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- Title
Is Fosfomycin a Potential Treatment Alternative for Multidrug-Resistant Gram-Negative Prostatitis?
- Authors
Gardiner, B. J.; Mahony, A. A.; Ellis, A. G.; Lawrentschuk, N.; Bolton, D. M.; Zeglinski, P. T.; Frauman, A. G.; Grayson, M. L.
- Abstract
Multidrug resistant Gram-negative (MDR-GNB) infections of the prostate are an increasing problem complicating trans-rectal ultrasound (TRUS)-guided prostate biopsy and urinary tract sepsis. Fosfomycin appears to achieve reasonable intra-prostatic concentrations in uninflamed prostate, such that it may be a potential option for prophylaxis pre-TRUS prostate biopsy and possibly for the treatment of MDR-GNB prostatitisBackground. 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 µg/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 µg/mL and 571 ± 418 µg/mL, 565 ± 149 minutes and 581 ± 150 minutes postdose, respectively. Mean overall prostate fosfomycin levels were 6.5 ± 4.9 µg/g (range, 0.7–22.1 µg/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 µg/g; P = .001). Only 1 patient had a mean prostatic fosfomycin concentration of <1 µg/g, whereas the majority (70%) had concentrations ≥4 µg/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.
- Subjects
FOSFOMYCIN; ANTIBACTERIAL agents; DRUG resistance in bacteria; PROSTATITIS treatment; GRAM-negative bacterial diseases; BACTERIAL disease treatment
- Publication
Clinical Infectious Diseases, 2014, Vol 58, Issue 4, pe101
- ISSN
1058-4838
- Publication type
Article
- DOI
10.1093/cid/cit704