UROLOGICAL ONCOLOGY Comparison of Different Rectal Cleansing Methods for Reducing Post-Procedural Infectious Complications After Transrectal Ultrasound-Guided Prostate Biopsy Jong Eun Lee1, Sang Soo Shin2,3*, Taek Won Kang4, Jin Woong Kim5, Suk Hee Heo2, Yong Yeon Jeong2 Purpose: To compare the efficacy of three different rectal cleansing methods for reducing post-procedural infectious complications after transrectal ultrasound (TRUS)-guided prostate biopsy. Materials and Methods: A total of 451 consecutive patients who underwent TRUS-guided prostate biopsy were prospectively included in this study. All patients received targeted antimicrobial prophylaxis and underwent bowel preparation through laxative administration. The patients were divided into three groups on the basis of the method of rectal cleansing immediately before the procedure. Group I patients (n =165) underwent cleansing of the perianal skin using povidone-iodine cotton balls; group II patients (n=116) received an injection of povidone-iodine solution (0.1 g/mL) into the anal and lower rectal canals; and group III patients (n =170) received direct manual cleansing of the mucosal surface of the anus and lower rectum using povidone-iodine cotton balls. The three groups were compared regarding the incidence of post-procedural infectious complications, re-hospitalization rates, and mean length of hospital stay using one-way ANOVA, the Chi-square test, and multiple logistic regression analysis. Results: Post-procedural infectious complications occurred in %11.2 ,%21.8, and %6.5 of groups I, II, and III, respectively (P < .001). The incidence of overall infectious complications was significantly lower in group II (%95 CI: 0.958–0.232, OR = 0.472, P = .038) and group III (%95 CI: 0.555–0.129, OR = 0.267, P < .001) than in group I. Re-hospitalization rates were %2.6 ,%9.7, and %0.6 in groups I, II, and III, respectively (P < .001). The incidence of re-hospitalization was significantly lower in group II (%95 CI: 0.869–0.070, OR = 0.247, P = .029) and group III (%95 CI: 0.421–0.007, OR = 0.055, P = .005) than in group I. The mean length of hospital stay was significantly longer in group I than in group III (P = .009). Conclusion: Combined with targeted antimicrobial prophylaxis, direct manual cleansing of the mucosal surface of the anus and lower rectum using povidone-iodine cotton balls was most effective in preventing post-procedural infectious complications among the three different rectal cleansing methods. Keywords: biopsy; infection; prostate; sepsis; transrectal INTRODUCTION Transrectal ultrasound (TRUS)-guided prostate bi-opsy in patients with suspected prostate cancer is currently the gold-standard procedure for prostate can- cer diagnosis.(1) Although it is generally recognized as safe and well tolerated, TRUS-guided prostate biopsy is an invasive method of obtaining prostate tissue sam- ples that may occasionally cause serious complications. Whereas the reported overall complication rates after prostate biopsy vary widely in previous studies, ranging from 2% to 10.4%, the rates of infectious complication requiring hospitalization range from 0% to 6.3%.(2-4) In- deed, infectious complications are a leading cause of prolonged hospital stay and financial burden after pros- tate biopsy. Therefore, numerous strategies have been proposed to minimize those complications.(5-7) As it was shown to be effective in reducing the rate of 1Department of Radiology, Chonnam National University Hwasun Hospital, Hwasun-gun, Jeonnam, South Korea. 2 Department of Radiology, 3 Center for Aging and Geriatrics, 4 Department of Urology, Chonnam National University Medical School, Gwangju, South Korea. 5 Department of Radiology, Chosun University Medical School, Gwangju, South Korea. *Correspondence: Department of Radiology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju 61469, South Korea. Tel: +82 62 2205882, Fax: +82 62 2264380, E-mail: kjradsss@gmail.com. Received May 2018 & Accepted February 2019 infectious complications before colorectal surgery,(8) rectal cleansing before prostate biopsy, along with prophylactic antibiotics, is well known to reduce the risk of infectious complications.