Reducing Infectious Complications Following Transrectal Ultrasoundguided Prostate Biopsy: A Systematic Review

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1 SYSTEMATIC REVIEW Reducing Infectious Complications Following Transrectal Ultrasoundguided Prostate Biopsy: A Systematic Review Jordon T. Walker, BS, Nirmish Singla, MD, Claus G. Roehrborn, MD Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX A rise in antimicrobial resistant uropathogens has generated a global increase in infections following transrectal ultrasound-guided prostate biopsy (TRUS-Bx). We performed a systematic search of Ovid MEDLINE and PubMed to comprehensively review strategies to mitigate infections. Of 1664 articles retrieved, 62 were included. The data suggest that augmented prophylaxis and povidone-iodine bowel preparation warrant consideration in regions with high rates of antimicrobial resistance. Transperineal biopsy may be a safer, equally effective alternative to TRUS-Bx in select cases. Recent international travel appears to increase patients risk for experiencing infections. These findings can aid clinicians in minimizing post-trus-bx infectious complications. [Rev Urol. 2016;18(2):73-89 doi: /riu0713] 2016 MedReviews, LLC KEY WORDS Transrectal ultrasound Prostate biopsy Urinary tract infection Systematic review Transrectal ultrasound-guided prostate biopsy (TRUS-Bx) is one of the most common urologic procedures performed worldwide, with over 1 million biopsies annually performed in the United States alone. 1 Overall, prostate biopsies are relatively safe and only approximately 5% of men develop infections after TRUS-Bx. 2 Fluoroquinolone (FQ) prophylaxis is routinely administered prior to biopsy to minimize infections. Alarmingly, however, there has been a sharp rise in infectious complications following TRUS-Bx in recent years. Nam and colleagues 3 reported an increase in 30-day hospital admission rates from 1.0% in 1996 to 4.1% in 2005 in Canada, and similar increases have been Vol. 18 No Reviews in Urology 73

2 Reducing Infectious Complications Following TRUS-Bx continued reported in Europe 4 and the United States. 5 Numerous studies attribute this rise to an increasing prevalence of FQ-resistant organisms 6 (specifically Escherichia coli sequence type 131) 7,8 and extended spectrum -lactamase (ESBL)- producing bacteria. 8,9 Current prophylactic recommendations in the American Urological Association Best Practice Policy Statement on Urologic Surgery Antimicrobial Prophylaxis heavily rely upon studies conducted before 2005, which predates the rise in antibioticresistant uropathogens. 10 Given the proliferation in research on strategies to prevent post-trus-bx infections, existing guidelines lag behind contemporary knowledge. This article systematically reviews optimal techniques to minimize post-trus-bx infections, to aid incorporation of contemporary research findings into clinical practice. Eligibility Screening Identification Included Records identified through database search (n = 2513) Additional records identified through other sources (n = 8) Records after duplicates removed (n = 1664) Records screened by title (n = 1664) Abstracts assessed for eligibility (n = 274) Full-text articles assessed for eligibility (n = 102) Studies included in qualitative synthesis (n = 62) Records excluded (n = 1390) Records excluded (no abstract, commentary only, irrelevant) (n = 172) Full-text articles excluded (included in prior metaanalysis, irrelevant) (n = 40) Methodology We conducted a systematic review of the Ovid MEDLINE and PubMed databases using Boolean search combinations of key terms (prostate biopsy, infection, complication, cost, management, organism, prevalence, resistance, and risk) to identify relevant articles published in English between January 1995 and December Reference lists of retrieved papers were searched and related articles were manually included. The Preferred Reporting Items for Systematic Reviews and Meta-analyses statement guided the search process, and the results of the systematic review are outlined in Figure 1. Antibiotic Prophylaxis A wide diversity of prophylactic antibiotics have been used (Table 1), and regimens can be divided into three approaches: monotherapy, Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flowchart of the search process. augmented prophylaxis ( 2 antibiotics), or rectal swab targeted prophylaxis. Monotherapy FQ antibiotics are the mainstay of first-line prophylaxis for TRUS-Bx. 11 However, a rising prevalence of FQ-resistant bacteria prompted multiple authors to investigate alternative monotherapy options. Retrieved studies primarily explored piperacillintazobactam, cephalosporins (eg, ceftriaxone), fosfomycin, and amoxicillin/clavulanic acid as monotherapy substitutes. Two recent meta-analyses reported piperacillin-tazobactam FQ antibiotics are the mainstay of first-line prophylaxis for TRUS-Bx. and ceftriaxone to be equally effective as FQs in preventing urinary tract infections (UTIs; range P ) and infectionrelated hospitalizations (range P ). 12,13 Similarly, one study reported no significant differences in the rate of afebrile and febrile UTIs in patients receiving either FQs (500 mg ciprofloxacin or 500 mg levofloxacin) or 3 g fosfomycin (P.05). 14 Recent data indicate that fosfomycin achieves a mean prostate-to-plasma concentration ratio of , which is higher than other more commonly used agents (the prostate-to-plasma ratio of amikacin is ). 15,16 Data regarding the 74 Vol. 18 No Reviews in Urology

