title: Optimal timing of oral fosfomycin administration for pre-prostate biopsy prophylaxis.
abstract: OBJECTIVE
  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.
authors: Department of Pharmacy Practice, Midwestern University, Chicago College of Pharmacy, Downers Grove, IL, USA Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL, USA.
authors: Nathaniel J
authors: NJ
authors: Rhodes
authors: Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia.
authors: Bradley J
authors: BJ
authors: Gardiner
authors: 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.
authors: Michael N
authors: MN
authors: Neely
authors: Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
authors: M Lindsay
authors: ML
authors: Grayson
authors: Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia Department of Clinical Pharmacology, Austin Health, Heidelberg, Victoria, Australia.
authors: Andrew G
authors: AG
authors: Ellis
authors: Department of Surgery, Urology Unit, University of Melbourne, Melbourne, Victoria, Australia Olivia Newton-John Cancer Research Institute, Austin Health, Heidelberg, Victoria, Australia.
authors: Nathan
authors: N
authors: Lawrentschuk
authors: Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia Department of Clinical Pharmacology, Austin Health, Heidelberg, Victoria, Australia.
authors: Albert G
authors: AG
authors: Frauman
authors: Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors: Kelly M
authors: KM
authors: Maxwell
authors: Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors: Teresa R
authors: TR
authors: Zembower
authors: 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.
authors: Marc H
authors: MH
authors: Scheetz
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019072:Antibiotic Prophylaxis / Q000379:methods*; D001706:Biopsy / Q000379:methods*; D004926:Escherichia coli / Q000187:drug effects; D005578:Fosfomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015233:Models, Statistical; D010865:Pilot Projects; D010949:Plasma / Q000737:chemistry; D011469:Prostatic Diseases / Q000175:diagnosis*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D005578:Fosfomycin
keywords: drug administration schedule; pharmacokinetics; prostate