Abstract
Background:
To prospectively evaluate the effects of rectal cleansing using a povidone-iodine (PI) and PI enhanced rectal enema on procedure-related infectious complications in patients undergoing transrectal prostate biopsy.
Methods:
Between September 2023 and March 2024, patients scheduled for their first transrectal ultrasound-guided prostate biopsy due to elevated prostate-specific antigen levels, suspicious multiparametric prostate magnetic resonance imaging findings, or abnormal digital rectal examination were prospectively randomized into 2 groups (n = 60 each). All patients received standard prophylactic measures, including antibiotic prophylaxis starting 1 day prior to the procedure and rectal mucosal cleansing with PI immediately before biopsy. Both groups additionally underwent rectal enema administration. In the intervention group, a PI enhanced rectal enema was administered by adding PI to the sodium phosphate enema solution, whereas the control group received a sodium phosphate enema alone. Post-procedural complications, including hematuria, hematospermia, rectal bleeding, fever, acute urinary retention, hospitalization, sepsis, and urine and blood culture results, were recorded and compared using chi-square tests.
Results:
In total of 120 patients were enrolled. The mean age in both groups was 66.6 years (± 7.20). Hospitalization due to febrile urinary tract infection occurred in 6 patients (10%) in the control group versus 2 patients (3.3%) in the study group. Positive urine cultures were found in 6 patients (10%) in the control group, while no positive cultures were detected in the study group, a statistically significant difference (P = .046). No significant differences were observed between the groups in terms of hematuria, hematospermia, rectal bleeding or acute urinary retention.
Conclusion:
Rectal cleansing with a PI and PI enhanced rectal enema prior to transrectal prostate biopsy significantly reduced the rate of positive urine cultures. Although the reductions in febrile urinary tract infections and sepsis-related hospitalizations were not statistically significant, the overall trend suggests a potential benefit. Given that infectious complications are the most common adverse events associated with transrectal biopsy, this simple and low-cost intervention may improve patient safety.
Keywords: enema, infectious complications, povidone-iodine, prostate cancer, rectal cleansing, transrectal prostate biopsy, urinary tract infection
1. Introduction
With the increasing aging population, the incidence of prostate cancer (PCa) is also increasing. PCa is the second most commonly diagnosed cancer in men.[1] The standard method for diagnosing PCa is prostate biopsy (PBx).[2] PBx can be performed via either the transrectal or the transperineal route. Transrectal ultrasound (TRUS)-guided biopsy is the most commonly used technique for PBx.[3]
TRUS plays a significant role in prostate diseases owing to its low cost, ease of application, and guidance during biopsy. Conventional PBx performed under TRUS guidance was performed systematically and randomly using 12-core tru-cut samples.[4]
Following the TRUS-biopsy procedure, complications such as hematuria, hematospermia, rectal bleeding, urinary tract infection (UTI), pain, fever, pyuria, and febrile urinary infection may occur. Studies have reported hospitalization rates due to infectious complications to range from 0 to 6.3%.[5]
Infectious complications are a leading cause of post-biopsy hospitalization and prolonged stays, prompting the development of multiple strategies to reduce their incidence.
It is known that antibiotic prophylaxis before TRUS-biopsy and cleansing of the rectal mucosa with povidone-iodine (PI) reduce procedure-related infectious complications.[6,7] However, despite these pre-biopsy interventions, the infectious complications persisted.
In this study, all patients received standard preventive measures prior to transrectal ultrasound-guided prostate biopsy (TRUS-Bx), including antibiotic prophylaxis and rectal cleansing with PI. In addition to these standard measures, both groups underwent rectal enema administration. The aim of the study was to evaluate whether enhancing the rectal enema with PI-enhanced enema, compared with sodium phosphate enema (enema) alone, would further reduce procedure-related infectious complications following TRUS-Bx.
2. Materials and methods
This prospective, randomized study aimed to evaluate whether enhancing a standard rectal enema with PI, in addition to standard prophylactic measures applied to all patients (antibiotic prophylaxis and rectal mucosal cleansing with PI), reduces procedure-related infectious complications after TRUS-Bx.