3 Reducing Infectious Complications Following TRUS-Bx -lactamase inhibitor amoxicillin/ clavulanic acid, in contrast, suggest it offers inferior protection compared with FQs. 17 Three independent studies in Denmark and the United Kingdom reported large increases in infectious complications following the replacement of ciprofloxacin prophylaxis with amoxicillin/clavulanic acid. 11,18,19 These results argue against the use of amoxicillin/clavulanic acid as monotherapy for TRUS-Bx. Although some empiric data support the efficacy of alternative agents for monotherapy, sample sizes are generally quite modest (range ), and further research is required to justify supplanting FQs as first-line prophylaxis. Augmented Prophylaxis Augmented prophylaxis has consistently demonstrated superior protection compared with monotherapy. 5,13,20-24 A recent meta-analysis of three randomized controlled trials (RCTs; n 659) documented the protective superiority of augmented prophylaxis in reducing UTIs (relative risk [RR] 4.64, 95% confidence interval [CI], ; P.0003) and hospitalizations (RR 5.91, 95% CI, ; P.004) following prostate biopsy. 13 FQs were most frequently coupled with aminoglycosides, specifically gentamicin and amikacin, in augmented prophylactic protocols. 20,21 In a retrospective study, Lorber and associates 21 reported an 83% reduction in urosepsis by augmenting FQ prophylaxis with a single 240-mg dose of intramuscular (IM) gentamicin (3.6% vs 0.6%; P.04). 21 Similar results were obtained in two studies when IM gentamicin (1 mg/kg and 80 mg, respectively) was added to ciprofloxacin prophylaxis in a quality improvement initiative at the Cleveland Clinic (Cleveland, OH; 10% vs 2.5%; P not reported) 5 and in a tertiary academic medical center in Texas (3.8% vs 0.6%; P.001). 22 Augmented prophylaxis using gentamicin is cost effective (an 80-mg vial costs $0.15), 25 and econometric analysis indicates the augmented regimen can produce savings of $15,700 per 100 patients due to avoided hospitalizations. 22 Amikacin was the second most frequently used aminoglycoside in augmented protocols. Kehinde and colleagues 23 reported a drastic reduction in septic events (1.7% vs 8.0%; P.001) after adding 500 mg intravenous (IV) amikacin before biopsy to standard FQ prophylaxis. Due to its effectiveness against E coli 23 and projected cost savings per patient ranging from $9.50 to $69.50 in avoided complication costs, amikacin may be a favorable adjunct to FQ prophylaxis. 26 Carbapenems were also frequently used in augmented protocols. In a recent New Zealand study, adding ertapenem to standard prophylaxis (ciprofloxacin and amoxicillin/clavulanic acid) substantially reduced rates of sepsis in a highrisk group (6.7% [95% CI, ] vs 0%; P.03). 24 Likewise, Shakil and associates 27 reported zero infectious complications following TRUS-Bx in patients with documented multidrug-resistant E coli FQs were most frequently coupled with aminoglycosides, specifically gentamicin and amikacin, in augmented prophylactic protocols. given IV ertapenem as prophylaxis. Thus, ertapenem currently appears to be highly effective in preventing microbial infections resistant to other agents. However, carbapenemase-producing bacteria have been reported in diverse regions of the world, including the United States, Israel, Greece, and Colombia. 28 Increasing carbapenem resistance may limit the utility of this class of antibiotics for future prophylaxis and justifies restricting carbapenems for treating only severe infections. Given the myriad combinations of augmented prophylaxis, it is reasonable to consider the relative effectiveness of various combinations. One study comparatively evaluated different augmented prophylaxis regimens. In a retrospective study, ciprofloxacin plus an IM aminoglycoside afforded inferior protection to levofloxacin plus an IM aminoglycoside in reducing severe infections (odds ratio [OR] 4.59; 95% CI, ; P.04). 29 Choice of aminoglycoside did not significantly affect infection rates (P.68), 29 thereby suggesting equivalent efficacy among different aminoglycosides. Although the literature supporting augmented prophylaxis in TRUS-Bx is robust, a number of shortcomings should be noted. Augmented prophylaxis is only a temporary solution to increased antimicrobial resistance, and widespread use of combinations of antibiotics will further exacerbate selection pressure for resistant microbes. Additionally, there is considerable heterogeneity in local sensitivity patterns of organisms causing post-trus-bx infections. Given such variability, it is important to consider the geographic context of reported literature findings and to evaluate their applicability to local patterns of resistance in urologic practices. Targeted Prophylaxis Targeted prophylaxis based on rectal swab culture has been extensively studied, yet ambiguity remains regarding the utility of routinely performing targeted Vol. 18 No Reviews in Urology 75

4 Reducing Infectious Complications Following TRUS-Bx continued TABLE 1 Selected Studies of Antibiotic Prophylaxis for TRUS-Bx Study Year Sample Size Methodology Country Standard Prophylaxis Alternative Prophylaxis Outcome Variables Adibi M Retrospective United States Oral 500 mg ciprofloxacin et al 22 twice daily for 3 d Antsupova V Retrospective Denmark Oral 500 mg ciprofloxacin et al 11 twice daily for 1 d Antsupova V Retrospective Denmark Oral 500 mg ciprofloxacin et al 11 twice daily for 1 d Dai J et al Retrospective United States Oral 500 mg ciprofloxacin (3 doses perioperatively) Duplessis CA Retrospective United States Oral 500 mg ciprofloxacin et al 67 twice daily for 3 d Horcajada JP Prospective Spain Oral 500 mg et al 17 amoxicillin/clavulanic acid 3 times daily for 5 d Standard 80 mg IM gentamicin 400 mg pivmecillinam plus 500/125 mg amoxicillin/clavulanic acid daily for 2 d before biopsy and three times daily for 2 d after biopsy 400 mg pivmecillinam plus 500/125 mg amoxicillin/clavulanic acid daily for 2 d before biopsy Rectal swab-targeted prophylaxis Rectal swab-targeted prophylaxis 2 g cefoxitin 1 h before biopsy and oral 750 mg ciprofloxacin twice daily for 5 d Hospitalization Bacteremia Bacteremia (cystitis, bacteriuria, pyelonephritis, bacteremia, sepsis) (bacteremia, fever, prostatitis, pyelonephritis, UTI, sepsis) Bacteremia, sepsis 76 Vol. 18 No Reviews in Urology

5 Reducing Infectious Complications Following TRUS-Bx Hori S et al Prospective United Kingdom Oral 500 mg ciprofloxacin 1 h before biopsy and twice daily for 3 d Hsieh T-Y Retrospective Taiwan Oral 500 mg levofloxacin et al 25 once daily for 5 d Kehinde EO Prospective Kuwait 4 doses of oral 500 mg et al 23 ciprofloxacin twice daily for 3 d Liss MA Retrospective United States Oral 500 mg ciprofloxacin et al 31 twice daily Lorber G Retrospective Israel Oral ciprofloxacin or et al 21 ciprofloxacin twice daily for 3 d Losco G Prospective New Zealand Oral 500 mg ciprofloxacin et al 24 and oral 625 mg amoxicillin/clavulanic acid 1 h before biopsy and twice daily for 3 d after biopsy Luong B Retrospective United States Oral 500 mg ciprofloxacin et al 54 twice daily for 4 d Oral 625 mg pamoxicillin/ clavulanic acid 1 h before biopsy and three times daily for 3 d Standard 80 mg IM gentamicin Sepsis Standard 500 mg IV amikacin Sepsis (chills, fever, macroscopic hematuria with blood clots, and severe LUTS) Rectal swab-targeted prophylaxis Sepsis Standard 240 mg IM gentamicin Sepsis Standard 1 g IM ertapenem Sepsis Oral 500 mg ciprofloxacin plus 1 g IM ceftriaxone (hospitalization, sepsis) (Continued) Vol. 18 No Reviews in Urology 77

