Bacterial Urinary Tract Infection after Fiducial Marker Placement or Prostate Biopsy William M. Mendenhall, MD1; Joseph A. Costa, DO2; Christopher R. Williams, MD2; Stephanie E. Harris, MD2; Stephen E. Mandia, MD2; Bradford S. Hoppe, MD, MPH1; Randal H. Henderson, MD1; Curtis M. Bryant, MD1; R. Charles Nichols, MD1; Nancy P. Mendenhall, MD1 1

University of Florida Proton Therapy Institute, Jacksonville, FL, USA Division of Urology at the University of Florida, College of Medicine, Jacksonville, FL, USA

2

Abstract

Submitted 25 Jun 2014 Accepted 05 Sep 2014 Published 31 Dec 2014 Corresponding author: William M. Mendenhall University of Florida Proton Therapy Institute 2015 N Jefferson St Jacksonville, FL 32206, USA Phone: þ1 (904) 588-1800 Fax: þ1 (904) 588-1300 [email protected] Review Article DOI 10.14338/IJPT-14-00010.1 cc Copyright *

2014 International Journal of Particle Therapy Distributed under Creative Commons CC-BY OPEN ACCESS

Fiducial markers placed in the prostate prior to treatment planning are often used in image guided radiation therapy to optimize beam alignment. A potential serious complication following fiducial marker placement or prostate biopsy is a bacterial urinary tract infection, particularly urosepsis, which requires hospitalization and aggressive antibiotic therapy. Patients usually undergo either procedure transrectally under ultrasound guidance and routinely receive antibiotic prophylaxis before and after the procedure, usually with fluoroquinolones (FQ), to reduce the risk of infection. There are few data pertaining to the risk of post fiducial marker placement infection so that most data pertain to post-biopsy bacterial urinary tract infection which has been increasing in recent years, primarily due to FQ-resistant gram-negative bacilli, usually Escherichia coli (E. coli). Strategies to reduce the risk of infection include empirically changing the prophylactic antibiotic regimen to include agents to which FQ-resistant bacteria are likely sensitive, obtaining a rectal swab culture prior to the procedure and tailoring the regimen based on the results of the sensitivity profile, and performing the procedure via the transperineal rather than the transrectal route. The transperineal route often requires more anesthesia and time and is thus more impractical to implement. Additionally, the data do not convincingly demonstrate an advantage associated with the transperineal route. A caveat is that most of the relevant data are from a time period when the risk of a bacterial urinary tract infection was probably lower. Thus the rectal swab cultures and targeted prophylaxis is likely the optimal strategy. Keywords: urinary tract infection, prostate, fiducial marker placement, bladder

Introduction Fiducial markers are often placed in the prostate prior to image guided radiation therapy (RT) to optimize beam alignment [1–6]. A potentially serious complication following transrectal ultrasound-guided fiducial marker placement is a bacterial urinary tract infection (UTI). A subset of these infections result in urosepsis, which requires hospitalization and may be life-threatening. There are few data pertaining to the risk of this complication so that most data relate to patients who undergo a transrectal ultrasound guided prostate biopsy (TRUSPB) [7–26]. Although the transperineal route is an option, the transrectal route is usually preferred because it requires less anesthesia

http://theijpt.org How to cite this article Mendenhall WM, Costa JA, Williams CR, Harris SE, Mandia SE, Hoppe BS, Henderson RH, Bryant CM, Nichols RC, Mendenhall NP. Bacterial Urinary Tract Infection after Fiducial Marker Placement or Prostate Biopsy. Int J Particle Ther. 2014;1(3):745–758.

