Fluoroquinolone Resistant Rectal Colonization Predicts Risk ofInfectious Complications after Transrectal Prostate Biopsy

Michael A. Liss,*,† Stephen A. Taylor,† Deepak Batura,† Deborah Steensels,†

Methee Chayakulkeeree,† Charlotte Soenens,† G. Gopal Rao,† Atreya Dash,†

Samuel Park,† Nishant Patel,† Jason Woo,† Michelle McDonald,† Unwanaobong Nseyo,†

Pooya Banapour,† Stephen Unterberg,† Thomas E. Ahlering,‡ Hendrik Van Poppel,§

Kyoko Sakamoto,† Joshua Fierer† and Peter C. Black†

From the University of California-San Diego (MAL, SP, NP, JW, MM, UN, PB, SU, KS, JF) and VA Healthcare San Diego (KS, JF), La Jolla,

University of California-Irvine, Orange (TEA), VA Healthcare Long Beach, Long Beach (TEA), California; University of British Columbia,

Vancouver, Canada (SAT, PCB); Department of Urology & Microbiology, Ealing Hospital NHS Trust and Northwest London Hospitals

NHS Trust, London, United Kingdom (DB, GGR); University Hospital Leuven, Gasthuisberg, Leuven, Belgium (DS, CS, HVP);

Siriraj Hospital, Mahidol University, Bangkok, Thailand (MC); and University of Washington, Seattle, Washington (AD)

Abbreviations

and Acronyms

FQ ¼ fluoroquinolone

FQR ¼ fluoroquinolone resistant

TRPB ¼ transrectal prostatebiopsy

Accepted for publication June 3, 2014.Presented at annual meeting of American

Urological Association, Orlando, Florida, May16e21, 2014.

Study received institutional review boardapproval.

iDASH is supported by the National Institutesof Health (NIH) through the NIH Roadmap forMedical Research, Grant U54HL108460.

* Correspondence: UCSD Moores CancerCenter, 3855 Health Sciences Drive, MC 0987,La Jolla, California 92093 (telephone: 858-822-7874; FAX: 858-822-6188; e-mail: mliss008@gmail.com).

† Nothing to disclose.‡ Financial interest and/or other relationship

with Astellas, Phillips and Intuitive Surgical.§ Financial interest and/or other relationship

with AstraZeneca, GenProbe, Pfizer, Ferring,Sanofi-Aventis, Bayer, Antigenics and Wyeth.

Editor’s Note: This article is thesecond of 5 published in thisissue for which category 1 CMEcredits can be earned. In-structions for obtaining creditsare given with the questions onpages 1896 and 1897.

Purpose: Infection after transrectal prostate biopsy has become an increasingconcern due to fluoroquinolone resistant bacteria. We determined whethercolonization identified by rectal culture can identify men at high risk forpost-transrectal prostate biopsy infection.

Materials and Methods: Six institutions provided retrospective data through astandardized, web based data entry form on patients undergoing transrectalprostate biopsy who had rectal culture performed. The primary outcome wasany post-transrectal prostate biopsy infection and the secondary outcome washospital admission 30 days after transrectal prostate biopsy. We used chi-squareand logistic regression statistical analysis.

Results: A total of 2,673 men underwent rectal culture before transrectal pros-tate biopsy from January 1, 2007 to September 12, 2013. The prevalence offluoroquinolone resistance was 20.5% (549 of 2,673). Fluoroquinolone resistantpositive rectal cultures were associated with post-biopsy infection (6.6% vs 1.6%,p <0.001) and hospitalization (4.4% vs 0.9%, p <0.001). Fluoroquinolone resis-tant positive rectal culture increased the risk of infection (OR 3.98, 95% CI2.37e6.71, p <0.001) and subsequent hospital admission (OR 4.77, 95% CI2.50e9.10, p <0.001). If men only received fluoroquinolone prophylaxis, theinfection and hospitalization proportion increased to 8.2% (28 of 343) and 6.1%(21 of 343), with OR 4.77 (95% CI 2.50e9.10, p <0.001) and 5.67 (95% CI3.00e10.90, p <0.001), respectively. The most common fluoroquinolone resistantbacteria isolates were Escherichia coli (83.7%). Limitations include the retro-spective study design, nonstandardized culture and interpretation of resistancemethods.

