Urinary tract infection (UTI) is one of the most common bacterial infections encountered in both community and hospital settings, accounting for a substantial proportion of outpatient consultations and antimicrobial prescriptions worldwide.[1] It is estimated that nearly 50–60% of women will experience at least one episode of UTI during their lifetime, and a considerable proportion of these individuals go on to develop recurrent infection.[2] Recurrent UTI (rUTI) is conventionally defined as the occurrence of two or more symptomatic episodes within six months, or three or more episodes within twelve months, following apparent clinical resolution of the preceding episode.[3] The pathogenesis of recurrent UTI is multifactorial and involves host factors such as anatomical abnormalities of the urinary tract, incomplete bladder emptying, sexual activity, post-menopausal oestrogen deficiency, diabetes mellitus, and immunosuppression, as well as microbial factors including adhesin-mediated uroepithelial colonisation, biofilm formation, and the persistence of intracellular bacterial reservoirs.[4,5] Escherichia coli remains the single most important uropathogen, being responsible for 50–90% of both uncomplicated and recurrent infections, followed by Klebsiella pneumoniae, Proteus mirabilis, Enterococcus species, Pseudomonas aeruginosa, and coagulase-negative staphylococci.[6,7] Over the past two decades, the empirical management of UTI has been increasingly complicated by the global emergence of multidrug-resistant (MDR) and extended-spectrum beta-lactamase (ESBL)-producing uropathogens.[8] Several Indian studies have documented a disturbing trend of escalating resistance to first-line agents such as ampicillin, co-trimoxazole, and fluoroquinolones among community- and hospital-acquired uropathogens.[9,10] Akram et al., in a study from Aligarh, reported high resistance rates to ampicillin and co-trimoxazole among uropathogens causing community-acquired UTI, with comparatively preserved susceptibility to nitrofurantoin and aminoglycosides.[9] Similarly, Taneja et al. from Chandigarh described a rising trend of ESBL production among Enterobacteriaceae isolated from urine samples in a tertiary care hospital in North India, underscoring the need for periodic local antibiograms rather than reliance on generalised international data.[11] Recurrent UTI carries considerable clinical and economic implications, including repeated healthcare visits, prolonged or repeated courses of antibiotics, risk of upper tract involvement and renal scarring, and, importantly, further selection pressure favouring antimicrobial resistance.[12,13] Despite the magnitude of the problem, there remains a relative paucity of Indian tertiary-care data specifically characterising the clinical profile, risk factor spectrum, and contemporary antibiotic susceptibility pattern of organisms isolated from patients with recurrent, as distinct from first-episode, UTI. Most existing healthcare studies from the Indian subcontinent has focused on UTI in general rather than on the recurrent subgroup, and local resistance patterns can vary considerably between institutions and geographic regions due to differences in antibiotic prescribing practices and infection control measures.[14,15] Given this background, the present study was undertaken to describe the clinical characteristics, associated risk factors, and the microbiological and antimicrobial susceptibility profile of uropathogens isolated from patients with recurrent UTI attending a tertiary care teaching hospital, with the aim of generating locally relevant data to guide rational empirical antibiotic selection and inform antimicrobial stewardship efforts. Aims and Objectives To study the socio-demographic and clinical profile of patients presenting with recurrent urinary tract infection. To identify the risk factors associated with recurrence of urinary tract infection. To determine the spectrum of uropathogens isolated from patients with recurrent UTI. To evaluate the antimicrobial susceptibility pattern of the isolated uropathogens, including the prevalence of ESBL production.