6 Reducing Infectious Complications Following TRUS-Bx continued Selected Studies of Antibiotic Prophylaxis for TRUS-Bx (Continued) Study Year Sample Size Methodology Country Standard Prophylaxis Alternative Prophylaxis Outcome Variables Madden T Retrospective United et al 19 Kingdom Oral 500 mg ciprofloxacin before biopsy and twice daily for 3-5 d after biopsy Ongün S Retrospective Turkey Oral 500 mg ciprofloxacin et al 14 or 500 mg levoflox- acin before biopsy and twice daily for 5 d after biopsy Roberts MJ Meta-analysis Multinational Empiric fluoroquinolone et al 30 prophylaxis Oral mg amoxicillin/clavulanic acid three times daily for 3 d after biopsy 120 mg gentamicin IV 10 min before biopsy (epididymo-orchitis, fever, prostatitis, sepsis, UTI) Oral 3 g fosfomycin Afebrile UTI, febrile UTI Rectal swab-targeted prophylaxis Shakil J et Prospective United States No comparator 1 g ertapenem IV for al d Summers SJ Retrospective United States Oral 500 mg ciprofloxacin et al 32 1 h before biopsy and twice daily for 3 d after biopsy Unnikrishnan Retrospective United States Oral 500 mg ciprofloxacin R et al 29 plus mg IM aminoglycoside Womble PR Prospective United States Oral 500 mg ciprofloxacin et al 20 twice daily for 1 d Rectal swab-targeted prophylaxis 750 mg levofloxacin mg IM aminoglycoside Standard 120 mg IM gentamicin (not defined) (not defined) (cystitis, bacteremia, pyelonephritis, sepsis) Mild infections (infections treated as outpatient), severe infections (infections requiring emergency room evaluation, hospital admission, or overnight stay within observation unit) Hospitalization 78 Vol. 18 No Reviews in Urology

7 Reducing Infectious Complications Following TRUS-Bx Womble PR Prospective United States Oral 500 mg ciprofloxacin et al 20 twice daily for 1 d Rectal swab-targeted prophylaxis Hospitalization Yang L Meta-analysis Multinational Monotherapy Augmented prophylaxis Antimicrobial resistant et al 13 bacteria on blood or urine culture, bacteremia, bacteriuria Yang L Meta-analysis Multinational Monotherapy Augmented prophylaxis Hospitalization, UTI et al 13 Yang L Meta-analysis Multinational Fluoroquinolone et al 13 (ciprofloxacin or levofloxacin) Ceftriaxone, chloramphenicol, or piperacillin-tazobactam Fever, hospitalization, UTI Zani EL Meta-analysis Multinational Fluoroquinolone et al 12 (ciprofloxacin or levofloxacin) Zani EL Meta-analysis Multinational Fluoroquinolone (ciprofloxacin et al 12 or levofloxacin) Zani EL Meta-analysis Multinational Fluoroquinolone et al 12 (ciprofloxacin or levofloxacin) Zani EL Meta-analysis Multinational Fluoroquinolone et al 12 (ciprofloxacin or levofloxacin) Ceftriaxone Hospitalization Piperacillin-tazobactam Hospitalization Ceftriaxone UTI Piperacillin-tazobactam UTI IM, intramuscular; IV, intravenous; LUTS, lower urinary tract symptoms; UTI, urinary tract infection. Vol. 18 No Reviews in Urology 79

8 Reducing Infectious Complications Following TRUS-Bx continued prophylaxis in patients undergoing TRUS-Bx. A meta-analysis of eight studies (n 2767) published between 2010 and 2013 strongly supports the efficacy of targeted prophylaxis over empirical FQ monotherapy for reducing infectious complications following TRUS-Bx (0.3% [95% CI, 0%-0.9%] vs 3.3% [95% CI, 2.6%-4.2%]; P.0003). 30 However, more recent studies failed to find a reduction in severe infectious complications with targeted prophylaxis. Liss and colleagues 31 found no difference in sepsis rates between patients receiving targeted prophylaxis versus empiric prophylaxis in a large study (n 5355) of 13 Kaiser Permanente Centers throughout the United States (0.44% vs 0.56%; P.568). Moreover, a recent statewide prospective study in Michigan (n 4087) reported similar hospitalization rates between patients receiving rectal culture-directed antibiotics and augmented prophylaxis (0.47% vs 0.58%; P not reported). 20 Similarly, two smaller studies conducted at a Veterans Affairs Hospital 32 and a US academic medical center 33 did not detect a significant difference in infectious complications between patients receiving targeted prophylaxis and those receiving empiric prophylaxis (P.13 and P.58, respectively). The failure of targeted prophylaxis to reduce severe infectious complications in large-scale studies calls into question whether it is appropriate for routine clinical practice. Additionally, there are numerous economic and logistic challenges to implementing targeted prophylaxis. Many of these challenges were highlighted at the 2014 AUA Quality Improvement Summit, including costs of additional labor, multiple clinic visits by patients, lack of adoption by microbiology laboratories, and requirements for special culture media. 5,23 Overall, the utility of targeted prophylaxis appears to be limited. Reports suggest only 6% to 9% of patients with FQ-resistant bacteria detected in their rectal flora develop infections following TRUS-Bx. 34,35 Hwang and coworkers 36 did not find an association between FQ-resistant bacteria or ESBL-producing bacteria on rectal culture and subsequent infectious complications (P.512 and P.363, respectively). Due to the considerable additional labor associated with targeted prophylaxis, the cost-to-benefit profile is unlikely to be favorable in the majority of patients. Nevertheless, as targeted prophylaxis mitigates concerns regarding accelerating antibiotic resistance, there may be a role for targeted prophylaxis in specific subgroups of patients most at risk for post-trus-bx infection. Biopsy Procedure The rising incidence of antimicrobial resistance has generated greater interest in using procedural The failure of targeted prophylaxis to reduce severe infectious complications in large-scale studies calls into question whether it is appropriate for routine clinical practice. 80 Vol. 18 No Reviews in Urology techniques to minimize infections. The majority of published literature focuses on three aspects of TRUS-Bx: prebiopsy bowel preparation, number of sampled cores, and biopsy needle disinfection techniques (Table 2). The transperineal approach to prostate biopsy has also generated interest in reducing infectious complications. Prebiopsy Bowel Preparation Evidence supporting the protective effect of prebiopsy bowel preparation varies based upon the agent used for rectal cleansing. The majority of studies investigating enemas (using sodium phosphate or saline) studies specifically evaluating povidone-iodine rectal cleansing, strongly support the use of a prebiopsy bowel preparation (topical, enema, or suppository) to reduce post-trus-bx infections. found no protective effect against post-trus-bx infections. 12,37-41 In contrast, studies specifically evaluating povidone-iodine rectal cleansing 36,42 strongly support the use of a prebiopsy bowel preparation (topical, enema, or suppository) to reduce post-trus-bx infections. In a meta-analysis of seven RCTs (n 2049), povidoneiodine disinfection plus antibiotics significantly reduced the rate of overall infectious complications compared with antibiotics alone (RR 0.23; 95% CI, ; P.0006), with significant reductions in both bacteremia (P.01) and fever (P.03). 42 Additionally, Hwang and colleagues 36 reported povidone-iodine enemas significantly reduced the incidence of bacteremia and sepsis (P.001) in a retrospective analysis at a Korean hospital. 36 Povidone-iodine offers a number of advantages in reducing post-trus-bx infections by decreasing rectal microbial counts prior to procedures in vitro, rapidly exerting its effects, and discouraging antimicrobial resistance. 43 These results can be used to guide the agent used for prebiopsy bowel preparation, as prebiopsy enemas are commonly performed by approximately 81% of US urologists, 44 but are not recommend in European guidelines. 45

