High Prevalence of Multidrug-Resistant Uropathogenic Escherichia coli with Marked Gender-Associated Resistance Patterns: A Retrospective Study from Northern Iran

High Prevalence of Multidrug-Resistant Uropathogenic Escherichia coli with Marked Gender-Associated Resistance Patterns: A Retrospective Study from Northern Iran | 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 High Prevalence of Multidrug-Resistant Uropathogenic Escherichia coli with Marked Gender-Associated Resistance Patterns: A Retrospective Study from Northern Iran Mehrdad Gholami, Mohammad Karimbakhsh, Faezeh Cheraghi, Ali ehsani, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8212293/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, with Escherichia coli (E. coli) accounting for up to 90% of cases. Risk factors include anatomical differences, poor hygiene, pregnancy, urinary obstruction, catheter use, urethral reflux, and spermicidal contraceptives. Common empiric treatments include amoxicillin, ciprofloxacin, amoxicillin/clavulanic acid, nitrofurantoin, and trimethoprim, but increasing antimicrobial resistance (AMR) complicates therapy. This study aimed to evaluate in vitro resistance patterns of common antimicrobials against uropathogenic E. coli (UPEC) and assess trends over time to inform empiric treatment strategies and reduce failures. Methods This retrospective, record-based study analyzed culture and sensitivity (C/S) reports of urine samples from inpatients at Imam Khomeini, Boo-Ali Sina, Razi, Zare, and Fatemeh Zahra hospitals in Sari, Iran, from March 2021 to the end of 2022. Ethical approval and laboratory permission were obtained. E. coli was identified using standard microbiological and biochemical methods. Antimicrobial susceptibility testing used the Kirby-Bauer disk diffusion method on Mueller-Hinton agar per CLSI 2021 guidelines, testing penicillins, cephalosporins, quinolones, aminoglycosides, sulfonamides, carbapenems, and nitrofurantoin. Data were compiled year-wise, with statistical analysis via IBM SPSS version 20. Results Of 1,804 E. coli -positive isolates, 64.7% were from females and 35.3% from males; age was recorded for 1,627 patients, with 41–60 years most frequent (33.3%). Highest susceptibility was to amikacin (92.0%), nitrofurantoin (83.7%), and gentamicin (80.3%); highest resistance to ampicillin (93.4%), ceftriaxone (66.1%), ciprofloxacin (63.9%), cefotaxime (63.8%), and cotrimoxazole (62.4%). Resistance was significantly higher in females for most agents, including ciprofloxacin (78.0% vs. 36.8%) and nitrofurantoin (84.4% vs. 3.0%, p = 0.027). Over 70% of isolates were MDR. Intermediate susceptibility was low (0.0-3.2%). Highest resistance rates occurred in patients with 7–10 day hospital stays. Conclusion High AMR in UPEC, particularly to empiric agents, underscores therapeutic challenges. Gender differences suggest tailored approaches for females. Regular surveillance is essential to optimize empiric therapy, minimize failures, and curb MDR spread in this region. Uropathogenic Escherichia coli Antimicrobial resistance Urinary tract infection Multidrug-resistant E. coli 1. Introduction Urinary tract infections (UTIs) are among the most prevalent bacterial infections globally, encompassing a wide range of conditions from simple cystitis to severe urosepsis ( 1 ). Major risk factors include anatomical differences, poor personal hygiene, pregnancy, urinary obstruction, extended catheter use, urethral reflux, and spermicidal contraceptive use ( 2 ). Escherichia coli ( E. coli ) is the primary causative agent responsible for up to 90% of UTI cases, with other pathogens such as Enterococci , Pseudomonas , Staphylococcus saprophyticus , and Klebsiella spp. ( 3 ). Five antimicrobials–amoxicillin, ciprofloxacin, amoxicillin/clavulanic acid, nitrofurantoin, and trimethoprim—constitute approximately 70–80% of the prescriptions. Most antimicrobial therapies for UTIs are initiated empirically before the culture results are obtained ( 4 ). Effective treatment of UTIs has become highly difficult because of the high resistance to commonly used antibacterial agents ( 5 ). Over the past few decades, there has been a global increase in antibiotic resistance in E. coli , highlighting the issue of inappropriate empirical antibiotic treatments for UTIs ( 6 ). Multidrug-resistant (MDR) uropathogens result in relevant morbidity and mortality, posing a serious threat to treatment success and patient survival ( 7 ). In our country, the issue of antimicrobial resistance (AMR) is worsening due to the overuse and misuse of antibiotics. There is no systematic national surveillance of antibiotic resistance, and data to measure the problem are lacking. This report aimed to assess in vitro resistance patterns of commonly used antimicrobials. These findings will aid in the development of the most effective empirical treatment ration for UTIs. It also highlights the changes in the susceptibility patterns of the most common uropathogenic Escherichia coli (UPEC), over time in this region, underscoring the need for regular monitoring to reduce therapeutic failures. 2. MATERIAL AND METHODS 2.1. Bacterial culture and identification A retrospective study based on records was conducted at the Department of Microbiology, in partnership with the Microbiology Departments of Imam Khomeini, Boo-Ali Sina, Razi, Zare, and Fatemeh Zahra teaching tertiary care hospitals located in Sari, Iran. This study encompassed all culture and sensitivity (C/S) reports of urine samples from inpatients admitted to various wards of these hospitals from March 2021 until the end of 2022. Ethical clearance was obtained from the institutional ethics committee, and authorization was obtained from the head of the hospital microbiology laboratory before data collection commenced. All urine C/S reports recorded in the laboratory registers from 2021 to 2022 were examined. E. coli isolates had been previously identified by the hospital microbiology laboratory using standard conventional microbiological and biochemical methods, such as colony morphology on MacConkey agar, indole positivity, and other routine biochemical tests. Reports showing positive growth of E. coli were included in the study, while isolates from repeat cultures of previously included patients and those identified as commensals or contaminants were excluded from the study. 2.2. Data collection Data were gathered from laboratory record registers, including detailed information such as patient age, sex, preliminary clinical diagnosis, sample receipt date, and comprehensive antimicrobial susceptibility outcomes. Urine culture findings and antibiotic susceptibility profiles of E. coli isolates were extracted from the culture and sensitivity (C/S) reports archived in the Microbiology Department of Imam Khomeini, Boo-Ali Sina, Razi, Zare, and Fatemeh Zahra hospitals for the years 2021–2022. The exclusion criteria included negative cultures, absence of culture requests, identification of other microbes, and urine samples collected after the start of empiric antibiotic treatment. 2.3. Antimicrobial susceptibility testing The resistance profiles of E. coli strains to empiric antibiotics were assessed by reviewing the susceptibility reports from urine cultures. Initially, the empiric antibiotics used to treat UTIs were identified. The antibiotics included in the susceptibility testing panel were verified to ensure that they covered the selected empiric antibiotics. Antibiotic susceptibility testing was performed according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI 2021) ( 8 ). Susceptibility results for each empiric antibiotic were interpreted using established clinical breakpoints, classifying the isolates as susceptible or resistant. Resistance pattern analysis encompassed the following antibiotics: broad-spectrum penicillin, third-generation cephalosporins, quinolones, aminoglycosides, sulfonamides, carbapenems, and nitrofurantoin. All data were collected and organized annually to compare resistance pattern trends over the years. In this study, MDR strains were identified as non-susceptible to at least one agent in three or more antimicrobial categories ( 9 ). C/S reports for other common uropathogens were also be examined. 