Conclusions: Colonization of fluoroquinolone resistant organisms in the rectumidentifies men at high risk for infection and subsequent hospitalization fromprostate biopsy, especially in those with fluoroquinolone prophylaxis only.

Key Words: infection; prostate; biopsy; drug resistance, microbial

0022-5347/14/1926-1673/0

THE JOURNAL OF UROLOGY®

© 2014 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.

http://dx.doi.org/10.1016/j.juro.2014.06.005

Vol. 192, 1673-1678, December 2014

Printed in U.S.A.www.jurology.com j 1673

1674 FLUOROQUINOLONE RESISTANT RECTAL COLONIZATION AND RISK OF POST-BIOPSY INFECTION

INFECTIOUS complications from transrectal prostatebiopsy have increased and have caused widespreadconcerns about the safety of the most common pro-cedure for the histological diagnosis of prostatecancer.1e3 Reports have shown infectious complica-tion rates of 3.6% to 5.0% and sepsis rates of 0.3% to3.1%, largely attributed to fluoroquinolone resistantbacteria.4e7

FQ antibiotic prophylaxis is used in the majorityof nearly 2 million prostate biopsies performed inNorth America and Europe each year.8 The emer-gence of FQR bacteria has led the urological com-munity to question the continued use of FQ forprophylaxis. A recent survey noted that as a resultof this concern more than 20% of U.S. urologists arealready using combination therapy.9e11 However,the identification of high risk groups to guide suchantibiotic augmentation has not been definitive.12

Rectal culture guided prophylaxis has beenshown to reduce the incidence of post-TRPB infec-tious complications in nonrandomized studies.13e15

Unfortunately, current studies have a limited sam-ple size to provide associations due to the low eventrate of biopsy infection. Thus, we formed an inter-national, multi-institutional collaboration to inves-tigate the natural history of FQR rectal colonizationand its association with prostate biopsy infection,which could justify the incorporation of preoperativerectal cultures in routine clinical care.

MATERIALS AND METHODS

PatientsAll men underwent TRPB as part of routine care and wereenrolled in an institutional review board approved studyat 1 of 6 institutions (supplementary table 1, http://jurology.com/). All institutions had a university affilia-tion. Subjects were eligible regardless of the antibioticused for prophylaxis but documentation of antibiotic se-lection was required. Rectal culture was obtained beforeTRPB from all patients in the study, but in no patient didthe culture direct the selection of antibiotic regimen inorder to investigate the natural history of fecal carriage offluoroquinolone resistant organisms. Therefore, we areable to determine the risk of infection with empiric, non-targeted prophylaxis and its correlation to the cultureresults performed in the context of previously institu-tional review board approved clinical studies. Patientfollowup was achieved with direct interview or chartreview. Infection was defined as a fever, urinary tractinfection, any additional antibiotic therapy, emergencyroom consultation for infectious purposes or hospitaladmission for infection.

Rectal Culture and Antimicrobial ResistanceDue to the retrospective nature of this multi-institutionalstudy, methods of obtaining and processing cultures werenot standardized across institutions. Rectal culture wasobtained with a culturette before or at the time of TRPB

(supplementary table 1, http://jurology.com/). Isolation offluoroquinolone resistant organisms included the use ofselective media with ciprofloxacin infused agar or anonselective media with antibiotic discs. All sites but oneused the Clinical and Laboratory Standards Instituteguidelines, with susceptible defined as a ciprofloxacinminimum inhibitory concentration of 1 mg/ml or less andresistance defined as a ciprofloxacin minimum inhibitoryconcentration of 4 mg/ml or greater.16 One site (England)used the British Society for Antimicrobial Chemotherapydefinition of resistance as a 16 mm or less zone of inhi-bition around a ciprofloxacin disk.17

Study DesignInstitutional review board approval was obtained at theUniversity of California, San Diego for the concept anduse of a secure, open source, electronic sharing networknamed iDASH (integrating Data for Analysis, Anonym-ization, and SHaring) housed at the San Diego Super-computer Center. Seven institutions that had publishedstudies involving rectal cultures taken before TRPB wereidentified by literature search. Of these institutions6 agreed to participate and contribute data throughiDASH (supplementary table 1, http://jurology.com/). Allinstitutions were required to sign a data contribution anddata use agreement. Additionally, all institutions wererequired to provide documentation of institutional reviewboard approval to participate in the study. Before sharingthe data the institutions were asked to review them foraccuracy. However, after the data were shared, other in-stitutions did not have access to the source data.

