Effectiveness of Selective Antibiotics Use in Esbl-Related UTIs.

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Kasun Prabuddha Aththanayaka, Yasoda Hansani Weerasinghe, Nimsha Sevwandika Weerakkody, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4535041/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Sep, 2024 Read the published version in BMC Microbiology → Version 1 posted 24 You are reading this latest preprint version Abstract Background – Urinary tract infections (UTIs) are the second most common infection, affecting 150 million people each year worldwide. Enterobacteriaceae species expressing extended-spectrum β-lactamases (ESBLs) are on the rise across the globe and are becoming a severe problem in the therapeutic management of clinical cases of urinary tract infection. Knowledge of the prevalence and antibiogram profile of such isolates is essential to develop an appropriate treatment methodology. This study aimed to investigate the prevalence of Enterobacteriaceae isolates exhibiting ESBL and their selective oral antibiogram profile at the district general hospital, Polonnaruwa. Results - A total of 4386 urine specimens received to the Microbiology Laboratory during the study period. Among them, 1081 (25%) showed positive results for urine culture while 200/1081 specimens showed ESBL isolates. Out of the selected 200 specimen’s majority (72%) of samples received from the In-Patient Department. There were 200 patients and reported that 115 (58%) were females and 85 (42%) were males. The majority (51%) of the patients belong to the age group of 55–74 years. Among the ESBLs positive specimens, the majority 74.5% (n = 149) identified organisms were E. coli followed by Klebsiella spp.17.5% (n = 35), Enterobacteriaceae 7% (n = 14) and only1% (n = 2) isolate of Proteus spp. Mecillinam (86.30%) and Nitrofurantoin (83.56%) showed higher effectiveness against E. coli . Nitrofurantoin showed the highest effectiveness against Klebsiella spp. (31.58%), other Enterobacteriaceae spp. (79%). Proteus spp. showed 100% effectiveness and resistance respectively against Ciprofloxacin, Cotrimoxazole and Nitrofurantoin. Conclusion - The most predominant ESBLs producing uro-pathogen was the E. coli in the study setting and E. coli had higher sensitivity rate against Mecillinam. Among currently used oral antibiotics Nitrofurantoin was the best choice for UTIs caused by ESBL producers. Escherichia coli Proteus spp. Klebsiella spp. Enterobacteriaceae Extended spectrum β-lactamase Urinary tract infection Figures Figure 1 Figure 2 1. Background Urinary Tract Infection (UTI) is the most common bacterial infection prevalent in both females and males. The incidence is more frequent in women than men due to shortness of urethra, easy contamination with fecal flora, and pregnancy [ 1 , 2 ]. Mostly, neonates, girls, young women, infants, young children, and older men are mainly vulnerable to UTIs [ 3 ]. Escherichia coli ( E. coli ) is the most frequent uropathogen accounting for 70–80% of cases of acute uncomplicated lower UTIs [ 4 ]. However, Klebsiella spp, Proteus spp, and Pseudomonas spp. are also reported as uropathogen which cause uncomplicated UTIs [ 5 ]. Extended-spectrum beta-lactamases (ESBLs) are plasmid-mediated enzymes [ 6 ] produced by the Enterobacteriaceae family, Klebsiella pneumoniae , and E. coli . Other Enterobacteriaceae, non-fermenting bacteria, Acinetobacter spp., and Pseudomonas spp. also produce ESBLs but the prevalence rate is low [ 5 ]. ESBLs are hydrolyzed and inactivated beta-lactam antibiotics, rendering them ineffective in treating infections caused by ESBLs-producing bacteria [ 7 ]. It’s responsible for the increasing antibiotic resistance globally to UTIs. Major risk factors of UTIs produced by ESBLs positive uropathogens are patients with numerous comorbidities, diabetes, long stay in nursing homes, frequent use of antibiotics, recurrent UTIs, older age, sex (male), and intravenous treatments or urinary tract abnormalities [ 7 ]. According to a WHO report published in 2021, ESBLs-producing Enterobacteriaceae are part of the group posing the highest risk to public health [ 8 ]. The increasing isolation of ESBLs-producing bacteria causing UTIs worldwide due to the failure of empirical therapy which may result in serious clinical complications such as sepsis, renal scarring, and prolonged hospitalization, compared to infection with non-ESBL strains [ 9 ]. Hence, ESBL producers have become a major multidrug-resistant pathogen, and several significant changes in ESBL-producing isolates have been witnessed worldwide in the last two decades [ 10 ]. Therefore ESBL production is needed to guide appropriate antimicrobial therapy [ 11 ] and minimize the risk of developing resistance to certain drugs soon [ 12 ]. Identification of drug-resistant microorganisms and available oral treatment options are essential for choosing an appropriate antibiotic that would enable to avoid the waste of time, and high medical costs and reduce the potential complications or rate of mortality. Further, that may reduce the development of multidrug-resistant bacteria [ 13 ]. 2. Methodology A total of 200 patients with positive urine cultures for ESBL-producing bacteria and suggestive of having UTI were enrolled in the study. The recruitment of patients was done by the Consultant Microbiologist at District General Hospital Polonnaruwa, depending on the clinical symptoms and medical history of the patients. Urine specimens were processed according to the standard guidelines [ 6 ]. On the first day of the samples receiving macroscopic appearance, culture on CLED (Cystine Lactose Electrolyte Deficient Agar) media and wet film examination were conducted. On the following day, culture plates were observed and gram stained and biochemical tests were conducted accordingly to identify the bacterial species. The uropathogen were grown on Hi-Crome UTI agar was presumptively identified based on the different contrasted colony colors produced by reactions of genus or species-specific enzymes and chromogenic substrates according to the manufacturer’s instructions. ESBL production was identified using the CLSI disc diffusion method, noting specific zone diameters that indicate a high level of suspicion for ESBL production using Cefpodoxime (10µg), Ceftazidime (30µg), Aztreonam (30µg), Cefotaxime (30µg), or Ceftriaxone (30µg) antibiotics. However, the use of more than one of these agents for screening improves the sensitivity of detection. Zone diameters indicate ESBL production. Antimicrobial susceptibility testing (AST) was performed using the standardized Kirby-Bauer disk diffusion method for Ciprofloxacin 10 µg, Nitrofurantoin 300 µg, Mecillinam 10 µg, Cotrimoxazole and interpretation was done following the CLSI guidelines, 2021. Statistical software SPSS version 21.0 was used for statistical analysis and calculations of the data set. The p values less than 0.05 were considered as statistical significance. 3. Results A total of 4386 urine specimens were received at the Microbiology Laboratory during the sample collection period of 1st April to 31st July 2023. Out of the 4386 specimens, 1081(24.6%) specimens showed culture-positive results with more than 10 5 CFU/ml. Among these culture-positive urine specimens, 200 (185%) specimens showed ESBLs producing uropathogens. The majority 143 (71.5%) specimens received from the inward departments (IWD) while 57 (28.5%) specimens received from the Out-Patient Departments (OPD). There were 200 patients and reported 115 (57.5%) were females and 85 (42.5%) were males. Frequency of UTI infection according to gender and age are shown in Fig. 1 . The highest number of patients reported ESBL producers in between the age category of 55–74 years while the majority were females (Fig. 1 ). Among the 200 ESBLs positive specimens, majority 74.5% (149/200) were E. coli followed by Klebsiella spp.17.5% (35/200), Enterobacteriaceae 7% (14/200) and only1% (2/200) isolate of Proteus spp. Number of cases according to the organism type and the age category (Child 14 years) [37] is tabulated in Table 1 . Table 1 Frequency of the isolated uropathogens according to the age Uro-pathogen UTI patient with ESBLS producer Statistic Total Adult Children E. coli 