2.4. Data analysis Statistical analysis were performed using IBM SPSS Statistics 20 (SPSS Inc., Chicago IL, USA). Descriptive statistics for continuous variables were calculated as means and standard deviations, and categorical variables were expressed as percentages. The Shapiro–Wilk test was used to assess the normality of continuous variables, with a p-value of ≤ 0.05 indicating a non-normal distribution. The impact of E. coli resistance and the presence or absence of susceptibility reporting on hospital length of stay was evaluated using a two-tailed Mann–Whitney U-test. The relationship between sex and resistance was assessed using Pearson’s chi-square test. Statistical significance was set at p < 0.05. 3. Result During the two-year study period from March 2021 to the end of 2022, 1,804 urine culture samples positive for E. coli were analyzed, with each isolate obtained from a different patient. No patient contributed more than one isolate per sample. Female patients predominated, comprising 1,167 (64.7%) of the cases, whereas male patients accounted for 637 (35.3%). Age was accurately recorded for 1,627 patients in this study. The most frequent age group was 41–60 years (n = 542, 33.3% of those with recorded age), followed by other age groups. The highest antibiotic resistance rates were observed among patients with a hospital stay of 7–10 days (Table 1 ). Patients were admitted from five tertiary care hospitals in Sari, Iran: Imam Khomeini, Boo-Ali Sina, Razi, Zare, and Fatemeh Zahra hospitals. Boo-Ali Sina Hospital contributed the largest number of isolates (n = 1,100, 61.0%), whereas Zare Hospital had the fewest (n = 29, 1.6%). Table 1 Demographic and clinical characteristics of the study sample (n = 1,804) Parameter n (%) Age (years) Data available for 1,627 patients Age categories (years) 1–10 175 (10.8%) 11–20 215 (13.2%) 21–40 160 (9.8%) 41–60 542 (33.3%) > 60 475 (29.2) Most frequent age group 41–60 years (n = 542, 33.3%) Gender Female 1,167 (64.7%) Male 637 (35.3%) Hospital of admission Boo-Ali Sina Hospital 1,100 (61%) Imam Khomeini Hospital 413 (22.9%) Razi Hospital 180 (10%) Fatemeh Zahra Hospital 82 (4.5%) Zare Hospital Duration of hospital stay with highest resistance rates 7–10 days 3.1. Overall Antimicrobial Susceptibility Pattern Among the nine most frequently tested antibiotics (≥ 1,000 isolates each), the highest susceptibility was observed against amikacin (92.0% susceptible, n = 1,682), followed by nitrofurantoin (83.7% susceptible, n = 1,581) and gentamicin (80.3% susceptible, n = 1,607). High resistance rates were noted for ampicillin (93.4% resistant, n = 1,295), ceftriaxone (66.1% resistant, n = 1,595), cefotaxime (63.8% resistant, n = 1,195), ciprofloxacin (63.9% resistant, n = 1,384), and cotrimoxazole (62.4% resistant, n = 1,506). Intermediate susceptibility was low for most agents, ranging from 0.0% to 3.2% (Table 2 ). Table 2 Antimicrobial susceptibility of E. coli isolates tested in ≥ 1,000 patients Antibiotic No. tested Susceptible n (%) Intermediate n (%) Resistant n (%) Amikacin 1,682 1,547 (92%) 0 (0%) 135 (8%) Gentamicin 1,607 1,290 (80.3%) 22 (1.45) 295 (18.4%) Cephalothin 1,595 505 (31.7%) 35 (2.2%) 1055 (66.1%) Nitrofurantoin 1,581 1,324 (83.75) 0 (0%) 257 (16.3%) Cotrimoxazole 1,506 566 (37.6%) 0 (0%) 940 (62.4%) Ceftazidime 1,482 615 (41.5%) 41 (2.8%) 826 (55.7%) Ciprofloxacin 1,384 475 (34.3%) 25 (1.8%) 884 (63.9%) Ampicillin 1,295 77 (5.9%) 8 (0.6%) 1,210 (93.4%) Cefotaxime 1,195 395 (33.1%) 38 (3.2%) 762 (63.8%) Among the antibiotics tested on 100–300 isolates, piperacillin-tazobactam showed favorable activity (76.6% susceptible, n = 269), whereas nalidixic acid exhibited high resistance (76.0% resistant, n = 258). The intermediate rates were 1.6–7.8% (Table 3 ). Table 3 Antimicrobial susceptibility patterns of antibiotics tested in 100–300 isolates Antibiotic No. tested Susceptible (%) Intermediate (%) Resistant (%) Piperacillin-tazobactam 269 76.6 4.1 19.3 Cefixime 260 59.2 3.5 37.3 Nalidixic acid 258 22.5 1.6 76 Ampicillin-sulbactam 231 33.3 7.8 58.9 Among the antibiotics tested in fewer than 100 isolates, carbapenems (imipenem and meropenem) retained high susceptibility (88.9–100%, n = 5–9), while cefepime showed 49.2% resistance (n = 59). Intermediate susceptibility varied by up to 13.6% (Table 4 ). Table 4 Antimicrobial susceptibility patterns of selected antibiotics tested in < 100 isolates Antibiotic No. tested Susceptible (%) Intermediate (%) Resistant (%) Imipenem 9 88.9 0 11.1 Meropenem 5 100 0 0 Levofloxacin 188 57.4 6.4 36.2 Cefepime 59 37.3 13.6 49.2 3.2. Association between Antibiotic Resistance and Sex A significant association was observed between patient sex and resistance to most tested antibiotics (Table 5 ). Resistance rates were markedly higher in female patients than in male patients for most agents. Specifically, resistance to ampicillin (96.5% in females vs. 70.0% in males), ceftriaxone (81.7% vs. 32.7%), cefotaxime (86.2% vs. 27.8%), ciprofloxacin (78.0% vs. 36.8%), cotrimoxazole (78.7% vs. 35.3%), ceftazidime (86.0% vs. 17.7%), and nalidixic acid (90.0% vs. 34.5%) was significantly higher in females (all p < 0.001). Resistance to nitrofurantoin was also significantly more common in women than in men (84.4% vs. 3.0%, p = 0.027). In contrast, no significant sex-based differences were found for amikacin (81.5% vs. 1.6%, p = 0.080) and gentamicin (89.8% vs. 2.3%, p = 0.080), although resistant isolates in both antibiotics were predominantly from female patients. Table 5 Association between gender and antimicrobial resistance in E.coli isolates. NS * : not significant Antibiotic Female Resistant / Tested (%) Male Resistant / Tested (%) p-value Ampicillin 1,105/1,145 (96.5%) 105/150 (70%) < 0.001 Cefotaxime 890/1,090 (81.7%) 165/505 (32.7%) < 0.001 Ciprofloxacin 709 / 909 (78.0%) 175 / 475 (36.8%) < 0.001 Cotrimoxazole 740 / 940 (78.7%) 200 / 566 (35.3%) < 0.001 Ceftazidime 710 / 826 (86.0%) 116 / 656 (17.7%) < 0.001 Nalidixic acid 180 / 200 (90.0%) 20 / 58 (34.5%) < 0.001 Nitrofurantoin 217 / 257 (84.4%) 40 / 1,324 (3.0%) 0.027 Gentamicin 265 / 295 (89.8%) 30 / 1,312 (2.3%) 0.080 (NS * ) Amikacin 110 / 135 (81.5%) 25 / 1,547 (1.6%) 0.080 (NS * ) 3.3. Summary of Empirical Antibiotic Coverage Of the 1,804 isolates, 122 (6.8%) lacked sensitivity reports, and 189 (10.5%) involved antibiotics that did not cover E. coli . Among tested agents, 1,476 (81.8%) isolates were susceptible to at least one commonly prescribed empiric antibiotic, while 1,493 (82.8%) showed resistance to one or more key empiric agents (Table 6 ). Table 6 Summary of antibiotic sensitivity and resistance patterns of E. coli isolates to commonly prescribed empiric antibiotics (n = 1,804) Parameter n (%) Antibiotics without sensitivity reports 122 (6.8%) Antibiotics not covering E. coli 189 (10.5%) Antibiotics to which E. coli is sensitive Nitrofurantoin 1,324 (83.7%) Amikacin 1,547 (92%) Gentamicin 1,290 (80.3%) Piperacillin-tazobactam 206 (76.6%) Carbapenems (imipenem/meropenem) 13 (92.9%) Antibiotics to which E. coli is resistant Ampicillin 1,210 (93.45) Ceftiaxone 1,055 (66.1%) Cefotaxime 762 (63.85) Ciprofloxacin 884 (63.95) Cotrimoxazole 940 (62.4%) Ceftazidime 826 (55.75) 4. Discussion This study revealed alarming levels of AMR among UPEC isolates recovered from hospitalized patients in five tertiary care hospitals in Sari, northern Iran, during 2021–2022. More than 70% of the 1,804 analyzed isolates were MDR, and resistance to most first- and second-line empiric agents exceeded 60%. These findings confirm the continuing deterioration of therapeutic options for UTIs in this region and highlight the marked sex-associated differences in resistance patterns. In our study, the highest rate of AMR was observed against ampicillin (93.4%), whereas the lowest resistance was observed against amikacin (8%). In comparison, Malekzadegan et al. reported the highest resistance to ampicillin (88.9%) and the lowest resistance to imipenem (0.8%) ( 10 ). In the present study, the highest antimicrobial resistance rates were observed in reducing order against ampicillin (93.4%), ciprofloxacin (63.9%), and co-trimoxazole (62.4%). Likewise, Tewawong et al., reported resistance rates of 84.1%, 65.4%, and 54.3% to the same three agents, respectively, indicating that the observed hierarchy of resistance (ampicillin > > ciprofloxacin ≈ co-trimoxazole) is a widespread phenomenon in many low- and middle-income settings ( 11 ). In the study by Zeng et al., more than 95% of isolates exhibited