Fluoroquinolone Use and Association with Fluoroquinolone-Resistance in Pre-Prostate Biopsy Stool Samples and Post-Biopsy Infection Angharad Webb, PharmD, BCPS, Scott Johns, PharmD, BCPS (AQ-ID), Joshua Fierer, MD VA San Diego Healthcare System, San Diego, CA UCSD Skaggs School of Pharmacy, San Diego, CA METHODS RESULTS CONCLUSIONS • Prophylactic antibiotic: 750mg x1 dose of ciprofloxacin • Stool collected on day of biopsy was screened for the presence of ciprofloxacin-R E. coli using 4/µg/ml in Maconkey’s agar • Data collected from each patient included: • Date of biopsy, presence of ciprofloxacin R, presence of ESBL E. coli, fluoroquinolone usage in the previous six months, type of fluoroquinolone including formulation, length of therapy, occurrence of post-biopsy infection • Patients with ciprofloxacin-R were matched in a 1:1 ratio with patients who had a biopsy on the same day but did not have ciprofloxacin R E. coli in feces. • Study period: February 14, 2012-February 14, 2013 • Inclusion Criteria: All patients receiving a prostate biopsy with stool culture during the study period • Exclusion Criteria: Patients with multiple biopsies • Chi square analysis was used to evaluate differences between groups • SPSS Statistical Analysis Software, version 20 was used Association Between Fluoroquinolone Use and Resistance • Fluoroquinolone use in the previous six months is not a reliable predictor of fluoroquinolone R E. coli in the stool • Stool culture is a reliable method for identifying patients at risk for post-biopsy infection, but less than 10% of patients with resistant bacteria got infected • The high rate of fluoroquinolone resistance despite a lack fluoroquinolone use suggests patients are acquiring resistant E. coli from the environment. • Increasing rates of ESBL-producing organisms towards the end of the study suggests an increasing prevalence of these organisms and could mean that infections will be more difficult to treat. Prostate biopsies have been associated with various infectious complications most commonly due to Escherichia coli (E. coli). Ciprofloxacin is the prophylactic antibiotic of choice. Fluoroquinolone resistance has been associated with increasing post-biopsy infection rates. Our study was developed to evaluate fluoroquinolone usage and the presence of ciprofloxacin-resistant E. coli and post-biopsy infection. Stool cultures were obtained on all patients the day of biopsy and evaluated for ciprofloxacin resistance. Patients with fluoroquinolone-resistance were case-matched in a 1:1 ratio with patients who had a biopsy on the same day over a one year period. 347 patients had a pre-biopsy stool culture. Of these, 63 patients had ciprofloxacin-resistant E. coli. 49 patients were case-matched with a patient without ciprofloxacin-resistant E. coli. No significant difference was found in previous fluoroquinolone use between the two groups (p=0.754). While limited by small sample size, there was no statistically significant difference in history of fluoroquinolone use (p=0.21). Four patients experienced a post-biopsy infection. Of these, three did not have a history of fluoroquinolone use. Previous fluoroquinolone use is not a reliable method for predicting fluoroquinolone resistance in E. coli in the stool. Obtaining a stool culture prior to biopsy remains the most effective method for screening for the presence of ciprofloxacin resistance and thus for the risk of post-biopsy infection. INTRODUCTION • Trans-rectal ultrasound (TRUS) guided prostate biopsies have been associated with infectious complications including cystitis, pyelonephritis, prostatitis, and bacteremia1,2 • Escherichia coli (E. coli) is the most common pathogen • AUA guidelines3 recommend a single dose of ciprofloxacin as the prophylactic antibiotic of choice • Increases in post-biopsy infection are unexplained; however, increasing fluoroquinolone resistance (R) has been suggested as a contributory factor2 • Increasing rates of Extended Spectrum Beta-Lactamaseproducing (ESBL) E. coli may also contribute to increasing resistance and infection rates • Prior fluoroquinolone use has been associated with infection with fluoroquinolone resistant E. coli • Highest correlations between colonization