149 129 (86.6%) 20 (13.4%) χ2 = 2.17 p = 0.537 Klebsiella spp. 35 33 (94.3%) 2 (5.7%) Proteus spp. 2 2 (100%) 0 (0.0%) Enterobacteriaceae 14 14 (100%) 0 (0.0%) Total 200 178 22 (Chi-squared test was used to analyze data) ESBL producers showed highest effectiveness against Mecillinam (89%) and least effectiveness against Ciprofloxacin. Antibiotic susceptibility is shown in Table 2 . The E. coli showed the highest sensitivity toward Nitrofurantoin and Mecillinam (83.2%) and (87.9%) respectively. Klebsiella spp. showed resistance to all three antibiotics including Ciprofloxacin (88.5%), Cotrimoxazole (88.5%), and Nitrofurantoin (60.0%). Further, Proteus spp. showed (100%) sensitivity to both Ciprofloxacin and Cotrimoxazole and 100% resistance to Nitrofurantoin. Other Gram-Negative isolates showed 100%sensitivity to Nitrofurantoin and 100% resistance to Ciprofloxacin and Cotrimoxazole. Table2. Antibiotic susceptibility according to the organism type Antibiotics Susceptibility Organisms E. coli Klebsiella spp. Proteus spp. Other coliforms Ciprofloxacin Sensitive 31 (20.8%) 4 (11.4%) 2 (100%) 0 Resistance 118 (79.1%) 31 (88.6%) 0 14 (100%) Nitrofurantoin Sensitive 124 (83.2%0 14 (40%) 0 14 (100%) Resistance 25 (16.8%) 21 (60%) 2(100%) 0 Cotrimoxazole Sensitive 40 (26.8%) 4 (11.4%) 2 (100%) 0 Resistance 109 (73.2%) 31 (88.6%) 0 14 (100%) Mecillinam Sensitive 131 (87.9%) - - - Resistance 18 (12.1%) - - - 4. Discussion The present study revealed that most of the UTI patients reported from inward departments of the hospital while only a limited number of cases were reported from outpatient departments, suggestive of hospital-acquired infection of ESBLs producing Enterobacteriaceae. The urine-positive culture-positive rate was reported as 24.6%. Similar results have been reported by Shakya et al. , 2017 in Nepal of 20.41% positive urine cultures out of 2029 non-repetitive mid-stream urine specimens. Yadav and Prakash, 2017 reported a 62.9% rate of urine culture positivity. In contrast, a very low percentage of urine culture positivity was reported at 6.52% in Iran [ 17 ]. These differences may be due to geographical area, time, and the diagnostic technique used [ 18 ]. Increasing coliform production of ESBLs is a global healthcare concern because of increasing antibiotic resistance and restricted treatment options [ 19 ]. In the present study, ESBL production was found in 18.5% (200/1081) in Polonnaruwa District. Another study done in different districts of Sri Lanka reported 28% and 33% in Colombo (2012), and 40% in Galle (2016) [ 15 , 20 ]. Comparatively in Sri Lanka, the rate of ESBLs producing isolation has changed with time and location. In 2019 the Centre for Disease Control and Prevention (CDC) reported that the global prevalence rate of ESBL production by coliforms has increased by 50% between 2012 and 2017 in the United States [ 25 ]. A similar study for Monitoring Antimicrobial Resistance Trends (SMART) observed the prevalence of urinary tract infections caused by ESBLs producing E. coli to increase from 7.8 to 18.3% between 2010 and 2014 in the US [ 26 ]. The ESBL-producing E.coli isolation rates increased at a faster rate in healthcare-associated settings than in the community between 2014 and 2020 in the USA[ 27 ]. Females are more prone to have UTI infections than males depending on several factors such as the anatomical structure of the urethra, hormonal imbalances, and behavioral changes. The present study also reported higher incidences of UTI in females compared to males. The present study reported that many of the UTI patients belong to the age category of 55–74 years. Many studies have reported that immune-compromised patients, elderly patients, diabetes mellitus patients, and those who are taking chemotherapy and prolonged antibiotic treatments are more prone to develop UTIs than the other populations. Similarly, Gharavi et al. , 2021 reported that the age groups of 60–75 (20.11%) and 45–60 (18%) years were frequently infected with uropathogens. The least number of patients were found in the age group 15–34 years (9%) and children (12%). The E. coli found to be the most predominant ESBLs producing uropathogens in this study. These results are in line with the previous studies conducted by Raja et al. , in 2019 and Liu et al. , in 2022 who reported E. coli isolation rates as 90% and 73.3% respectively. The members of the Enterobacteriaceae family, E. coli and Klebsiella spp. are identified as common causative agents of UTIs as they possess several factors including adhesion, pili, fimbriae, and P1 blood group genotype receptor, which contribute to the attachment of bacteria to the urothelium [ 31 ]. The development of novel antimicrobials is not keeping up with developing resistance, from this time it is necessary to re-evaluate and revive overlooked and older antimicrobials. Fosfomycin, Colistin, Rifampicin, and Polymyxin B are some of the older revived antimicrobials that are used effectively these days for the treatment of superbugs. Mecillinam is an Amido penicillin with selective and good activity against Gram-negative isolates. Many European and Scandinavian countries have recently included Mecillinam in their empirical treatment guidelines, especially for the treatment of community-based urinary tract Infections (UTIs). Many studies from Belgium, the United Kingdom, France, and Norway have reported good in vitro as well as In vivo activity of Mecillinam against extended-spectrum beta-lactamase-producing Gram-negative isolates. The important prospective benefits of Mecillinam are that it is available as an oral prodrug, it has a suitable twice-daily dosage regimen, it replaces carbapenems and its use is less associated with a high risk of Clostridium difficile associated diarrhea [38]. In ourstudy, Mecillinam identified as the most effective antibiotic against E. coli. Similarly, Raja et al. , 2019 and Kresken et al. , 2022 reported Mecillinam sensitivity toward E. coli was 96% and 86.3% respectively. 5. Conclusion In the present study, E. coli was the most predominant ESBL-producing uropathogen with the highest sensitivity towards Mecillinam. Among currently used oral antibiotics Nitrofurantoin is the best choice for UTIs caused by ESBL producers. Abbreviations E. coli: Escherichia coli UTI: Urinary Tract Infection ESBL: Extended Spectrum of Beta-Lactamase CDC: Disease Control and Prevention IWD: Inward Department OPD: Out-Patients Department Declarations Acknowledgments We thank all academic and non-academic staff members of The open university, Nawala, Sri Lanka, and Teaching Hospital, Polonnaruwa. Authors’ contributions This work was performed as a collaboration among all the authors. All the authors read and approved the final manuscript. Availability of data and materials Data are available upon request from the authors. Ethical approval and consent to participate. The study was approved by the Ethical Review Committee of the Teaching Hospital, Polonnaruwa, and (DGHP/ERC/2023/01). A letter of authorization was obtained from Teaching hospital, Polonnaruwa before data collection . Consent for publication Not applicable. Competing interests The authors declare that they have no competing interest. References Yadav K, Prakash S. Screening of ESBL Producing Multidrug Resistant E. coli from Urinary Tract Infection Suspected Cases in Southern Terai of Nepal. J Infect Dis Diagnosis. 2017;02(02). 10.4172/2576-389x.1000116 . Tula A, Mikru A, Alemayehu T, Dobo B. Bacterial Profile and Antibiotic Susceptibility Pattern of Urinary Tract Infection among Pregnant Women Attending Antenatal Care at a Tertiary Care Hospital in Southern Ethiopia, Can. J. Infect. Dis. Med. Microbiol., vol. 2020, 2020, 10.1155/2020/5321276 . Yadav K, Prakash S, Serayi R, Shilpkar T, Shrestha S. Antimicrobial susceptibility test of pathogens isolated from urinary tract infection suspected cases. Janaki Med Coll J Med Sci. 2014;2(1):28–34. 10.3126/jmcjms.v2i1.11393 . Care P. Resistance to Mecillinam and Nine Other Antibiotics for Oral Use in Escherichia coli Isolated from Urine Specimens of, 2022. Priyadharshana U, Piyasiri LB, Wijesinghe C. Prevalence, antibiotic sensitivity pattern and genetic analysis of extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella spp among patients with community acquired urinary tract infection in Galle district, Sri Lanka. Ceylon Med J. Dec. 2019;64(4):140. 