9 Reducing Infectious Complications Following TRUS-Bx TABLE 2 Selected Studies on Procedural Techniques Impacting Infectious Complications Following TRUS-Bx Study Year Sample Size Methodology Country Standard Technique Alternative Technique Outcome Variables Bennet HY ,577 Meta-analysis Multinational TRUS-Bx Transperineal prostate et al 51 biopsy Hospitalization, sepsis Berger AP Retrospective Austria 6 or 10 biopsy cores 15 biopsy cores et al 55 (epididymitis, fever, hospitalization, mortality, prostatitis) Bruyere F et al Prospective France Antibiotics alone Antibiotics plus enema (fever with positive urine culture, LUTS) Carey and Retrospective United States Antibiotics alone Antibiotics plus enema Korman 41 (epididymitis, hospitalization, prostatitis, UTI) Carignan A Retrospective Canada Antibiotics alone Antibiotics plus enema (not et al 65 defined) Grummet JP Prospective Australia No comparator Transperineal prostate et al 47 biopsy Grummet JP Systematic et al 47 review Australia No comparator Transperineal prostate biopsy Hsieh T-Y Retrospective Taiwan biopsy cores 10 biopsy cores et al 25 (chills, fever, macroscopic hematuria with blood clots, severe LUTS) Hwang EC Retrospective Korea Antibiotics alone Antibiotics plus povidoneiodine et al 36 disinfection Sepsis Sepsis FQ-resistant rectal culture, (fever, bacteremia, prostatitis, UTI, sepsis) (Continued) Vol. 18 No Reviews in Urology 81

10 Reducing Infectious Complications Following TRUS-Bx continued Selected Studies on Procedural Techniques Impacting Infectious Complications Following TRUS-Bx (continued) Study Year Sample Size Methodology Country Standard Technique Alternative Technique Outcome Variables Issa MM Retrospective United States Antibiotics alone Antibiotics plus formalin et al 52 (10%) disinfection of biopsy needle Sepsis, UTI Kam SC Retrospective Korea Antibiotics alone Antibiotics plus enema Infectious complication et al 56 (prostatitis) Kam SC Retrospective Korea 6 biopsy cores 12 biopsy cores Infectious complication et al 56 (prostatitis) Luong B Retrospective United States 14 biopsy cores biopsy cores et al 54 (hospitalization, sepsis) Park DS Retrospective Korea Antibiotics alone Antibiotics plus povidoneiodine et al 43 disinfection Rectal bacterial count Pepe P Retrospective Italy 12 biopsy cores biopsy cores et al 50 (emergency department visit, epididymo-orchitis, fever, hospitalizations, prostatitis, UTI, sepsis) Pu C et al Meta-analysis Multinational Placebo Povidone-iodine disinfection Pu C et al Meta-analysis Multinational Antibiotics alone Antibiotics plus povidoneiodine disinfection (bacteremia, bacteriuria, and fever) (bacteremia, bacteriuria, and fever) 82 Vol. 18 No Reviews in Urology

11 Reducing Infectious Complications Following TRUS-Bx Pu C et al Meta-analysis Multinational Antibiotics alone Antibiotics plus povidoneiodine disinfection Ruddick F Retrospective Canada Antibiotics alone Antibiotics enemas Sepsis et al 40 (bacteremia, bacteriuria, and fever) Simsir A Retrospective Turkey Varied number of biopsy et al 53 cores Singla N et al (unpublished data) N/A Sepsis Retrospective United States Antibiotics alone Antibiotics formalin (10%) disinfection of biopsy needle Vyas L et al Retrospective United Kingdom Wagenlehner Prospective Multinational Varied number of biopsy FM et al 2 cores (range1-40) Zani EL Meta-analysis Multinational Antibiotics alone (varied et al 12 regimen) Zani EL Meta-analysis Multinational Antibiotics alone (varied et al 12 regimen) Zani EL Meta-analysis Multinational Antibiotics alone (varied et al 12 regimen) No comparator Transperineal prostate biopsy Zaytoun OM Retrospective United States Oral 500 mg ciprofloxacin et al 37 1 h before biopsy UTI N/A UTI Epididymo-orchitis, hospitalization, sepsis Antibiotics enema Bacteriuria Antibiotics enema Bacteremia Antibiotics enema Fever Oral 500 mg ciprofloxacin for 3 d enema (positive urine culture), sepsis FQ, fluoroquinolone; LUTS, lower urinary tract symptoms; TRUS-Bx, transrectal ultrasound-guided prostate biopsy; UTI, urinary tract infection. Vol. 18 No Reviews in Urology 83

12 Reducing Infectious Complications Following TRUS-Bx continued Transrectal Versus Transperineal Biopsy Initial research indicates transperineal prostate biopsy may be equally effective as TRUS-Bx for detecting prostate cancer with a lower incidence of severe infections Transperineal biopsy poses a lower risk for infection because the method avoids seeding of the prostate gland with rectal flora. 46,47,49,50 A study on transperineal biopsies performed in Melbourne, Australia, found a 0% rate of sepsis among 245 patients. 47 The authors also conducted an analysis of the literature published from 2003 to 2013 and found only a 0.076% sepsis rate among 6609 patients undergoing transperineal biopsy. 47 A more recent meta- analysis of 165 studies (n 162,577) directly compared rates of hospitalization and sepsis following TRUS-Bx versus transperineal biopsy and found fewer complications with the transperineal approach (1.1% vs 0.9% and 0.8% vs 0.1%, respectively), although the differences were not statistically significant. 51 Considering transperineal biopsy is equivalent to TRUS-Bx in the diagnosis of prostate cancer, 48 transperineal biopsy may represent a highly effective alternative to TRUS-Bx for reducing severe infectious complications. Despite the suggested greater safety profile, there are a number of disadvantages associated with transperineal biopsy, such as the requirement for general anesthesia, higher costs, greater labor time, and the necessity for specialized equipment. 47 Nonetheless, the lower rate of severe complications makes transperineal biopsy a promising alternative to TRUS-Bx. Formalin Disinfection Formalin disinfection has been proposed as a cost-neutral means to reduce infectious complications. A recent report by Issa and colleagues 52 suggests that using formalin (10%) wash to disinfect the needle tip after each biopsy Transperineal biopsy poses a lower risk for infection because the method avoids seeding of the prostate gland with rectal flora. core sampling may minimize post- TRUS-Bx infections (0.30% vs 0.80%; P.13). Although the use of formalin failed to reach statistical significance in the clinical sample, the authors performed ex vivo experiments that offer strong empiric support for the ability of formalin to completely inhibit the growth of FQ-resistant bacteria. Indeed, in a recent retrospective study formalin (10%) wash demonstrated a protective effect in reducing postbiopsy infections (OR 0.37; 95% CI, ; P.013) (N. Singla, unpublished data, 2015). Formalin disinfection of the biopsy needle directly lowers the inoculum of bacteria present on the biopsy needle and is effective against both FQ-sensitive and FQ-resistant bacteria (N. Singla, unpublished data, 2015). 52 Moreover, formalin disinfection is cost neutral and requires minimal additional labor on the part of the clinician. However, no prospective studies or RCTs have explored the efficacy of formalin disinfection of the biopsy needle. Well-powered RCTs are warranted before formalin disinfection can be recommended for widespread clinical implementation. Number of Sampled Cores Although one retrospective study reported an increased risk of infection with a greater number of sampled biopsy cores, 53 most studies found no significant relationship between the number of cores sampled during TRUS-Bx and postbiopsy infection rates or complications. 25,37,54-56 Risk Factors A number of reports recommended limiting the use of more intensive and costly preventive measures to patients at high risk for infection. 20,26,57,58 To do so, there is a clear need to accurately identify high-risk patients. Although the literature is replete with putative risk factors for post-trus-bx infection, few offer definitive prognostic value. Below we present a qualitative synthesis of the risk factors for post-trus-bx infection most extensively studied in the literature (see Table 3 for all risk factors studied). Prior Antibiotic Exposure Among the variables found to be associated with post-trus-bx infection, prior antibiotic exposure is the most extensively studied. 6,30,36,38,39,59 Multiple studies document a strong association between prior antibiotic exposure and risk of harboring FQ-resistant organisms. Pooled analysis of nine studies (n 2541) in a recent metaanalysis identified prior FQ use (OR 4.2; 95% CI, ; P.02) as a significant risk factor for the presence of FQ-resistant bacteria in the rectal flora. 30 Similarly, Tsu and associates 60 recently reported that patients with antimicrobial exposure in the past 5 years were more likely to harbor antimicrobialresistant organisms in their rectums (OR 1.550; P.04). Contrary to the expected results based on these studies, prior antibiotic exposure has not been consistently linked to greater rates of severe infectious complications. Multivariate analysis of patient records at a Korean hospital indicated FQ exposure was 84 Vol. 18 No Reviews in Urology