(9) A recent systemic review and meta-analysis revealed that rectal cleansing using povidone-iodine before prostate biopsy significantly reduced the rate of infectious complications compared to the control group.(10) When a combination of povi- done-iodine and prophylactic antibiotics is used, these effects are further accentuated.(4,10) However, as optimal rectal cleansing methods have not been standardized, various protocols have been used.(11-13) Raman et al. re- ported that soaking the rectum and painting the perianal area with povidone-iodine gauze before prostate biopsy reduced the post-biopsy infectious complications rate from 4.3% to 0.6%.(12) In a study by AbuGhosh et al., the anterior rectal mucosa was directly cleansed using an examiner’s finger and a thin layer of gauze soaked in Urology Journal/Vol 17 No. 1/ January-February 2020/ pp. 42-49. [DOI: 10.22037/uj.v0i0.4583] Vol 17 No 01 January-February 2020 43 povidone-iodine.(13) To the best of our knowledge, the effectiveness of these various methods of rectal cleans- ing has not been meticulously compared. Therefore, the aim of this study was to compare the efficacy of different rectal cleansing measures for re- ducing post-procedural infectious complications after TRUS-guided prostate biopsy. MATERIALS AND METHODS Patients This study was approved by our institutional review board, and written informed consent was obtained from all patients. During a one-year of study period, 456 consecutive patients from a single tertiary center who underwent TRUS-guided prostate biopsy under hos- pitalization were prospectively included in this study. Among them, five patients who did not undergo rectal swab culture for the targeted antimicrobial prophylaxis because of the following reasons were excluded from the study: (1) four patients were already hospitalized for the evaluation of bone metastasis of unknown origin, and (2) one patient was already on antibiotic treatment because of a severe urinary tract infection (UTI). Final- ly, 451 patients were enrolled in this study. The indications for biopsy were as follows: (1) prostate specific antigen (PSA) value greater than 4 ng/mL (n = 407, 90.2%); (2) concerning findings on digital rectal examination such as a nodule, induration, and asymme- try or concerning abnormal lesions on TRUS or prostate MR imaging (n = 16, 3.5%); (3) the presence of both (1) and (2) (n = 24, 5.3%); and (4) atypia on a previous prostate needle biopsy (n = 4, 0.9%). During the study period, one of three different rectal cleansing methods was used just prior to the procedure. The rectal cleans- ing method was applied differently every month for randomization. Each method was used for a total of four months during the study period of one year. Group I patients underwent cleansing of the perianal skin using povidone-iodine cotton balls (Figure 1A); group II pa- tients received an injection of povidone-iodine solution (0.1 g/mL) into the anal and lower rectal canals (Figure 1B); group III patients underwent direct manual cleans- ing of the mucosal surface of the anus and lower rectum using forceps and povidone-iodine cotton balls (Figure 1C). Pre-procedural Preparations All patients were admitted to the hospital one day prior to the procedure. They received targeted antimicrobial prophylaxis on the basis of the rectal swab culture re- sults. The rectal swab samples were obtained two weeks before the biopsy and cultured on MacConkey’s agar (KOMED) containing 1 μg/mL ciprofloxacin overnight at 37℃ in ambient air. All isolates were subjected to organism identification and antimicrobial susceptibility testing using an automated microbial system (VITEK® 2). If quinolone resistance was not observed in the re- sults of the rectal swab culture, the patients received an- tibiotic prophylaxis consisting of a total of three intra- venous injections of ciprofloxacin (400 mg) at morning and evening of day of biopsy, and the morning after the procedure. However, in cases of quinolone resistance, the