susceptibility to piperacillin-tazobactam, whereas in our study, the susceptibility rate to this agent was 76.6% ( 12 ). One of the most striking findings was a pronounced sex disparity in resistance profiles. Female patients exhibited significantly higher resistance rates to nearly all tested agents, with the most dramatic differences observed for ciprofloxacin (78.0% vs. 36.8%), ceftriaxone (81.7% vs. 32.7%), cefotaxime (86.2% vs. 27.8%), cotrimoxazole (78.7% vs. 35.3%), and even nitrofurantoin (84.4% susceptible in females vs. 3.0% resistance in males, p = 0.027). This pattern cannot be explained by differences in hospital stay duration alone, as resistance peaked in the 7–10-day stay group, regardless of sex. The higher resistance burden in females most likely reflects greater previous exposure to antibiotics for recurrent or complicated UTIs, frequent use of broad-spectrum agents in obstetric/gynecological settings, and possibly the community circulation of highly resistant clones among women. These observations strongly argue for gender-stratified empiric treatment guidelines in our region: while nitrofurantoin and aminoglycosides remain reasonable first-line choices for uncomplicated UTIs in females, alternative agents or early culture-guided therapy should be considered in males only when the risk of resistance is deemed low. In the current study, the highest susceptibility rates were observed in diminishing order against amikacin (92%), nitrofurantoin (83.75%), and gentamicin (80.3%). In contrast, Pirouzi et al., reported the highest susceptibility rates in declining order effective against nitrofurantoin (81%), gentamicin (73.9%), and amikacin (71.9%) ( 13 ). The pattern of resistance to antimicrobial agents identified in this study is very similar to that found in earlier regional studies, showing consistently high resistance to ampicillin while maintaining relatively good susceptibility to amikacin, nitrofurantoin, and gentamicin. However, the significantly reduced susceptibility to piperacillin-tazobactam compared to that in some previous reports highlights the need for continued monitoring. 5. Limitation This study had several limitations inherent to its retrospective design. First, data were collected from the laboratory registers of hospitalized patients only; community-acquired UTIs were not represented, which may have overestimated resistance rates. Second, clinical details such as previous antibiotic exposure, recurrence of UTI, presence of urinary catheters, pregnancy status, and underlying comorbidities were not systematically recorded and could not be analyzed as potential confounders of the observed sex differences. Third, molecular characterization of resistance mechanisms (e.g., ESBL, AmpC, and carbapenemase production) and phylogenetic grouping were not performed, limiting insight into the genetic basis of the high MDR prevalence and sex-associated patterns. Finally, carbapenems and some other reserve agents were tested in very few isolates, preventing reliable conclusions about their true activities in this population. Prospective studies incorporating detailed clinical metadata and genomic analyses are warranted to address these gaps. 6. Conclusion Monitoring antibiotic resistance is crucial in combating AMR. E. coli isolates from UTIs highlighted the greatest sensitivity to amikacin and nitrofurantoin, while exhibiting the most resistance to ampicillin. A higher incidence of resistant strains was found in females than in males, indicating that antibiotic treatments should be customized according to patient characteristics, such as sex, age, existing health conditions, and prior antibiotic use. Continuous local surveillance of UPEC resistance patterns, as demonstrated in this study, is essential for guiding rational empirical prescribing, reducing treatment failures, and slowing the further emergence of resistance. Future prospective studies incorporating detailed clinical data, molecular characterization of resistance mechanisms, and community-based sampling are required to refine personalized treatment strategies, clarify the drivers of sex-specific resistance profiles, and ultimately improve clinical outcomes of urinary tract infections in our population. Declarations Ethics approval and consent to participate The experimental protocols were established approved by the ethics committee of Mazandaran University of Medical Sciences (Ethical ID: IR.MAZUMS.REC.1402.613). All methods were carried out in the accordance with relevant guidelines and regulations. Consent for publication Not applicable. Competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Data curation Faezeh Cheraghi, Mehrdad gholami Formal analysis Mohammad Karimbakhsh, Ali Ehsani, Mehrdad gholami Investigation Mohammad Karimbakhsh, Ali Ehsani, Mehrdad gholami Methodology Mohammad Karimbakhsh, Ali Ehsani, Mehrdad gholami, Faezeh Cheraghi Project administration Mehrdad gholami, Mohammad Ahanjan Resources Mohammad Karimbakhsh, Ali Ehsani, Mehrdad gholami, Faezeh Cheraghi Validation Mohammad Karimbakhsh, Ali Ehsani, Mehrdad gholami, Faezeh Cheraghi Visualization Mohammad Karimbakhsh, Ali Ehsani Writing–original draft Mohammad Karimbakhsh, Ali Ehsani, Mehrdad gholami, Faezeh Cheraghi Funding This work was funded by Mazandaran University of Medical Sciences, Sari, Iran (Grant No.: 18834). This article was extracted from the MD thesis of Faezeh Cheraghi, approved by the Immunogenetics Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Author Contribution Conceptualization: Mohammad Karimbakhsh, Ali Ehsani, Mohammad AhanjanData curation: Faezeh Cheraghi, Mehrdad gholamiFormal analysis: Mohammad Karimbakhsh, Ali Ehsani, Mehrdad gholamiInvestigation: Mohammad Karimbakhsh, Ali Ehsani, Mehrdad gholamiProject administration: Mehrdad gholami, Mohammad AhanjanResources: Mohammad Karimbakhsh, Ali Ehsani, Mehrdad gholami, Faezeh CheraghiValidation: Mohammad Karimbakhsh, Ali Ehsani, Mehrdad gholami, Faezeh CheraghiVisualization: Mohammad Karimbakhsh, Ali EhsaniWriting–original draft: Mohammad Karimbakhsh, Ali Ehsani, Mehrdad gholami, Faezeh Cheraghi Acknowledgement We wish to thank all of the staff of the Imam Khomeini, Bu-Ali Sina, Razi, Fatemeh Zahra and Zare teaching and treatment hospital for assisting in conducting this research Availability of data and materials Not applicable. References Kim DS, Lee JW. Urinary tract infection and microbiome. Diagnostics. 2023;13(11):1921. 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Impact of inappropriate empirical antibiotic treatment on clinical outcomes of urinary tract infections caused by Escherichia coli: a retrospective cohort study. J global Antimicrob Resist. 2021;26:148–53. Fatima T, Rafiq S, Iqbal A, Husnain S. Prevalence and antibiogram of MDR E. coli strains isolated from UTI patients—1-Year retrospective study at Nishtar medical hospital, Multan. SN Compr Clin Med. 2020;2(4):423–31. Edrisi S, Karimbakhsh M, Ahanjan M, Keshavarzi S, Gholami M. Presence of bla-AmpC (FOX) Gene in Klebsiella pneumoniae Isolates Collected From Different Clinical Specimens of Hospitalized Patients in North of Iran. Res Mol Med. 2024;12(1):31–8. Birgani AH, Goli HR, Siadat SD, Fateh A, Nikbin VS, Sakhaee F, et al. Virulence genes, efflux pumps, and molecular typing of Klebsiella pneumoniae isolates from North Iran. AMB Express. 2025;15(1):36. Malekzadegan Y, Khashei R, Sedigh Ebrahim-Saraie H, Jahanabadi Z. Distribution of virulence genes and their association with antimicrobial resistance among uropathogenic Escherichia coli isolates from Iranian patients. BMC Infect Dis. 2018;18(1):572. Tewawong N, Kowaboot S, Pimainog Y, Watanagul N, Thongmee T, Poovorawan Y. Distribution of phylogenetic groups, adhesin genes, biofilm formation, and antimicrobial resistance of uropathogenic Escherichia coli isolated from hospitalized patients in Thailand. PeerJ. 2020;8:e10453. Zeng Q, Xiao S, Gu F, He W, Xie Q, Yu F et al. Antimicrobial resistance and molecular epidemiology of uropathogenic Escherichia coli isolated from female patients in Shanghai, China. Frontiers in cellular and infection microbiology. 2021;11:653983. Pirouzi A, Foruozandeh H, Farahani A, Shamseddin J, Mohseni H, Abdollahi A, et al. Investigation of antimicrobial resistance pattern among Escherichia coli strains isolated from patients referred to Amir Al-Momenin Hospital, Gerash, Iran. Gene. Cell Tissue. 