title: Is fosfomycin a potential treatment alternative for multidrug-resistant gram-negative prostatitis?
abstract: 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 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.
authors.affiliation: Department of Infectious Diseases.
authors.forename: B J
authors.initials: BJ
authors.lastname: Gardiner
authors.forename: A A
authors.initials: AA
authors.lastname: Mahony
authors.forename: A G
authors.initials: AG
authors.lastname: Ellis
authors.forename: N
authors.initials: N
authors.lastname: Lawrentschuk
authors.forename: D M
authors.initials: DM
authors.lastname: Bolton
authors.forename: P T
authors.initials: PT
authors.lastname: Zeglinski
authors.forename: A G
authors.initials: AG
authors.lastname: Frauman
authors.forename: M L
authors.initials: ML
authors.lastname: Grayson
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D005578:Fosfomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011467:Prostate / Q000737:chemistry*; D011472:Prostatitis / Q000188:drug therapy*; D044967:Serum / Q000737:chemistry; D053719:Tandem Mass Spectrometry; D014556:Urine / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D005578:Fosfomycin
keywords: fosfomycin; infection; prostate; prostatectomy; urology