10.4038/cmj.v64i4.8990 . Liu H, Qiu S, Chen M, Lyu J, Yu G, Xue L. A clinical prediction tool for extended-spectrum β-lactamase-producing Enterobacteriaceae urinary tract infection. BMC Infect Dis. 2022;22(1):1–13. 10.1186/s12879-022-07040-y . Aboumarzouk OM. Extended spectrum beta – lactamase urinary tract infections, 6, 2, pp. 2012–3, 2014. Naushad VA et al. Epidemiology of urinary tract infection in adults caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae – a case–control study from Qatar, IJID Reg., vol. 3, no. May, pp. 278–286, 2022, 10.1016/j.ijregi.2022.05.001 . Mandracchia VJ, Hayes DW, Yoho RM, Hayes MF. Diagnosis, Differential and Treatment Options. Nat Rev Microbiol. 2016;13:34. 10.1038/nrmicro3432.Urinary . Doi Y, Iovleva A, Bonomo RA. The ecology of extended-spectrum b-lactamases (ESBLs) in the developed world. J Travel Med. 2017;24:44–51. 10.1093/jtm/taw102 . Aggarwal A, et al. Clinical & immunological erythematosus patients characteristics in systemic lupus Maryam. J Dent Educ. 2012;76(11):1532–9. 10.4103/ijmr.IJMR . Li B, Webster TJ. Bacteria antibiotic resistance: New challenges and opportunities for implant-associated orthopedic infections. J Orthop Res. 2018;36(1):22–32. 10.1002/jor.23656 . Bryce A, Hay AD, Lane IF, Thornton HV, Wootton M, Costelloe C. Global prevalence of antibiotic resistance in paediatric urinary tract infections caused by Escherichia coli and association with routine use of antibiotics in primary care: Systematic review and meta-analysis, BMJ (Online), vol. 352. BMJ Publishing Group, Mar. 15, 2016. 10.1136/bmj.i939 . Behzadi Payam AP, Elham B, Edyta A. Hic-14-14, 14, pp. 1–12, 2019. Dissanayake D, Fernando S, Chandrasiri N. The distribution and characteristics of Extended-Spectrum β-Lactamase producing Escherichia coli and Klebsiella species among urinary isolates in a tertiary care hospital. Sri Lankan J Infect Dis. Aug. 2012;2(2):30. 10.4038/sljid.v2i2.4235 . Shakya P, Shrestha D, Maharjan E, Sharma VK, Paudyal R. ESBL Production Among E. coli and Klebsiella spp. Causing Urinary Tract Infection: A Hospital Based Study. Open Microbiol J. 2017;11(1):23–30. 10.2174/1874285801711010023 . Gharavi MJ, Zarei J, Roshani-Asl P, Yazdanyar Z, Sharif M, Rashidi N. Comprehensive study of antimicrobial susceptibility pattern and extended spectrum beta-lactamase (ESBL) prevalence in bacteria isolated from urine samples. Sci Rep. 2021;11(1):1–11. 10.1038/s41598-020-79791-0 . Nanoty VV, Agrawal GN, Tankhiwale SS. Evaluation of Antibiotic Resistance and β- lactamase Production in Clinical Isolates from a Tertiary Care Hospital in Central India. J Clin Basic Res. 2018;2(1):1–5. 10.29252/jcbr.2.1.1 . Falodun OI, Morakinyo YM, Fagade OE. Determination of water quality and detection of Extended Spectrum Beta-Lactamase producing Gram-negative bacteria in selected rivers located in Ibadan, Nigeria. Jordan J Biol Sci. 2018;11(1):107–12. Tillekeratne LG, et al. Extended-spectrum β-lactamase-producing Enterobacteriaceae as a common cause of urinary tract infections in Sri Lanka. Infect Chemother. 2016;48(3):160–5. 10.3947/ic.2016.48.3.160 . Habeeb MA, Sarwar Y, Ali A, Salman M, Haque A. Rapid emergence of ESBL producers in E. coli causing urinary and wound infections in Pakistan. Pakistan J Med Sci. 2013;29(2):540–4. 10.12669/pjms.292.3144 . Mukherjee M, Basu S, MuKherjee SKM, Majumder M. Multidrug-resistance and extended spectrum beta-lactamase production in uropathogenic E. coli which were isolated from hospitalized patients in Kolkata, India. J Clin Diagn Res. 2013;7(3):449–53. 10.7860/JCDR/2013/4990.2796 . Nandagopal B, et al. Frequency of extended spectrum β-lactamase producing urinary isolates of Gram-negative bacilli among patients seen in a multispecialty hospital in Vellore district, India. Indian J Med Microbiol. 2015;33(2):282–5. 10.4103/0255-0857.153563 . Chander A, Shrestha CD. Prevalence of extended spectrum beta lactamase producing Escherichia coli and Klebsiella pneumoniae urinary isolates in a tertiary care hospital in Kathmandu, Nepal. BMC Res Notes. 2013;6(1). 10.1186/1756-0500-6-487 . CDC. Antibiotic Resistance Threats in The United States 2019, Cdc, vol. 10, no. 1, 2019, 10.1186/s13756-020-00872-w . Ontario P. Trends in the Rates of Extended-Spectrum- b -Lactamase-Producing Enterobacterales Isolated from Urine Cultures during the COVID-19, 2021. Raphael E, Glymour MM, Chambers HF. Trends in prevalence of extended-spectrum beta-lactamase-producing Escherichia coli isolated from patients with community- and healthcare-associated bacteriuria: results from 2014 to 2020 in an urban safety-net healthcare system. Antimicrob Resist Infect Control. 2021;10(1):1–13. 10.1186/s13756-021-00983-y . Akhtar N, Rahman R, Sultana S, Rahman MR. Antimicrobial Sensitivity Pattern of Bacterial Pathogens Associated with Urinary Tract Infection. Delta Med Coll J. 2017;5(2):57–62. 10.3329/dmcj.v5i2.33342 . HAKKOYMAZ H. The assessment of etiology and risk factors of urinary tract infections in geriatric patients admitted to emergency department. J Surg Med. 2022;6(5):1–1. 10.28982/josam.726628 . Raja NS. Oral treatment options for patients with urinary tract infections caused by extended spectrum βeta-lactamase (ESBL) producing Enterobacteriaceae. J Infect Public Health. 2019;12(6):843–6. 10.1016/j.jiph.2019.05.012 . Shilpakar A, Ansari M, Rai KR, Rai G, Rai SK. Prevalence of multidrug-resistant and extended-spectrum beta-lactamase producing Gram-negative isolates from clinical samples in a tertiary care hospital of Nepal. Trop Med Health. 2021;49(1). 10.1186/s41182-021-00313-3 . Kresken M, Pfeifer Y, Wagenlehner F, Werner G, Wohlfarth E. Jun., Resistance to Mecillinam and Nine Other Antibiotics for Oral Use in Escherichia coli Isolated from Urine Specimens of Primary Care Patients in Germany, 2019/20, Antibiotics, 11, 6, 2022, 10.3390/antibiotics11060751 . Schwaber MJ, Navon-Venezia S, Schwartz D, Carmeli Y. High levels of antimicrobial coresistance among extended-spectrum-β- lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother. 2005;49(5):2137–9. 10.1128/AAC.49.5.2137-2139.2005 . Brumfitt W. Efficacy and safety profile of long-term nitrofurantoin in urinary infections: 18 years’ experience, pp. 363–71, 1998. Wijesooriya W, Herath YB, Sugandhi RAI. Antibiotic sensitivity pattern for non-beta lactam antibiotics and carbapenems in extended-spectrum beta-lactamase (ESBL) producing uropathogens versus non- ESBL producing uropathogens, no. October, pp. 92–99, 2017. Wagenlehner FME, Hoyme U, Kaase M, Fünfstück R, Naber KG, Schmiemann G. Unkomplizierte harnwegsinfektionen. Dtsch Arztebl. 2011;108(24):415–23. 10.3238/arztebl.2011.0415 . S. Kumar, “Risk factors and outcome of urinary tract infections by extended spectrum,” Sri Lanka Journal of Child Health, pp. 1-7, 2022. Kaleem, Fatima et al. “Reviving the role of mecillinam against extended spectrum beta-lactamase producing enterobacterales.” Iranian journal of microbiology vol. 14,5 (2022): 662-668. doi:10.18502/ijm.v14i5.10959 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4535041","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":321689073,"identity":"01d14f17-1848-4153-8a2d-d6b5c649a08d","order_by":0,"name":"Kasun Prabuddha Aththanayaka","email":"","orcid":"","institution":"Teaching hospital ,Polonnaruwa","correspondingAuthor":false,"prefix":"","firstName":"Kasun","middleName":"Prabuddha","lastName":"Aththanayaka","suffix":""},{"id":321689074,"identity":"65e2bacd-6a9c-4fe0-aa91-97c734b1ef2d","order_by":1,"name":"Yasoda Hansani Weerasinghe","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAr0lEQVRIiWNgGAWjYNCCCij94ADRWs5A6QSitTC2kaJF3n+N4YOP82wSG9gPP2BIOENYB4PhjTfGhjO3pSU28KQZMCTcIEbLjLPbpHm3HU5sYMgBOuwDcVq2//47B6iF/w2RWuT5e7cxMzYAtUiAbCHGYQYS/J8le46lGbdJPDM4QJT35fuPJX74UWMj28+f/PDBh2PE2HIjAcJgA+IDRGgA2UKculEwCkbBKBjJAAC38TxlEGl+kwAAAABJRU5ErkJggg==","orcid":"","institution":"Open University of Sri Lanka","correspondingAuthor":true,"prefix":"","firstName":"Yasoda","middleName":"Hansani","lastName":"Weerasinghe","suffix":""},{"id":321689078,"identity":"3928c0e9-bd0b-4b14-9e8a-b31a7f67f3ca","order_by":2,"name":"Nimsha Sevwandika