UTI after marker placement or prostate biopsy

and is more convenient [1, 27, 28]. Patients almost always undergo a course of antibiotic prophylaxis prior to, and following, the procedure to reduce the risk of a bacterial UTI. The antibiotics of choice are fluoroquinolones (FQ). The incidence of urosepsis due to FQresistant bacteria, primarily Escherichia coli (E. coli) has been increasing over the last few years likely due to antimicrobial resistance rather than virulence genotype [24, 25]. The aim of this paper is to review the incidence of bacterial UTIs after fiducial marker placement or TRUSPB, the factors associated with an increased likelihood of this complication, and to discuss how to reduce the risk of this adverse event. Because there are few data pertaining to fiducial marker placement, most of the discussion will focus on post prostate biopsy bacterial infections.

Incidence of Bacterial Urinary Tract Infection following Transrectal Fiducial Marker Placement or Prostate Biopsy Sanders and Buchan reported on 1421 patients who underwent TRUSPB in Christchurch Hospital (New Zealand) between 2010 and 2011 [29]. All patients received prophylactic antibiotics with ciprofloxacin (cipro) 250 mg orally (PO) twice daily (BID) for 4 days starting 2 hours before the procedure unless there was a history of a prior adverse reaction. Forty patients (2.8%) required hospitalization to Christchurch Hospital at the median of 2 days after biopsy for a bacterial infection; the median hospital stay was 3 days. Midstream urine culture was positive in 26 patients (65%), primarily for E. coli (23 patients). Thirty-eight patients had blood cultures and 20 (53%) were positive, the majority (16 patients) for E. coli. A urine and/or blood culture, positive for E. coli, was obtained in 27 patients which was resistant to amoxicillin in 82% and to FQ in 52%. A combination of gentamicin and ceftriaxone was the most effects regime for the E. coli cultured. Carignan et al [30] reported on 5798 patients who underwent TRUSPB at the Universite´ de Sherbrooke (Quebec, Canada) between 2002 and 2011. All patients underwent routine antibiotic prophylaxis with cipro in conjunction with biopsy. Forty-eight patients (0.83%) developed urinary sepsis. The rate of urinary infections increased from 0.52 per 100 biopsies during 2002 to 2009 to 2.15 per 100 biopsies in 2010 to 2011 (p,0.001). E. coli was the predominant pathogen and was identified in 75% of patients with UTIs. Independent risk factors for post-biopsy infection included diabetes, hospitalization during the preceding month, chronic obstructive pulmonary disease, and biopsy during 2010 to 2011. Campeggi et al [31] reported on 3000 patients who underwent a 21-core TRUSPB ´ between 2006 and 2009 at the Henri Mondor Hospital (Creteil, France). All patients received a 7 day course of FQ prophylaxis. Twenty patients (0.67%) developed a bacterial prostatitis requiring hospitalization within roughly 2.9 days (range, 1 to 7 days). E. coli was isolated in all 20 patients; 95% were resistant to FQ and amoxicillin. Resistance was also detected as follows: amoxiclav (70%), trimethoprim sulfamethoxazole (70%), 3rd generation cephalosporins (25%), and amikacin (5%). None were resistant to imipenem. Ehdaie et al [32] reported on 403 patients on active surveillance for prostate cancer who underwent a 14-core TRUSPB between January 2011 and January 2012 at the Memorial Sloan-Kettering Cancer Center (New York, NY, USA). Prophylactic FQ antibiotics were given to 92% of patients and intramuscular (IM) gentamicin was administered to 28%. Fourteen patients (3.5%) developed a bacterial infection; 13 patients required hospitalization. Five patients had positive urine cultures, 4 of the 5 had FQ-resistant bacteria. Factors potentially impacting the probability of developing a bacterial UTI were analyzed and included diabetes mellitus, benign prostatic hypertrophy, antibiotic regimen, and the

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Table 1. Incidence of bacterial UTI after prostate biopsy.