2020;7(1):1–6. 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Iranri","correspondingAuthor":false,"prefix":"","firstName":"Faezeh","middleName":"","lastName":"Cheraghi","suffix":""},{"id":572829358,"identity":"3723d097-33fb-4b3d-a3ea-75991ac5f781","order_by":3,"name":"Ali ehsani","email":"","orcid":"","institution":"Department of Medical Microbiology and Virology, Faculty of Medicine, Mazandaran University of Medical Sciences, Farah Abad blv, Khazar Square, Sari, Mazandaran, Iranri","correspondingAuthor":false,"prefix":"","firstName":"Ali","middleName":"","lastName":"ehsani","suffix":""},{"id":572829359,"identity":"143bbac9-5057-4c48-92aa-d989c11432f9","order_by":4,"name":"Mohammad Ahanjan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA90lEQVRIiWNgGAWjYDACCQiWY2Pm//gAyObhI1aLMT97g7EBSAsbUVqAIHFmzwEzMJugFv7Zzc8eWNTcYdxwIyGt8muOnQwbA/PDRzfwWXLnmLmBxLFnzAY3Eo7dlt2WDHQYm7FxDj5rbiSYSUiwHWYzuJHYdltyGzNQCw+bND4t8jfSv0lI/DvMY3Ajma1Ycls9YS0GN3LMJCTbDktI9hxjY/y47TBhLYY3csokJPsOG/Cz9zBLM247zsPGTMAvcjfSt0lLfDtc38bMw/jx57Zqe3725oeP8XofCJglYAweMElAOQgwfoAxfhChehSMglEwCkYeAAC6u0XolWnc+QAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Medical Microbiology and Virology, Faculty of Medicine, Mazandaran University of Medical Sciences, Farah Abad blv, Khazar Square, Sari, Mazandaran, Iranri","correspondingAuthor":true,"prefix":"","firstName":"Mohammad","middleName":"","lastName":"Ahanjan","suffix":""}],"badges":[],"createdAt":"2025-11-26 11:23:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8212293/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8212293/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":100264683,"identity":"009c362a-679c-459e-bf5a-42234286ecdb","added_by":"auto","created_at":"2026-01-14 17:56:04","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":39038,"visible":true,"origin":"","legend":"","description":"","filename":"MainManuscript.docx","url":"https://assets-eu.researchsquare.com/files/rs-8212293/v1/b67fb5c674858824989f5b87.docx"},{"id":100264684,"identity":"b07fd1e4-ee84-40aa-a45c-4d10863dd6f4","added_by":"auto","created_at":"2026-01-14 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08:12:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":881645,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8212293/v1/13549334-6af6-4246-bec7-a35d9d5aaf66.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"High Prevalence of Multidrug-Resistant Uropathogenic Escherichia coli with Marked Gender-Associated Resistance Patterns: A Retrospective Study from Northern Iran","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eUrinary tract infections (UTIs) are among the most prevalent bacterial infections globally, encompassing a wide range of conditions from simple cystitis to severe urosepsis (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Major risk factors include anatomical differences, poor personal hygiene, pregnancy, urinary obstruction, extended catheter use, urethral reflux, and spermicidal contraceptive use (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). \u003cem\u003eEscherichia coli\u003c/em\u003e (\u003cem\u003eE. coli\u003c/em\u003e) is the primary causative agent responsible for up to 90% of UTI cases, with other pathogens such as \u003cem\u003eEnterococci\u003c/em\u003e, \u003cem\u003ePseudomonas\u003c/em\u003e, \u003cem\u003eStaphylococcus saprophyticus\u003c/em\u003e, and \u003cem\u003eKlebsiella\u003c/em\u003e spp. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Five antimicrobials\u0026ndash;amoxicillin, ciprofloxacin, amoxicillin/clavulanic acid, nitrofurantoin, and trimethoprim\u0026mdash;constitute approximately 70\u0026ndash;80% of the prescriptions. Most antimicrobial therapies for UTIs are initiated empirically before the culture results are obtained (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Effective treatment of UTIs has become highly difficult because of the high resistance to commonly used antibacterial agents (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Over the past few decades, there has been a global increase in antibiotic resistance in \u003cem\u003eE. coli\u003c/em\u003e, highlighting the issue of inappropriate empirical antibiotic treatments for UTIs (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Multidrug-resistant (MDR) uropathogens result in relevant morbidity and mortality, posing a serious threat to treatment success and patient survival (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). In our country, the issue of antimicrobial resistance (AMR) is worsening due to the overuse and misuse of antibiotics. There is no systematic national surveillance of antibiotic resistance, and data to measure the problem are lacking. This report aimed to assess in vitro resistance patterns of commonly used antimicrobials. These findings will aid in the development of the most effective empirical treatment ration for UTIs. It also highlights the changes in the susceptibility patterns of the most common uropathogenic \u003cem\u003eEscherichia\u003c/em\u003e coli (UPEC), over time in this region, underscoring the need for regular monitoring to reduce therapeutic failures.\u003c/p\u003e"},{"header":"2. MATERIAL AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Bacterial culture and identification\u003c/h2\u003e \u003cp\u003eA retrospective study based on records was conducted at the Department of Microbiology, in partnership with the Microbiology Departments of Imam Khomeini, Boo-Ali Sina, Razi, Zare, and Fatemeh Zahra teaching tertiary care hospitals located in Sari, Iran. This study encompassed all culture and sensitivity (C/S) reports of urine samples from inpatients admitted to various wards of these hospitals from March 2021 until the end of 2022. Ethical clearance was obtained from the institutional ethics committee, and authorization was obtained from the head of the hospital microbiology laboratory before data collection commenced. All urine C/S reports recorded in the laboratory registers from 2021 to 2022 were examined. \u003cem\u003eE. coli\u003c/em\u003e isolates had been previously identified by the hospital microbiology laboratory using standard conventional microbiological and biochemical methods, such as colony morphology on MacConkey agar, indole positivity, and other routine biochemical tests. Reports showing positive growth of \u003cem\u003eE. coli\u003c/em\u003e were included in the study, while isolates from repeat cultures of previously included patients and those identified as commensals or contaminants were excluded from the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Data collection\u003c/h2\u003e \u003cp\u003eData were gathered from laboratory record registers, including detailed information such as patient age, sex, preliminary clinical diagnosis, sample receipt date, and comprehensive antimicrobial susceptibility outcomes. Urine culture findings and antibiotic susceptibility profiles of \u003cem\u003eE. coli\u003c/em\u003e isolates were extracted from the culture and sensitivity (C/S) reports archived in the Microbiology Department of Imam Khomeini, Boo-Ali Sina, Razi, Zare, and Fatemeh Zahra hospitals for the years 2021\u0026ndash;2022. The exclusion criteria included negative cultures, absence of culture requests, identification of other microbes, and urine samples collected after the start of empiric antibiotic treatment.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Antimicrobial susceptibility testing\u003c/h2\u003e \u003cp\u003eThe resistance profiles of \u003cem\u003eE. coli\u003c/em\u003e strains to empiric antibiotics were assessed by reviewing the susceptibility reports from urine cultures. Initially, the empiric antibiotics used to treat UTIs were identified. The antibiotics included in the susceptibility testing panel were verified to ensure that they covered the selected empiric antibiotics. Antibiotic susceptibility testing was performed according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI 2021) (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Susceptibility results for each empiric antibiotic were interpreted using established clinical breakpoints, classifying the isolates as susceptible or resistant. Resistance pattern analysis encompassed the following antibiotics: broad-spectrum penicillin, third-generation cephalosporins, quinolones, aminoglycosides, sulfonamides, carbapenems, and nitrofurantoin. All data were collected and organized annually to compare resistance pattern trends over the years. In this study, MDR strains were identified as non-susceptible to at least one agent in three or more antimicrobial categories (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). C/S reports for other common uropathogens were also be examined.