Weerakkody","email":"","orcid":"","institution":"Open University of Sri Lanka","correspondingAuthor":false,"prefix":"","firstName":"Nimsha","middleName":"Sevwandika","lastName":"Weerakkody","suffix":""},{"id":321689081,"identity":"0ba25a72-8b08-4ede-a4c3-a4f1fa5cf22d","order_by":3,"name":"Gayani Geethika Samarasinghe","email":"","orcid":"","institution":"Teaching hospital ,Polonnaruwa","correspondingAuthor":false,"prefix":"","firstName":"Gayani","middleName":"Geethika","lastName":"Samarasinghe","suffix":""},{"id":321689082,"identity":"fa6effa5-546f-4d1b-bc44-5bed279befaa","order_by":4,"name":"Upul Priyadarshana","email":"","orcid":"","institution":"Teaching hospital ,Polonnaruwa","correspondingAuthor":false,"prefix":"","firstName":"Upul","middleName":"","lastName":"Priyadarshana","suffix":""}],"badges":[],"createdAt":"2024-06-05 15:10:35","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4535041/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4535041/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12866-024-03495-y","type":"published","date":"2024-09-21T15:57:12+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":60448087,"identity":"b3cbb0fa-42e4-41df-9e38-d5c616f6335e","added_by":"auto","created_at":"2024-07-16 22:11:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":5756,"visible":true,"origin":"","legend":"\u003cp\u003eFrequency of UTI infection according to gender and age.\u003c/p\u003e","description":"","filename":"Onlinedrawingimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4535041/v1/22f72c41084c214ba881952d.png"},{"id":60448890,"identity":"bcdbf511-9d28-4782-b697-b01047b235fe","added_by":"auto","created_at":"2024-07-16 22:19:50","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":5253,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of drug sensitivity and resistance of antibiotics among ESBL producers.\u003c/p\u003e","description":"","filename":"Onlinedrawingimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-4535041/v1/fcca848e1b6357e4f31dcb32.png"},{"id":65104195,"identity":"bed787b8-b056-45dd-bdcf-4aed7cdd6ab1","added_by":"auto","created_at":"2024-09-23 16:12:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":535293,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4535041/v1/99411fb1-b685-44b7-aab6-1beba4d6ae58.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eEffectiveness of Selective Antibiotics Use in Esbl-Related UTIs.\u003c/p\u003e","fulltext":[{"header":"1. Background","content":"\u003cp\u003eUrinary Tract Infection (UTI) is the most common bacterial infection prevalent in both females and males. The incidence is more frequent in women than men due to shortness of urethra, easy contamination with fecal flora, and pregnancy [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Mostly, neonates, girls, young women, infants, young children, and older men are mainly vulnerable to UTIs [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. \u003cem\u003eEscherichia coli\u003c/em\u003e (\u003cem\u003eE. coli\u003c/em\u003e) is the most frequent uropathogen accounting for 70\u0026ndash;80% of cases of acute uncomplicated lower UTIs [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, \u003cem\u003eKlebsiella\u003c/em\u003e spp, \u003cem\u003eProteus\u003c/em\u003e spp, and \u003cem\u003ePseudomonas\u003c/em\u003e spp. are also reported as uropathogen which cause uncomplicated UTIs [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eExtended-spectrum beta-lactamases (ESBLs) are plasmid-mediated enzymes [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] produced by the Enterobacteriaceae family, \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e, and \u003cem\u003eE. coli\u003c/em\u003e. Other Enterobacteriaceae, non-fermenting bacteria, \u003cem\u003eAcinetobacter\u003c/em\u003e spp., and \u003cem\u003ePseudomonas\u003c/em\u003e spp. also produce ESBLs but the prevalence rate is low [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. ESBLs are hydrolyzed and inactivated beta-lactam antibiotics, rendering them ineffective in treating infections caused by ESBLs-producing bacteria [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. It\u0026rsquo;s responsible for the increasing antibiotic resistance globally to UTIs. Major risk factors of UTIs produced by ESBLs positive uropathogens are patients with numerous comorbidities, diabetes, long stay in nursing homes, frequent use of antibiotics, recurrent UTIs, older age, sex (male), and intravenous treatments or urinary tract abnormalities [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAccording to a WHO report published in 2021, ESBLs-producing Enterobacteriaceae are part of the group posing the highest risk to public health [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The increasing isolation of ESBLs-producing bacteria causing UTIs worldwide due to the failure of empirical therapy which may result in serious clinical complications such as sepsis, renal scarring, and prolonged hospitalization, compared to infection with non-ESBL strains [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHence, ESBL producers have become a major multidrug-resistant pathogen, and several significant changes in ESBL-producing isolates have been witnessed worldwide in the last two decades [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Therefore ESBL production is needed to guide appropriate antimicrobial therapy [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] and minimize the risk of developing resistance to certain drugs soon [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Identification of drug-resistant microorganisms and available oral treatment options are essential for choosing an appropriate antibiotic that would enable to avoid the waste of time, and high medical costs and reduce the potential complications or rate of mortality. Further, that may reduce the development of multidrug-resistant bacteria [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e"},{"header":"2. Methodology","content":"\u003cp\u003eA total of 200 patients with positive urine cultures for ESBL-producing bacteria and suggestive of having UTI were enrolled in the study. The recruitment of patients was done by the Consultant Microbiologist at District General Hospital Polonnaruwa, depending on the clinical symptoms and medical history of the patients.\u003c/p\u003e \u003cp\u003eUrine specimens were processed according to the standard guidelines [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. On the first day of the samples receiving macroscopic appearance, culture on CLED (Cystine Lactose Electrolyte Deficient Agar) media and wet film examination were conducted. On the following day, culture plates were observed and gram stained and biochemical tests were conducted accordingly to identify the bacterial species. The uropathogen were grown on Hi-Crome UTI agar was presumptively identified based on the different contrasted colony colors produced by reactions of genus or species-specific enzymes and chromogenic substrates according to the manufacturer\u0026rsquo;s instructions. ESBL production was identified using the CLSI disc diffusion method, noting specific zone diameters that indicate a high level of suspicion for ESBL production using Cefpodoxime (10\u0026micro;g), Ceftazidime (30\u0026micro;g), Aztreonam (30\u0026micro;g), Cefotaxime (30\u0026micro;g), or Ceftriaxone (30\u0026micro;g) antibiotics. However, the use of more than one of these agents for screening improves the sensitivity of detection. Zone diameters indicate ESBL production. Antimicrobial susceptibility testing (AST) was performed using the standardized Kirby-Bauer disk diffusion method for Ciprofloxacin 10 \u0026micro;g, Nitrofurantoin 300 \u0026micro;g, Mecillinam 10 \u0026micro;g, Cotrimoxazole and interpretation was done following the CLSI guidelines, 2021. Statistical software SPSS version 21.0 was used for statistical analysis and calculations of the data set. The p values less than 0.05 were considered as statistical significance.