RCF, LLF, VJGB and RGE; \u003cstrong\u003eWriting original draft\u003c/strong\u003e: RBM, LLF, VJGB, RGE, SE and RCF; \u003cstrong\u003eReview and editing\u003c/strong\u003e: RCF, LLF, VJGB, RGE, SE, BC and EW; \u003cstrong\u003eVisualization\u003c/strong\u003e: RBM, RCF and VJGB; \u003cstrong\u003eSupervision\u003c/strong\u003e: RCF and VJGB; \u003cstrong\u003eProject administration\u003c/strong\u003e: RCF, LLF, VJGB and RGE. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all staff members of two healthcare structures and all participants who agreed to participate to this study. \u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDonkor ES, Osei JA, Anim-Baidoo I, Darkwah S. Risk of Asymptomatic Bacteriuria among People with Sickle Cell Disease in Accra, Ghana. \u003cem\u003eDiseases\u003c/em\u003e. 2017; 5(1). 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PLoS ONE. 2021;16(8):e0255956.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNkengkana OA, Founou RC, Founou LL, Dimani BD, Koudoum PL, Zemtsa JR, et al. Phenotypic and genotypic characterization of multidrug resistant and extended-spectrum β-lactamase-producing Enterobacterales isolated from clinical samples in the western region in Cameroon. BMC Infect Dis. 2023;23(1):819.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSaid MM, Msanga DR, Mtemisika CI, Silago V, Mirambo MM, Mshana SE. Extended Spectrum β-Lactamase Producing Lactose Fermenting Bacteria Colonizing Children with Human Immunodeficiency Virus, Sickle Cell Disease and Diabetes Mellitus in Mwanza City, Tanzania: A Cross-Sectional Study. \u003cem\u003eTrop Med Infect Dis\u003c/em\u003e. 2022; 7(8). Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://mdpi-res.com/d_attachment/tropicalmed/tropicalmed-07-00144/article_deploy/tropicalmed-07-00144.pdf?version=1658477495\u003c/span\u003e\u003cspan address=\"https://mdpi-res.com/d_attachment/tropicalmed/tropicalmed-07-00144/article_deploy/tropicalmed-07-00144.pdf?version=1658477495\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMaghembe RS, Magulye MAK, Eilu E, Sekyanzi S, Mwesigwa S, Katagirya E. Chromosomal and plasmid-encoded virulence and multidrug resistance of \u003cem\u003eEscherichia coli\u003c/em\u003e ST58/24 infecting a 2-year-old sickle cell patient with sepsis in Kampala Uganda, East Africa. Heliyon. 2024;10(9):e30187.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAlima Yanda AN, Nansseu JRN, Mbassi Awa HD, Tatah SA, Seungue J, Eposse C, et al. Burden and spectrum of bacterial infections among sickle cell disease children living in Cameroon. BMC Infect Dis. 2017;17(1):211.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAra\u0026uacute;jo MRB, Sant'Anna LO, Santos N, Seabra LF, Santos LSD. Monitoring fluoroquinolone resistance among ESBL-positive and ESBL-negative Escherichia coli strains isolated from urinary tract infections: An alert for empirical treatment. Rev Soc Bras Med Trop. 2023;56:e0513.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAldred KJ, Kerns RJ, Osheroff N. Mechanism of quinolone action and resistance. Biochem. 2014;53(10):1565\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBayaba S, Founou RC, Tchouangueu FT, Dimani BD, Mafo LD, Nkengkana OA, et al. High prevalence of multidrug resistant and extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolated from urinary tract infections in the West region, Cameroon. BMC Infect Dis. 2025;25(1):115.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFounou RC, Founou LL, Essack SY. Clinical and economic impact of antibiotic resistance in developing countries: A systematic review and meta-analysis. PLoS ONE. 2017;12(12):e0189621.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSaidu Y, Masong MC, Francoise N, Ngenge BM, Ndansi E, Foma MK. Sickle cell disease in Cameroon: Taking out the neglect and highlighting key opportunities for sustainable control. PLOS Glob Pub Health. 2024;4(10):e0003668.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAsinobi AO, Fatunde OJ, Brown BJ, Osinusi K, Fasina NA. Urinary tract infection in febrile children with sickle cell anaemia in Ibadan, Nigeria. Ann Trop Paed. 2003;23(2):129\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMava Y, Bello M, Ambe JP, Zailani SB. Antimicrobial sensitivity pattern of organisms causing urinary tract infection in children with sickle cell anemia in Maiduguri, Nigeria. Niger J Clin Pract. 