Ciprofloxacin-Resistant Bacteria on Pre-Prostate Biopsy Rectal Swab Culture: A Northwest Ohio Study

Patients and Methods

After Institutional Review Board approval was obtained from The University of Toledo, a retrospective chart review was completed for all patients who underwent rectal swab culture within the Department of Urology between January 1, 2012 and December 31, 2015. Patient demographic information including age, number of previous biopsies, dates of previous biopsies, and surgeon were collected. Assessment of recent fluoroquinolone exposure was difficult because many patients had either traveled to our facility from out of town, or were under the care of a family practice physician not associated with our system. Febrile infectious complications within 30 days of biopsy were tracked by reviewing all clinic and admission documentation for each of the patients included in the study. In the event of a patient phone call, outside admission, or outside clinic visit for a post-biopsy complication, documentation was completed in our outpatient medical record. Inclusion criteria for our study included age greater than 18 years, males with a possibility of needing a prostate biopsy in the future, and swabs completed by urology faculty or staff. Exclusion criteria included age less than 18 years of age and rectal swab completed outside of the Department of Urology.

All rectal swab cultures were grown in selective brain-heart infusion (BHI) broth containing ciprofloxacin. If growth was noted, the presence of ciprofloxacin-resistant bacteria was confirmed but identification was not completed. If no growth was observed, absence of ciprofloxacin resistance was assumed and patients undergoing TRUS prostate biopsy were given ciprofloxacin. In the presence of growth, ciprofloxacin-resistant bacteria were confirmed but no identification or susceptibilities were performed. These patients were routinely given ampicillin and gentamicin intravenously immediately prior to biopsy. This changed in 2014 when we began preforming bacterial identification and sensitivity studies on resistant bacteria (Table 1). In short, starting in 2014 if growth was noted in the ciprofloxacin containing BHI broth the specimen was plated and all morphologies were identified and sensitivities tested. In all cases only a single isolate was noted. This allowed us to use targeted prophylaxis. Because 80% of resistant isolates were sensitive to a first-generation cephalosporin, this was the most commonly administered antibiotic class to this group (Table 1). Antibiotic duration was determined by the treating physician, however, only two regimens were used. Approximately 50% of the patients received a single dose of antibiotic agent prior to biopsy, whereas the others received a three-day course starting the day prior to biopsy. In the rare event the isolate required intravenous antibiotic agent administration, a single dose was given. Statistical analyses were performed using SPSS software (IBM Corporation, Armonk, NY). Parameters were compared by t-test, χ², and analysis of variance (ANOVA) analyses, where appropriate.

Results

Three hundred eleven rectal swabs were preformed over the four-year period (2012–2015). In total 14.9% (n = 47) of these swabs harbored ciprofloxacin-resistant bacteria, of which 20 patients had identification and sensitivity testing completed during the study period. Identification testing demonstrated Escherichia coli growth in 19 of 20 of these patients, and Enterobacter cloacae in 1 of 20 patients. The average age at time of rectal swab culture was 64 (± 8.7 standard deviation [SD]) years old for all patients. There was no difference in mean age between ciprofloxacin-resistant and ciprofloxacin-sensitive populations. The numbers of swabs per year were 53, 58, 87, 133 for 2012, 2013, 2014, and 2015, respectively. The percentage of patients with ciprofloxacin-resistant bacteria was 13.2%, 13.8%, 19.5%, and 13.3%, respectively, per year of study. The mean patient age for each calendar year was 65.8, 63.1, 63.6, and 64.0, respectively; 52 of the 311 patients (16.7%) had undergone TRUS prostate biopsy previously. Of the 311 patients who underwent rectal swab testing, 202 (65.0%) eventually had a TRUS prostate biopsy during the study period. There was no increase in ciprofloxacin-resistant bacteria across years (p > 0.62); there was no correlation between resistance and patient age (p > 0.96); and there was no correlation between previous biopsy and ciprofloxacin resistance (p > 0.67). These results are summarized in Tables 2 and 3. In total, two symptomatic infections were noted within 30 days of biopsy in those patients who underwent trans-rectal biopsy. One patient was admitted for Escherichia coli sepsis, and the other was discharged from the emergency department with a urinary tract infection. Neither of these patients harbored ciprofloxacin-resistant bacteria on their pre-operative culture, however, both of their infections were attributed to ciprofloxacin-resistant Escherichia coli.

