With empiric single drug antimicrobial prophylaxis for TRUSP the hospitalization rate for infections is 0 to 6.3%.2 Two approaches to address this have been developed. Empiric augmented prophylaxis has shown initially promising results. However, it is often influenced by local hospital antibiograms, fails to assess the rectal source of the post-biopsy infections, and its use will likely be directly related to increasing antimicrobial resistance. Alternatively, rectal swab cultures can 1) determine the population of fluoroquinolone-resistant (FQR)-GNB in the rectal flora, 2) identify specific patients with FQ -GNB and 3) guide targeted single drug and augmented prophylaxis [7, 14, 16, 19, 23, 24]. The presence of FQ-R bacteria in the rectal flora constitutes a five-fold increase in the rate and potential severity of post-biopsy infections in patients receiving empiric fluoroquinolone prophylaxis [25]. This finding supports the utilization of pre-biopsy rectal cultures to identify patients at increased risk and to select targeted prophylaxis that is most likely to be effective. These principles were supported by this prospective cohort study, which showed a very low, i.e. 0.6%, sepsis rate and equivalent infectious complication rates among patients with CR-GNB or CS-GNB rectal flora who received targeted prophylaxis per our protocol.
In our study, the FQ resistance rate was 15.7%. We agree with Van Besien et al. [25] who stated that the benefit of targeted prophylaxis depends on local FQ-R prevalence rates. A randomized, blinded trial would subject the approximately 20% of patients who harbor FQ-R flora and receive FQ prophylaxis to the known 5-fold higher risk of infectious complications [25]. Similarly, empiric augmented prophylaxis could also subject patients to ineffective antimicrobial prophylaxis. For example, gentamicin is frequently used for augmented prophylaxis, but gentamicin resistance was present in 20% of the bacteria isolated from our patients with CR-GNB rectal flora (Fig. 2).
Our infectious complication rate in the per-protocol patients of 1.9% improved upon the 2.6% infection rate prior to the introduction of this protocol [14]. We used very stringent criteria: inclusion of all patients with symptoms of urinary tract infection irrespective of urine or blood cultures and phone screening at 7-and 30-days. Indeed, of the 9 patients identified, 3 had negative cultures before antimicrobial therapy was initiated and 3 were negative at 7 days but positive within 30 days. More importantly, only 4 (0.8%) had significant clinical infections and only 2 were culture-proven, febrile UTI (0.2%) and sepsis (0.2%).
Of the 9 patients with infections, only 3 had prior exposure to fluoroquinolones, a rate similar to those who did not become infected. Of the 6 patients with positive cultures, 3 were prophylaxis failures, i.e. the infecting bacteria was susceptible to the prophylactic drug given, (ciprofloxacin 2, and amikacin 1). Since all of these patients received their prophylaxis per protocol, we cannot implicate noncompliance of the patient or medical error. Breakthrough infections were probably due to excessive inoculum at the time of biopsy and/or an unrecognized host risk factor(s). Three patients were infected with bacteria with antimicrobial susceptibility breakpoints that showed resistance whereas the pre-biopsy rectal bacteria were susceptible. This could be due to sampling error of the rectal flora, lack of detection on the selective media or increasing antimicrobial resistance between the time of the culture and the biopsy. Although incorporating a lower concentration of ciprofloxacin into the screening media may have rendered the two rectal cultures with intermediate susceptibility ciprofloxacin-resistant, this extremely low incidence in our opinion would not support lowering the ciprofloxacin concentration in the screening media in our population.
Of the 6 culture-proven infections, the bacteria were multidrug resistant in 5, and of these, 2 were ESBLs. Williamson et al. noted similar results [26]. We identified trends in risk factors, e.g. history of UTI, however the incidence of infections was too low to achieve statistical significance [12, 24, 27,28,29].
This study is limited in that it was a single institution study and, for ethical reasons, was not blinded or controlled. Erectile dysfunction, a potential complication of TRUSP, was not evaluated, but it may occur as a result of inflammation induced by infection [30]. Thus, targeted prophylaxis could have other indirect benefits. Larger, multicenter studies are necessary to study this approach and its generalizability.
Additionally, this study does not claim superiority to empiric augmented prophylaxis in terms of infection reduction. However, it is likely that antimicrobial prophylaxis based on real time sensitivity data will be more durable and will likely outperform empiric prophylaxis as bacterial resistance inevitably increases. It is possible that more extended use of augmented prophylaxis or use of multiday therapy [16, 29, 31, 32] would have reduced our infectious complications further, but adherence to the guidelines of antimicrobial stewardship favors limited, single drug targeted prophylaxis for most patients.