patients received a total of three intravenous injec- tions of prophylactic ceftriaxone (500 mg) before and after the procedure. All patients also underwent bowel preparation using laxatives the day before the proce- dure. To minimize pain during the procedure, intrave- nous dripping of 100 mL of physiologic saline mixed with ketamine (10 mg/mL) was started one hour prior to the biopsy. Biopsy Protocol The patient was positioned in the left lateral decubitus position with their knees bent. All patients underwent rectal cleansing using one of three different methods immediately before the procedure. TRUS-guided pros- tate biopsy was performed using an 18-gauge fully automated biopsy gun with a needle length of 20 cm, cutting notch size of 1.6 cm, and stroke length of 22 mm (Acecut; CIVCO Medical Solutions, Kalona, IA, USA) under ultrasonographic guidance (LOGIC E9; GE Healthcare, Milwaukee, WI, USA) by one expe- rienced radiologist. During the procedure, the biopsy needle was inserted via a steering device attached to the 5.0 to 7.5 MHz transducer to visualize the needle path parallel to the electronic guideline provided by the US images. A total of eight tissue specimens were taken from the prostate gland, with two cores in each of the Rectal cleansing methods in prostate biopsy-Lee et al. Figure 1. Illustrations showing the three different rectal cleansing methods. A. Group I: cleansing of the perianal skin using povidone-iodine cotton balls. B. Group II: injection of povidone-iodine solution (0.1 g/ mL) into the anal and lower rectal canals. C. Group III: direct manual cleansing of the mucosal surface of the anus and lower rectum using povidone-iodine cotton balls. four regions (right upper, right lower, left upper, and left lower) of the prostate gland. Further, in cases with a suspicious focal lesion in the middle part in both pros- tate glands on ultrasound images, tissue samples were additionally obtained at those portions. Immediately after the core tissues were extracted, manual compres- sion of the prostate gland using the US probe was per- formed to prevent possible post-procedural bleeding. In addition, color Doppler US was performed to careful- ly check for any significant post-biopsy bleeding. The patients were discharged the day after the procedure if there were no complications, and they were routinely followed up on an out-patient basis within one month after discharge. In cases of unexpected complications, they were re-admitted via the emergency department. Data Analysis The electronic medical records of three groups were meticulously analyzed, including demographic data, prostate volume, PSA level, presence of infectious and non-infectious complications, and underlying dis- ease including diabetes mellitus (DM), by one urolo- gist who was blinded to the information regarding the rectal cleansing method applied to the patients. Moreo- ver, past history of Foley catheter insertion within one month before the procedure, antimicrobial use within three months, UTI or prostatitis within three months, hospitalization within six months, prostate biopsy with- in one year, and fluoroquinolone (FQ) resistance were also investigated. The presence or absence of FQ resist- ance was determined by the culture results of the rectal swab samples obtained two weeks before the biopsy. Infectious complications after biopsy were considered present if the patients showed asymptomatic bacteriuria or pyuria, symptomatic UTI or prostatitis with or with- out fever (> 37.8 °C), bacteremia, sepsis, or systemic inflammatory response syndrome (SIRS) at any time up to one month after the procedure. SIRS was de- fined by the presence of two of the following clinical findings: body temperature higher than 38 °C or lower than 36 °C, heart rate higher than 90/min, hyperventi- lation evidenced by a respiratory rate higher than 20/ min or PaCO2 lower than 32 mmHg, and white blood cell count higher than 12,000/μL or lower than 4,000/ μL.