Study Design and Setting This hospital-based, cross-sectional, observational study was conducted in the Department of Urology, in collaboration with the Departments of Ophthalmology, of a tertiary care teaching hospital, over a period of 18 months. Study Population A total of 250 clinically diagnosed patients of recurrent urinary tract infection attending the outpatient and inpatient departments during the study period were enrolled by consecutive sampling after obtaining written informed consent. Institutional Ethics Committee approval was obtained prior to commencement of the study. Inclusion Criteria • Patients of either sex and any age group presenting with recurrent UTI, defined as two or more symptomatic, culture-confirmed episodes within the preceding six months, or three or more episodes within the preceding twelve months, were included. • Patients willing to give informed consent (or assent with guardian consent in the case of minors) were enrolled. Exclusion Criteria Patients on antibiotics within 48 hours prior to sample collection (unless clinically unavoidable), those with indwelling urinary catheters in situ for less than 48 hours (to exclude contamination-related isolates), pregnant women with asymptomatic bacteriuria only, and patients unwilling to give consent were excluded from the study. Sample Collection and Transport A detailed clinical history including age, sex, presenting complaints, duration and frequency of episodes, comorbid illnesses, and predisposing factors was recorded on a pre-designed proforma. Mid-stream clean-catch urine samples (or catheter-aspirated samples where clinically indicated) were collected under aseptic precautions in a sterile, wide-mouthed, leak-proof container and transported to the microbiology laboratory within two hours of collection, or refrigerated at 4°C if immediate transport was not possible. Microbiological Processing Urine samples were subjected to semi-quantitative culture on Cystine Lactose Electrolyte Deficient (CLED) agar and MacConkey agar using a calibrated standard inoculation loop (0.001 mL), followed by incubation at 37°C for 18–24 hours. A colony count of ≥10⁵ colony-forming units per millilitre (CFU/mL) of a single predominant organism was considered as significant bacteriuria as per standard criteria. Identification of isolates was carried out using standard colony morphology, Gram staining, and a battery of biochemical tests (catalase, oxidase, indole, citrate utilisation, urease, triple sugar iron agar, and the analytical profile index [API] system, where applicable). Antimicrobial Susceptibility Testing Antimicrobial susceptibility testing of all significant isolates was performed on Mueller-Hinton agar by the Kirby-Bauer disc diffusion method and interpreted as per current Clinical and Laboratory Standards Institute (CLSI) guidelines.[16] The antibiotic panel tested included ampicillin, co-trimoxazole, nitrofurantoin, ciprofloxacin, levofloxacin, gentamicin, amikacin, cefotaxime, ceftazidime, piperacillin-tazobactam, imipenem, meropenem, and colistin. Escherichia coli ATCC 25922 and Klebsiella pneumoniae ATCC 700603 were used as quality control strains. Screening for extended-spectrum beta-lactamase (ESBL) production among Enterobacteriaceae isolates was performed using the combined disc diffusion method with ceftazidime and ceftazidime-clavulanic acid discs, as recommended by CLSI.[16] Multidrug resistance (MDR) was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories. Statistical Analysis Data were entered into Microsoft Excel and analysed using SPSS software (sample version 25.0). Descriptive statistics were expressed as frequencies, percentages, and mean ± standard deviation. The Chi-square test (or Fisher's exact test, where applicable) was used to compare categorical risk factor variables between the recurrent UTI group and a comparison group of first-episode UTI patients. A p-value of <0.05 was considered statistically significant.