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Data analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis were performed using IBM SPSS Statistics 20 (SPSS Inc., Chicago IL, USA). Descriptive statistics for continuous variables were calculated as means and standard deviations, and categorical variables were expressed as percentages. The Shapiro\u0026ndash;Wilk test was used to assess the normality of continuous variables, with a p-value of \u0026le;\u0026thinsp;0.05 indicating a non-normal distribution. The impact of \u003cem\u003eE. coli\u003c/em\u003e resistance and the presence or absence of susceptibility reporting on hospital length of stay was evaluated using a two-tailed Mann\u0026ndash;Whitney U-test. The relationship between sex and resistance was assessed using Pearson\u0026rsquo;s chi-square test. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Result","content":"\u003cp\u003eDuring the two-year study period from March 2021 to the end of 2022, 1,804 urine culture samples positive for \u003cem\u003eE. coli\u003c/em\u003e were analyzed, with each isolate obtained from a different patient. No patient contributed more than one isolate per sample. Female patients predominated, comprising 1,167 (64.7%) of the cases, whereas male patients accounted for 637 (35.3%). Age was accurately recorded for 1,627 patients in this study. The most frequent age group was 41\u0026ndash;60 years (n\u0026thinsp;=\u0026thinsp;542, 33.3% of those with recorded age), followed by other age groups. The highest antibiotic resistance rates were observed among patients with a hospital stay of 7\u0026ndash;10 days (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Patients were admitted from five tertiary care hospitals in Sari, Iran: Imam Khomeini, Boo-Ali Sina, Razi, Zare, and Fatemeh Zahra hospitals. Boo-Ali Sina Hospital contributed the largest number of isolates (n\u0026thinsp;=\u0026thinsp;1,100, 61.0%), whereas Zare Hospital had the fewest (n\u0026thinsp;=\u0026thinsp;29, 1.6%).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and clinical characteristics of the study sample (n\u0026thinsp;=\u0026thinsp;1,804)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eData available for 1,627 patients\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge categories (years)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e175 (10.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u0026ndash;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e215 (13.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e21\u0026ndash;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e160 (9.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e41\u0026ndash;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e542 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e475 (29.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMost frequent age group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41\u0026ndash;60 years (n\u0026thinsp;=\u0026thinsp;542, 33.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,167 (64.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e637 (35.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital of admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBoo-Ali Sina Hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,100 (61%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImam Khomeini Hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e413 (22.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRazi Hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e180 (10%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFatemeh Zahra Hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82 (4.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZare Hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of hospital stay with highest resistance rates\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u0026ndash;10 days\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Overall Antimicrobial Susceptibility Pattern\u003c/h2\u003e \u003cp\u003eAmong the nine most frequently tested antibiotics (\u0026ge;\u0026thinsp;1,000 isolates each), the highest susceptibility was observed against amikacin (92.0% susceptible, n\u0026thinsp;=\u0026thinsp;1,682), followed by nitrofurantoin (83.7% susceptible, n\u0026thinsp;=\u0026thinsp;1,581) and gentamicin (80.3% susceptible, n\u0026thinsp;=\u0026thinsp;1,607). High resistance rates were noted for ampicillin (93.4% resistant, n\u0026thinsp;=\u0026thinsp;1,295), ceftriaxone (66.1% resistant, n\u0026thinsp;=\u0026thinsp;1,595), cefotaxime (63.8% resistant, n\u0026thinsp;=\u0026thinsp;1,195), ciprofloxacin (63.9% resistant, n\u0026thinsp;=\u0026thinsp;1,384), and cotrimoxazole (62.4% resistant, n\u0026thinsp;=\u0026thinsp;1,506). Intermediate susceptibility was low for most agents, ranging from 0.0% to 3.2% (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAntimicrobial susceptibility of \u003cem\u003eE. coli\u003c/em\u003e isolates tested in \u0026ge;\u0026thinsp;1,000 patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntibiotic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo. tested\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSusceptible n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIntermediate n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eResistant n (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmikacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1,682\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,547 (92%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e135 (8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGentamicin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1,607\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,290 (80.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (1.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e295 (18.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCephalothin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1,595\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e505 (31.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35 (2.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1055 (66.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNitrofurantoin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1,581\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,324 (83.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e257 (16.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCotrimoxazole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1,506\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e566 (37.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e940 (62.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCeftazidime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1,482\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e615 (41.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41 (2.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e826 (55.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCiprofloxacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1,384\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e475 (34.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25 (1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e884 (63.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmpicillin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1,295\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77 (5.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (0.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,210 (93.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCefotaxime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1,195\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e395 (33.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e762 (63.