Urinary tract infection (UTI) remains a primary healthcare-associated complication following cystoscopy, increasing morbidity, healthcare costs, and patient discomfort [1, 2]. While cystoscopy is a fundamental diagnostic and therapeutic tool for lower urinary tract disorders, passing the instrument disrupts the protective mucosal barrier and introduces resident urethral flora into the sterile bladder [3, 4, 5]. Pressurized irrigation fluid further promotes retrograde bacterial translocation [3]. Although standard pre-procedural preparation involves external skin antisepsis, the distal urethral lumen remains an unaddressed bacterial reservoir [6, 7, 8]. Given global antimicrobial resistance concerns, routine antibiotic prophylaxis is discouraged, emphasizing the need for effective non-antibiotic infection control strategies [9, 10, 11]. Intra-urethral povidone-iodine (5%) instillation provides broad-spectrum microbicidal activity without selecting for resistant organisms [12, 13]. This randomized controlled trial evaluates whether pre-procedural distal urethral instillation of povidone-iodine reduces post-cystoscopy UTIs, lower urinary tract symptoms, pyuria, and antibiotic requirements in male patients [1, 12, 13]. Aims and Objectives Aim To evaluate the effectiveness of pre-procedural distal urethral povidone-iodine preparation in reducing post-cystoscopy infectious complications among male patients undergoing cystoscopy [1]. Objectives Primary Objective: To compare the occurrence of post-cystoscopy urinary tract infection (UTI) between male patients receiving distal urethral povidone-iodine preparation and those undergoing standard preparation alone [1]. Secondary Objective 1: To assess the efficacy of distal urethral povidone-iodine preparation on post-procedural urinary symptoms, including dysuria, frequency, urgency, and fever [1]. Secondary Objective 2: To compare the occurrence of pyuria and urine culture positivity following cystoscopy between the study groups at Day 2, Day 7, and Day 30 follow-up intervals [1]. Secondary Objective 3: To evaluate the need for therapeutic antibiotic therapy and hospital admission due to post-cystoscopy infectious complications in both groups [1]. Secondary Objective 4: To study the pattern of distal urethral microbial flora and its association with post-cystoscopy urinary tract infection [1]. Secondary Objective 5: To determine the safety and clinical utility of distal urethral povidone-iodine preparation as a simple, cost-effective, non-antibiotic strategy for preventing post-cystoscopy infections in routine urological practice [1].

Study Design and Setting: This study was designed as a prospective, randomized controlled trial (RCT) conducted at the Department of Urology, Chettinad Hospital and Research Institute, Kelambakkam, Tamil Nadu, India, between October 2024 and May 2026 [1]. Ethical clearance was obtained from the Institutional Human Ethics Committee (Ref No: IHEC-I/3200/24) [1]. All participants provided written informed consent prior to enrollment in accordance with Declaration of Helsinki principles [1]. Study Population and Selection Criteria: A total of 240 eligible male patients aged 18–75 years scheduled for office cystoscopy were recruited using consecutive sampling [1]. Inclusion criteria specified sterile pre-procedure urine cultures (<10⁵ CFU/mL) processed within one week prior to the procedure [1]. Key exclusion criteria included active UTI, indwelling urinary catheters >1 week, immunosuppression or chronic steroid use, gross hematuria, stone manipulation during endoscopy, genitourinary tuberculosis, radiation cystitis, or catheterization >3 days post-procedure [1]. Randomization and Allocation Concealment: Participants were randomly assigned (1:1 ratio) into two parallel groups of 120 patients each using a computer-generated randomization table [1]. Allocation concealment was maintained using sequentially numbered, opaque, sealed envelopes opened