A total of 250 patients meeting the criteria for recurrent UTI were enrolled during the study period. Of these, 189 (75.6%) were female and 61 (24.4%) were male, giving a female-to-male ratio of approximately 3.1:1. The mean age of the study population was 42.6 ± 14.8 years, with the maximum number of patients (38.4%) belonging to the 21–40 year age group. Diabetes mellitus was the most common comorbidity, present in 71 (28.4%) patients, followed by urinary catheterisation (10.8%) and renal calculi (13.6%). The detailed socio-demographic and clinical profile of the study population is depicted in Table 1. Table 1: Socio-demographic and clinical profile of patients with recurrent UTI (n = 250) Characteristic No. of Patients (n=250) Percentage (%) Sex Female 189 75.6 Male 61 24.4 Age group (years) <20 18 7.2 21–40 96 38.4 41–60 84 33.6 >60 52 20.8 Residence Urban 162 64.8 Rural 88 35.2 Comorbid conditions Diabetes mellitus 71 28.4 Renal calculi / urolithiasis 34 13.6 Pregnancy 22 8.8 Benign prostatic hyperplasia 19 7.6 Indwelling catheter use 27 10.8 None identified 77 30.8 Clean-catch/mid-stream urine culture yielded significant growth in 246 of 250 samples (98.4%), including 18 samples with polymicrobial growth (two organisms), resulting in a total of 268 isolates. Escherichia coli was the most frequently isolated organism, accounting for 139 (51.9%) of all isolates, followed by Klebsiella pneumoniae (17.9%), Enterococcus species (9.0%), Pseudomonas aeruginosa (7.1%), Staphylococcus aureus (4.9%), Proteus mirabilis (4.1%), coagulase-negative Staphylococcus (3.0%), and Candida species (2.2%). The distribution of uropathogens is shown in Table 2. Table 2: Distribution of uropathogens isolated from patients with recurrent UTI (n = 268 isolates) Organism Isolated No. of Isolates (n=268) Percentage (%) Escherichia coli 139 51.9 Klebsiella pneumoniae 48 17.9 Enterococcus species 24 9.0 Pseudomonas aeruginosa 19 7.1 Staphylococcus aureus 13 4.9 Proteus mirabilis 11 4.1 Coagulase-negative Staphylococcus 8 3.0 Candida species 6 2.2 Total 268 100.0 On antimicrobial susceptibility testing, both E. coli and K. pneumoniae isolates showed high rates of resistance to ampicillin (sensitivity of 18.7% and 12.5% respectively) and co-trimoxazole (sensitivity of 34.5% and 29.2% respectively). Susceptibility to fluoroquinolones was also markedly reduced, with only 41.0% of E. coli and 37.5% of K. pneumoniae isolates being sensitive to ciprofloxacin. In contrast, high susceptibility was retained to nitrofurantoin (88.5% for E. coli), amikacin (84.9% and 79.2% respectively), and the carbapenems imipenem (97.1% and 93.8%) and meropenem (96.4% and 91.7%). Colistin retained near-universal activity against both organisms. The complete antibiotic susceptibility profile is presented in Table 3. Table 3: Antibiotic susceptibility pattern of Escherichia coli and Klebsiella pneumoniae isolates Antibiotic E. coli (n=139) % Sensitive K. pneumoniae (n=48) % Sensitive Ampicillin 18.7 12.5 Co-trimoxazole 34.5 29.2 Ciprofloxacin 41.0 37.5 Levofloxacin 44.6 39.6 Gentamicin 68.3 62.5 Amikacin 84.9 79.2 Nitrofurantoin 88.5 56.3 Cefotaxime 46.8 41.7 Ceftazidime 45.3 39.6 Piperacillin-tazobactam 76.3 70.8 Imipenem 97.1 93.8 Meropenem 96.4 91.7 Colistin 99.3 97.9 Extended-spectrum beta-lactamase (ESBL) production was detected in 80 of 187 (42.8%) E. coli and K. pneumoniae isolates tested by the combined disc method — in 59/139 (42.4%) E. coli and 21/48 (43.8%) K. pneumoniae isolates (Table 4a). Overall, 96 (38.4%) patients had at least one isolate meeting the criteria for multidrug resistance. Table 4a: Prevalence of ESBL production among E. coli and K. pneumoniae isolates Organism ESBL Producers, n (%) Non-ESBL, n (%) Escherichia coli (n=139) 59 (42.4) 80 (57.6) Klebsiella pneumoniae (n=48) 21 (43.8) 27 (56.2) Overall (n=187) 80 (42.8) 107 (57.2) On comparing risk factors between the 250 patients with recurrent UTI and a reference group of 180 patients presenting with a first episode of UTI during the same period, diabetes mellitus (28.4% vs 13.3%, p = 0.001), post-menopausal status (23.2% vs 11.7%, p = 0.003), prior antibiotic exposure within the preceding three months (44.8% vs 25.6%, p < 0.001), renal calculi (13.6% vs 6.1%, p = 0.014), indwelling urinary catheterisation (10.8% vs 5.0%, p = 0.032), and low daily fluid intake (25.6% vs 16.1%, p = 0.019) were found to be significantly associated with recurrence. Sexual activity, although more frequent among sexually active women in the recurrent group, did not reach statistical significance (33.2% vs 27.2%, p = 0.171). These findings are summarised in Table 4. Table 4: Comparison of risk factors between recurrent UTI and first-episode UTI groups Risk Factor Recurrent UTI (n=250) n (%) First-episode UTI (n=180) n (%) p value Diabetes mellitus 71 (28.4) 24 (13.3) 0.001 Post-menopausal status 58 (23.2) 21 (11.7) 0.003 Urinary catheterisation 27 (10.8) 9 (5.0) 0.032 Renal calculi 34 (13.6) 11 (6.1) 0.014 Prior antibiotic use (<3 months) 112 (44.8) 46 (25.6) <0.001 Sexual activity (in sexually active women) 83 (33.2) 49 (27.2) 0.171 Low fluid intake 64 (25.6) 29 (16.1) 0.019