13 Reducing Infectious Complications Following TRUS-Bx TABLE 3 Selected Studies Investigating Risk Factors for Antimicrobial Resistance or Infectious Complications Following TRUS-Bx Study Year Sample Size Methodology Country Risk Factors Outcome Variables Akduman B et al Retrospective United States Prolonged FQ antibiotic exposure Sepsis Bruyere F et al Prospective France Age, antibiotic exposure, history of prostatitis, PSA, type and duration of antibiotics Carignan A Retrospective Canada Age, chronic renal failure, COPD, diabetes, et al 65 metastatic neoplasm, prior hospitalization within 1 mo, PSA, urinary catheter, and urologic pathology Cohen JE et al Prospective United States Age, diabetes, dyslipidemia, heart disease, hypertension, prostate volume, and PSA Dai J et al Retrospective United States Age, prior biopsy, prior hospitalization, PSA, and race/ethnicity Duplessis CA Retrospective United States Age, antibiotic exposure, prior biopsies, et al 67 prophylaxis (ciprofloxacin), and race/ethnicity Ehdaie B et al Prospective United States Age, antibiotic exposure, benign prostatic hypertrophy, diabetes, and prior biopsies Hsieh T-Y et al Retrospective Taiwan Age, antibiotic prophylaxis, diabetes, hypertension, and prostate cancer Hwang EC Retrospective Korea Antibiotic exposure, diabetes, povidoneiodine et al 36 enema, prostate volume, and PSA (fever with positive urine culture, LUTS) (not defined) FQ-resistant rectal flora FQ-resistant rectal flora (bacteremia, fever, prostatitis, pyelonephritis, UTI, sepsis) (fever, hospitalization for infection, positive blood or urine culture) (chills, fever, macroscopic hematuria with blood clots, severe LUTS) FQ-resistant rectal culture, Infectious complications (fever, bacteremia, prostatitis, UTI, sepsis) Kam SC et al Retrospective Korea Age, prostate volume, and PSA Infectious complication (prostatitis) Kamdar C et al Retrospective United States Hospital employee and relative of hospital Bacteremia employee (Continued) Vol. 18 No Reviews in Urology 85

14 Reducing Infectious Complications Following TRUS-Bx continued Selected Studies Investigating Risk Factors for Antimicrobial Resistance or Infectious Complications Following TRUS-Bx (continued) Study Year Sample Size Methodology Country Risk Factors Outcome Variables Kehinde EO Prospective Kuwait Chronic renal failure, diabetes, prostatitis, et al 23 steroid therapy, and UTI Liss MA et al Retrospective United States Augmented prophylaxis, diabetes, FQ-resistant bacteria on rectal culture Sepsis Hospitalization, infectious complication (not defined) Loeb S et al Retrospective United States Prior biopsy Hospitalization, infectious complications (bacteremia, cystitis, endocarditis, hypotension, postoperative infection, prostatitis, pyelonephritis, sepsis, UTI) Luong B et al Retrospective United States Age, antibiotic exposure, PSA, and race/ethnicity Mosharafa AA Retrospective Egypt Age, chronic constipation/diverticular et al 39 disease, diabetes, enema use, FQ exposure, hypertension, and prostatitis at biopsy Patel U et al Prospective United Kingdom (hospitalization, sepsis) Prostatitis Antibiotic exposure and international travel Sepsis Simsir A et al Retrospective Turkey Age, diabetes, prior biopsies, prostate volume, prostatitis at biopsy, PSA, and urethral catheter Summers SJ Retrospective United States Antibiotic exposure, diabetes, immunosuppression, et al 32 prior biopsies Sepsis (bacteremia, cystitis, pyelonephritis, sepsis) Tsu JH et al Prospective China Antibiotic exposure and diabetes ESBL-producing bacteria and FQ-resistant bacteria in rectal flora Wagenlehner FM Prospective Multinational et al 2 Age, antibiotic exposure, prebiopsy bacteriuria, preoperative bowel preparation, presence of inflammation in biopsy samples, prior biopsies, prostate volume, PSA, use of anesthesia at biopsy, and UTI history Williamson DA et al Retrospective New Zealand International travel ESBL-producing bacteria in rectal flora UTI COPD, chronic obstructive pulmonary disease; ESBL, extended-spectrum -lactamase; FQ, fluoroquinolone; LUTS, lower urinary tract symptoms; PSA, prostate-specific antigen; UTI, urinary tract infection; TRUS-Bx, transrectal ultrasound-guided prostate biopsy. 86 Vol. 18 No Reviews in Urology

