Optimal timing of oral fosfomycin administration for pre-prostate biopsy prophylaxis

• Published in: Journal of antimicrobial chemotherapy Vol. 70; no. 7; pp. 2068 - 2073
• Main Authors: Rhodes, Nathaniel J., Gardiner, Bradley J., Neely, Michael N., Grayson, M. Lindsay, Ellis, Andrew G., Lawrentschuk, Nathan, Frauman, Albert G., Maxwell, Kelly M., Zembower, Teresa R., Scheetz, Marc H.
• Format: Journal Article
• Language: English
• Published: England Oxford Publishing Limited (England) 01.07.2015
• Subjects: Administration, Oral; Aged; Algorithms; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Antibiotic Prophylaxis - methods; Biopsy; Biopsy - methods; E coli; Escherichia coli; Escherichia coli - drug effects; Fosfomycin - administration & dosage; Fosfomycin - pharmacokinetics; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Models, Statistical; Pilot Projects; Plasma; Plasma - chemistry; Prostatic Diseases - diagnosis; Simulation; Time Factors; pharmacokinetics; prostate; drug administration schedule
• ISSN: 0305-7453; 1460-2091; 1460-2091
• DOI: 10.1093/jac/dkv067

As the optimal administration time for fosfomycin peri-procedural prophylaxis is unclear, we sought to determine optimal administration times for fosfomycin peri-procedural prophylaxis. Plasma, peripheral zone and transition zone fosfomycin concentrations were obtained from 26 subjects undergoing transurethral resection of the prostate (TURP), following a single oral dose of 3 g of fosfomycin. Population pharmacokinetic modelling was completed with the Nonparametric Adaptive Grid (NPAG) algorithm (Pmetrics package for R), with a four-compartment model. Plasma and tissue concentrations were simulated during the first 24 h post-dose, comparing these with EUCAST susceptibility breakpoints for Escherichia coli, a common uropathogen. Non-compartmental-determined pharmacokinetic values in our population were similar to those reported in the package insert. Predicted plasma concentrations rapidly increased after the first hour, giving more than 90% population coverage for organisms with an MIC ≤4 mg/L over the first 12 h post-dose. Organisms with higher MICs fared much worse, with organisms at the EUCAST breakpoint being covered for <10% of the population at any time. Transitional zone prostate concentrations exceeded 4 mg/L for 90% of the population between hours 1 and 9. Peripheral zone prostate concentrations were much lower and only exceeded 4 mg/L for 70% of the population between hours 1 and 4. Until more precise plasma and tissue data are available, we recommend that fosfomycin prophylaxis be given 1-4 h prior to prostate biopsy. We do not recommend fosfomycin prophylaxis for subjects with known organisms with MICs >4 mg/L.