Discussion

Prostate biopsies in the United States are performed routinely without targeted prophylaxis. Ciprofloxacin is routinely given peri-operatively, and is recommended within the American Urological Association's antimicrobial prophylaxis guidelines. However, there is growing concern that infections from ciprofloxacin-resistant bacteria after prostate biopsy are increasing [3,4]. Within the last decade, a growing body of evidence supports the use of targeted prophylaxis [7–9]. The current study was undertaken to determine the prevalence of ciprofloxacin resistance within our population, and to track this prevalence over time. Infectious complications and risk factors for resistance were also queried.

Although the present study failed to demonstrate increasing resistance to ciprofloxacin within the rectal vault over the study period, we did find a significant overall resistance rate of 14.9%. Interestingly, no study to date has documented changes in ciprofloxacin resistance in the rectal vault across time. This is likely because of short study periods in which rapidly changing resistances are not expected. One strength of the present study was a longer study period. However, should increasing resistance be present longitudinally, four years was insufficient to document this. Data from a long-term, multi-center study may be needed to prove, or dispel, changes in ciprofloxacin resistance within the rectal vault across time.

Contrary to a previously published report [3], our data failed to demonstrate that previous prostate biopsy was a risk factor for harboring resistant bacteria. It is possible this finding was specific to their population as other reviewed studies came to conclusions similar to ours. Further studies including analysis of exposure to ciprofloxacin at varying time points prior to rectal swab and prostate biopsy are needed to better answer this question.

In agreement with reports showing that ciprofloxacin-resistant Escherichia coli exhibit stronger virulence compared to non-resistant Escherichia coli [3, 4], both of the post-biopsy infectious complications in the present study were attributed to ciprofloxacin resistant Escherichia coli. Interestingly both patients had no resistance noted on pre-biopsy swabs. We are not aware of any peri-operative fluoroquinolone exposure in either of these patients that may have induced resistance between the time of the swabs and biopsy. Thus, although resistance testing may be both sensitive and specific for uncovering ciprofloxacin resistance in the rectal vault, it is certainly not perfect. More importantly, however, the low complication rate of the present study suggests the utility of targeted prophylaxis. Because of this low complication rate we advocate for resistance testing with bacterial identification and sensitivity reporting if possible. This allows for targeted therapy and good antimicrobial stewardship in an era of ever-increasing antibiotic resistance. Also, directed narrow-spectrum coverage with cephalexin or trimethoprim/sulfamethoxazole in patients harboring ciprofloxacin-resistant bacteria may further prolong the clinical utility of broader spectrum agents. As for whether a single peri-operative dose or a three-day antibiotic course is more efficacious remains to be seen. In our study a single dose appears to be sufficient, however, our study was not powered to assess for this difference. Taken together we recommend either a single or three-day course of ciprofloxacin if no resistance is present, and a similar course of tailored, narrowed therapy based on sensitivities in situations of resistance.

Our study does have several limitations. First, because many of our patients had either traveled to our facility from out of town or were under the care of a family practice physician not associated with our system, recent exposure to fluoroquinolones was difficult to assess. Previous prostate biopsy and age were thus used as adjuncts for fluoroquinolone exposure. Second, although every effort was made to document post-biopsy complications, it is possible some patients were treated at outside facilities and records were not available. Third, our study was not powered to assess for differences in three-day dosing versus a single peri-operative dose of antibiotic agents. Further studies are needed to address this. Last, we plan to continue collecting susceptibility data from our patients who are rectally colonized with ciprofloxacin-resistant organisms. This would allow us to build a regional antibiogram that can be used in selecting the best pre-operative prophylaxis in our community, especially by urologists who do not have access to ciprofloxacin resistance testing.

Conclusion

Ciprofloxacin-resistant bacteria are prevalent in the rectal vaults of older men in northwestern Ohio. This can have an impact on the risk for infection after trans-rectal procedures such as prostate biopsy. We recommend pre-operative rectal swab cultures coupled with directed prophylaxis to ensure appropriate, targeted antibiotic use in an era of increased bacterial resistance.