Is Fosfomycin a Potential Treatment Alternative for Multidrug-Resistant Gram-Negative Prostatitis?

Background. Multidrug-resistant gram-negative bacterial (MDR-GNB) infections of the prostate are an increasing problem worldwide, particularly complicating transrectal ultrasound (TRUS)-guided prostate biopsy. Fluoroquinolone-based regimens, once the mainstay of many protocols, are increasingly ineffective. Fosfomycin has reasonable in vitro and urinary activity (minimum inhibitory concentration breakpoint <= 64 mu g/mL) against MDR-GNB, but its prostatic penetration has been uncertain, so it has not been widely recommended for the prophylaxis or treatment of MDR-GNB prostatitis. Methods. In a prospective study of healthy men undergoing a transurethral resection of the prostate for benign prostatic hyperplasia, we assessed serum, urine, and prostatic tissue (transition zone [TZ] and peripheral zone [PZ]) fosfomycin concentrations using liquid chromatography-tandem mass spectrometry, following a single 3-g oral fosfomycin dose within 17 hours of surgery. Results. Among the 26 participants, mean plasma and urinary fosfomycin levels were 11.4 +/- 7.6 mu g/mL and 571 +/- 418 mu g/mL, 565 +/- 149 minutes and 581 +/- 150 minutes postdose, respectively. Mean overall prostate fosfomycin levels were 6.5 +/- 4.9 mu g/g (range, 0.7-22.1 mu g/g), with therapeutic concentrations detectable up to 17 hours following the dose. The mean prostate to plasma ratio was 0.67 +/- 0.57. Mean concentrations within the TZ vs PZ prostate regions varied significantly (TZ, 8.3 +/- 6.6 vs PZ, 4.4 +/- 4.1 mu g/g; P=.001). Only 1 patient had a mean prostatic fosfomycin concentration of <1 mu g/g, whereas the majority (70%) had concentrations >= 4 mu g/g. Conclusions. Fosfomycin appears to achieve reasonable intraprostatic concentrations in uninflamed prostate following a single 3-g oral dose, such that it may be a potential option for prophylaxis pre-TRUS prostate biopsy and possibly for the treatment of MDR-GNB prostatitis. Formal clinical studies are now required.