Statistical AnalysisSample size or power analysis was not performed due tothe retrospective study design. However, to detect a 50%reduction in infection rates, studies would need to enroll1,700 to 2,000 patients. Due to the multiple institutionswith various data sets, missing data were a significantlimitation. Therefore, for this study we included onlyvariables with a sample size of 2,000 patients to avoidpartial data being influenced heavily by a particularinstitution. The primary outcome was any infectionattributed to the TRPB and the secondary outcome washospitalization after TRPB because of infection.

We classified patients as FQR colonized or not based onresults of rectal cultures regardless of how they wereobtained. Using these 2 groups a chi-square analysis wasperformed to determine if there was an increased risk ofinfection in the culture positive group. Any potentialassociations with demographic parameters were investi-gated to identify at risk or protective features frominfection. We performed a logistic regression to determinethe degree of risk that FQR colonization had on post-TRPB infection and hospital admission from infection.Statistical significance was set at p ¼ 0.05.

RESULTSA total of 2,673 men were included in the study witha median age of 66 years (range 27 to 89) who un-derwent rectal culture beforeTRPBbetween January1, 2007 and September 12, 2013 at 6 institutions

FLUOROQUINOLONE RESISTANT RECTAL COLONIZATION AND RISK OF POST-BIOPSY INFECTION 1675

(supplementary table 1, http://jurology.com/). Themajority of patients (93%; 2,474 of 2,673) received afluoroquinolone before biopsy and 24% (643 of 2,673)received more than 1 antibiotic. FQ selective mediawas used in 43% of cultures (1,151 of 2,673). Only2 of 6 study sites (1,054 of 2,673 patients; 39.4%)performed prospective studies including telephonefollowup.

FQR bacteria were isolated from 20.5% of rectalcultures (549 of 2,673). The overall infection ratewas 2.6% (69 of 2,673) and the hospital admissionrate for infection was 1.6% (44 of 2,673). Post-biopsyinfection was noted in 1.6% (33 of 2,091) of patientswith a negative FQR culture vs 6.6% (36 of 549)of men with positive cultures for FQR bacteria(p <0.001). Patients who had a positive culture yetonly received FQ prophylaxis had an 8.2% (28 of343) infection rate compared to 1.8% (28 of 1,533) inthose with a negative culture (see figure). Whenpatients with a FQR positive culture were givencombined therapy the infection risk decreasedfrom 8.2% to 6.2%, but this was not statisticallysignificant (p¼0.651).

Hospitalization for infection occurred in only0.9% (24 of 2,224) of men with a negative culture forFQR bacteria vs 4.4% (20 of 549) of those with apositive FQR culture (p <0.001). In patients who

Proportion of patients with infectious complications after TRPB bas

presented with infection after TRPB, 76% of positivecultures grew E. coli. More patients were identifiedwith an infectious complication if they received atelephone call compared to retrospective chartreview (62.3% vs 35.6%, p <0.001, supplementarytable 1, http://jurology.com/).

Univariate analysis of these variables is dis-played in table 1. Followup was significantlydifferent as verbal confirmation will likely find moreinfections than chart review. The only clinicallysignificant factor that varied between those who hadan infectious complication after TRPB and thosewho did not was FQR rectal culture (52.2% vs19.7%, p <0.001).