immediately prior to the procedure [1]. Outcome assessment was conducted by clinical assessors blinded to group allocation and culture results [1]. Intervention and Procedural Protocol Prophylaxis Policy: In accordance with American Urological Association (AUA) best-practice statements, no peri-procedural systemic prophylactic antibiotics were administered [1]. Pre-Procedural Preparation: All patients trimmed pubic hair on the eve of the procedure and bathed on the morning of cystoscopy [1]. Standard genital antiseptic prep and sterile draping were applied [1]. Prior to cystoscopy, a intra-urethral swab was obtained to culture baseline distal urethral flora [1]. Intervention Group (Group A, n=120): Patients received gentle distal urethral irrigation with 10 mL of 5% w/v povidone-iodine solution, retained in the urethral lumen for 2 minutes prior to scope insertion [1]. Control Group (Group B, n=120): Patients underwent standard cystoscopy without intra-urethral antiseptic instillation [1]. Endoscopic Technique: All cystoscopies were performed under local anesthesia (2% lignocaine gel) using rigid (20F) or flexible cystoscopes [1, 3]. Equipment high-level disinfection was standardized using 2% glutaraldehyde for 20 minutes [1]. Follow-Up and Outcome Evaluation Follow-Up Schedule: Participants were evaluated for 30 days post-procedure [1]. Routine clean-catch midstream urine microscopy and cultures were obtained on Days 2, 7, and 30 in all participants, as well as upon any new-onset urinary symptom development [1]. Primary Outcome: Occurrence of post-cystoscopy UTI, defined as new-onset lower urinary tract symptoms associated with significant bacterial growth (≥10⁵ CFU/mL) on urine culture within 30 days [1]. Secondary Outcomes: Post-procedural dysuria, frequency, urgency, and fever; pyuria; Day 2, 7, and 30 urine culture positivity; therapeutic antibiotic requirements; hospital admission rates; and distal urethral flora patterns [1]. Statistical Analysis Analytical Methods: Continuous variables were expressed as mean ± standard deviation (SD) and compared using independent sample t-tests or Mann-Whitney U tests [1]. Categorical variables were presented as frequencies and percentages and compared using Chi-square (χ²) or Fisher's exact tests [1]. A p-value < 0.05 was considered statistically significant [1]. All statistical analyses were conducted using standard statistical software [1].

assessed for eligibility. Fifty-eight patients were excluded (21 refused, 19 did not meet inclusion criteria, and 18 met exclusion criteria). The remaining 240 eligible patients were successfully enrolled and randomized into two equal groups of 120 patients each: Group A (Povidone-Iodine instillation) and Group B (Control group). All 240 participants completed the 30-day study protocol with zero losses to follow-up [1]. Baseline demographic and clinical characteristics were comparable between both study cohorts. The mean age was 47.82 ± 11.26 years in Group A and 48.15 ± 10.94 years in Group B (p = 0.973), with the 41–50 years age bracket representing the largest proportion (23.3%) [1]. BMI distribution, diabetes mellitus (47.5% vs 52.5%, p = 0.653), smoking status (48.6% vs 51.4%, p = 0.776), and indications for cystoscopy (predominantly BPH evaluation at 22.1% and LUTS at 20.8%) showed no statistically significant differences between groups [1]. Furthermore, procedural parameters including type of cystoscopy (flexible in 68.8% vs rigid in 31.2%, p = 0.676), mean procedure duration (8.76 ± 2.35 min vs 9.28 ± 2.29 min, p = 0.085), prior history of UTI (26.7% overall, p = 0.559), and pre-procedure urine analysis findings (mild pyuria in 24.6%, p = 0.294) were well-matched at baseline [1, 3]. Primary and Secondary Clinical Outcomes Post-Cystoscopy UTI Incidence: Post-cystoscopy urinary tract infection (the primary endpoint) developed in 26 of the 240 participants (10.8% overall). Significantly fewer patients in the intervention