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong the antibiotics tested on 100\u0026ndash;300 isolates, piperacillin-tazobactam showed favorable activity (76.6% susceptible, n\u0026thinsp;=\u0026thinsp;269), whereas nalidixic acid exhibited high resistance (76.0% resistant, n\u0026thinsp;=\u0026thinsp;258). The intermediate rates were 1.6\u0026ndash;7.8% (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAntimicrobial susceptibility patterns of antibiotics tested in 100\u0026ndash;300 isolates\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntibiotic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo. tested\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSusceptible (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIntermediate (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eResistant (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePiperacillin-tazobactam\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e269\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e76.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCefixime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e260\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e59.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNalidixic acid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e258\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmpicillin-sulbactam\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e231\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e33.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e58.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong the antibiotics tested in fewer than 100 isolates, carbapenems (imipenem and meropenem) retained high susceptibility (88.9\u0026ndash;100%, n\u0026thinsp;=\u0026thinsp;5\u0026ndash;9), while cefepime showed 49.2% resistance (n\u0026thinsp;=\u0026thinsp;59). Intermediate susceptibility varied by up to 13.6% (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAntimicrobial susceptibility patterns of selected antibiotics tested in \u0026lt;\u0026thinsp;100 isolates\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntibiotic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo. tested\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSusceptible (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIntermediate (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eResistant (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImipenem\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMeropenem\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLevofloxacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e188\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCefepime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e49.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Association between Antibiotic Resistance and Sex\u003c/h2\u003e \u003cp\u003eA significant association was observed between patient sex and resistance to most tested antibiotics (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Resistance rates were markedly higher in female patients than in male patients for most agents. Specifically, resistance to ampicillin (96.5% in females vs. 70.0% in males), ceftriaxone (81.7% vs. 32.7%), cefotaxime (86.2% vs. 27.8%), ciprofloxacin (78.0% vs. 36.8%), cotrimoxazole (78.7% vs. 35.3%), ceftazidime (86.0% vs. 17.7%), and nalidixic acid (90.0% vs. 34.5%) was significantly higher in females (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Resistance to nitrofurantoin was also significantly more common in women than in men (84.4% vs. 3.0%, p\u0026thinsp;=\u0026thinsp;0.027). In contrast, no significant sex-based differences were found for amikacin (81.5% vs. 1.6%, p\u0026thinsp;=\u0026thinsp;0.080) and gentamicin (89.8% vs. 2.3%, p\u0026thinsp;=\u0026thinsp;0.080), although resistant isolates in both antibiotics were predominantly from female patients.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation between gender and antimicrobial resistance in \u003cem\u003eE.coli\u003c/em\u003e isolates. NS\u003csup\u003e*\u003c/sup\u003e: not significant\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntibiotic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale Resistant / Tested (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale Resistant / Tested (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmpicillin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1,105/1,145 (96.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e105/150 (70%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCefotaxime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e890/1,090 (81.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e165/505 (32.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCiprofloxacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e709 / 909 (78.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e175 / 475 (36.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCotrimoxazole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e740 / 940 (78.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e200 / 566 (35.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCeftazidime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e710 / 826 (86.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e116 / 656 (17.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNalidixic acid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e180 / 200 (90.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 / 58 (34.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNitrofurantoin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e217 / 257 (84.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 / 1,324 (3.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGentamicin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e265 / 295 (89.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 / 1,312 (2.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.080 (NS\u003csup\u003e*\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmikacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e110 / 135 (81.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 / 1,547 (1.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.080 (NS\u003csup\u003e*\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Summary of Empirical Antibiotic Coverage\u003c/h2\u003e \u003cp\u003eOf the 1,804 isolates, 122 (6.8%) lacked sensitivity reports, and 189 (10.5%) involved antibiotics that did not cover \u003cem\u003eE. coli\u003c/em\u003e. Among tested agents, 1,476 (81.8%) isolates were susceptible to at least one commonly prescribed empiric antibiotic, while 1,493 (82.8%) showed resistance to one or more key empiric agents (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of antibiotic sensitivity and resistance patterns of \u003cem\u003eE. coli\u003c/em\u003e isolates to commonly prescribed empiric antibiotics (n\u0026thinsp;=\u0026thinsp;1,804)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntibiotics without sensitivity reports\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e122 (6.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntibiotics not covering E. coli\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e189 (10.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAntibiotics to which E. coli is sensitive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNitrofurantoin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,324 (83.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmikacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,547 (92%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGentamicin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,290 (80.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePiperacillin-tazobactam\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e206 (76.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCarbapenems (imipenem/meropenem)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (92.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAntibiotics to which E. coli is resistant\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmpicillin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,210 (93.45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCeftiaxone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,055 (66.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCefotaxime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e762 (63.85)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCiprofloxacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e884 (63.95)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCotrimoxazole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e940 (62.