Author

Institution

No. of patients

Antibiotic

(dates)

prophylaxis

UTIs

Sanders and Buchan [29]

Christchurch

1421 (2010–2011)

Cipro

2.8% required

Carignan et al [30]

Hospital Universite

5798 (2002–2011)

Cipro

hospitalization 0.83% sepsis

3000 (2006–2009)

Quinolones

0.67% required

403 (2011–2012)

Quinolones

de Sherbrooke Campeggi et al [31]

Henri Mondor

Edhaie et al [32]

MSKCC

hospitalization

Patel et al [33]

The Prostate Centre- London

316 (2008–2010)

3.2% required

þ/- Gentamicin

hospitalization

Cipro, Gentamicin,

5% required

Metonidazole

hospitilization

Abbreviations: UTI, urinary tract infection; MSKCC, Memorial Sloan Kettering Cancer Center.

number of prior prostate biopsies. Only the number of prior TRUSPBs significantly increased the risk of infection which was 1.3 times higher for every prior biopsy. Patel et al [33] reported on 316 patients who underwent a TRUSPB at The Prostate Centre (London, UK) between June 2008 and June 2010. Antibiotic prophylaxis consisted of cipro 500 mg BID for 5 days starting 24 hours before the biopsy and gentamicin 120 mg to 160 mg intravenously (IV) and metronidazole suppository 1 g immediately before the biopsy. Sixteen patients (5%) developed a bacterial infection necessitating hospitalization. Cultures were positive in 10 of 16 patients (63%), all with E. coli that was resistant to cipro and amoxicillin and variably to gentamicin and co-amoxiclav. Nearly all were sensitive to meropenem. Both recent travel (p¼0.04) and antibiotic use within 4 weeks (p¼0.025) were associated with an increased risk of infection unrelated to the country visited or the type of antibiotic used. Williamson et al [34] evaluated all male patients (N¼258) admitted to the Auckland City Hospital (New Zealand) between 2006 and 2010 with community onset E. coli bacterium and compared those having undergone a recent TRUSPB with the remaining patients. Forty-seven of 258 patients (18%) were admitted after a recent TRUSPB and were twice as likely to require admission to the intensive care unit (25% vs 12%) and to have a higher rate of resistance to gentamicin (43%), trimethoprim sulfamethoxazole (60%) and cipro (62%), as well as all 3 agents in combination (19%). The incidence of bacterial UTI after TRUSPB is summarized in Table 1. Berglund et al [35] reported on 50 consecutive patients who underwent Calypsot transducer placement (Varian Medical Systems, Palo Alto, CA) prior to RT at the Cleveland Clinic (Cleveland, OH, USA) between February 2008 and October 2010. Patients received a 3-day course of cipro 500 mg PO BID starting the night before the procedure. Five of 50 patients (10%) developed a bacterial infection including grade 2 UTI (3 patients), grade 3 epidural abscess and osteomyelitis requiring open debridement and lumbar fusion (1 patient), and a methicillin-resistant Staphylococcus aureus (S. aureus) prostate abscess (1 patient). Culture identified the responsible bacteria in 4 of 5 patients; 3 of 4 had FQ-resistant E. coli. Langenhuijsen et al [36] reported on 209 patients who underwent transrectal ultrasound (US) guided placement of 4 gold fiducial markers prior to image guided RT (IGRT) at Radboud University Nijmegen Medical Centre (Nijmegen, The Netherlands) between 2001

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Table 2. Incidence of bacterial UTI after transrectal fiducials.

Author

Institution

No. of patients (dates)

Antibiotic prophylaxis

UTIs

Berglund et al [35]

Cleveland Clinic

50 (2008–2010)

Cipro

Langenhuijsen et al [36]

University of Nijmegen

209 (2001–2005)

Cipro

10% 1.9%

Igdem et al [37]

Istanbul Bilim University

135 (2005–2008)

Cipro

2.2%

Linden et al [38]

Jefferson University

98 (2003–2006)

Quinolones

0%

Brown et al [39]

Princess Alexandra Hospital

20 (2007)

Trimethoprim

5%

Thompson et al [40]

Peter McCallum Cancer Center

28 (2007)

Cipro

0%

Kably et al [42]