with resistant bacteria and a history of fluoroquinolone usage occur within 3-6 months prior4 • New antibiotic regimens have been proposed for prophylaxis including fosfomycin5. However, further research is needed to justify the cost-effectiveness of these more expensive regimens. • Due to increasing infection rates, our facility began obtaining stool cultures the day of biopsy and testing for ciprofloxacin resistance RESEARCH POSTER PRESENTATION DESIGN © 2012 www.PosterPresentations.com PATIENT SELECTION 347 patients with prostate biopsy 1 patient excluded for multiple biopsies during study period 63 patients (+) cipro R 283 patients (-) cipro R 49 patients case matched based on day of biopsy 45 40 Number of Patients ABSTRACT 81.6% 35 83.6% (+) Resistance (-) Resistance 30 25 20 15 P=0.481 10 5 18.3% 16.3% 0 FQ Use No FQ Use FQ Use in Previous Six Months Presence of ESBL E. coli: • 5 patients included in final analysis • 3 patients had no previous FQ use • 2 patients had a history of FQ use • 2 patients with an ESBL developed a post-biopsy infection • 3/5 patients with an ESBL were cultured during the last 2 months of the study period Post-Biopsy Infection: • 4 patients had a post-biopsy infection • All infections were due to ciprofloxacin R E. coli • Only 1 patient with a post-biopsy infection had a history of FQ use • Post-biopsy infections included: • Cystitis (2) • Prostatitis (2) • Bacteremia (1) DISCUSSION/LIMITATIONS RESULTS • Additional patient demographic data: • 49 patients case-matched • 63 patients had cipro-R • 14 excluded due to case-matching • 6 patients had ESBL-producing isolates* • 45 patients (13%) had a history of fluoroquinolone usage • 4 patients experienced a post-biopsy infection *One patient not included in final analysis due to case matching • Prescription records were obtained using VA data. Patients may have received fluoroquinolones from outside sources • During the prostate biopsy, lidocaine is used as a topical anesthetic which may have some antibacterial properties • The sample size of this study is comparable to previous studies • Post-biopsy infection was consistently associated with ciprofloxacin R, suggesting a need for other prophylactic strategies REFERENCES 1.Batura D, Rao GG. The national burden of infection after prostate biopsy in England and Wales: a wake-up call for better prevention. J Antimicrob Chemother. 2013;68: 247-9. 2. Loeb S, Carter, HB, Berndt SI, et al. Complications after prostate biopsy: data from SEER-Medicare. J Urology. 2011;186:1830-4. 3. American Urological Association Education and Research. Best Practice Policy Statement on Urologic Surgery Antimicrobial Prophylaxis 2012. Available at: http://www.auanet.org/content/health-policy/quality/pdf/AUASUNA/PNBWhitePaper.pdf 4. Schechner V, Temkin E, Harbath S, et al. Epidemiological interpretation of studies examining the effect of antibiotic usage on resistance. Clin Microbiol Reviews. 2013; 26(2):289-307. 5. Ongun S, Aslan G, Avakan-Oquz V, et al. The effectiveness of single-dose fosfomycin as antimicrobial prophylaxis for patients undergoing transrectal ultrasound-guided biopsy of the prostate. Urol Int. 2012;89(4):439-44. 6. Kaesbohrer A, Schroeter A, Tenhagen BA, et al. Emerging antimicrobial resistance in commensal Escherichia coli with public health prevalence. Zoonoses and Public Health. 2012; 59(Suppl 2): 158-65. 7. Williamson DA, Barrett LK, Rogers BA, et al. Infectious complications following transrecetal-ultrasound (TRUS) guided prostate biopsy: new challenges in the era of multi-drug resistant Escherichia coli. CID 2013 Advanced Access 3/26/2013. 8. Taylor S, Margolick J, Abughosh Z, et al. Ciprofloxacin resistance in the faecal carriage of patients undergoing transrectal ultrasound guided prostate biopsy. BJU International. 2013;1-8. 9. Fantin B, Duval X, Massias L, et al. Ciprofloxacin dosage and emergence of resistance in human commensal bacteria. JID. 2009;200:390-8. ACKNOWLEDGEMENTS Special thanks to our microbiology laboratory for their support with this project and assistance with collecting the data. CONTACT INFORMATION • Angharad Webb: • Email: [email protected] • Address: C/O Pharmacy Service 119 3350 La Jolla Village Drive San Diego, CA 92122