2.1. Ethics
The study protocol was approved by the Hitit University Clinical Research Ethics Committee (Decision No: 2023-90, 13.09.2023) and institutional permission was obtained from the Education R&D EPK Unit (Decision No: 40600303/604.02). Written informed consent was obtained from all participants.
2.2. Participants
Eligible participants were patients undergoing PBx with at least one of the following indications: prostate-specific antigen > 2.5 ng/mL, abnormal digital rectal examination, or suspicious multiparametric magnetic resonance imaging lesions (Prostate Imaging Reporting and Data System score 3–5).[8] All patients had sterile urine cultures prior to the procedure and were fully oriented and cooperative at the time of biopsy.
Exclusion criteria were untreated or recent (< 10 days) UTI, poorly controlled diabetes mellitus (disregulated blood glucose levels), bleeding diathesis (defined as known coagulation disorders, platelet count < 100,000/μL, international normalized ratio > 1.5, or activated partial thromboplastin time above the normal range), immunodeficiency, use of immunosuppressive therapy, known PI allergy, PBx within the preceding 3 months, ongoing anticoagulant or antiplatelet therapy that could not be safely discontinued according to current guidelines, or permanent urinary catheterization.
2.3. Randomization
A total of 120 patients were randomized in a 1:1 ratio to the study (PI-enhanced enema) or control (enema only) group using sequentially numbered, sealed opaque envelopes prepared by an independent researcher. Neither participants nor the urologist performing the biopsy were blinded to group allocation due to the nature of the intervention. To minimize potential bias, outcome assessment was standardized using predefined clinical and microbiological criteria.
2.4. Intervention
The study group received rectal cleansing with a PI-enhanced enema (135 mL sodium phosphate enema + 10 mL PI) 1 hour before biopsy, whereas the control group received sodium phosphate enema alone. In both groups, the enema was retained in the rectum for a minimum of 10 minutes to ensure adequate contact. All patients underwent additional rectal PI application to the rectal mucosa using gauze immediately before biopsy and received oral cefixime (400 mg/day) starting 1 day prior to the procedure and continued for 7 days.
2.5. Biopsy procedure
All biopsies were performed by a single experienced urologist. Under biplanar TRUS guidance, local anesthesia was administered bilaterally to the periprostatic regions using 10 mL of prilocaine. All biopsy cores were obtained in a systematic and random manner, and no magnetic resonance imaging-targeted biopsies were performed. A standard 12-core biopsy was performed using an 18-gauge needle, with samples taken from the base, mid-gland, and apex of both prostatic lobes.[9]
2.6. Outcomes
The primary outcome was the occurrence of procedure-related infectious complications within 30 days after transrectal PBx, defined as febrile UTI or sepsis requiring hospitalization.
Positive urine and blood culture results were evaluated only in patients who developed infectious complications and were used to support the diagnosis.
Secondary outcomes included noninfectious complications such as hematuria, hematospermia, rectal bleeding, and acute urinary retention.
2.7. Follow-up
Patients were contacted by telephone daily for 7 days and reexamined on day 14 for pathology review. A final telephone follow-up was conducted on day 30. Patients without complications were discharged from follow-up.
2.8. Definitions
Infectious complications were defined as fever (> 37.8°C) accompanied by lower urinary tract symptoms (urgency, frequency, dysuria, or pyuria) within 30 days post-biopsy.[10] All patients with febrile UTIs were hospitalized. Urine and blood cultures were obtained only from patients who developed procedure-related infectious complications, such as febrile UTI or sepsis, during follow-up. Routine urine cultures were not repeated in asymptomatic patients. Sepsis was defined as systemic inflammatory response syndrome with microbiologically confirmed bacteriuria or bacteremia. The systemic inflammatory response syndrome criteria included body temperature > 38°C or < 36°C, respiratory rate > 20 breaths/minute or PaCO2 < 32 mm Hg, heart rate > 90 beats per minute, white blood cell count > 12,000/mm3 or < 4000/mm3, or > 10% immature neutrophils.[11] Patients with sepsis were managed in the intensive care unit (ICU).