University of Miami

75 (2010–2013)

Cipro

2.7%

Abbreviation: UTI, urinary tract infection.

and 2005. Patients received cipro 500 mg BID for 3 days beginning the day prior to the procedure. Four patients (1.9%) developed a fever that responded to additional antibiotics. Igdem et al [37] reported on 135 patients who underwent transrectal US guided placement of 3 gold fiducial markers prior to intensity modulated RT (IMRT) at Istanbul Bilim University (Istanbul, Turkey) between 2005 and 2008. Patients received cipro 500 mg BID for 3 days beginning the day of the procedure. Three patients (2.2%) developed a bacterial UTI documented by urine culture and were successfully treated with additional antibiotics. No patient required hospitalization. Linden et al [38] reported on 98 patients who US guided transrectal placement of 3 gold fiducial markers prior to IMRT at the Thomas Jefferson University (Philadelphia, PA) between 2003 and 2006. Patients received prophylactic oral antibiotics, usually with quinolones, for 2 days beginning the day before the procedure. No patient experienced a bacterial UTI. Brown et al [39] reported on 20 patients who underwent transrectal US guided placement of 3 gold fiducial markers prior to image IGRT beginning in 2007 at the Princess Alexandra Hospital (Brisbane, Australia). Patients received prophylactic trimethoprim antibiotics. One patient (5%) developed a bacterial UTI. Thompson et al [40] reported on 28 patients who underwent transrectal US guided placement of 2 to 5 gold fiducial markers prior to IGRT at the Peter MacCallum Cancer Center (Melbourne, Australia) in 2007. Patients received prophylactic cipro. No patient developed sepsis or required hospitalization. Yang et al [41] reported on 16 patients who underwent transrectal US guided placement of a minimum of 3 gold fiducial markers prior to IMRT at the University of Miami between 2007 and 2008. Patients received IV cipro the day of the procedure and then orally for 5 days thereafter. No patient experienced a bacterial UTI. Kably et al [42] subsequently reported on 75 patients who underwent transrectal US guided gold fiducial marker placement prior to IGRT at the University of Miami between 2010 and 2013. Seventy-two patients were previously untreated, 2 had a local recurrence after prostatectomy, and 1 had a local recurrence after cryotherapy. Patients received a 3 day course of oral cipro beginning the day before the procedure. Two patients (2.7%) developed a bacterial UTI; 1 of 2 required hospitalization due to E. coli sepsis that was resistant to cipro, levaquin, and ampicillin. The incidence of bacterial UTIs after transrectal placement of fiducials is summarized in Table 2. Thus the incidence of post TRUSPB appears to be increasing primarily due to an increasing incidence of multidrug resistant E. coli which may be more virulent than other community onset E. coli infections [43–48]. Some patients may be at an increased risk for developing a post-biopsy bacterial UTI, such as those having undergone a recent prostate

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biopsy and/or a history of recent antibiotic use. Limited data suggest that the risk of post transrectal fiducial marker placement may be similar to that observed after TRUSPB, which is not surprising given that essentially all of these patients have undergone a recent prostate biopsy with antibiotic prophylaxis.

Strategies to Reduce the Risk of Post-Procedure Bacterial Urinary Tract Infection Strategies to reduce the risk of post-procedure bacterial UTI can be broadly stratified into empiric changes in the prophylactic regimen, directed changes in the prophylactic regimen based on rectal swab cultures, and changing the procedure route from transrectal to transperineal [28, 44, 45, 48–69]. Essentially all of these data pertain to patients who have undergone a TRUSPB so that the results must be extrapolated to those undergoing fiducial marker placement prior to IGRT.