2012;15(4):420\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSangeda RZ, Yohana J, Jonathan A, Manyanga VP, Soka D, Makani J. Prevalence of Urinary Tract Infections and Antibiogram of Bacteria Isolated From Children With Sickle Cell Disease in Tanzania. Cureus. 2024;16(4):e58786.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSrisuwananukorn A, Han J, Raslan R, Gowhari M, Hussain F, Njoku F, et al. Antimicrobial resistance is a risk factor for mortality in adults with sickle cell disease. Haematologica. 2021;106(6):1745\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSaid MM, Msanga DR, Mtemisika CI, Silago V, Mirambo MM, Mshana SE. Extended Spectrum β-Lactamase Producing Lactose Fermenting Bacteria Colonizing Children with Human Immunodeficiency Virus, Sickle Cell Disease and Diabetes Mellitus in Mwanza City, Tanzania: A Cross-Sectional Study. Trop Med Infect Dis. 2022;7(8).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDjim-Adjim-Ngana K, Mbiakop BW, Oumar LA, Munshili Njifon HL, Tchinda Fossi C, Enyegue ELE, et al. Phenotypic characterization and epidemiology of extended-spectrum β-lactamase-producing Enterobacteriaceae strains from urinary tract infections in Garoua, Cameroon. Front Public Health. 2023;11:1187934.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOuchar Mahamat O, Lounnas M, Hide M, Dumont Y, Tidjani A, Kamougam K, et al. High prevalence and characterization of extended-spectrum \u0026szlig;-lactamase producing Enterobacteriaceae in Chadian hospitals. BMC Infect Dis. 2019;19(1):205.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKoirala S, Khadka S, Sapkota S, Sharma S, Khanal S, Thapa A, et al. Prevalence of CTX-M β-Lactamases Producing Multidrug Resistant Escherichia coli and Klebsiella pneumoniae among Patients Attending Bir Hospital, Nepal. Biomed Res Int. 2021;2021:9958294.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRezaei S, Tajbakhsh S, Naeimi B, Yousefi F. Investigation of gyrA and parC mutations and the prevalence of plasmid-mediated quinolone resistance genes in Klebsiella pneumoniae clinical isolates. BMC Microbiol. 2024;24(1):265.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGomaa EA, Ehab MF, Abdellatif AM, Ahmed ME, El Sayed ZM, Mofreh MM. Study of plasmid mediated quinolone resistance genes among Escherichia coli and Klebsiella pneumoniae isolated from pediatric patients with sepsis. Sci Rep. 2024;14(1):11849.\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":"UTIs, Escherichia coli, K. pneumoniae, ESBL, Sikcle cell, Cameroon","lastPublishedDoi":"10.21203/rs.3.rs-7696682/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7696682/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eExtended-spectrum β-lactamase producing-\u003cem\u003eE. coli\u003c/em\u003e (ESBL-\u003cem\u003eEc\u003c/em\u003e) and \u003cem\u003eK. pneumoniae\u003c/em\u003e (ESBL-\u003cem\u003eKp\u003c/em\u003e) are pathogens of critical priority that urgently required research and development of new antibiotics. Fluoroquinolones are broad-spectrum antibiotics commonly used to treat urinary tract infections (UTIs) among patients living with sickle cell disease (SCD). This study aims at determining the prevalence, phenotypic and genotypic characterizatics of plasmid-mediated quinolone resistance genes among ESBL-\u003cem\u003eEc\u003c/em\u003e and ESBL-\u003cem\u003eKp\u003c/em\u003e isolated from SCD patients with UTIs in Yaound\u0026eacute;, Cameroon.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA cross-sectional study was conducted in two healthcare facilities from February to June, 2024. Mid-stream urine samples were collected from UTI patients living with SCD. ESBL-\u003cem\u003eEc\u003c/em\u003e and ESBL-\u003cem\u003eKp\u003c/em\u003e isolates were biochemical identified using API20E following the manufacturer\u0026rsquo;s instructions. The antimicrobial susceptibility test was performed using the Kirby-Bauer disk diffusion method. ESBL-phenotype was screened using the double-disk synergy test and confirm by plating onto ChromAgar\u0026trade; ESBL medium. Antimicrobial resistance genes were detected using polymerase chain reaction methods. The data analysis was performed using Excel 2016 and IBM SPSS version 20.