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCeftazidime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e826 (55.75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":" \u003cp\u003eThis study revealed alarming levels of AMR among UPEC isolates recovered from hospitalized patients in five tertiary care hospitals in Sari, northern Iran, during 2021\u0026ndash;2022. More than 70% of the 1,804 analyzed isolates were MDR, and resistance to most first- and second-line empiric agents exceeded 60%. These findings confirm the continuing deterioration of therapeutic options for UTIs in this region and highlight the marked sex-associated differences in resistance patterns.\u003c/p\u003e \u003cp\u003eIn our study, the highest rate of AMR was observed against ampicillin (93.4%), whereas the lowest resistance was observed against amikacin (8%). In comparison, Malekzadegan et al. reported the highest resistance to ampicillin (88.9%) and the lowest resistance to imipenem (0.8%) (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). In the present study, the highest antimicrobial resistance rates were observed in reducing order against ampicillin (93.4%), ciprofloxacin (63.9%), and co-trimoxazole (62.4%). Likewise, Tewawong et al., reported resistance rates of 84.1%, 65.4%, and 54.3% to the same three agents, respectively, indicating that the observed hierarchy of resistance (ampicillin\u0026thinsp;\u0026gt;\u0026thinsp;\u0026gt;\u0026thinsp;ciprofloxacin\u0026thinsp;\u0026asymp;\u0026thinsp;co-trimoxazole) is a widespread phenomenon in many low- and middle-income settings (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). In the study by Zeng et al., more than 95% of isolates exhibited susceptibility to piperacillin-tazobactam, whereas in our study, the susceptibility rate to this agent was 76.6% (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). One of the most striking findings was a pronounced sex disparity in resistance profiles. Female patients exhibited significantly higher resistance rates to nearly all tested agents, with the most dramatic differences observed for ciprofloxacin (78.0% vs. 36.8%), ceftriaxone (81.7% vs. 32.7%), cefotaxime (86.2% vs. 27.8%), cotrimoxazole (78.7% vs. 35.3%), and even nitrofurantoin (84.4% susceptible in females vs. 3.0% resistance in males, p\u0026thinsp;=\u0026thinsp;0.027). This pattern cannot be explained by differences in hospital stay duration alone, as resistance peaked in the 7\u0026ndash;10-day stay group, regardless of sex. The higher resistance burden in females most likely reflects greater previous exposure to antibiotics for recurrent or complicated UTIs, frequent use of broad-spectrum agents in obstetric/gynecological settings, and possibly the community circulation of highly resistant clones among women. These observations strongly argue for gender-stratified empiric treatment guidelines in our region: while nitrofurantoin and aminoglycosides remain reasonable first-line choices for uncomplicated UTIs in females, alternative agents or early culture-guided therapy should be considered in males only when the risk of resistance is deemed low.\u003c/p\u003e \u003cp\u003eIn the current study, the highest susceptibility rates were observed in diminishing order against amikacin (92%), nitrofurantoin (83.75%), and gentamicin (80.3%). In contrast, Pirouzi et al., reported the highest susceptibility rates in declining order effective against nitrofurantoin (81%), gentamicin (73.9%), and amikacin (71.9%) (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). The pattern of resistance to antimicrobial agents identified in this study is very similar to that found in earlier regional studies, showing consistently high resistance to ampicillin while maintaining relatively good susceptibility to amikacin, nitrofurantoin, and gentamicin. However, the significantly reduced susceptibility to piperacillin-tazobactam compared to that in some previous reports highlights the need for continued monitoring.\u003c/p\u003e"},{"header":"5. Limitation","content":"\u003cp\u003eThis study had several limitations inherent to its retrospective design. First, data were collected from the laboratory registers of hospitalized patients only; community-acquired UTIs were not represented, which may have overestimated resistance rates. Second, clinical details such as previous antibiotic exposure, recurrence of UTI, presence of urinary catheters, pregnancy status, and underlying comorbidities were not systematically recorded and could not be analyzed as potential confounders of the observed sex differences. Third, molecular characterization of resistance mechanisms (e.g., ESBL, AmpC, and carbapenemase production) and phylogenetic grouping were not performed, limiting insight into the genetic basis of the high MDR prevalence and sex-associated patterns. Finally, carbapenems and some other reserve agents were tested in very few isolates, preventing reliable conclusions about their true activities in this population. Prospective studies incorporating detailed clinical metadata and genomic analyses are warranted to address these gaps.\u003c/p\u003e"},{"header":"6. Conclusion","content":" \u003cp\u003eMonitoring antibiotic resistance is crucial in combating AMR. \u003cem\u003eE. coli\u003c/em\u003e isolates from UTIs highlighted the greatest sensitivity to amikacin and nitrofurantoin, while exhibiting the most resistance to ampicillin. A higher incidence of resistant strains was found in females than in males, indicating that antibiotic treatments should be customized according to patient characteristics, such as sex, age, existing health conditions, and prior antibiotic use. Continuous local surveillance of UPEC resistance patterns, as demonstrated in this study, is essential for guiding rational empirical prescribing, reducing treatment failures, and slowing the further emergence of resistance. Future prospective studies incorporating detailed clinical data, molecular characterization of resistance mechanisms, and community-based sampling are required to refine personalized treatment strategies, clarify the drivers of sex-specific resistance profiles, and ultimately improve clinical outcomes of urinary tract infections in our population.\u003c/p\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003eThe experimental protocols were established approved by the ethics committee of Mazandaran University of Medical Sciences (Ethical ID: IR.MAZUMS.REC.1402.613). All methods were carried out in the accordance with relevant guidelines and regulations.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eConsent for publication\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCompeting interests\u003c/strong\u003e \u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eData curation\u003c/h2\u003e \u003cp\u003eFaezeh Cheraghi, Mehrdad gholami\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eFormal analysis\u003c/strong\u003e \u003cp\u003eMohammad Karimbakhsh, Ali Ehsani, Mehrdad gholami\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eInvestigation\u003c/strong\u003e \u003cp\u003eMohammad Karimbakhsh, Ali Ehsani, Mehrdad gholami\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eMethodology\u003c/strong\u003e \u003cp\u003eMohammad Karimbakhsh, Ali Ehsani, Mehrdad gholami, Faezeh Cheraghi\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eProject administration\u003c/strong\u003e \u003cp\u003eMehrdad gholami, Mohammad Ahanjan\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eResources\u003c/strong\u003e \u003cp\u003eMohammad Karimbakhsh, Ali Ehsani, Mehrdad gholami, Faezeh Cheraghi\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eValidation\u003c/strong\u003e \u003cp\u003eMohammad Karimbakhsh, Ali Ehsani, Mehrdad gholami, Faezeh Cheraghi\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eVisualization\u003c/strong\u003e \u003cp\u003eMohammad Karimbakhsh, Ali Ehsani\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eWriting\u0026ndash;original draft\u003c/strong\u003e \u003cp\u003eMohammad Karimbakhsh, Ali Ehsani, Mehrdad gholami, Faezeh Cheraghi\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis work was funded by Mazandaran University of Medical Sciences, Sari, Iran (Grant No.: 18834). This article was extracted from the MD thesis of Faezeh Cheraghi, approved by the Immunogenetics Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceptualization: Mohammad Karimbakhsh, Ali Ehsani, Mohammad AhanjanData curation: Faezeh Cheraghi, Mehrdad gholamiFormal analysis: Mohammad Karimbakhsh, Ali Ehsani, Mehrdad gholamiInvestigation: Mohammad Karimbakhsh, Ali Ehsani, Mehrdad gholamiProject administration: Mehrdad gholami, Mohammad AhanjanResources: Mohammad Karimbakhsh, Ali Ehsani, Mehrdad gholami, Faezeh CheraghiValidation: Mohammad Karimbakhsh, Ali Ehsani, Mehrdad gholami, Faezeh CheraghiVisualization: Mohammad Karimbakhsh, Ali EhsaniWriting\u0026ndash;original draft: Mohammad Karimbakhsh, Ali Ehsani, Mehrdad gholami, Faezeh Cheraghi\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe wish to thank all of the staff of the Imam Khomeini, Bu-Ali Sina, Razi, Fatemeh Zahra and Zare teaching and treatment hospital for assisting in conducting this research\u003c/p\u003e\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKim DS, Lee JW. Urinary tract infection and microbiome. Diagnostics. 