2.9. Sample size calculation
An a priori power analysis was performed using G*Power (version 3.1; Heinrich-Heine-Universität Düsseldorf, Germany). Assuming an incidence of febrile UTI of 10% in the control group and 2% in the PI + enema group, with a 2-sided α of 0.05 and 80% power, a minimum of 55 patients per group was required to detect this difference using a chi-square test for proportions. To account for potential dropouts, 60 patients were enrolled in each group (total n = 120).
2.10. Statistical analysis
The normality of quantitative variables was assessed using the Kolmogorov–Smirnov test. For normally distributed variables, group comparisons were performed using the independent samples t-test, while the Mann–Whitney U test was applied for non-normally distributed variables. Categorical variables, including the primary outcome (positive urine culture), were compared using the chi-squared test or Fisher exact test, as appropriate. Risk differences with 95% confidence intervals were calculated for the primary outcome. Statistical parameters are expressed as mean ± standard deviation, median (min–max), and number (percentage). No missing data were observed for the analyzed outcomes. Statistical significance was set at P < .05. Data were analyzed using IBM SPSS Statistics for Windows, version 22.0 (IBM Corp.).
3. Results
Between September 2023 and May 2024, a total of 120 patients who underwent TRUS-guided biopsy at our clinic were included in the study. The demographic data of the patients are presented in Table 1.
Table 1.
Demographic data.
| Total | Enema | PI-enhanced enema | P | |
|---|---|---|---|---|
| Case, n | 120 | 60 | 60 | |
| Age | 66.60 ± 7.20 | 66.60 ± 6.80 | 66.70 ± 7.60 | .950 |
| BMI | 27.0 (14.7–37.2) | 27.7 (19.5–37.2) | 26.5 (14.7–35.2) | .598 |
| tPSA | 6.75 (0.5–100) | 6.9 (2.6–49.2) | 6.6 (0.5–100.0) | .823 |
| Prostate Volume | 61.25 (20–180) | 60.0 (25.0–180.0) | 62.5 (20.0–175.0) | .310 |
| HT (n, %) | 37 (30.8) | 22 (36.7) | 15 (25.0) | .166 |
| DM (n, %) | 32 (26.6) | 20 (33.3) | 12 (20.0) | .099 |
| CAD (n, %) | 25 (20.8) | 16 (26.7) | 9 (15.0) | .116 |
BMI = body mass index, CAD = coronary artery disease, DM = diabetes mellitus, HT = hypertension, n = number of patients, PI = povidone-iodine, tPSA = total prostate-specific antigen.
No statistically significant differences were observed between the groups regarding demographic characteristics (e.g., age and body mass index), serum prostate-specific antigen levels, prostate volumes assessed by transrectal ultrasonography, or the presence of comorbid conditions (Table 1).
According to the Clavien–Dindo classification, all noninfectious complications observed in this study were categorized as Grade I, as they required no pharmacological treatment beyond standard supportive care, no invasive intervention, and no prolonged hospitalization.
Infectious complications occurred in 6 patients (10%) in the enema group and 2 patients (3.3%) in the PI-enhanced enema group (P = .272). All patients were hospitalized and treated with parenteral antibiotics based on culture results. Sepsis developed in 2 patients (3.3%) in the enema group, requiring ICU care, while no sepsis or ICU admissions occurred in the PI-enhanced enema group (P = .496) (Table 2). Sepsis-related deaths were not observed.
Table 2.
Complications.
| Enema | PI-enhanced enema | P | |
|---|---|---|---|
| Fever (n, %) | 6 (10.0) | 2 (3.3) | .272 |
| Hematospermia (n, %) | 25 (41.7) | 26 (43.3) | .853 |
| Hematuria (n, %) | 16 (26.7) | 21 (35.0) | .323 |
| Dysuria (n, %) | 18 (30.0) | 10 (16.7) | .083 |
| Rectal Bleeding (n, %) | 12 (20.0) | 5 (8.3) | .083 |
| Acute Urinary Retention (n, %) | 1 (1.7) | 1 (1.7) | .067 |
| Febrile Urinary Infection (n, %) | 6 (10.0) | 2 (3.3) | .272 |
| Sepsis (n, %) | 2 (3.3) | 0 (0.0) | .496 |
Chi-square test; Exact test, a: 0.05.
indicates significant difference between groups.n = number of patients, PI = povidone-iodine.