Empiric Changes in the Prophylactic Regimen AbuGhosh et al [49] reported on 865 patients who underwent TRUSPB at the University of British Columbia (Vancouver, Canada) between 2009 and 2011. All patients received cipro prophylaxis and had a prebiopsy rectal swab culture. Patients were randomized to rectal cleansing with povidone-iodine (421 patients) or no cleansing (444 patients). Infections were defined as fever .38.08C, UTI, or sepsis. Infections were observed in 31 patients (3.5%), including 11 (2.6%) who received rectal cleansing versus 20 (4.5%) controls (p¼0.15). Sepsis was observed in 4 patients (1.0%) who received povidone-iodine versus 7 controls (1.6%; p¼0.55). Multivariate analysis revealed that cipro-resistant bacteria detected on rectal swab cultures (p¼0.002) and a history of taking cipro within 3 months of biopsy (p¼0.009) predicted infection. Although rectal cleansing with povidone-iodine reduced the risk of bacterial infection by 42%, the risk reduction was not statistically significant. Adibi et al [50] reported on 600 patients who underwent a TRUSPB at the University of Texas Southwestern (Dallas, TX, USA) between January 2010 and December 2011. Between January 2010 and December 2010, 290 patients received a standard prophylactic regimen of cipro for 3 days unless allergic in which a 3-day course of Bactrim DS was employed. From January 2011 to December 2011, gentamicin 80 mg IM was added to the standard prophylactic antibiotic regimen. Eleven of 290 patients (3.8%) required hospitalization for a bacterial UTI after standard prophylaxis compared with 2 of 310 patients (0.6%) who underwent the augmented prophylactic regimen (p,0.001). Of the 11 patients admitted after standard prophylaxis, 73% had a FQ-resistant E. coli UTI and only 9% had bacteria resistant to gentamicin. Chan et al [51] reported on 367 patients who underwent a TRUSPB at the Chinese University of Hong Kong between November 2007 and July 2009 and were randomized into 2 prophylactic antibiotic regimens: (1) Group A (179 patients), amoxicillin-clavulanate 1 g 2 hours before biopsy and then every 12 hours times 2 and (2) Group B (188 patients), amoxicillin as above plus cipro 250 mg 2 hours before biopsy and then every 12 hours times 2 after the biopsy. In Group A, 7 of 179 patients (3.91%) developed a bacterial UTI compared with 1 of 188 patients (0.53%) in Group B (p¼0.008). Five of 8 patients who developed a bacterial UTI required hospitalization. Manecksha et al [52] reported on 1183 patients who underwent TRUSPB at the Adelaide and Meath Hospital (Dublin, Ireland) between January 2008 and December