In previous studies diabetes has been recognizedas being associated with infection and was selectedfor multivariate analysis.18 We also included anti-biotic augmentation and bowel preparation as thesehave suggested a reduced risk of infection.9 Fourmultivariate models were used to determine theassociation of rectal culture with infection andhospital admission in the overall cohort and in asubset of patients who only received FQ prophylaxis(table 2). The FQ only group excluded those who didnot take a FQ before biopsy or those who receiveda second antibiotic. The odds ratios of infectionin patients with a positive FQR culture were 3.98

ed on clinical history of FQ exposure and rectal culture results

Table 1. Demographics

No Infection Infectionp

ValueSampleSize

No. pts 2,604 69Median pt age (IQR) 66 (61e71) 66 (60e71) 0.549 2,669Median ng/ml prostate

specific antigen (IQR)5.81 (4.0e8.3) 5.7 (4.0e8.49) 0.814 1,967

Median mm3 prostatesize (transrectalultrasound)(IQR)

43 (29e63) 44 (23.8e65.8) 0.778 1,989

No. race/ethnicity (%): 0.504 1,290White/Caucasian 857 (68.0) 24 (82.8) 881Black/African-American 118 (9.4) 2 (6.9) 120Hispanic/Latino 52 (4.1) 0 (0) 52Asian 156 (12.4) 2 (6.9) 158Other 78 (6.2) 1 (3.4) 79

No. diabetes (%): 0.849 2,059Yes 315 (15.8) 10 (16.7)No 1,684 (84.2) 50 (83.8)

No. antibioticaugmentation (2 ormore antibiotics)(%):

0.109 2,669

Yes 632 (24.3) 11 (15.9)No 1,968 (75.7) 58 (84.1)

No. bowel preparation(enema orsuppository)(%):

0.259 2,661

Yes 1,749 (67.5) 51 (73.9)No 843 (32.5) 18 (26.1)

No. followup (%): <0.001 2,672Pt contact 927 (35.6) 43 (62.3)Chart review 1,676 (64.4) 26 (37.7)

No. FQR rectal culture (%): <0.001 2,673Yes 513 (19.7) 36 (52.2)No 2,091 (80.3) 33 (47.8)

1676 FLUOROQUINOLONE RESISTANT RECTAL COLONIZATION AND RISK OF POST-BIOPSY INFECTION

(95% CI 2.37e6.71, p <0.001) for the entire cohortand 4.71 (95% CI 2.75e8.07, p <0.001) for the FQonly group. The odds ratios for patients who had ahospital admission related to prostate biopsy were4.77 (95% CI 2.50e9.10, p <0.001) for the entirecohort and 5.67 (95% CI 3.00e10.90, p <0.001) forthe FQ only group.

The most common bacteria isolated from rectalculture were E. coli (83.7%, supplementary table 2,http://jurology.com/). Of the FQR organisms manyhad resistance to multiple antibiotics. The mostcommonly used antibiotics to supplement FQ pro-phylaxis were gentamicin, amikacin, trimethoprim/sulfamethoxazole and ceftriaxone. However, FQRbacteria were also resistant to these antibiotics in

Table 2. Multivariate analysis

Overall Risk

OR (95% CI)

Entire cohort (all antibiotic combinations, 2,052):Diabetes 1.40 (0.75e2.61)Antibiotic augmentation (2 or more antibiotics) 0.35 (0.08e1.78)Bowel preparation (enema or suppository) 0.85 (0.41e1.77)FQR pos rectal culture 3.98 (2.37e6.71)

FQ only prophylaxis (1,794):Diabetes 1.40 (0.73e2.67)Bowel preparation 0.844 (0.39e1.83)FQR pos rectal culture 4.71 (2.75e8.07)

27%, 41% and 21% of cases, respectively. Imipenem,meropenem and amikacin had the lowestco-resistance rates. Clinical isolates were recoveredin 42% of those with infection, the majority beingE. coli (76%), of which 79% were FQR.

DISCUSSIONPatients harboring FQR organisms on rectal culturebefore TRPB have a greater than threefold higherrisk of infection and of subsequent hospitalizationthan men without FQR organisms. Moreover, ifa patient has a positive rectal culture and onlyreceives FQ prophylaxis, he has a nearly sixfoldhigher risk of hospital admission for infectiouscomplications. Patients with a negative culture areadequately treated with the current standard FQprophylaxis and have a risk of infection of approxi-mately 1% (see figure). We confirm the major sourceof infectious complications from TRPB is FQRE. coli, which can be multidrug resistant.8,19 Broadspectrum antibiotics should be initiated with po-tential assistance from infectious disease physiciansif post-prostate biopsy infection is encountered.