In the enema group, 6 patients (10%) had positive urine cultures of Escherichia coli in 5 and Enterococcus faecium in 1 whereas all urine cultures in the PI-enhanced enema group were sterile, showing a statistically significant difference (P = .046). Blood cultures were positive for E. coli in 2 patients (3.3%) in the enema group, while all cultures in the PI-enhanced enema group were sterile; this difference was not statistically significant (P = .320) (Table 3).
Table 3.
Urine and blood culture results among patients who developed post-biopsy infectious complications.
| Test | Result | Enema | PI-enhanced enema | P |
|---|---|---|---|---|
| Urine Culture | E. coli (n, %) | 5 (8.3) | 0 (0.0) | .046* |
| E. faecium (n, %) | 1 (1.7) | 0 (0.0) | ||
| Sterile (n, %) | 0 (0) | 2 (3.3) | ||
| Blood Culture | E. coli (n, %) | 2 (3.3) | 0 (0.0) | .320 |
| Sterile (n, %) | 4 (6.7) | 2 (3.3) |
E. coli = Escherichia coli, E. faecium = Enterococcus faecium, n = number of patients, PI = povidone-iodine.
indicates significant difference between groups.
4. Discussion
Infectious complications remain the most clinically significant adverse events following TRUS-Bx, despite the routine use of antibiotic prophylaxis and rectal antiseptic preparation. These complications are primarily attributed to translocation of rectal flora into the prostate and bloodstream during needle passage through the rectal mucosa. Consequently, various strategies targeting rectal bacterial load reduction have been investigated to further improve procedural safety.
It is well established that rectal mucosal cleansing with PI immediately before biopsy reduces post-biopsy infectious complications by decreasing rectal bacterial colonization, particularly Escherichia coli strains.[6,7,12] However, infection rates have not been completely eliminated, suggesting that conventional rectal antisepsis alone may be insufficient in fully addressing bacterial burden within the rectal lumen.
In the present study, all patients received standardized preventive measures, including antibiotic prophylaxis and rectal mucosal cleansing with PI immediately before biopsy. In addition, both groups underwent rectal preparation with a enema. The key distinguishing intervention was the enhancement of the enema with PI in the study group, applied 1 hour prior to the procedure. This design allowed us to specifically evaluate whether augmenting mechanical rectal cleansing with an antiseptic agent could provide additive protection beyond standard prophylaxis.
The observed reduction in positive urine cultures in the PI-enhanced enema group suggests that earlier and more comprehensive rectal decontamination may play a critical role in minimizing bacterial translocation during biopsy. Unlike immediate pre-biopsy mucosal wiping with PI, which primarily affects the superficial rectal mucosa, the administration of a PI-containing enema may reduce bacterial load throughout the rectal lumen, including areas not directly reached by gauze-based cleansing.
Several previous studies have investigated rectal PI application using different modalities, such as rectal injection, suppositories, or mucosal wiping. A prospective randomized study by Park et al demonstrated that PI suppository use before TRUS-Bx significantly reduced infectious complications compared to antibiotic prophylaxis alone.[12] However, in most of these studies, PI was administered only in the intervention arm, whereas control groups did not receive PI-based rectal antisepsis.
In the study by Lee et al, PI was applied either by instillation into the anal canal and lower rectum or by direct manual mucosal cleansing using PI–soaked cotton balls. In contrast, our study combined 2 complementary approaches in the intervention group: rectal preparation with a PI–enhanced sodium phosphate enema administered 1 hour before biopsy, followed by immediate pre-biopsy rectal mucosal cleansing with PI, which was also applied to both groups as part of standard prophylaxis.[13]
Our study differs from prior literature in that both groups received PI rectal mucosal cleansing immediately before biopsy, reflecting real-world standard practice. The additional benefit observed with the PI-enhanced enema therefore suggests that the timing, depth, and method of PI delivery are clinically relevant. This distinction is important, as it indicates that not only the presence of an antiseptic agent, but also its method of administration, may influence infection risk.