(14) Re-hospitalization was defined as re-admission to the hospital due to infectious complications related to the TRUS-guided prostate biopsy. Any additional hospitalization due to other diseases was not included in the data analysis. The length of hospital stay was de- fined as the total number of days spent in the hospital, excluding hospitalized time due to medical conditions other than the TRUS-guided biopsy. Non-infectious complications after the procedure included pain, hema- turia, hematospermia, rectal bleeding, and acute urinary retention (AUR). The intensity of pain was measured on the evening of the biopsy using the numeric pain rat- Urological Oncology 44 Table 1. Demographics and clinical characteristics of patients. Group I (N = 165) Group II (N = 116) Group III (N = 170) P-value Age, year; mean ± SD 68.63 ± 8.11 68.94 ± 8.52 67.49 ± 8.54 .282 Prostate volume, cc; mean ± SD 45.48 ± 27 41.57 ± 22.51 36.72 ± 15.59 .001 PSA level, ng/mL; median (IQR) 6.4 (3.6-10.5) 6.0 (4.2-10.1) 6.7 (4.3-11.9) .083 Diabetes mellitus (%) 30 (18.2) 23 (19.8) 33 (19.4) .932 Chronic kidney disease (%) 12 (7.3) 15 (12.9) 29 (17.1) .025 Foley catheter insertion state (%) 6 (3.6) 2 (1.7) 3 (1.8) .457 Recent antimicrobial use (%) 27 (16.4) 24 (20.7) 24 (14.1) .339 Recent hospitalization (%) 16 (9.7) 9 (7.8) 10 (5.9) .427 Recent history of UTI or prostatitis (%) 10 (6.1) 9 (7.8) 13 (7.6) .809 Recent history of prostate biopsy (%) 1 (0.6) 1 (0.9) 3 (1.8) .574 FQ resistance (%)a 55 (33.3) 53 (45.7) 89 (52.4) .002 Rectal swap culture result .102 E. coli (%) 147 (89.1) 106 (91.4) 144 (84.7) K. pneumonia (%) 2 (1.2) 5 (4.3) 8 (4.7) Other (%) 9 (5.5) 5 (4.3) 8 (4.7) No growth (%) 7 (4.2) 0 (0) 10 (5.9) Biopsy result .140 BPH (%) 99 (60) 55 (47.4) 83 (48.8) Prostate cancer (%) 59 (35.8) 52 (44.8) 81 (47.6) ASAP (%) 4 (2.4) 7 (6.0) 5 (2.9) Other (%) 3 (1.8) 2 (1.7) 1 (0.6) Abbreviations: PSA, Prostate Specific Antigen; IQR, Interquartile Range; UTI, Urinary Tract Infection; FQ, Fluoroquinolone; BPH, Benign Prostate Hyperplasia; ASAP, Atypical Small Acinar Proliferation. aOverall FQ resistance was 43.7%. Group I (N = 165) Group II (N = 116) Group III (N = 170) P-value Overall infectious complications (%) 36 (21.8) 13 (11.2) 11 (6.5) < .001 Asymptomatic bacteriuria/pyuria 7 (4.2) 9 (7.8) 4 (2.4) .092 UTI or prostatitis without fever 13 (7.9) 1 (0.9) 6 (3.5) .015 UTI or prostatitis with fever 10 (6.1) 1 (0.9) 0 (0) .001 Bacteremia or sepsis or SIRS 6 (3.6) 2 (1.7) 1 (0.6) .133 Re-hospitalization (%) 16 (9.7) 3 (2.6) 1 (0.6) < .001 Mean length of hospital stay, days; mean ± SD 3.42 ± 1.43 3.22 ± 1.41 3.04 ± 0.54 .012 Abbreviations: UTI, Urinary Tract Infection; SIRS, Systemic Inflammatory Response Syndrome. Table 2. Comparison among three groups with respect to post-procedural infectious complications, re-hospitalization, and mean length of hospital stay Rectal cleansing methods in prostate biopsy-Lee et al. Vol 17 No 01 January-February 2020 45 ing scale (NPRS), with an 11-point numeric scale rang- ing from ‘0’ representing ‘no pain’ to ‘10’ representing ‘worst pain imaginable’.(15) Other non-infectious com- plications were defined as events that developed at any time during the follow-up period of one month. Statistical Analysis Comparison of the incidence of post-procedural com- plications, re-hospitalization rates, and length of hospi- tal stay among the three groups according to the meth- od of rectal cleansing were assessed using one-way ANOVA for continuous variables and the Pearson Chi- square test for categorical variables. Multiple logistic regression analysis was performed to estimate adjusted odds ratios (ORs) to investigate which factors among the baseline clinical characteristics (rectal cleansing method, age, prostate volume, DM, Foley catheter in- sertion, recent antimicrobial use, recent hospitalization, recent history of UTI, prostatitis, prostate biopsy, and FQ resistance) significantly influenced the incidence of post-procedural infectious complications and re-hospi- talization rates. All statistical analyses were performed using IBM SPSS Statistics for Windows, Version 23.0 (IBM Corp., Armonk, NY, USA). A P value less than 0.05 was considered significant. RESULTS A total of 451 