Background: Multidrug resistant Gram-negative (MDR-GNB) infections of the prostate are an increasing problem worldwide, particularly complicating trans-rectal 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 (MIC 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 (TURP) for benign prostatic hyperplasia (BPH), 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 mins and 581±150 mins post-dose, 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: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=0.001). Only one patient had a mean prostatic FOS concentration of < 1 µg/g, while the majority (70%) had concentrations ≥4 µg/g.
Conclusions: Fosfomycin appears to achieve reasonable intra-prostatic 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.
Written by:
Gardiner B, Mahony A, Ellis A, Lawrentschuk N, Bolton D, Zeglinski P, Frauman A, Grayson M. Are you the author?
Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia.
Reference: Clin Infect Dis. 2013 Oct 28. Epub ahead of print.
doi: 10.1093/cid/cit704
PubMed Abstract
PMID: 24170195
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