From a mechanistic perspective, the combination of enema and PI may exert both mechanical and biological effects. The enema facilitates evacuation of fecal material, while PI provides broad-spectrum antimicrobial activity against gram-negative and gram-positive bacteria.[14] The earlier administration of this combination may allow sufficient contact time for antiseptic action and sustained reduction of rectal bacterial load at the time of needle traversal. Although reductions in febrile UTIs and sepsis-related hospitalizations did not reach statistical significance, the consistent trend toward fewer infectious events in the PI-enhanced enema group is clinically meaningful. Importantly, no sepsis or ICU admissions occurred in the intervention group, supporting the potential protective effect of this approach in preventing severe infectious outcomes.
5. Limitations
This study has several limitations. First, rectal swab cultures were not obtained before or after enema administration, limiting direct assessment of rectal flora changes and antimicrobial resistance patterns. Second, the sample size may have been insufficient to detect statistically significant differences in rare outcomes such as sepsis. Additionally, the limited number of culture-positive cases precluded detailed analysis of pathogen-specific resistance profiles. Nevertheless, the increasing resistance of rectal flora, particularly E. coli, to commonly used prophylactic antibiotics highlights the need for adjunctive nonantibiotic preventive strategies. In this context, rectal preparation with a PI-enhanced enema may reduce bacterial load independently of antibiotic susceptibility. Despite these limitations, the prospective randomized design and standardized prophylactic protocol strengthen the internal validity of our findings.
6. Conclusions and recommendations
With the increasing number of prostate biopsies performed worldwide, the effective management of procedure-related complications has become increasingly critical. Infectious complications remain a major concern because of their potential morbidity and mortality. In this study, rectal cleansing with a PI-enhanced enema prior to TRUS-guided biopsy was associated with a numerical reduction in infectious complications, although the difference was not statistically significant. Notably, E. coli was significantly less frequent in the urine cultures of infected patients in the PI-enhanced enema group, and no sepsis cases were observed in this group. These findings suggest the potential benefits of an enhanced rectal preparation. However, larger-scale prospective studies are necessary to validate the effectiveness of such strategies in preventing post-biopsy infections.
Author contributions
Conceptualization: Mücahit Doğan.
Data curation: Mücahit Doğan.
Formal analysis: Mücahit Doğan.
Investigation: Mücahit Doğan.
Methodology: Mücahit Doğan, Cemil Aydin.
Project administration: Mücahit Doğan.
Resources: Mücahit Doğan, Muhammet İhsan Öztürk.
Software: Mücahit Doğan.
Supervision: Cemil Aydin, Musa Ekici, Mehmet Murat Baykam.
Validation: Mücahit Doğan, Cemil Aydin, Mustafa Serdar Çağlayan.
Visualization: Mücahit Doğan.
Writing – original draft: Mücahit Doğan.
Writing – review & editing: Mücahit Doğan, Cemil Aydin.
Abbreviations:
- ICU
- intensive care unit
- PCa
- prostate cancer
- PBx
- prostate biopsy
- PI
- povidone-iodine
- TRUS
- transrectal ultrasound
- TRUS-Bx
- transrectal ultrasound guided prostate biopsy
- UTI
- urinary tract infection.
This prospective, randomized, single-center study was approved by the Institutional Review Board of Hitit University Clinical Research Ethics Committee (Approval No: 2023-90; Approval date: September 13, 2023). Written informed consent was obtained from all participants prior to enrollment. This study was conducted in accordance with the principles of the Declaration of Helsinki.
The authors have no funding and conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
How to cite this article: Doğan M, Aydin C, Ekici M, Çağlayan MS, Öztürk Mİ, Baykam MM. The effect of povidone-iodine-enhanced rectal enema on procedure-related infectious complications before transrectal ultrasound-guided prostate biopsy: A prospective randomized study. Medicine 2026;105:20(e48830).
Contributor Information
Cemil Aydin, Email: cemilaydin78@yahoo.com.tr.
Musa Ekici, Email: musaekici40@gmail.com.
Mustafa Serdar Çağlayan, Email: serdar.09.09@hotmail.com.
Muhammet İhsan Öztürk, Email: ozturkm.ihsan@gmail.com.
Mehmet Murat Baykam, Email: mbaykam@yahoo.com.
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