patients enrolled in this study were divid- ed into Group I (n = 165), II (n = 116), and III (n = 170), respectivey. The mean age of the patients was 68.28 ± 8.38 years, the mean prostate volume was 41.17 ± 22.38 cc, and the median PSA level (interquatile range) was 6.5 (4.1-10.8) ng/mL. According to the biopsy, the final diagnosis was benign prostate hyperplasia (n=237, 52.5%), prostate cancer (n = 192, 42.6%), atyp- ical small acinar proliferation (ASAP) (n = 16, 3.5%), and others (n=6, 1.3%). The results of the rectal swab culture performed before the biopsy were E. coli (n = 397, 88%), K. pneumonia (n=15, 3.3%), others (n=22, 4.9%), and no bacterial growth (n=17, 3.8%). Overall, FQ resistance was observed in 197 (43.7%) patients. The demographics and clinical characteristics of the pa- tients were compared among the three groups based on a method of rectal cleansing (Table 1). The mean pros- tate volume was significantly smaller in group III than in groups I and II (P = .001). The incidence of chronic kidney disease was different among the three groups (P = .025). Meanwhile, there were no statistically signifi- cant differences among the three groups in terms of age, PSA level, DM, Foley catheter insertion state, recent antimicrobial use, recent hospitalization, recent history of UTI or prostatitis, recent history of prostate biopsy, and biopsy results. Overall, post-procedural infectious complications oc- curred in 60 (13.3%) of 451 patients, among which 36 (21.8%), 13 (11.2%), and 11 (6.5%) cases developed in groups I, II, and III, respectively (P < .001) (Table 2). The incidence of overall post-procedural infectious complications was significantly lower in groups II (P = .025) and III (P < .001) than group I. However, there was no significant difference between groups II and III. Infectious complications consisted of asymptomatic bacteriuria or pyuria (n = 20, 4.4%), UTI or prostatitis without fever (n = 20, 4.4%), UTI or prostatitis with fever (n = 11, 2.4%), bacteremia, sepsis, or SIRS (n = 9, 2%). E. coli was the cause of bacteremia in all cases (n = 9), among which 50% were FQ-resistant E coli. Among various post-procedural infectious complica- tions, UTI or prostatitis occurred more frequently in group I than in groups II and III. Re-hospitalization rates were 9.7%, 2.6%, and 0.6% in groups I, II, and III, respectively (P < .001). Sub-group Table 3. Comparison among three groups with respect to post-procedural non-infectious complications Group I (N = 165) Group II (N = 116) Group III (N = 170) P-value Pain, NPRS; mean ± SD 1.64 ± 0.86 1.54 ± 0.96 1.49 ± 0.62 .211 Hematuria (%) 47 (28.5) 41 (35.3) 45 (26.5) .254 Hematospermia (%) 1 (0.6) 1 (0.6) 0 (0) .518 Rectal bleeding (%) 4 (2.4) 4 (3.4) 2 (1.2) .429 AUR (%) 5 (3) 8 (6.9) 2 (1.2) .029 Abbreviations: NPRS, Numeric Pain Rating Scale; AUR, Acute Urinary Retention. OR P-value 95% CI Rectal cleansing methoda Group II 0.472 .038 0.232–0.958 Group III 0.267 < .001 0.129–0.555 Age 1.013 .527 0.974–1.053 Prostate volume 0.994 .377 0.980–1.008 Diabetes Mellitus 0.806 .587 0.369–1.757 Chronic kidney disease 2.075 .112 0.844–5.099 Foley catheter insertion state 5.509 .016 1.380–22.001 Recent antimicrobial use 1.036 .943 0.392–2.737 Recent hospitalization 1 .026 .964 0.343–3.068 Recent history of UTI or prostatitis 1.962 .263 0.603–6.388 Recent history of prostate biopsy 2.638 .407 0.266–26.124 FQ resistance 0.873 .662 0.474–1.608 Abbreviations: OR, Odds Ratio; CI, Confidence Interval; UTI, Urinary Tract Infection; FQ, Fluoroquinolone. aThe reference category is Group I. Table 4. Influence of various clinical characteristics on post-procedural infectious complications Rectal cleansing methods in prostate biopsy-Lee et al. analysis showed that there were significant differences between groups I and II (P = .028) and groups I and III (P < .001). However, there was no significant difference between groups II and III. The mean length of hospital stay was 3.42 ± 1.43 days, 3.22 ± 1.41 days, and 3.04 ± 0.54 days in groups I, II, and III, respectively. While the mean hospital stay was significantly