The current FQ based prophylaxis before TRPBhas come under scrutiny due to a substantialincrease in post-TRPB infections due to FQRbacteria.20 Concern about infection has led in-vestigators to attempt to identify new means toprevent post-TRPB infections, including steriliza-tion of the rectum, antibiotic augmentation andtransperineal biopsy.7,13e15,21e24 These studies haveshown incremental improvements in preventinginfection. However, they have not led to changes incurrent clinical practice.

Perhaps the most refined and promising methodis the use of targeted prophylaxis, which uses rectalculture to tailor the antibiotic prophylaxis regimento specific bacterial resistance patterns.13 Deter-mining the optimal prophylaxis regimen based onculture results would be the next step in developingthis strategy. However, we argue that the first stepin the process of reducing infection is to identifythose men at high risk.

of Infection Risk of Hospitalization

p Value OR (95% CI) p Value

0.292 1.73 (0.84e3.55) 0.1340.152 0.26 (0.04e1.95) 0.1910.669 0.58 (0.26e1.28) 0.176

<0.001 4.77 (2.50e9.10) <0.001

0.311 1.58 (0.74e3.35) 0.2380.688 0.62 (0.27e1.44) 0.276

<0.001 5.67 (3.00e10.90) <0.001

FLUOROQUINOLONE RESISTANT RECTAL COLONIZATION AND RISK OF POST-BIOPSY INFECTION 1677

Recent commentary suggests that the currentuniversal approach by which every patient receivesthe same empiric antibiotic(s) is not likely to be thefuture of prophylaxis before TRPB.25,26 Theuniversalaugmentation approach does not account for vari-ability in resistance rates at various locations andresistance changes over time. While many urologistsadvocate adding a second empiric antibiotic, our datasuggest that FQR organisms are also often resistantto other common antibiotics (supplementary table 2,http://jurology.com/). Moreover, this approach mayhave unforeseen consequences such as side effects ofantibiotics not well-known by urologists, increasedresistance and increased cost.

Effective prophylactic antibiotic selection isdifficult even assuming that all drugs are equallyeffective for TRPB prophylaxis. Moreover, indis-criminate use of additional antibiotics may promotefurther drug resistance, affecting future antibioticeffectiveness in the face of the limited developmentof new antibiotics.27 Prospective clinical trialsare needed to determine the use of rectal cultureperformed weeks before prostate biopsy, whichantimicrobials will be effective and the cost-effectiveness of this approach.

Other risk factors associated with post-TRPBinfection include a history of diabetes, indwellingurethral catheter, recent hospitalization, recenttravel to high risk countries and recent use ofantibiotics (especially fluoroquinolones).12,28 Ourstudy had limited data on the clinical history ofpatients in terms of recent antibiotic use. However,clinical history may be an imperfect tool for esti-mating risk due to recall bias. Future investigationswill include optimizing test characteristics (sensi-tivity and specificity) and performing predictivemodeling using clinical history to further riskstratify patients.

Limitations of this study include the retrospec-tive nature of the data collection, in which the mainbias pertained to the various methods of datacollection and culture techniques. However, varia-tion in the collection from a wide range of patientpopulations may add to the generalizability of thestudy. By collecting the raw data our study can beinformative as we were able to investigate the riskof infection in men with FQR rectal colonizationwho only received FQ prophylaxis, which would nothave been possible with a meta-analysis. Physiciansmay have chosen to alter or augment prophylaxisfor high risk patients based on clinical factors ormedical history, which would have likely selectedout high risk individuals biasing the results.Nonselective media may be less likely to captureFQR organisms than selective media, and the yieldof FQR organisms should be tested in the samepopulation and ideally from the same culture swab.

Moreover, the interpretation of resistance mayvary among institutions. Some institutions con-tacted patients directly and some only performedchart review to identify complications, which maybias the data toward a lower rate of infection. Toinclude a more definitive outcome we used hospitaladmission as a secondary outcome because it has ahigher likelihood of being captured on retrospectivechart review, thereby yielding a more strict defini-tion of infection. Moreover, hospital admission is animportant factor for severity of infection and overallcost of the complication.