15 Reducing Infectious Complications Following TRUS-Bx independently associated with infectious complications following prostate biopsy (OR 6.10; 95% CI, ; P.008). 36 However, an international prospective study failed to find an association between prior antibiotic exposure and increased risk for infectious complications (P.05). 2 Prior antibiotic use was also not a significant predictor of post-trus-bx hospitalization in a recent study (P.61). 54 Other reports have documented a disconnect between rates of FQ-resistant bacteria in the rectal flora and subsequent symptomatic infections. In a study by Liss and coworkers, 34 only approximately 3% of patients with rectal swab culture results positive for FQ-resistant organisms developed an infection due to FQ-resistant bacteria. However, a subsequent study by the same group found that rectal colonization with FQ-resistant bacteria significantly predicted both infections and hospitalizations following TRUS-Bx. 35 More data are needed to establish a definitive relationship. Perhaps antibiotic exposure increases the quantity of FQ-resistant microbes in the rectal flora, but this increase may not directly translate into an increase in clinically significant infections. Thus, the prognostic significance of prior antibiotic exposure may be limited in predicting patients most likely to experience post-trus-bx infections. Number of Prior Biopsies A history of prior biopsies has not been definitively shown to increase patients risk for post-trus-bx infection. Although some data suggest a greater number of prior biopsies increases patients risk of harboring FQ-resistant organisms, 53,61 a meta-analysis of nine studies indicates that previous biopsies are not a statistically significant risk factor for harboring FQ-resistant rectal bacteria (OR 0.92; 95% CI, ; P.29). 30 Furthermore, in a recent, large analysis of Surveillance, Epidemiology and End Results (SEER)-Medicare data (n 17,523), repeat biopsy was not associated with a greater risk of infectious complications compared with initial biopsy (OR 0.81; 95% CI, ; P.39). 62 The risk of hospitalization was significantly lower for repeat biopsies than initial biopsies (OR 0.63; 95% CI, ; P not reported) and the duration between biopsies did not predict hospitalization. 62 Numerous other studies also failed to find a significant association between the number of prior biopsies and post-trus-bx infection. 2,21,33,37,63 Presence of FQ-resistant Bacteria in the Rectal Flora Limited data exist supporting the association between harboring FQ-resistant organisms in the the prognostic significance of prior antibiotic exposure may be limited in predicting patients most likely to experience post-trus-bx infections. rectal flora and likelihood of post- TRUS-Bx infection. FQ-resistant rectal cultures were recently demonstrated to significantly increase patients risk of developing an infection (OR 3.98; 95% CI, ; P.001) and hospitalization (OR 4.77; 95% CI, ; P.001) following TRUS-Bx in a large (n 2673) multi-institutional study. 35 However, only 6.6% of men with positive rectal culture results actually developed infections. 35 Therefore, positive rectal culture results appear to increase a patient s risk for post-trus-bx infections, but such infections are still relatively uncommon in this higherrisk group. International Travel Recent international travel has consistently been linked to increased risk of infection in published reports. In a prospective study of all men undergoing TRUS-Bx in a United Kingdom hospital, patients with recent international travel (RR 2.7; 95% CI, ; P.04) and patients with antibiotic use within 4 weeks of the biopsy (RR 4.0; 95% CI, ; P.025) had a greater risk of infectious complications requiring hospitalization. 57 Risk of infection was not associated with travel to a specific country (P.05). 57 The finding that international travel increases the risk of infection after TRUS-Bx corresponds with a report noting an increase in the percentage of patients with antimicrobial resistant E coli in their rectal flora after traveling abroad, from 7.8% (95% CI, ) before travel to 49% (95% CI, ) after travel. 64 Diabetes Data regarding the relationship between diabetes and enhanced risk for infection are equivocal. In a number of series, diabetics were at significantly greater risk for developing infectious complications. 23,54,60,63,65,66 However, multiple studies failed to replicate this association. 25,29,35,39,61 Race Asian and nonwhite race emerged as a risk factor for post-trus-bx infections in a number of series, 1,34,67 but not others. 63 The correlation between Asian race and increased risk of harboring FQ-resistant pathogens may be Vol. 18 No Reviews in Urology 87