The present study describes the clinical and microbiological profile of 250 patients with recurrent urinary tract infection attending a tertiary care teaching hospital. A clear female preponderance (75.6%) was observed, which is consistent with the well-established anatomical predisposition of women to UTI owing to a shorter urethra, its proximity to the anus, and hormonal influences on the vaginal and periurethral flora.[2,17] This finding mirrors observations from several Indian studies; Kothari and Sagar, in a multicentric study from Rajasthan, similarly reported a marked female predominance among patients with community-acquired UTI.[10] The mean age of the study population (42.6 ± 14.8 years) and the peak incidence in the 21–40 year age group are comparable to reports by Mishra et al. from Odisha, who observed the highest burden of recurrent and hospital-associated UTI among sexually active young and middle-aged adults, attributable to sexual activity, pregnancy, and increased health-seeking behaviour in this age group.[18] The relatively higher proportion of elderly patients (20.8% aged >60 years) in the present study likely reflects the contribution of age-related factors such as benign prostatic hyperplasia in men and pelvic floor dysfunction or post-menopausal oestrogen deficiency in women, both of which are recognised predisposing factors for recurrence.[19,20] Escherichia coli emerged as the predominant uropathogen in the present study (51.9%), a finding that is in close agreement with the vast majority of Indian and international studies on both uncomplicated and recurrent UTI.[6,21] Ganesh et al., in a South Asian study, similarly reported E. coli as the leading isolate followed by Klebsiella species.[7] The predominance of E. coli is attributed to its possession of specific virulence factors, including type 1 and P fimbriae, haemolysin, and aerobactin, which facilitate uroepithelial adherence, ascent to the upper urinary tract, and formation of intracellular bacterial communities that may serve as a reservoir for recurrence.[4,5] The second most common isolate, Klebsiella pneumoniae (17.9%), and the relatively higher proportion of Enterococcus species (9.0%) in the present series are consistent with the changing spectrum of uropathogens noted in several recent Indian tertiary-care studies, possibly reflecting a rise in catheter-associated and hospital-influenced infections within the recurrent UTI subgroup.[8,22] A matter of significant clinical concern in the present study was the high level of resistance observed to commonly prescribed empirical agents. Only 18.7% and 34.5% of E. coli isolates were sensitive to ampicillin and co-trimoxazole respectively, rendering these agents largely unsuitable for empirical therapy in this population. Comparable high resistance to ampicillin and co-trimoxazole has been documented by Akram et al. from Aligarh (resistance exceeding 70–80%) and by Niranjan and Malini from Bengaluru, who similarly reported declining susceptibility of E. coli to conventional first-line oral agents among hospitalised patients.[9,23] The relatively preserved susceptibility to nitrofurantoin (88.5%) observed in the present study is in keeping with multiple Indian reports and supports current international and national guideline recommendations favouring nitrofurantoin as a preferred first-line agent for uncomplicated and recurrent lower UTI, given its favourable resistance profile and minimal impact on gut flora compared with fluoroquinolones.[24,25] The reduced susceptibility to fluoroquinolones noted in this study (41.0% for ciprofloxacin among E. coli) is particularly noteworthy, as fluoroquinolones have historically been widely and often indiscriminately prescribed for UTI in Indian outpatient settings, both by clinicians and through over-the-counter access.[26] This trend of escalating fluoroquinolone resistance has been echoed by Yadav and Prakash and by Taneja et al., both of whom emphasised the urgent need for antibiotic stewardship programmes and restriction of empirical fluoroquinolone use for uncomplicated UTI in India.[11,27] The near-complete preservation of susceptibility to carbapenems (imipenem 97.1%, meropenem 96.4%) and colistin (99.3%) in the present study, while reassuring, also underscores the importance of reserving these last-resort agents strictly for complicated or MDR infections, given the well-documented global risk of emerging carbapenem and colistin resistance among Enterobacteriaceae.