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Title: Optimal timing of oral fosfomycin administration for pre-prostate biopsy prophylaxis.
Austin 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
Affiliation: Department of Clinical Pharmacology, Austin Health, Heidelberg, Victoria, Australia
Department of Pharmacy Practice, Midwestern University, Chicago College of Pharmacy, Downers Grove, IL, USA
Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL, USA
Laboratory of Applied Pharmacokinetics and Bioinformatics, Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA
Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Department of Surgery, Urology Unit, University of Melbourne, Melbourne, Victoria, Australia
Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia
Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
Issue Date: 22-Mar-2015
Publication information: The Journal of Antimicrobial Chemotherapy 2015; 70(7): 2068-73
Abstract: 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.
Gov't Doc #: 25802286
DOI: 10.1093/jac/dkv067
Journal: The Journal of antimicrobial chemotherapy
Type: Journal Article
Subjects: drug administration schedule
Appears in Collections:Journal articles

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