16 Reducing Infectious Complications Following TRUS-Bx continued linked to the higher prevalence of FQ-resistant and ESBL-producing uropathogens in Asian countries. 60 Prostate Volume and Prostate-specific Antigen Two studies reported prostate volume or enlargement (benign prostatic hypertrophy) as a risk factor for infection, 53,66 but multiple other studies did not support this association. 2,38,56,61,63 No study reported prostate-specific antigen as a significant predictor of infectious risk. 2,21,38,54,60,61 Age One study found age to be a significant predictor of infectious risk. In this report, age was significantly associated with reduced risk of infection (OR 0.91; 95% CI, ; P.02). 29 In the majority of studies, however, age did not predict risk of infection. 2,21,25,53,54,60,61,63 Other Factors Multiple other risk factors for infectious complications have been cited in the literature, including chronic obstructive pulmonary disease, 36,65 heart disease, 63 medical occupation, 68 and presence of an indwelling catheter, 53,65 but insufficient data exist to make definitive statements regarding their relevance to predisposing patients for infectious complications. Conclusions Rising infection rates following TRUS-Bx are an urgent concern given the increased associated cost and morbidity. Herein, we have systematically reviewed contemporary methods to reduce infections following TRUS-Bx and identified a number of actionable strategies. Data suggest that augmented prophylaxis is warranted in regions with high rates of antimicrobial resistance, with aminoglycosides as the most appropriate adjunct to FQ prophylaxis. The ultimate choice for prophylaxis should be tailored to regional susceptibility patterns and local antibiograms, however. Povidone-iodine bowel preparation and transperineal biopsy are two procedural techniques that effectively lower infection rates. Among risk factors, only history of recent international travel is consistently associated with greater risk for infectious complications, and heightened vigilance may be warranted in these patients. Given recent concerns regarding over-diagnosis of prostate cancer, 69 it is critical that the urology community continues to minimize risks and costs in performing TRUS-Bx. References 1. Loeb S, Carter HB, Berndt SI, et al. Complications after prostate biopsy: data from SEER-Medicare. J Urol. 2011;186: Wagenlehner FM, van Oostrum E, Tenke P, et al; GPIU investigators. Infective complications after prostate biopsy: outcome of the Global Prevalence Study of Infections in Urology (GPIU) 2010 and 2011, a prospective multinational multicentre prostate biopsy study. Eur Urol. 2013;63: Nam RK, Saskin R, Lee Y, et al. Increasing hospital admission rates for urological complications after transrectal ultrasound guided prostate biopsy. J Urol. 2010;183: Aly M, Dyrdak R, Nordstrom T, et al. Rapid increase in multidrug-resistant enteric bacilli blood stream infection after prostate biopsy: a 10-year populationbased cohort study. Prostate. 2015;75: Averch T, Tessier C, Clemens JQ, et al. AUA Quality Improvement Summit 2014: conference proceedings on infectious complications of transrectal prostate needle biopsy. American Urological Association website. practices-resources/quality/white-papers/qi-summit. pdf. Accessed April 27, Taylor S, Margolick J, Abughosh Z, et al. Ciprofloxacin resistance in the faecal carriage of patients undergoing transrectal ultrasound guided prostate biopsy. BJU Int. 2013;111: Williamson DA, Roberts SA, Paterson DL, et al. Escherichia coli bloodstream infection after transrectal ultrasound-guided prostate biopsy: implications of fluoroquinolone-resistant sequence type 131 as a major causative pathogen. Clin Infect Dis. 2012;54: Zowawi HM, Harris PN, Roberts MJ, et al. The emerging threat of multidrug-resistant Gram-negative bacteria in urology. Nat Rev Urol. 2015;12: Song W, Choo SH, Sung HH, et al. Incidence and management of extended-spectrum beta-lactamase and quinolone-resistant Escherichia coli infections after prostate biopsy. Urology. 2014;84: Wolf JS Jr., Bennett CJ, Dmochowski RR, et al; Urologic Surgery Antimicrobial Prophylaxis Best Practice Policy Panel. Best practice policy statement on urologic surgery antimicrobial prophylaxis. J Urol. 2008;179: Antsupova V, Norgaard N, Bisbjerg R, et al. Antibiotic prophylaxis for transrectal prostate biopsy-a new strategy. J Antimicrob Chemother. 2014;69: Zani EL, Clark OAC, Rodrigues Netto Jr N. Antibiotic prophylaxis for transrectal prostate biopsy. Cochrane Database Syst Rev. 2011;(5):CD Yang L, Gao L, Chen Y, et al. Prophylactic antibiotics in prostate biopsy: a meta-analysis based on randomized controlled trials. Surg Infect (Larchmt). 2015;16: Ongün S, Aslan G, Avkan-Oguz V. The effectiveness of single-dose fosfomycin as antimicrobial prophylaxis for patients undergoing transrectal ultrasound-guided biopsy of the prostate. Urol Int. 2012;89: Gardiner BJ, Mahony AA, Ellis AG, et al. Is fosfomycin a potential treatment alternative for multidrugresistant gram-negative prostatitis? Clin Infect Dis. 2014;58:e Goto T, Makinose S, Ohi Y, et al. Diffusion of piperacillin, cefotiam, minocycline, amikacin and ofloxacin into the prostate. Int J Urol. 1998;5: Horcajada JP, Busto M, Grau S, et al. High prevalence of extended-spectrum beta-lactamase-producing enterobacteriaceae in bacteremia after transrectal ultrasound-guided prostate biopsy: a need for changing preventive protocol. Urology. 2009;74: Hori S, Sengupta A, Joannides A, et al. Changing antibiotic prophylaxis for transrectal ultrasound-guided prostate biopsies: are we putting our patients at risk? BJU Int. 2010;106: Madden T, Doble A, Aliyu SH, Neal DE. Infective complications after transrectal ultrasound-guided prostate biopsy following a new protocol for antibiotic prophylaxis aimed at reducing hospital-acquired infections. BJU Int. 2011;108: Womble PR, Linsell SM, Gao Y, et al; Michigan Urological Surgery Improvement Collaborative. A statewide intervention to reduce hospitalizations after prostate biopsy. J Urol. 2015;194: Lorber G, Benenson S, Rosenberg S, et al. A single dose of 240 mg gentamicin during transrectal prostate biopsy significantly reduces septic complications. Urology. 2013;82: Adibi M, Hornberger B, Bhat D, et al. Reduction in hospital admission rates due to post-prostate biopsy infections after augmenting standard antibiotic prophylaxis. J Urol. 2013;189: Kehinde EO, Al-Maghrebi M, Sheikh M, Anim JT. Combined ciprofloxacin and amikacin prophylaxis in the prevention of septicemia after transrectal ultrasound guided biopsy of the prostate. J Urol. 2013;189: Losco G, Studd R, Blackmore T. Ertapenem prophylaxis reduces sepsis after transrectal biopsy of the prostate. BJU Int. 2014;113(suppl 2): Hsieh T-Y, Kao Y-L, Wang S-C, et al. Adding gentamicin to fluoroquinolone-based antimicrobial prophylaxis reduces transrectal ultrasoundguided prostate biopsy-related infection rate. Urological Science website. article/s (15)00072-x/fulltext. doi: dx.doi.org/ /j.urols Accessed April 27, Adibi M, Pearle MS, Lotan Y. Cost-effectiveness of standard vs intensive antibiotic regimens for transrectal ultrasonography (TRUS)-guided prostate biopsy prophylaxis. BJU Int. 2012;110(2 Pt 2):E86-E Shakil J, Piracha N, Prasad N, et al. Use of outpatient parenteral antimicrobial therapy for transrectal ultrasound-guided prostate biopsy prophylaxis in the setting of community-associated multidrugresistant Escherichia coli rectal colonization. Urology. 2014;83: Risk assessment on the spread of carbapenemaseproducing Enterobacteriaceae (CPE) through patient transfer between healthcare facilities, with special emphasis on cross-border transfer. European Centre for Disease Prevention and Control website _Risk_assessment_resistant_CPE.pdf. Accessed April 27, Vol. 18 No Reviews in Urology