[28] The detection of ESBL production in 42.8% of E. coli and K. pneumoniae isolates in this study is broadly concordant with the range of 30–60% reported across various Indian tertiary care centres over the past decade.[11,29] Sharma and Paul reported a similarly high prevalence of ESBL-producing and multidrug-resistant uropathogens among hospitalised patients in Assam, attributing this trend to widespread empirical and often unregulated antibiotic use, both in hospital and community settings.[29] ESBL-producing organisms are typically co-resistant to multiple antibiotic classes owing to co-located resistance genes on plasmids, which considerably narrows the choice of effective oral empirical agents and often necessitates the use of injectable carbapenems, further amplifying selection pressure for carbapenem resistance.[30] With regard to risk factors, diabetes mellitus, post-menopausal status, prior antibiotic exposure, renal calculi, indwelling catheterisation, and reduced fluid intake were significantly associated with recurrence in the present study. These findings are consistent with the classical case-control study by Scholes et al., which identified diabetes, recent sexual intercourse, spermicide use, and a maternal history of UTI as independent risk factors for recurrent UTI in young women.[31] Similarly, Hooton, in a comprehensive review, highlighted the role of post-menopausal urogenital atrophy and incomplete bladder emptying as important contributors to recurrence in older women.[32] The strong association observed between prior antibiotic exposure and recurrence in the present study is biologically plausible and has also been reported by Al-Badr and Al-Shaikh, who postulated that antecedent antibiotic use may disrupt protective vaginal and gut microbiota, facilitating recolonisation by resistant uropathogenic strains and thereby perpetuating a cycle of recurrent infection and further antibiotic exposure.[33] The findings of the present study have several practical implications. First, the high resistance to ampicillin, co-trimoxazole, and fluoroquinolones suggests that these agents should be avoided for empirical therapy of recurrent UTI in this setting pending culture and sensitivity results, in line with recommendations of the Indian Council of Medical Research (ICMR) Treatment Guidelines for Antimicrobial Use in Common Syndromes.[25] Second, the substantial burden of ESBL-producing organisms reinforces the need for robust infection control practices, particularly among catheterised and diabetic patients, who constitute a high-risk group for recurrence and drug-resistant infection. Finally, the identification of modifiable risk factors such as low fluid intake and unnecessary antibiotic exposure offers scope for targeted patient education and antimicrobial stewardship interventions to reduce the burden of recurrence. Limitations This study has certain limitations. Being a single-centre, hospital-based study, the findings may not be entirely generalisable to the community at large or to other geographic regions with differing local resistance patterns. Molecular characterisation of resistance genes and virulence factors was not performed, and the comparison group of first-episode UTI patients was drawn from the same hospital population rather than the general community. Longitudinal follow-up to assess treatment outcomes and long-term recurrence rates was also beyond the scope of the present study. Multicentric studies with molecular characterisation of resistance mechanisms are recommended to validate and extend these findings.

Recurrent urinary tract infection remains a common and clinically significant problem, particularly among women and patients with diabetes mellitus, post-menopausal status, urinary catheterisation, or renal calculi. Escherichia coli continues to be the predominant uropathogen, and the high prevalence of resistance to ampicillin, co-trimoxazole, and fluoroquinolones observed in this study seriously limits the utility of these agents for empirical treatment. Nitrofurantoin, aminoglycosides, and carbapenems retained good in vitro activity, but the substantial burden of ESBL-producing and multidrug-resistant isolates is a cause for concern and calls for judicious, culture-guided antibiotic prescribing. Regular local antibiogram surveillance, strengthened infection control measures, patient education regarding modifiable risk factors, and institution of formal antimicrobial stewardship programmes are recommended to optimise the management of recurrent UTI and to curb the further spread of antimicrobial resistance in this setting.

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