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2009. Patients biopsied in 2008 (Group A, 558 patients) received ofloxacin 400 mg immediately before biopsy followed by 200 mg every 12 hours for 3 days whereas those biopsied in 2009 (Group B, 625 patients) received ofloxacin 200 mg every 12 hours for 3 days starting 24 hours before the biopsy. In Group A, 20 of 558 patients (3.6%) developed a bacterial UTI compared with 10 of 625 patients (1.6%) in Group B (p¼0.03). E. coli was the most frequently isolated organism. Overall, 7 of 13 positive urine cultures (54%) were FQ resistant and 5 of 13 (40%) were multidrug resistant. All patients with positive cultures had organisms sensitive to meropenem. Madden et al [55] reported on 709 patients who underwent a TRUSPB between 2008 and 2009 at Cambridge University Hospitals (UK). Cipro prophylaxis was initially employed in 454 patients and 11 (2.4%) developed a bacterial UTI. The prophylactic regimen was changed to co-amoxiclav and gentamicin and 33 of 255 patients (12.9%) developed a bacterial UTI. The prophylactic regimen was switched back to cipro with a subsequent decrease in the likelihood of bacterial UTI. Batura et al [58] reported on 871 patients who underwent TRUSPB at Northwick Park Hospital (London, UK) between 2006 and 2008; antibiotic prophylaxis varied over the study period. Prior to 2007, the regimen consisted of cipro 500 mg PO BID for 5 days starting 2 days before biopsy, co-amoxiclav 1.2 g IV immediately before biopsy and 625 mg PO three times daily after biopsy, and metronidazole suppository 500 mg after biopsy. Fourteen of 281 patients (4.9%) developed a bacterial UTI, 7 patients (2.5%) became septic, and 13 of 14 were cipro resistant. After 2006, the prophylactic regimen was switched to cipro 500 mg PO BID for 5 days beginning 2 days before biopsy, co-amoxiclav 625 mg PO 3 times daily for 5 days beginning 2 days before biopsy, and amikacin 1 g IV immediately before biopsy. The PO co-amoxiclav was discontinued after August 2008. After 2006, 8 of 590 patients (1.4%) developed a bacterial UTI (p¼0.02) and 2 patients (0.3%) became septic (p¼0.002). Lorber et al [62] reported on 4655 patients who underwent TRUSPB at HadassahHebrew University between 2001 and 2012. All patients received a 3-day course of cipro or oxfloxacin; after 2007 an increasing dose of gentamicin IM was included in the prophylactic regimen. One hundred ten patients (2.4%) required hospitalization for urosepsis; 90 of 110 (82%) had positive blood and/or urine cultures. Of these, 86% were positive for E. coli which was FQ resistant. The following rates of urosepsis were observed: oxfloxacin, 3.6%; oxfloxacin plus gentamicin 80 mg, 3.5% (p¼1.0); oxfloxacin plus gentamicin 160 mg, 2.7% (p¼0.27); and oxfloxacin plus gentamicin 240 mg, 0.6% (p¼0.04). Issa et al [68] reported on 1642 patients who underwent a TRUSPB at Emory University (Atlanta, GA, USA) between 2008 and 2012. All had a negative urine culture, a bisacodyl enema, and a 3-day course of FQ antibiotics. Prior to each core, the needle was placed in 10% formalin. Five patients (0.3%) had a mild uncomplicated UTI and 2 patients were hospitalized for sepsis with blood and urine cultures positive for FQ-resistant E. coli. Compared with historical controls, the use of 10% formalin resulted in reduction of bacterial UTIs from 0.8% to 0.3% (p¼0.13).

Rectal Swab and Culture Series where rectal swab cultures were obtained prior to the procedure can be stratified into those where the antibiotic prophylactic regimen was not altered based on the results and those where it was tailored based on the culture and sensitivity profile. Steensels et al [44] reported on 342 patients who underwent rectal swab/cultures prior to TRUSPB between 2009 and 2010. Patients were excluded if the cultures were negative,