longer in group I than in group III (P = .009), there was no significant difference between groups I and II and groups II and III. Regarding non-infectious post-procedural complica- tions, the overall NPRS was 1.56 ± 0.81. The incidence of hematuria, hematospermia, rectal bleeding, and AUR after TRUS biopsy was 29.5% (n = 133), 0.4% (n = 2), 2.2% (n = 10), and 3.3% (n = 15), respectively (Table 3). Among these non-infectious complications, the in- cidence of AUR was significantly lower in group III than II (P = .029). However, there were no significant differences among the three groups in terms of other non-infectious complications. Among the various clinical characteristics including rectal cleansing method, age, prostate volume, DM, Foley catheter insertion, recent antimicrobial use, re- cent hospitalization, recent history of UTI, prostatitis, prostate biopsy, and FQ resistance, the rectal cleansing method and Foley catheter insertion were significant factors for the occurrence of post-procedural infectious complication (Table 4). The incidence of post-proce- dural infectious complications was significantly re- duced in group II (OR = 0.472, 95% CI: 0.232-0.958, P = .038) and group III (OR = 0.267, 95% CI: 0.129- 0.555, P < .001) as compared to group I. In addition, Foley catheter insertion state (OR = 5.509, 95% CI: 1.380-22.001, P = .016) was an independent predictor of infectious complications after TRUS biopsy. Mean- while, re-hospitalization rates were significantly influ- enced by the rectal cleansing method, recent history of UTI or prostatitis, and recent history of prostate biopsy (Table 5). Among the three groups, re-hospitalization rates were significantly lower in group II (OR = 0.247, 95% CI: 0.070-0.869, P = .029) and group III (OR = 0.055, 95% CI: 0.007-0.421, P = .005) than in group I. DISCUSSION The human gastrointestinal tract normally harbors nu- merous microbiomes, and the highest concentration of microbiomes is present in the rectum. Damage to the barrier function of the rectal mucosa can result in en- trance of viable rectal microbiomes and their virulent products into systemic circulation, which may result in sepsis, SIRS, multiple organ dysfunction syndrome, and even death. This phenomenon is called “bacterial trans- location”, and various rectal procedures and operations can facilitate translocation of normal microbiomes.(16) However, exactly how the bacterial colonies from the rectum enter directly into the bloodstream, urine, or prostate tissue through the biopsy needle and lead to infectious complications remains to be elucidated. Several studies comparing transperineal and transrec- tal prostate biopsy have suggested that these rectal microbiomes may be closely related to the infectious complications of prostate biopsy.(3,17) The transperine- al route for prostate biopsy, which represents an alter- native pathway to avoid direct contact with the rectal microbiome, has shown a significantly lower incidence of infectious complications compared to the typical transrectal route.(3) According to a study by Grummet el al., the rate of re-hospitalization for infection was zero among 245 patients.(17) Furthermore, a systemic review of the literature published from 2003 to 2013 found that transperineal prostate biopsy resulted in only a 0.076% re-hospitalization rate for sepsis,(17) which is significant- ly lower than that reported for transrectal prostate biop- sy.(3,4) However, despite the advantage of a decreased rate of serious infectious complications, transperineal prostate biopsy is not widely used because it is difficult to perform under local anesthesia and incurs relative- ly higher costs, and requires specialized equipment.(17) Therefore, methods that have the potential to minimize the effect of rectal microbiomes in transrectal prostate biopsy are relatively preferred. Several studies reported that bowel preparation using a disinfectant agent such as povidone-iodine signifi- cantly reduced post-procedural infectious complica- tions,(11,18,19) including a previous study showing that rectal cleansing with povidone-iodine effectively re- duced the colony count of rectal microbiomes including FQ-resistant E.coli owing to its bactericidal activity.