Format

Send to

Choose Destination
J Antimicrob Chemother. 2015 Jul;70(7):2068-73. doi: 10.1093/jac/dkv067. Epub 2015 Mar 22.

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

Author information

1
Department of Pharmacy Practice, Midwestern University, Chicago College of Pharmacy, Downers Grove, IL, USA Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL, USA.
2
Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia.
3
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.
4
Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
5
Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia Department of Clinical Pharmacology, Austin Health, Heidelberg, Victoria, Australia.
6
Department of Surgery, Urology Unit, University of Melbourne, Melbourne, Victoria, Australia Olivia Newton-John Cancer Research Institute, Austin Health, Heidelberg, Victoria, Australia.
7
Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
8
Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
9
Department of Pharmacy Practice, Midwestern University, Chicago College of Pharmacy, Downers Grove, IL, USA Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL, USA mscheetz@nm.org.

Abstract

OBJECTIVES:

As the optimal administration time for fosfomycin peri-procedural prophylaxis is unclear, we sought to determine optimal administration times for fosfomycin peri-procedural prophylaxis.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

drug administration schedule; pharmacokinetics; prostate

PMID:
25802286
DOI:
10.1093/jac/dkv067
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center