group developed post-cystoscopy UTI compared to controls: 7 of 120 patients (5.8%) in Group A versus 19 of 120 patients (15.8%) in Group B (χ² = 6.21, df = 1, p = 0.013), representing an absolute risk reduction of 10.0 percentage points [1]. Symptomatic and Laboratory Morbidity: Evaluation of secondary clinical and laboratory outcomes demonstrated consistent and statistically significant benefits in the povidone-iodine arm [1]: Dysuria: Post-procedural dysuria occurred significantly less frequently in Group A (7 patients, 5.8%) than in Group B (19 patients, 15.8%) (χ² = 6.21, df = 1, p = 0.013) [1]. Urgency: Post-procedural urinary urgency was observed in 6 patients (5.0%) in Group A compared to 16 patients (13.3%) in Group B, showing a statistically significant reduction (χ² = 5.00, df = 1, p = 0.025) [1]. Frequency: Post-procedural urinary frequency was lower in Group A (5.8%) than Group B (12.5%), though this difference did not reach formal statistical significance (χ² = 3.20, df = 1, p = 0.074) [1]. Pyuria: Post-procedural pyuria paralleled infection rates, occurring in 7 patients (5.8%) in Group A versus 19 patients (15.8%) in Group B (χ² = 6.21, df = 1, p = 0.013) [1]. Fever: Post-procedure fever was uncommon overall (6.7% total) and occurred in 6 patients (5.0%) in Group A and 10 patients (8.3%) in Group B (p = 0.301) [1]. Antibiotic Therapy: Therapeutic antibiotic requirements were significantly reduced in Group A (7 patients, 5.8%) compared to Group B (19 patients, 15.8%) (χ² = 6.21, df = 1, p = 0.013) [1]. Hospital Admission: Hospital admissions for severe infectious complications were required in 2 patients (1.7%) in Group A and 6 patients (5.0%) in Group B (p = 0.150) [1]. Summary of Key Trial Outcomes Clinical / Microbiological Parameter Group A: Povidone-Iodine (n=120) Group B: Control (n=120) Statistical Value (χ² / t, p-value) Post-Cystoscopy UTI 7 (5.8%) 19 (15.8%) χ² = 6.21, df = 1, p = 0.013* Post-Procedure Dysuria 7 (5.8%) 19 (15.8%) χ² = 6.21, df = 1, p = 0.013* Post-Procedure Urgency 6 (5.0%) 16 (13.3%) χ² = 5.00, df = 1, p = 0.025* Post-Procedure Frequency 7 (5.8%) 15 (12.5%) χ² = 3.20, df = 1, p = 0.074 Post-Procedure Pyuria 7 (5.8%) 19 (15.8%) χ² = 6.21, df = 1, p = 0.013* Post-Procedure Fever 6 (5.0%) 10 (8.3%) χ² = 1.07, df = 1, p = 0.301 Antibiotic Required 7 (5.8%) 19 (15.8%) χ² = 6.21, df = 1, p = 0.013* Hospital Admission Required 2 (1.7%) 6 (5.0%) χ² = 2.07, df = 1, p = 0.150 Day 7 Urine Culture Positive 7 (5.8%) 19 (15.8%) χ² = 6.21, df = 1, p = 0.013* Microbiological Findings Distal Urethral Flora: Analysis of baseline distal urethral swab cultures revealed a statistically significant association with study group allocation (χ² = 10.45, df = 3, p = 0.015), with normal commensal flora more frequently isolated in Group A (42 patients, 33.3%) compared to Group B (21 patients) [1]. Coagulase-negative Staphylococci were the most prevalent isolate overall (28.3%), followed by normal commensal flora (26.3%), mixed skin flora (25.4%), and Corynebacterium spp. (20.0%) [1]. Urine Culture Dynamics and Pathogen Distribution: Among culture-positive cases, Enterococcus spp. was the most frequently isolated pathogen (5.0% total), followed by E. coli (2.1%), Klebsiella spp. (2.1%), and Pseudomonas spp. (1.7%) [1]. Urine culture positivity rates varied across follow-up intervals: Day 2 culture positivity was rare and comparable between groups (3 in Group A vs 4 in Group B, p = 0.701) [1]. However, Day 7 urine culture positivity showed a highly significant reduction in Group A (7 patients, 5.8%) versus Group B (19 patients, 15.8%) (χ² = 6.21, df = 1, p = 0.013), serving as the primary microbiological confirmation of post-cystoscopy UTI [1]. Day 30 persistent culture positivity was low overall (3.3%) and comparable between groups (2 vs 6, p = 0.150) [1]. Among patients developing UTIs, the mean day of detection was 4.00 ± 2.31 days in Group A and 3.95 ± 1.75 days in Group B (p = 0.951) [1].