(19) Moreover, as compared to antibiotic prophylaxis alone, rectal cleansing using povidone-iodine in addition to antibiotic prophylaxis was shown to be more effective in lowering the incidence of infectious complications following prostate biopsy.(3,5,20) However, a prospective randomized trial reported that although rectal cleansing with povidone-iodine before TRUS-guided prostate biopsy had led to a 42% decrease in the relative risk of post-procedural infectious complications, it was not Table 5. Influence of various clinical characteristics on re-hospitalization rates OR P-value 95% CI Rectal cleansing measurea Group II 0.247 .029 0.070–0.869 Group III 0.055 .005 0.007–0.421 Age 0.975 .448 0.914–1.040 Prostate volume 0.970 .055 0.941–1.001 Diabetes Mellitus 2.482 .135 0.753–8.184 Chronic kidney disease 2.049 .369 0.429–9.789 Foley catheter insertion state 0.455 .628 0.019–11.001 Recent antimicrobial use 0.745 .698 0.167–3.331 Recent hospitalization 0.922 .926 0.166–5.114 Recent history of UTI or prostatitis 5.934 .006 1.660–21.214 Recent history of prostate biopsy 19.024 .030 1.322–273.824 FQ resistance 1.232 .697 0.432–3.513 Abbreviations: OR, Odds Ratio; CI, Confidence Interval; UTI, Urinary Tract Infection; FQ, Fluoroquinolone. aThe reference category is Group I. Rectal cleansing methods in prostate biopsy-Lee et al. Urological Oncology 46 Vol 17 No 01 January-February 2020 47 statistically significant.(13) Currently, American Uro- logical Association (AUA) and European Association of Urology guidelines recommend rectal cleansing with povidone-iodine plus antibiotic prophylaxis be- fore transrectal prostate biopsy if the local risk of in- fectious complications is high.(3,21) Regarding the rectal cleansing protocol, a variety of pre-procedural rectal preparation methods have been used thus far.(11-13,18,19,22) Ghafoori et al. demonstrated that the injection of pov- idone-iodine solution into the rectum significantly de- creased the rate of post-procedural infectious complica- tions.(11) A study by Park et al. claimed that soaking the rectum with a povidone-iodine suppository was more effective than a povidone-iodine enema.(19) Chen et al. adopted a direct method of cleansing the rectal muco- sa overlying the prostate gland using povidone-iodine gauze that showed a 9.6% reduction in the incidence of post-procedural infectious complications.(22) Anoth- er study reported that this direct cleansing of the rectal vault and perianal area by povidone-iodine reduced the rate of post-procedural infectious complications by de- creasing rectal microbial colonization.(18) In our study, we compared the effectiveness of three rectal cleansing methods for reducing post-procedural infectious com- plications. The incidence of post-procedural infectious complications and re-hospitalization rates were lowest in patients who underwent direct manual cleansing of the mucosal surface of the anus and lower rectum using forceps and povidone-iodine cotton balls. Additionally, this group of patients showed the shortest mean length of hospital stay. Thus, our results may positively sup- port the expectation that, among various rectal cleans- ing methods, direct manual rectal cleansing may be the most effective way to yield a bactericidal effect and de- crease rectal microbial colonization before TRUS-guid- ed prostate biopsy. Prophylactic antibiotics is one of the well-known meth- ods of minimizing infectious complications caused by rectal microbiomes in TRUS-guided prostate biopsy. (23,24) According to AUA guidelines, antibiotic prophy- laxis is recommended in all patients.(23) In general, FQ antibiotics are the most preferable choice of drugs.(21) Since E. coli is the etiology of most infectious com- plications following prostate biopsy, the selection of prophylactic antibiotics focuses on this bacteria.(25) However, despite FQ-based prophylaxis, a noticeable increase in the prevalence of multi-resistant organisms including FQ-resistant organisms has recently been re- ported, which has contributed to the increased incidence of infectious complications.