We cannot exclude the possibility that patientswere hospitalized at institutions other than wherethe biopsy was performed. Again, this would lead toan underestimation of risk. We focused on the nat-ural history of FQR organisms in the rectum. Mostcultures were obtained at the time of biopsy and wewould not have been able to change clinical practice.One previous small study showed concordanceamong cultures obtained in the office at the time ofbiopsy.29 However, a larger cohort is needed.

Another limitation is that we were unable toobtain many of the sensitivity profiles of the clinicalinfection isolates. The small number of patients(7%) who did not have FQ prophylaxis was includedin the overall analysis with the augmentation groupto obtain the overall infection risk in all patients.Then we selected out those with FQ prophylaxisonly as shown in the figure and provided analysisfor both groups. The lack of infection isolateswas significant but consistent with other studiesshowing difficulty in capturing cultures on read-mission due to hospital location, receipt of antibi-otics before culture or the specimen not beingobtained. The univariate analysis was limited dueto missing documentation in the majority of studies.We are currently investigating predictive modelsthat include infection history adjusting for missingdata, which is beyond the scope of this study. Ourfindings coincide with the current literature sug-gesting that the majority of post-biopsy infectionsare related to FQR organisms, mainly E. coli.

CONCLUSIONSFecal carriage of FQR organisms poses a significantincreased risk of TRPB infectious complications.The risk is increased in those patients who carry theresistant organisms and only have FQ prophylaxis.We suggest further investigation of rectal cultureperformed before biopsy to identify high riskindividuals who may need altered prophylaxis.

ACKNOWLEDGMENTSJ. Kellogg Parsons, Florin Vaida and TheodoreGaniats provided critical review of the manuscript.

1678 FLUOROQUINOLONE RESISTANT RECTAL COLONIZATION AND RISK OF POST-BIOPSY INFECTION

REFERENCES

1. Loeb S, Carter HB, Berndt SI et al: Complicationsafter prostate biopsy: data from SEER-Medicare.J Urol 2011; 186: 1830.

2. Wagenlehner FM, van Oostrum E, Tenke P et al:Infective complications after prostate biopsy:outcome of the Global Prevalence Study ofInfections in Urology (GPIU) 2010 and 2011, aprospective multinational multicentre prostatebiopsy study. Eur Urol 2013; 63: 521.

3. Nam RK, Saskin R, Lee Y et al: Increasing hos-pital admission rates for urological complicationsafter transrectal ultrasound guided prostatebiopsy. J Urol 2010; 183: 963.

4. Carignan A, Roussy JF, Lapointe V et al:Increasing risk of infectious complications aftertransrectal ultrasound-guided prostate biopsies:time to reassess antimicrobial prophylaxis? EurUrol 2012; 62: 453.

5. Dumford D 3rd, Suwantarat N, Bhasker V et al:Outbreak of fluoroquinolone-resistant Escher-ichia coli infections after transrectal ultrasound-guided biopsy of the prostate. Infect ControlHosp Epidemiol 2013; 34: 269.

6. Mosharafa AA, Torky MH, El Said WM et al:Rising incidence of acute prostatitis followingprostate biopsy: fluoroquinolone resistance andexposure is a significant risk factor. Urology2011; 78: 511.

7. Abughosh Z, Margolick J, Goldenberg SL et al:A prospective randomized trial of povidone-iodine prophylactic cleansing of the rectumbefore transrectal ultrasound guided prostatebiopsy. J Urol 2013; 189: 1326.

8. Loeb S, Vellekoop A, Ahmed HU et al: System-atic review of complications of prostate biopsy.Eur Urol 2013; 64: 876.

9. Wagenlehner FM, Pilatz A, Waliszewski P et al:Reducing infection rates after prostate biopsy.Nat Rev Urol 2014; 11: 80.

10. Feliciano J, Teper E, Ferrandino M et al: Theincidence of fluoroquinolone resistant infectionsafter prostate biopsyeare fluoroquinolones stilleffective prophylaxis? J Urol 2008; 179: 952.