2023;13(11):1921.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhalil A, Raja I, Hussain I, Jan M, Nafees MA, Jahan Z et al. Prevalence of Escherichia coli in suspected urinary tract infected patients and their sensitivity pattern against various antibiotics in Gilgit-Baltistan, Pakistan. Pakistan J Zool. 2014;46(6).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharma N, Gupta A, Walia G, Bakhshi R. Pattern of antimicrobial resistance of Escherichia coli isolates from urinary tract infection patients: A three year retrospective study. J Appl Pharm Sci. 2016;6(1):062\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcCowan C, Bakhshi A, McConnachie A, Malcolm W, Barry SJ, Santiago VH, et al. E. coli bacteraemia and antimicrobial resistance following antimicrobial prescribing for urinary tract infection in the community. BMC Infect Dis. 2022;22(1):805.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVazouras K, Velali K, Tassiou I, Anastasiou-Katsiardani A, Athanasopoulou K, Barbouni A, et al. Antibiotic treatment and antimicrobial resistance in children with urinary tract infections. J global Antimicrob Resist. 2020;20:4\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhu H, Chen Y, Hang Y, Luo H, Fang X, Xiao Y, et al. Impact of inappropriate empirical antibiotic treatment on clinical outcomes of urinary tract infections caused by Escherichia coli: a retrospective cohort study. J global Antimicrob Resist. 2021;26:148\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFatima T, Rafiq S, Iqbal A, Husnain S. Prevalence and antibiogram of MDR E. coli strains isolated from UTI patients\u0026mdash;1-Year retrospective study at Nishtar medical hospital, Multan. SN Compr Clin Med. 2020;2(4):423\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEdrisi S, Karimbakhsh M, Ahanjan M, Keshavarzi S, Gholami M. Presence of bla-AmpC (FOX) Gene in Klebsiella pneumoniae Isolates Collected From Different Clinical Specimens of Hospitalized Patients in North of Iran. Res Mol Med. 2024;12(1):31\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBirgani AH, Goli HR, Siadat SD, Fateh A, Nikbin VS, Sakhaee F, et al. Virulence genes, efflux pumps, and molecular typing of Klebsiella pneumoniae isolates from North Iran. AMB Express. 2025;15(1):36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMalekzadegan Y, Khashei R, Sedigh Ebrahim-Saraie H, Jahanabadi Z. Distribution of virulence genes and their association with antimicrobial resistance among uropathogenic Escherichia coli isolates from Iranian patients. BMC Infect Dis. 2018;18(1):572.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTewawong N, Kowaboot S, Pimainog Y, Watanagul N, Thongmee T, Poovorawan Y. Distribution of phylogenetic groups, adhesin genes, biofilm formation, and antimicrobial resistance of uropathogenic Escherichia coli isolated from hospitalized patients in Thailand. PeerJ. 2020;8:e10453.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeng Q, Xiao S, Gu F, He W, Xie Q, Yu F et al. Antimicrobial resistance and molecular epidemiology of uropathogenic Escherichia coli isolated from female patients in Shanghai, China. Frontiers in cellular and infection microbiology. 2021;11:653983.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePirouzi A, Foruozandeh H, Farahani A, Shamseddin J, Mohseni H, Abdollahi A, et al. Investigation of antimicrobial resistance pattern among Escherichia coli strains isolated from patients referred to Amir Al-Momenin Hospital, Gerash, Iran. Gene. Cell Tissue. 2020;7(1):1\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Uropathogenic Escherichia coli, Antimicrobial resistance, Urinary tract infection, Multidrug-resistant E. coli","lastPublishedDoi":"10.21203/rs.3.rs-8212293/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8212293/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eUrinary tract infections (UTIs) are among the most common bacterial infections worldwide, with \u003cem\u003eEscherichia coli\u003c/em\u003e (E. coli) accounting for up to 90% of cases. Risk factors include anatomical differences, poor hygiene, pregnancy, urinary obstruction, catheter use, urethral reflux, and spermicidal contraceptives. Common empiric treatments include amoxicillin, ciprofloxacin, amoxicillin/clavulanic acid, nitrofurantoin, and trimethoprim, but increasing antimicrobial resistance (AMR) complicates therapy. This study aimed to evaluate in vitro resistance patterns of common antimicrobials against uropathogenic \u003cem\u003eE. coli\u003c/em\u003e (UPEC) and assess trends over time to inform empiric treatment strategies and reduce failures.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective, record-based study analyzed culture and sensitivity (C/S) reports of urine samples from inpatients at Imam Khomeini, Boo-Ali Sina, Razi, Zare, and Fatemeh Zahra hospitals in Sari, Iran, from March 2021 to the end of 2022. Ethical approval and laboratory permission were obtained. \u003cem\u003eE. coli\u003c/em\u003e was identified using standard microbiological and biochemical methods. Antimicrobial susceptibility testing used the Kirby-Bauer disk diffusion method on Mueller-Hinton agar per CLSI 2021 guidelines, testing penicillins, cephalosporins, quinolones, aminoglycosides, sulfonamides, carbapenems, and nitrofurantoin. Data were compiled year-wise, with statistical analysis via IBM SPSS version 20.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOf 1,804 \u003cem\u003eE. coli\u003c/em\u003e-positive isolates, 64.7% were from females and 35.3% from males; age was recorded for 1,627 patients, with 41\u0026ndash;60 years most frequent (33.3%). Highest susceptibility was to amikacin (92.0%), nitrofurantoin (83.7%), and gentamicin (80.3%); highest resistance to ampicillin (93.4%), ceftriaxone (66.1%), ciprofloxacin (63.9%), cefotaxime (63.8%), and cotrimoxazole (62.4%). Resistance was significantly higher in females for most agents, including ciprofloxacin (78.0% vs. 36.8%) and nitrofurantoin (84.4% vs. 3.0%, p\u0026thinsp;=\u0026thinsp;0.027). Over 70% of isolates were MDR. Intermediate susceptibility was low (0.0-3.2%). Highest resistance rates occurred in patients with 7\u0026ndash;10 day hospital stays.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eHigh AMR in UPEC, particularly to empiric agents, underscores therapeutic challenges. Gender differences suggest tailored approaches for females. Regular surveillance is essential to optimize empiric therapy, minimize failures, and curb MDR spread in this region.\u003c/p\u003e","manuscriptTitle":"High Prevalence of Multidrug-Resistant Uropathogenic Escherichia coli with Marked Gender-Associated Resistance Patterns: A Retrospective Study from Northern Iran","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-14 17:55:57","doi":"10.21203/rs.3.rs-8212293/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7a195710-5cb4-4903-bca5-e1fda3d88d36","owner":[],"postedDate":"January 14th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-14T17:56:02+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-14 17:55:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8212293","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8212293","identity":"rs-8212293","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}