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had no antibiotic prophylaxis, or antibiotics other than FQ. Of the remaining 236 patients, 52 (22%) had cipro resistant E. coli. Seven of 236 patients (3.0%) developed bacterial UTIs, all with cipro resistant E. coli. By comparison, no patient with a rectal swab culture revealing cipro sensitive organisms developed a bacterial UTI (p,0.01). Minamida et al [45] reported on 100 patients who had a rectal swab culture prior to TRUSPB between April and December 2010 at the Kitasato University Hospital (Kanagawa, Japan). Antibiotic prophylaxis consisted of levofloxacin (levaquin) 500 mg PO QD for 3 days beginning 2 hours before biopsy. Thirteen patients (13%) had cultures positive for FQ-resistant E. coli; 4 of 13 (31%) had a bacterial UTI compared with 0 of 87 patients with cultures revealing FQ sensitive organisms (p,0.01). Liss et al [57] reported on 136 patients who underwent rectal swab cultures prior to TRUSPB at the University of California, Irvine, (Irvine, CA, USA) between January 2009 and March 2010. Thirty patients (22%) had cultures positive for FQ-resistant E. coli. Cultures of 29 patients with FQ-resistant E. coli revealed them to be susceptible to the following antibiotics: amikacin, 100%; cefazolin, 79%; ceftazidime, 93%; cefepime, 93%; impenem, 100%; nitrofuratoin, 100%; piperacillin-tazobactam, 90%; gentamicin, 66%; and trimethoprim-sulfamethoxazole, 62%. Qi et al [66] reported on 991 patients who underwent a rectal swab culture followed by TRUSPB at Northwestern University (Chicago, IL, USA) between July 2010 and September 2011. Cipro resistant organisms were detected in 193 patients (19.4%); 167 of 193 (87%) were E. coli. Taylor et al [69] reported on 865 patients who underwent TRUSPB at the University of British Columbia between 2009 and 2011. All had prebiopsy urine and rectal swab cultures and a post-biopsy urine culture. Cipro resistant gram-negative coliforms were detected in 19% of rectal cultures; E. coli was the most prevalent gram-negative rectal isolate (80.9%) and accounted for 90.6% of cipro resistance. Liss et al [64] reported on 58 patients who underwent TRUSPB at the University of California, Irvine (Irvine, CA, USA); rectal cultures were obtained a median of 2 weeks before biopsy and again just prior to biopsy to detect FQ-resistant organisms. Fifty-four of 58 pairs (93%) of rectal cultures were concordant. Overall, sensitivity was 95.9%, specificity was 77.8%, negative predictive value was 95.9%, and positive predictive value was 77.8%. Taylor et al [54] reported on 457 patients who underwent TRUSPB at Northwestern University between July 2010 and March 2011. Standard cipro prophylaxis without a rectal swab culture was employed in 345 patients (76%); rectal swab cultures to detect FQresistant bacteria were obtained prior to biopsy in 112 patients and those with FQ-resistant bacteria received targeted prophylaxis. Twenty-two of 112 patients (19.6%) had FQresistant organisms; none developed a bacterial UTI. Nine of 345 patients (2.6%) who received standard prophylaxis developed a bacterial UTI including 1 patient who developed sepsis (p¼0.12). Seven of 9 had FQ-resistant bacteria. The authors estimated that it would be necessary for 38 patients to undergo rectal swab cultures prior to TRUSPB to avoid 1 bacterial UTI. Duplessis et al [53] reported on 235 patients who underwent rectal swab cultures prior to TRUSPB between March 2010 and March 2011 and had their antibiotic prophylaxis customized based on the results. Thirty-two patients (14%) had FQ-resistant E. coli. No patient developed a post-biopsy infection. In contrast, 3 of 103 patient (2.9%) biopsies in the 4 months prior to routinely obtaining a rectal swab culture developed a post-biopsy bacterial UTI.