Summary of Findings and Clinical Interpretation: This prospective randomized controlled trial provides robust clinical evidence that pre-procedural distal urethral preparation with 5% povidone-iodine significantly reduces infectious complications following office cystoscopy in male patients. Specifically, intra-urethral povidone-iodine instillation resulted in a statistically significant decrease in post-cystoscopy UTI incidence (5.8% vs. 15.8%, p = 0.013), an absolute risk reduction of 10.0%, alongside marked reductions in post-procedural dysuria, urgency, pyuria, and therapeutic antibiotic requirements [1]. Pathophysiological Rationale and Mechanism: The pathogenesis of post-cystoscopy urinary tract infection is fundamentally rooted in the mechanical introduction of resident microbial flora from the distal urethra into the bladder lumen [1, 3, 4]. While conventional pre-procedural antisepsis focuses on external genital cleansing, the intra-urethral lumen—particularly the fossa navicularis and penile urethra—harbors a dense commensal and opportunistic microbial population that remains untouched by superficial skin prep [6, 7, 8]. When an endoscope is passed, mucosal micro-abrasions allow these resident organisms to invade host tissues, while irrigation fluid facilitates retrograde bacterial seeding [3, 4, 5]. Our baseline microbiological data confirms this anatomical vulnerability, demonstrating a diverse array of resident flora dominated by Coagulase-negative Staphylococci (28.3%), mixed skin flora (25.4%), and Corynebacterium species (20.0%) [1]. By instilling 5% povidone-iodine into the distal urethra and retaining it for two minutes prior to instrumentation, we successfully neutralized this internal reservoir, effectively interrupting the chain of endogenous infection without causing adverse mucosal toxicity [1, 12, 13]. Implications for Antimicrobial Stewardship: These findings carry profound implications for antimicrobial stewardship in urology. In the era of escalating global antimicrobial resistance (AMR) and the rapid spread of multidrug-resistant organisms (MDROs), major urological guidelines strongly discourage routine systemic antibiotic prophylaxis for uncomplicated office cystoscopy [9, 10, 11]. However, clinicians frequently face a clinical dilemma: balancing the risk of procedure-induced infection against the imperative to avoid unnecessary antibiotic exposure [9, 10]. Our results demonstrate that local mucosal antisepsis bridges this gap. By achieving a significant reduction in infectious morbidity (10% absolute risk reduction) using a topical antiseptic agent, clinicians can protect patients without administering systemic antibiotics, thereby avoiding adverse drug reactions, allergic events, and the selective pressure driving antibiotic resistance [12, 13]. Furthermore, the reduction in post-procedural morbidity directly translated into decreased therapeutic antibiotic consumption (5.8% vs. 15.8%, p = 0.013) and a trend toward fewer hospital admissions, highlighting substantial pharmacoeconomic and patient-comfort benefits [1]. Strengths and Limitations: The strengths of this study include its prospective randomized controlled design, adequate sample size (240 patients) with complete 30-day follow-up and zero attrition, strict allocation concealment, and blinding of outcome assessors [1]. Moreover, adherence to AUA guidelines ensuring no confounding systemic prophylactic antibiotics were administered strengthens attribution of outcomes directly to the intervention [1]. Potential limitations include the exclusion of female patients and high-risk populations (such as those with indwelling catheters or active urinary sepsis), meaning our findings are primarily generalizable to adult males undergoing outpatient diagnostic or surveillance cystoscopy [1]. Additionally, while symptom evaluation and microbiological cultures were rigorously tracked at Days 2, 7, and 30, multicenter trials across diverse global populations would further validate these findings and evaluate cost-utility ratios [1].

Pre-procedural distal urethral preparation with 5% povidone-iodine instillation is a simple, safe, inexpensive, and highly effective non-antibiotic intervention that significantly reduces the incidence of post-cystoscopy urinary tract infections, local urinary symptoms, pyuria, and therapeutic antibiotic requirements in male patients undergoing office cystoscopy. Given its clear clinical efficacy and alignment with modern antimicrobial stewardship principles, intra-urethral povidone-iodine antisepsis should be strongly considered as a standard routine preparatory protocol in outpatient urological practice [1, 9, 12, 13].

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