(26) Therefore, the need for a new prophylactic antibiotics regimen has arisen. Currently, targeted antibiotics prophylaxis using a rectal swab is considered one of the more effective regimens. (29,30) According to a meta-analysis, the incidence of in- fectious complications following transrectal prostate biopsy in the targeted antibiotic prophylaxis group was lower than in the empirical group.(31) However, the use- fulness of targeted prophylaxis in preventing post-pro- cedural infectious complications remains controversial. A study by Liss et al. found no significant difference in the rate of sepsis between groups receiving targeted prophylaxis versus empirical prophylaxis,(32) and all of the causative organisms of sepsis after prostate biopsy were FQ-sensitive E. coli despite adequate FQ proph- ylaxis. In our study, the causative organisms of sepsis were always E coli, of which only 50% were FQ-resist- ant E coli. Based on these results, it can be assumed that FQ prophylaxis for FQ-sensitive E. coli found in the rectal flora does not always prevent sepsis. Further in- vestigations are necessary to determine which virulence factors besides FQ resistance are involved in post-biop- sy sepsis despite sufficient antibiotic prophylaxis.(33,34) Recent urinary catheterization is one of the known risk factors for post-procedural infectious complications. Simsir et al. reported that the presence of a urinary catheter had predictive risk value for sepsis following TRUS-guided prostate biopsy because the catheter can become an important mediator of microbial coloniza- tion.(35) In our study, recent urinary catheterization in- creased the risk of overall infectious complications by five-fold. However, given that it is frequently used for short periods of time in most clinical situations, the urinary catheter may be more typically associated with minor infectious complications such as bacteriuria.(36) In our study, the mean prostate volume was significant- ly smaller in group III. Therefore, there would be a pos- sibility that a difference in baseline prostate size could produce bias or influence on the rate of postprocedur- al infectious complications. However, in multivariate analysis in our study, no significant association between the prostate volume and infectious complications was found. This result is in agreement with other studies.(3,26) Our study has several limitations. First, the study design was retrospective. Therefore, it was difficult to defini- tively assure that all patients underwent the same fol- low-up assessment. And also, future studies including a randomized clinical trial are needed to validate our results. Second, although urinalysis was performed in all patients, additional evaluation including urine cul- ture, blood culture, or other laboratory studies were performed only in symptomatic patients. Thus, those who were asymptomatic or had mild symptoms did not undergo these additional studies. CONCLUSIONS Combined with targeted antimicrobial prophylaxis, direct manual cleansing of the mucosal surface of the anus and lower rectum using povidone-iodine cotton balls was most effective in preventing post-procedural infectious complications among the three different rec- tal cleansing methods. ACKNOWLEDGEMENT This work was supported by the funds from the Na- tional Research Foundation of Korea (2018R1D- 1A3B07043473) and the Chonnam National Universi- ty Hospital Research Institute of Clinical Medicine in South Korea (CRI18091-2). CONFLICT OF INTEREST The authors report no conflict of interest. REFERENCES 1. Shariat SF, Roehrborn CG. Using biopsy to detect prostate cancer. Rev Urol. 2008;10:262- 80. 2. Liss MA, Ehdaie MB, Loeb S, et al. An update of the American Urological Association white paper on the prevention and treatment of the more common complications related to Rectal cleansing methods in prostate biopsy-Lee et al. prostate biopsy. J Urol. 2017;198:329-34. 3. 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