17 Reducing Infectious Complications Following TRUS-Bx 29. Unnikrishnan R, El-Shafei A, Klein EA, et al. For single dosing, levofloxacin is superior to ciprofloxacin when combined with an aminoglycoside in preventing severe infections after prostate biopsy. Urology. 2015;85: Roberts MJ, Williamson DA, Hadway P, et al. Baseline prevalence of antimicrobial resistance and subsequent infection following prostate biopsy using empirical or altered prophylaxis: a bias-adjusted meta-analysis. Int J Antimicrob Agents. 2014;43: Liss MA, Kim W, Moskowitz D, Szabo RJ. Comparative effectiveness of targeted vs empirical antibiotic prophylaxis to prevent sepsis from transrectal prostate biopsy: a retrospective analysis. J Urol. 2015;194: Summers SJ, Patel DP, Hamilton BD, et al. An antimicrobial prophylaxis protocol using rectal swab cultures for transrectal prostate biopsy. World J Urol. 2015;33: Dai J, Leone A, Mermel L, et al. Rectal swab culturedirected antimicrobial prophylaxis for prostate biopsy and risk of postprocedure infection: a cohort study. Urology. 2015;85: Liss MA, Chang A, Santos R, et al. Prevalence and significance of fluoroquinolone resistant Escherichia coli in patients undergoing transrectal ultrasound guided prostate needle biopsy. J Urol. 2011;185: Liss MA, Taylor SA, Batura D, et al. Fluoroquinolone resistant rectal colonization predicts risk of infectious complications after transrectal prostate biopsy. J Urol. 2014;192: Hwang EC, Jung SI, Seo YH, et al. Risk factors for and prophylactic effect of povidone-iodine rectal cleansing on infectious complications after prostate biopsy: a retrospective cohort study. Int Urol Nephrol. 2015;47: Zaytoun OM, Anil T, Moussa AS, et al. Morbidity of prostate biopsy after simplified versus complex preparation protocols: assessment of risk factors. Urology. 2011;77: Bruyère F, Malavaud S, Bertrand P, et al. Prosbiotate: a multicenter, prospective analysis of infectious complications after prostate biopsy. J Urol. 2015;193: Mosharafa AA, Torky MH, El Said WM, Meshref A. Rising incidence of acute prostatitis following prostate biopsy: fluoroquinolone resistance and exposure is a significant risk factor. Urology. 2011;78: Ruddick F, Sanders P, Bicknell SG, Crofts P. Sepsis rates after ultrasound-guided prostate biopsy using a bowel preparation protocol in a community hospital. J Ultrasound Med. 2011;30: Carey JM, Korman HJ. Transrectal ultrasound guided biopsy of the prostate. Do enemas decrease clinically significant complications? J Urol. 2001;166: Pu C, Bai Y, Yuan H, et al. Reducing the risk of infection for transrectal prostate biopsy with povidone-iodine: a systematic review and meta-analysis. Int Urol Nephrol. 2014;46: Park DS, Hwang JH, Choi DK, et al. Control of infective complications of transrectal prostate biopsy. Surg Infect (Larchmt). 2014;15: Jeon SS, Woo SH, Hyun JH, et al. Bisacodyl rectal preparation can decrease infectious complications of transrectal ultrasound-guided prostate biopsy. Urology. 2003;62: Grabe M, Bjerklund-Johansen T, Botto H, et al. Guidelines on urological infections. European Association of Urology website. uploads/18_urological-infections_lr.pdf. Accessed April 27, Murphy DG, Weerakoon M, Grummet J. Is zero sepsis alone enough to justify transperineal prostate biopsy? BJU Int. 2014;114: Grummet JP, Weerakoon M, Huang S, et al. Sepsis and superbugs : should we favour the transperineal over the transrectal approach for prostate biopsy? BJU Int. 2014;114: Shen PF, Zhu YC, Wei WR, et al. The results of transperineal versus transrectal prostate biopsy: a systematic review and meta-analysis. Asian J Androl. 2012;14: Vyas L, Acher P, Kinsella J, et al. Indications, results and safety profile of transperineal sector biopsies (TPSB) of the prostate: a single centre experience of 634 cases. BJU Int. 2014;114: Pepe P, Aragona F. Morbidity after transperineal prostate biopsy in 3000 patients undergoing 12 vs 18 vs more than 24 needle cores. Urology. 2013;81: Bennett HY, Roberts MJ, Doi SA, Gardiner RA. The global burden of major infectious complications following prostate biopsy. Epidemiol Infect. 2016;144: Issa MM, Al-Qassab UA, Hall J, et al. Formalin disinfection of biopsy needle minimizes the risk of sepsis following prostate biopsy. J Urol. 2013;190: Simsir A, Kismali E, Mammadov R, et al. Is it possible to predict sepsis, the most serious complication in prostate biopsy? Urol Int. 2010;84: Luong B, Danforth T, Visnjevac O, et al. Reduction in hospital admissions with the addition of prophylactic intramuscular ceftriaxone before transrectal ultrasonography-guided prostate biopsies. Urology. 2015;85: Berger AP, Gozzi C, Steiner H, et al. Complication rate of transrectal ultrasound guided prostate biopsy: a comparison among 3 protocols with 6, 10 and 15 cores. J Urol. 2004;171: Kam SC, Choi SM, Yoon S, et al. Complications of transrectal ultrasound-guided prostate biopsy: impact of prebiopsy enema. Korean J Urol. 2014;55: Patel U, Dasgupta P, Amoroso P, et al. Infection after transrectal ultrasonography-guided prostate biopsy: increased relative risks after recent international travel or antibiotic use. BJU Int. 2012;109: Williamson DA, Masters J, Freeman J, Roberts S. Travel associated extended spectrum lactamaseproducing escherichia coli bloodstream infection following transrectal ultrasound guided prostate biopsy. BJU international. 2012;109:E21-E Akduman B, Akduman D, Tokgöz H, et al. Long-term fluoroquinolone use before the prostate biopsy may increase the risk of sepsis caused by resistant microorganisms. Urology. 2011;78: Tsu JH, Ma WK, Chan WK, et al. Prevalence and predictive factors of harboring fluoroquinolone-resistant and extended-spectrum beta-lactamase-producing rectal flora in Hong Kong Chinese men undergoing transrectal ultrasound-guided prostate biopsy. Urology. 2015;85: Ehdaie B, Vertosick E, Spaliviero M, et al. The impact of repeat biopsies on infectious complications in men with prostate cancer on active surveillance. J Urol. 2014;191: Loeb S, Carter HB, Berndt SI, et al. Is repeat prostate biopsy associated with a greater risk of hospitalization? Data from SEER-Medicare. J Urol. 2013;189: Cohen JE, Landis P, Trock BJ, et al. Fluoroquinolone resistance in the rectal carriage of men in an active surveillance cohort: longitudinal analysis. J Urol. 2015;193: Kennedy K, Collignon P. Colonisation with Escherichia coli resistant to critically important antibiotics: a high risk for international travellers. Eur J Clin Microbiol Infect Dis. 2010;29: Carignan A, Roussy JF, Lapointe V, et al. Increasing risk of infectious complications after transrectal ultrasound-guided prostate biopsies: time to reassess antimicrobial prophylaxis? Eur Urol. 2012;62: Loeb S, van den Heuvel S, Zhu X, et al. Infectious complications and hospital admissions after prostate biopsy in a European randomized trial. Eur Urol. 2012;61: Duplessis CA, Bavaro M, Simons MP, et al. Rectal cultures before transrectal ultrasound-guided prostate biopsy reduce post-prostatic biopsy infection rates. Urology. 2012;79: Kamdar C, Mooppan UM, Gulmi FA, Kim H. Multi-drug resistant bacteremia after transrectal ultrasound guided prostate biopsies in hospital employees and their relatives. Urology. 2008;72: Moyer VA. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2012;157: MAIN POINTS Augmented prophylaxis consisting of standard fluoroquinolones and aminoglycosides is warranted in areas burdened by high rates of antimicrobial resistance. Povidone-iodine bowel preparation, prior to transrectal ultrasound-guided prostate biopsy (TRUS-Bx), effectively lowers the rate of post TRUS-Bx infections. The transperineal biopsy approach is associated with fewer severe complications and should be considered as an alternative to TRUS-Bx in select cases. Recent international travel is the only risk factor consistently associated with greater risk for experiencing infectious complications following TRUS-Bx. The increasing prevalence of antimicrobial-resistant uropathogens justifies the timely implementation of effective methods to reduce the rate of infections after TRUS-Bx. Vol. 18 No Reviews in Urology 89