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003eA total of 4386 urine specimens were received at the Microbiology Laboratory during the sample collection period of 1st April to 31st July 2023. Out of the 4386 specimens, 1081(24.6%) specimens showed culture-positive results with more than 10\u003csup\u003e5\u003c/sup\u003e CFU/ml. Among these culture-positive urine specimens, 200 (185%) specimens showed ESBLs producing uropathogens. The majority 143 (71.5%) specimens received from the inward departments (IWD) while 57 (28.5%) specimens received from the Out-Patient Departments (OPD). There were 200 patients and reported 115 (57.5%) were females and 85 (42.5%) were males. Frequency of UTI infection according to gender and age are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The highest number of patients reported ESBL producers in between the age category of 55\u0026ndash;74 years while the majority were females (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAmong the 200 ESBLs positive specimens, majority 74.5% (149/200) were \u003cem\u003eE. coli\u003c/em\u003e followed by \u003cem\u003eKlebsiella\u003c/em\u003e spp.17.5% (35/200), Enterobacteriaceae 7% (14/200) and only1% (2/200) isolate of \u003cem\u003eProteus\u003c/em\u003e spp. Number of cases according to the organism type and the age category (Child\u0026thinsp;\u0026lt;\u0026thinsp;14 years and Adults\u0026thinsp;\u0026gt;\u0026thinsp;14 years) [37] is tabulated in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFrequency of the isolated uropathogens according to the age\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\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eUro-pathogen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUTI patient with ESBLS producer\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eStatistic\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAdult\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChildren\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eE. coli\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e149\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e129 (86.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (13.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eχ2\u0026thinsp;=\u0026thinsp;2.17\u003c/p\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.537\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eKlebsiella\u003c/em\u003e spp.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (94.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (5.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eProteus\u003c/em\u003e spp.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEnterobacteriaceae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e178\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e (Chi-squared test was used to analyze data)\u003c/p\u003e \u003cp\u003eESBL producers showed highest effectiveness against Mecillinam (89%) and least effectiveness against Ciprofloxacin.\u003c/p\u003e \u003cp\u003eAntibiotic susceptibility is shown in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The \u003cem\u003eE. coli\u003c/em\u003e showed the highest sensitivity toward Nitrofurantoin and Mecillinam (83.2%) and (87.9%) respectively. \u003cem\u003eKlebsiella\u003c/em\u003e spp. showed resistance to all three antibiotics including Ciprofloxacin (88.5%), Cotrimoxazole (88.5%), and Nitrofurantoin (60.0%). Further, \u003cem\u003eProteus\u003c/em\u003e spp. showed (100%) sensitivity to both Ciprofloxacin and Cotrimoxazole and 100% resistance to Nitrofurantoin. Other Gram-Negative isolates showed 100%sensitivity to Nitrofurantoin and 100% resistance to Ciprofloxacin and Cotrimoxazole.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTable2.\u003c/strong\u003e Antibiotic susceptibility according to the organism type\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.806988352745424%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAntibiotics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.80199667221298%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSusceptibility\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"65.3910149750416%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOrganisms\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.934010152284262%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eE. coli\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.111675126903553%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eKlebsiella\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;spp.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.096446700507613%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eProteus\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003espp.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.85786802030457%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOther coliforms\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.780730897009967%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCiprofloxacin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.770764119601328%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSensitive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.93687707641196%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e31 (20.8%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.780730897009967%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e4 (11.4%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.116279069767442%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e2 (100%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.614617940199336%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.287968441814595%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eResistance\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.485207100591715%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e118 (79.1%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.73767258382643%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e31 (88.6%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.94871794871795%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.54043392504931%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e14 (100%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.780730897009967%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNitrofurantoin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.770764119601328%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSensitive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.93687707641196%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e124 (83.2%0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.780730897009967%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e14 (40%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.116279069767442%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.614617940199336%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e14 (100%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.287968441814595%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eResistance\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.485207100591715%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e25 (16.8%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.73767258382643%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e21 (60%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.94871794871795%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e2(100%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.54043392504931%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.780730897009967%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCotrimoxazole\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.770764119601328%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSensitive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.93687707641196%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e40 (26.8%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.780730897009967%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e4 (11.4%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.116279069767442%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e2 (100%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.614617940199336%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.287968441814595%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eResistance\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.485207100591715%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e109 (73.2%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.73767258382643%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e31 (88.6%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.94871794871795%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.54043392504931%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e14 (100%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.780730897009967%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMecillinam\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.770764119601328%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSensitive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.93687707641196%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e131 (87.9%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.780730897009967%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.116279069767442%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.614617940199336%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.287968441814595%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eResistance\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.485207100591715%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e18 (12.1%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.73767258382643%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.94871794871795%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.54043392504931%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe present study revealed that most of the UTI patients reported from inward departments of the hospital while only a limited number of cases were reported from outpatient departments, suggestive of hospital-acquired infection of ESBLs producing Enterobacteriaceae. The urine-positive culture-positive rate was reported as 24.6%. Similar results have been reported by Shakya \u003cem\u003eet al.\u003c/em\u003e, 2017 in Nepal of 20.41% positive urine cultures out of 2029 non-repetitive mid-stream urine specimens. Yadav and Prakash, 2017 reported a 62.9% rate of urine culture positivity. In contrast, a very low percentage of urine culture positivity was reported at 6.52% in Iran [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. These differences may be due to geographical area, time, and the diagnostic technique used [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIncreasing coliform production of ESBLs is a global healthcare concern because of increasing antibiotic resistance and restricted treatment options [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In the present study, ESBL production was found in 18.5% (200/1081) in Polonnaruwa District. Another study done in different districts of Sri Lanka reported 28% and 33% in Colombo (2012), and 40% in Galle (2016) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Comparatively in Sri Lanka, the rate of ESBLs producing isolation has changed with time and location.\u003c/p\u003e \u003cp\u003eIn 2019 the Centre for Disease Control and Prevention (CDC) reported that the global prevalence rate of ESBL production by coliforms has increased by 50% between 2012 and 2017 in the United States [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. A similar study for Monitoring Antimicrobial Resistance Trends (SMART) observed the prevalence of urinary tract infections caused by ESBLs producing \u003cem\u003eE. coli\u003c/em\u003e to increase from 7.8 to 18.3% between 2010 and 2014 in the US [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The ESBL-producing \u003cem\u003eE.coli\u003c/em\u003e isolation rates increased at a faster rate in healthcare-associated settings than in the community between 2014 and 2020 in the USA[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFemales are more prone to have UTI infections than males depending on several factors such as the anatomical structure of the urethra, hormonal imbalances, and behavioral changes. The present study also reported higher incidences of UTI in females compared to males. The present study reported that many of the UTI patients belong to the age category of 55\u0026ndash;74 years. Many studies have reported that immune-compromised patients, elderly patients, diabetes mellitus patients, and those who are taking chemotherapy and prolonged antibiotic treatments are more prone to develop UTIs than the other populations. Similarly, Gharavi \u003cem\u003eet al.\u003c/em\u003e, 2021 reported that the age groups of 60\u0026ndash;75 (20.11%) and 45\u0026ndash;60 (18%) years were frequently infected with uropathogens. The least number of patients were found in the age group 15\u0026ndash;34 years (9%) and children (12%).\u003c/p\u003e \u003cp\u003eThe \u003cem\u003eE. coli\u003c/em\u003e found to be the most predominant ESBLs producing uropathogens in this study. These results are in line with the previous studies conducted by Raja \u003cem\u003eet al.\u003c/em\u003e, in 2019 and Liu \u003cem\u003eet al.\u003c/em\u003e, in 2022 who reported \u003cem\u003eE. coli\u003c/em\u003e isolation rates as 90% and 73.3% respectively. The members of the Enterobacteriaceae family, \u003cem\u003eE. coli\u003c/em\u003e and \u003cem\u003eKlebsiella\u003c/em\u003e spp. are identified as common causative agents of UTIs as they possess several factors including adhesion, pili, fimbriae, and P1 blood group genotype receptor, which contribute to the attachment of bacteria to the urothelium [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe development of novel antimicrobials is not keeping up with developing resistance, from this time it is necessary to re-evaluate and revive overlooked and older antimicrobials. Fosfomycin, Colistin, Rifampicin, and Polymyxin B are some of the older revived antimicrobials that are used effectively these days for the treatment of superbugs. Mecillinam is an Amido penicillin with selective and good activity against Gram-negative isolates. Many European and Scandinavian countries have recently included Mecillinam in their empirical treatment guidelines, especially for the treatment of community-based urinary tract Infections (UTIs). Many studies from Belgium, the United Kingdom, France, and Norway have reported good \u003cem\u003ein vitro\u003c/em\u003e as well as In vivo activity of Mecillinam against extended-spectrum beta-lactamase-producing Gram-negative isolates. The important prospective benefits of Mecillinam are that it is available as an oral prodrug, it has a suitable twice-daily dosage regimen, it replaces carbapenems and its use is less associated with a high risk of \u003cem\u003eClostridium difficile\u003c/em\u003e associated diarrhea [38].\u003c/p\u003e \u003cp\u003eIn ourstudy, Mecillinam identified as the most effective antibiotic against \u003cem\u003eE. coli.\u003c/em\u003e Similarly, Raja \u003cem\u003eet al.\u003c/em\u003e, 2019 and Kresken \u003cem\u003eet al.\u003c/em\u003e, 2022 reported Mecillinam sensitivity toward \u003cem\u003eE. coli\u003c/em\u003e was 96% and 86.3% respectively.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eIn the present study, \u003cem\u003eE. coli\u003c/em\u003e was the most predominant ESBL-producing uropathogen with the highest sensitivity towards Mecillinam. Among currently used oral antibiotics Nitrofurantoin is the best choice for UTIs caused by ESBL producers.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eE. coli: Escherichia coli UTI: Urinary Tract Infection ESBL: Extended Spectrum of Beta-Lactamase CDC: Disease Control and Prevention IWD: Inward Department OPD: Out-Patients Department\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all academic and non-academic staff members of The open university, Nawala, Sri Lanka, and Teaching Hospital, Polonnaruwa.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was performed as a collaboration among all the authors. All the authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData are available upon request from the authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethical Review Committee of the Teaching Hospital, Polonnaruwa, and (DGHP/ERC/2023/01). A letter of authorization was obtained from Teaching hospital, Polonnaruwa before data collection\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eYadav K, Prakash S. Screening of ESBL Producing Multidrug Resistant E. coli from Urinary Tract Infection Suspected Cases in Southern Terai of Nepal. J Infect Dis Diagnosis. 