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 90 urine samples were collected and analysed during the study period. The prevalences of \u003cem\u003eEscherichia coli\u003c/em\u003e and \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e were 7,7% (7/90) and 10% (10/90) respectively. Among these, the rate of ESBL production was 57,14% (4/7) for \u003cem\u003eE. coli\u003c/em\u003e and 60% (6/10) for \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e. The prevalences of ciprofloxacin non-susceptible among ESBL-\u003cem\u003eEc\u003c/em\u003e and ESBL-\u003cem\u003eKp\u003c/em\u003e were 12,5% (1/8) and 87,5% (7/8) respectively. High antimicrobial resistance rate was observed for amoxicillin, amoxicillin\u0026thinsp;+\u0026thinsp;clavulanic acid, ceftazidime, thrimethoprim, pefloxacin. The most common resistance genes detected encoding for β-lactam and fluoroquinolone resistance were \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eCTX\u0026minus;M\u003c/sub\u003e, \u003cem\u003eoqx\u003c/em\u003eA, \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eTEM\u003c/sub\u003e, \u003cem\u003eqnr\u003c/em\u003eS respectively.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThe findings revealed a high burden of fluoroquinolone resistance in ESBL-\u003cem\u003eEc\u003c/em\u003e and ESBL-\u003cem\u003eKp\u003c/em\u003e among SCD patients with UTIs. This study emphasizes the necessity for monitoring and surveillance of resistant strains against β-lactam and fluoroquinolone antibiotics among this vulnerable population. It is thus crucial to implement antimicrobial stewardship programs at the local and national levels and develop the appropriate protocols for antibiotic usage in these healthcare facilities to curb the emergence and escalation of these growing resistant bacteria.\u003c/p\u003e","manuscriptTitle":"Molecular characterization of Plasmid-Mediated Quinolone Resistance (PMQR) and Extended-Spectrum β-Lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolated from Urinary Tract Infections (UTIs) among patients living with Sickle Cell Diseases (SCD) in Yaoundé, Cameroon","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-16 01:54:02","doi":"10.21203/rs.3.rs-7696682/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-21T10:12:57+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-16T11:29:52+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-15T05:47:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"100474005821643342718175548443628752156","date":"2025-10-07T03:43:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-06T13:05:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"14044777124269479470798879510073264696","date":"2025-10-06T12:13:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"90637581836974779400232546441915144959","date":"2025-10-06T08:03:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"208265789872348008412988296007988476427","date":"2025-10-05T09:43:57+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-03T10:28:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"66656007770117841715251102741757744759","date":"2025-10-01T22:45:59+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-01T21:37:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-30T11:23:59+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-26T01:42:38+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-26T01:42:01+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Microbiology","date":"2025-09-23T16:57:14+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":"857788ed-2254-4a73-9976-c2a2279a008d","owner":[],"postedDate":"October 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-06T11:25:21+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-16 01:54:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7696682","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7696682","identity":"rs-7696682","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}