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Transperineal versus Transrectal Route Pinkstaff et al [59] reported on 210 patients who underwent transperineal prostate biopsy at the Mayo Clinic Jacksonville between 1999 and 2003. All patients had 1 or more prior biopsies; the mean number of cores obtained was 21.2 (range, 12 to 41). All patients had a 3 day peri-operative course of antibiotics, usually with FQ. Twenty-four patients (11%) developed post-biopsy urinary retention; no patient experienced a bacterial UTI. Miller et al [28] reported on 197 prostate biopsies in 178 patients at the Nambour General Hospital (Nambour, Australia) between 1996 and 2001. Eighty-one transperineal biopsies were obtained in 75 patients and 116 transrectal biopsies in 103 patients. Patients who received transperineal biopsies did not receive antibiotic prophylaxis whereas those who underwent transrectal biopsies usually had IV gentamicin prior to the procedure and 3 to 5 days of trimethoprim post-biopsy. Overall, complications were observed in 22.2% after transperineal biopsy versus 19.8% after transrectal biopsy (p¼0.773). Sepsis was observed in 1.2% after transperineal biopsy compared with 0% after transrectal biopsy (p¼0.411). Hara et al [27] reported on 246 patients who underwent a 12-core prostate biopsy at the Kawasaki Medical School (Kawasaki, Japan) between May 2003 and October 2005. Patients were randomized to receive either a transperineal biopsy (126 patients) or a transrectal biopsy (120 patients). All patients received levaquin 200 mg on the day of the biopsy. The rate of prostate cancer detection was 42.1% after transperineal biopsy compared with 48.3% after transrectal biopsy (p¼0.323). Bacterial UTI did not occur in any patient after a transperineal biopsy versus 2 of 120 patients (1.7%) after transrectal biopsy. Takenaka et al [63] reported on 200 patients who underwent a prostate biopsy at Kobe University and the Kawasaki Medical School between May 2003 and September 2004. Patients were randomized to transperineal biopsy (100 patients) or transrectal biopsy (100 patients). No patient had undergone a previous prostate biopsy. All patients received antibiotic prophylaxis for 1 day with 300 mg of levaquin. The prostate cancer detection rate was 47% after transperineal biopsy and 53% after transrectal biopsy (p¼0.48). There was no difference in the overall rate of complications or the risk of bacterial UTI after transperineal biopsy (19% and 1%) compared with transrectal (20% and 2%) biopsy. Pepe and Aragona [67] reported on 4000 patients who underwent transperineal prostate biopsy at Cannizzaro Hospital (Catania, Italy) between 1991 and 2012. Six cores were obtained in 612 patients, 12 cores in 1428 patients, 18 cores in 1330 patients, and .24 cores in the remainder. All patients received antibiotic prophylaxis with levaquin 500 mg QD for 3 days beginning the day before the procedure. Infectious complications included UTI, 2.5%; prostatitis, 0.7%; and sepsis, 0%. Vyas et al [70] reported on 634 patients who underwent a transperineal prostate biopsy at Guy’s Hospital (London, United Kingdom) between 2007 and 2011. The procedure was usually performed under general anesthesia; 24 to 38 cores were obtained. Antibiotic prophylaxis consisted of Amikacin 500 mg IV at induction followed by cipro 500 mg twice daily for 3 days. Postoperative urinary retention was observed in 11 patients (1.7%); 2 patients required hospitalization for peri-urethral bleeding. No patients developed urosepsis.

Conclusions The risk of a bacterial UTI following TRUSPB is rising due to an increasing incidence of antibiotic resistant organisms, particularly FQ-resistant E. coli. Similar risks likely exist after

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transrectal placement of fiducial markers for target localization prior to RT. Patients who have had fiducial markers placed are all probably at high risk because all have had at least one prostate biopsy that was likely performed with antibiotic prophylaxis. Three general strategies exist to reduce this risk: (1) empirically changing the antibiotic prophylaxis, (2) rectal swab culture and targeted antibiotic prophylaxis, and (3) using the transperineal rather than the transrectal route. One of the problems with assessing the efficacy of these strategies is that series including patients who have undergone these procedures as recently as the early 2000s likely had a lower risk of resistant bacteria compared with patients undergoing the procedure today. This is particularly pertinent when comparing the transperineal route to the transrectal route. While there is understandable resistance to change, continuing routine FQ prophylaxis will likely result in an increasing risk of potentially severe urosepsis. The disadvantage of rectal swab culture is that it must be obtained far enough in advance of the procedure to obtain the results to change the prophylactic regimen if necessary. However, if obtained in advance, the antibiotic prophylaxis can be targeted based on the culture and sensitivity results. The disadvantage with the transperineal route is that it may require additional anesthesia and time and is thus more difficult to implement. The advantage of the transperineal approach is that the rectal bacterial flora are avoided and routine antibiotic prophylaxis, which would further increase the development of resistant organisms, might be avoided as well. However, the available data do not convincingly demonstrate an advantage associated with the transperineal route. Thus, rectal swab culture and targeted antibiotic prophylaxis is probably the best alternative.

ADDITIONAL INFORMATION AND DECLARATIONS Conflicts of Interest Disclosure: The authors have no conflicts to disclose. Acknowledgements: The authors thank Dr. Roger O’Bryan for his contributions and the Editorial Staff at the University of Florida, Department of Radiation Oncology.

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