2017;02(02). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4172/2576-389x.1000116\u003c/span\u003e\u003cspan address=\"10.4172/2576-389x.1000116\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTula A, Mikru A, Alemayehu T, Dobo B. Bacterial Profile and Antibiotic Susceptibility Pattern of Urinary Tract Infection among Pregnant Women Attending Antenatal Care at a Tertiary Care Hospital in Southern Ethiopia, Can. J. Infect. Dis. Med. Microbiol., vol. 2020, 2020, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1155/2020/5321276\u003c/span\u003e\u003cspan address=\"10.1155/2020/5321276\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYadav K, Prakash S, Serayi R, Shilpkar T, Shrestha S. Antimicrobial susceptibility test of pathogens isolated from urinary tract infection suspected cases. Janaki Med Coll J Med Sci. 2014;2(1):28\u0026ndash;34. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3126/jmcjms.v2i1.11393\u003c/span\u003e\u003cspan address=\"10.3126/jmcjms.v2i1.11393\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCare P. Resistance to Mecillinam and Nine Other Antibiotics for Oral Use in Escherichia coli Isolated from Urine Specimens of, 2022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePriyadharshana U, Piyasiri LB, Wijesinghe C. Prevalence, antibiotic sensitivity pattern and genetic analysis of extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella spp among patients with community acquired urinary tract infection in Galle district, Sri Lanka. Ceylon Med J. Dec. 2019;64(4):140. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4038/cmj.v64i4.8990\u003c/span\u003e\u003cspan address=\"10.4038/cmj.v64i4.8990\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu H, Qiu S, Chen M, Lyu J, Yu G, Xue L. A clinical prediction tool for extended-spectrum β-lactamase-producing Enterobacteriaceae urinary tract infection. BMC Infect Dis. 2022;22(1):1\u0026ndash;13. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12879-022-07040-y\u003c/span\u003e\u003cspan address=\"10.1186/s12879-022-07040-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAboumarzouk OM. Extended spectrum beta \u0026ndash; lactamase urinary tract infections, 6, 2, pp. 2012\u0026ndash;3, 2014.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNaushad VA et al. Epidemiology of urinary tract infection in adults caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae \u0026ndash; a case\u0026ndash;control study from Qatar, IJID Reg., vol. 3, no. May, pp. 278\u0026ndash;286, 2022, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ijregi.2022.05.001\u003c/span\u003e\u003cspan address=\"10.1016/j.ijregi.2022.05.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMandracchia VJ, Hayes DW, Yoho RM, Hayes MF. Diagnosis, Differential and Treatment Options. Nat Rev Microbiol. 2016;13:34. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/nrmicro3432.Urinary\u003c/span\u003e\u003cspan address=\"10.1038/nrmicro3432.Urinary\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDoi Y, Iovleva A, Bonomo RA. The ecology of extended-spectrum b-lactamases (ESBLs) in the developed world. J Travel Med. 2017;24:44\u0026ndash;51. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/jtm/taw102\u003c/span\u003e\u003cspan address=\"10.1093/jtm/taw102\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAggarwal A, et al. Clinical \u0026amp; immunological erythematosus patients characteristics in systemic lupus Maryam. J Dent Educ. 2012;76(11):1532\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4103/ijmr.IJMR\u003c/span\u003e\u003cspan address=\"10.4103/ijmr.IJMR\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi B, Webster TJ. Bacteria antibiotic resistance: New challenges and opportunities for implant-associated orthopedic infections. J Orthop Res. 2018;36(1):22\u0026ndash;32. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/jor.23656\u003c/span\u003e\u003cspan address=\"10.1002/jor.23656\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBryce A, Hay AD, Lane IF, Thornton HV, Wootton M, Costelloe C. Global prevalence of antibiotic resistance in paediatric urinary tract infections caused by Escherichia coli and association with routine use of antibiotics in primary care: Systematic review and meta-analysis, BMJ (Online), vol. 352. BMJ Publishing Group, Mar. 15, 2016. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bmj.i939\u003c/span\u003e\u003cspan address=\"10.1136/bmj.i939\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBehzadi Payam AP, Elham B, Edyta A. Hic-14-14, 14, pp. 1\u0026ndash;12, 2019.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDissanayake D, Fernando S, Chandrasiri N. The distribution and characteristics of Extended-Spectrum β-Lactamase producing Escherichia coli and Klebsiella species among urinary isolates in a tertiary care hospital. Sri Lankan J Infect Dis. Aug. 2012;2(2):30. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4038/sljid.v2i2.4235\u003c/span\u003e\u003cspan address=\"10.4038/sljid.v2i2.4235\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShakya P, Shrestha D, Maharjan E, Sharma VK, Paudyal R. ESBL Production Among E. coli and Klebsiella spp. Causing Urinary Tract Infection: A Hospital Based Study. Open Microbiol J. 2017;11(1):23\u0026ndash;30. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2174/1874285801711010023\u003c/span\u003e\u003cspan address=\"10.2174/1874285801711010023\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGharavi MJ, Zarei J, Roshani-Asl P, Yazdanyar Z, Sharif M, Rashidi N. Comprehensive study of antimicrobial susceptibility pattern and extended spectrum beta-lactamase (ESBL) prevalence in bacteria isolated from urine samples. Sci Rep. 2021;11(1):1\u0026ndash;11. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41598-020-79791-0\u003c/span\u003e\u003cspan address=\"10.1038/s41598-020-79791-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNanoty VV, Agrawal GN, Tankhiwale SS. Evaluation of Antibiotic Resistance and β- lactamase Production in Clinical Isolates from a Tertiary Care Hospital in Central India. J Clin Basic Res. 2018;2(1):1\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.29252/jcbr.2.1.1\u003c/span\u003e\u003cspan address=\"10.29252/jcbr.2.1.1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFalodun OI, Morakinyo YM, Fagade OE. Determination of water quality and detection of Extended Spectrum Beta-Lactamase producing Gram-negative bacteria in selected rivers located in Ibadan, Nigeria. Jordan J Biol Sci. 2018;11(1):107\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTillekeratne LG, et al. Extended-spectrum β-lactamase-producing Enterobacteriaceae as a common cause of urinary tract infections in Sri Lanka. Infect Chemother. 2016;48(3):160\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3947/ic.2016.48.3.160\u003c/span\u003e\u003cspan address=\"10.3947/ic.2016.48.3.160\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHabeeb MA, Sarwar Y, Ali A, Salman M, Haque A. Rapid emergence of ESBL producers in E. coli causing urinary and wound infections in Pakistan. Pakistan J Med Sci. 2013;29(2):540\u0026ndash;4. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.12669/pjms.292.3144\u003c/span\u003e\u003cspan address=\"10.12669/pjms.292.3144\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMukherjee M, Basu S, MuKherjee SKM, Majumder M. Multidrug-resistance and extended spectrum beta-lactamase production in uropathogenic E. coli which were isolated from hospitalized patients in Kolkata, India. J Clin Diagn Res. 2013;7(3):449\u0026ndash;53. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7860/JCDR/2013/4990.2796\u003c/span\u003e\u003cspan address=\"10.7860/JCDR/2013/4990.2796\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNandagopal B, et al. Frequency of extended spectrum β-lactamase producing urinary isolates of Gram-negative bacilli among patients seen in a multispecialty hospital in Vellore district, India. Indian J Med Microbiol. 