11. Hillelsohn JH, Duty B, Blute ML Jr et al:Variability of transrectal ultrasound-guidedprostate biopsy prophylactic measures. Can JUrol 2012; 19: 6573.

12. Simsir A, Kismali E, Mammadov R et al: Is itpossible to predict sepsis, the most seriouscomplication in prostate biopsy? Urol Int 2010;84: 395.

13. Taylor AK, Zembower TR, Nadler RB et al:Targeted antimicrobial prophylaxis using rectalswab cultures in men undergoing transrectalultrasound guided prostate biopsy is associatedwith reduced incidence of postoperative infec-tious complications and cost of care. J Urol2012; 187: 1275.

14. Suwantarat N, Dumford DM 3rd, Ponce-Terashima R et al: Modification of antimicrobialprophylaxis based on rectal culture results toprevent fluoroquinolone-resistant Escherichiacoli infections after prostate biopsy. Infect Con-trol Hosp Epidemiol 2013; 34: 973.

15. Duplessis CA, Bavaro M, Simons MP et al: Rectalcultures before transrectal ultrasound-guidedprostate biopsy reduce post-prostatic biopsyinfection rates. Urology 2012; 79: 556.

16. Clinical and Laboratory Standards Institute:Performance Standards for Antimicrobial Sus-ceptibility Testing: Twenty-First InformationalSupplement, CLSI document M100-S21. Wayne,Pennsylvania: Clinical and Laboratory StandardsInstitute 2011.

17. British Society for Antimicrobial Chemotherapy:BSAC Methods for Antimicrobial SusceptibilityTesting, Version 12. Birmingham: British Societyfor Antimicrobial Chemotherapy 2013.

18. Lundstr€om KJ, Drevin L, Carlsson S et al:Nationwide population based study of infectionsafter transrectal ultrasound guided prostatebiopsy. J Urol 2014; 192: 1116.

19. Qi C, Malczynski M, Schaeffer AJ et al: Char-acterization of ciprofloxacin resistant Escherichiacoli isolates among men undergoing evaluation

for transrectal ultrasound guided prostate biopsy.J Urol 2013; 190: 2026.

20. Williamson DA, Barrett LK, Rogers BA et al:Infectious complications following transrectalultrasound-guided prostate biopsy: new chal-lenges in the era of multidrug-resistant Escher-ichia coli. Clin Infect Dis 2013; 57: 267.

21. Adibi M, Hornberger B, Bhat D et al: Reductionin hospital admission rates due to post-prostatebiopsy infections after augmenting standardantibiotic prophylaxis. J Urol 2013; 189: 535.

22. Issa MM, Al-Qassab UA, Hall J et al: Formalindisinfection of biopsy needle minimizes the riskof sepsis following prostate biopsy. J Urol 2013;190: 1769.

23. Lorber G, Benenson S, Rosenberg S et al: Asingle dose of 240 mg gentamicin duringtransrectal prostate biopsy significantly reducesseptic complications. Urology 2013; 82: 998.

24. Lorber G, Duvdevani M, Friedman M et al:Sustained-release antibacterial varnish-coatedbiopsy needle for reduction of infection ratesfollowing prostate biopsy-in vitro model. JEndourol 2013; 27: 277.

25. Gettman MT: Better understanding of minimizinginfectious complications after transrectal pros-tate biopsy. Eur Urol 2012; 62: 460.

26. Krieger JN: Prophylaxis in urology is no longereasyeshould we use more or fewer antibiotics?J Urol 2013; 190: 1972.

27. Hughes JM: Preserving the lifesaving power ofantimicrobial agents. JAMA 2011; 305: 1027.

28. Taylor S, Margolick J, Abughosh Z et al: Cipro-floxacin resistance in the faecal carriage ofpatients undergoing transrectal ultrasoundguided prostate biopsy. BJU Int 2013; 111: 946.

29. Liss MA, Nakamura KK, Meuleners Ret al: Screening rectal culture to identifyfluoroquinolone-resistant organisms beforetransrectal prostate biopsy: do the cultureresults between office visit and biopsycorrelate? Urology 2013; 82: 67.