2015;33(2):282\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4103/0255-0857.153563\u003c/span\u003e\u003cspan address=\"10.4103/0255-0857.153563\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChander A, Shrestha CD. Prevalence of extended spectrum beta lactamase producing Escherichia coli and Klebsiella pneumoniae urinary isolates in a tertiary care hospital in Kathmandu, Nepal. BMC Res Notes. 2013;6(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/1756-0500-6-487\u003c/span\u003e\u003cspan address=\"10.1186/1756-0500-6-487\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCDC. Antibiotic Resistance Threats in The United States 2019, Cdc, vol. 10, no. 1, 2019, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s13756-020-00872-w\u003c/span\u003e\u003cspan address=\"10.1186/s13756-020-00872-w\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOntario P. Trends in the Rates of Extended-Spectrum- b -Lactamase-Producing Enterobacterales Isolated from Urine Cultures during the COVID-19, 2021.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRaphael E, Glymour MM, Chambers HF. Trends in prevalence of extended-spectrum beta-lactamase-producing Escherichia coli isolated from patients with community- and healthcare-associated bacteriuria: results from 2014 to 2020 in an urban safety-net healthcare system. Antimicrob Resist Infect Control. 2021;10(1):1\u0026ndash;13. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s13756-021-00983-y\u003c/span\u003e\u003cspan address=\"10.1186/s13756-021-00983-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkhtar N, Rahman R, Sultana S, Rahman MR. Antimicrobial Sensitivity Pattern of Bacterial Pathogens Associated with Urinary Tract Infection. Delta Med Coll J. 2017;5(2):57\u0026ndash;62. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3329/dmcj.v5i2.33342\u003c/span\u003e\u003cspan address=\"10.3329/dmcj.v5i2.33342\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHAKKOYMAZ H. The assessment of etiology and risk factors of urinary tract infections in geriatric patients admitted to emergency department. J Surg Med. 2022;6(5):1\u0026ndash;1. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.28982/josam.726628\u003c/span\u003e\u003cspan address=\"10.28982/josam.726628\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRaja NS. Oral treatment options for patients with urinary tract infections caused by extended spectrum βeta-lactamase (ESBL) producing Enterobacteriaceae. J Infect Public Health. 2019;12(6):843\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jiph.2019.05.012\u003c/span\u003e\u003cspan address=\"10.1016/j.jiph.2019.05.012\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShilpakar A, Ansari M, Rai KR, Rai G, Rai SK. Prevalence of multidrug-resistant and extended-spectrum beta-lactamase producing Gram-negative isolates from clinical samples in a tertiary care hospital of Nepal. Trop Med Health. 2021;49(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s41182-021-00313-3\u003c/span\u003e\u003cspan address=\"10.1186/s41182-021-00313-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKresken M, Pfeifer Y, Wagenlehner F, Werner G, Wohlfarth E. Jun., Resistance to Mecillinam and Nine Other Antibiotics for Oral Use in Escherichia coli Isolated from Urine Specimens of Primary Care Patients in Germany, 2019/20, Antibiotics, 11, 6, 2022, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/antibiotics11060751\u003c/span\u003e\u003cspan address=\"10.3390/antibiotics11060751\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchwaber MJ, Navon-Venezia S, Schwartz D, Carmeli Y. High levels of antimicrobial coresistance among extended-spectrum-β- lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother. 2005;49(5):2137\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1128/AAC.49.5.2137-2139.2005\u003c/span\u003e\u003cspan address=\"10.1128/AAC.49.5.2137-2139.2005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrumfitt W. Efficacy and safety profile of long-term nitrofurantoin in urinary infections: 18 years\u0026rsquo; experience, pp. 363\u0026ndash;71, 1998.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWijesooriya W, Herath YB, Sugandhi RAI. Antibiotic sensitivity pattern for non-beta lactam antibiotics and carbapenems in extended-spectrum beta-lactamase (ESBL) producing uropathogens versus non- ESBL producing uropathogens, no. October, pp. 92\u0026ndash;99, 2017.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWagenlehner FME, Hoyme U, Kaase M, F\u0026uuml;nfst\u0026uuml;ck R, Naber KG, Schmiemann G. Unkomplizierte harnwegsinfektionen. Dtsch Arztebl. 2011;108(24):415\u0026ndash;23. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3238/arztebl.2011.0415\u003c/span\u003e\u003cspan address=\"10.3238/arztebl.2011.0415\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003eS. Kumar, \u0026ldquo;Risk factors and outcome of urinary tract infections by extended spectrum,\u0026rdquo; \u003cem\u003eSri Lanka Journal of Child Health,\u0026nbsp;\u003c/em\u003epp. 1-7, 2022.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eKaleem, Fatima et al. \u0026ldquo;Reviving the role of mecillinam against extended spectrum beta-lactamase producing enterobacterales.\u0026rdquo; \u003cem\u003eIranian journal of microbiology\u003c/em\u003e vol. 14,5 (2022): 662-668. doi:10.18502/ijm.v14i5.10959\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"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":"Escherichia coli, Proteus spp., Klebsiella spp., Enterobacteriaceae, Extended spectrum β-lactamase, Urinary tract infection","lastPublishedDoi":"10.21203/rs.3.rs-4535041/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4535041/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground \u0026ndash;\u003c/h2\u003e \u003cp\u003eUrinary tract infections (UTIs) are the second most common infection, affecting 150\u0026nbsp;million people each year worldwide. Enterobacteriaceae species expressing extended-spectrum β-lactamases (ESBLs) are on the rise across the globe and are becoming a severe problem in the therapeutic management of clinical cases of urinary tract infection. Knowledge of the prevalence and antibiogram profile of such isolates is essential to develop an appropriate treatment methodology. This study aimed to investigate the prevalence of Enterobacteriaceae isolates exhibiting ESBL and their selective oral antibiogram profile at the district general hospital, Polonnaruwa.\u003c/p\u003e\u003ch2\u003eResults -\u003c/h2\u003e \u003cp\u003eA total of 4386 urine specimens received to the Microbiology Laboratory during the study period. Among them, 1081 (25%) showed positive results for urine culture while 200/1081 specimens showed ESBL isolates. Out of the selected 200 specimen\u0026rsquo;s majority (72%) of samples received from the In-Patient Department. There were 200 patients and reported that 115 (58%) were females and 85 (42%) were males. The majority (51%) of the patients belong to the age group of 55\u0026ndash;74 years. Among the ESBLs positive specimens, the majority 74.5% (n\u0026thinsp;=\u0026thinsp;149) identified organisms were \u003cem\u003eE. coli\u003c/em\u003e followed by \u003cem\u003eKlebsiella\u003c/em\u003e spp.17.5% (n\u0026thinsp;=\u0026thinsp;35), Enterobacteriaceae 7% (n\u0026thinsp;=\u0026thinsp;14) and only1% (n\u0026thinsp;=\u0026thinsp;2) isolate of \u003cem\u003eProteus\u003c/em\u003e spp. Mecillinam (86.30%) and Nitrofurantoin (83.56%) showed higher effectiveness against \u003cem\u003eE. coli\u003c/em\u003e. Nitrofurantoin showed the highest effectiveness against \u003cem\u003eKlebsiella\u003c/em\u003e spp. (31.58%), other Enterobacteriaceae spp. (79%). Proteus spp. showed 100% effectiveness and resistance respectively against Ciprofloxacin, Cotrimoxazole and Nitrofurantoin.\u003c/p\u003e\u003ch2\u003eConclusion -\u003c/h2\u003e \u003cp\u003eThe most predominant ESBLs producing uro-pathogen was the \u003cem\u003eE. coli\u003c/em\u003e in the study setting and \u003cem\u003eE. coli\u003c/em\u003e had higher sensitivity rate against Mecillinam. Among currently used oral antibiotics Nitrofurantoin was the best choice for UTIs caused by ESBL producers.\u003c/p\u003e","manuscriptTitle":"Effectiveness of Selective Antibiotics Use in Esbl-Related UTIs.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-16 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