title: Optimizing intravenous fosfomycin dosing in combination with carbapenems for treatment of Pseudomonas aeruginosa infections in critically ill patients based on pharmacokinetic/pharmacodynamic (PK/PD) simulation.
abstract: OBJECTIVE
  The purpose of the study was to determine the optimal dosing regimen of intravenous fosfomycin for the treatment of Pseudomonas aeruginosa (PA) based on PK/PD targets.
  
  
  METHODS
  A total of 120 PA isolates were recovered from various clinical specimens at university hospital in Thailand. Minimum Inhibitory Concentrations (MICs) of all the isolates were determined by the E-test method. PK parameters were obtained from a published study. Monte Carlo simulation was performed to calculate the percentage of target attainment (PTA) and cumulative fraction of response (CFR).
  
  
  RESULTS
  MIC90 of fosfomycin alone, fosfomycin in combination with carbapenem, carbapenems alone and carbapenems in combination with fosfomycin were >1,024, 1,024, >32 and 32μg/ml, for multidrug resistant (MDR)-PA and 512, 128, 8 and 3μg/ml respectively, for non-MDR PA. Approximately 40% of the non-MDR PA were carbapenem-resistant strains. For non-MDR PA with CRPA, fosfomycin 16g continuous infusion in combination with carbapenems provided %PTA of approximately 80 and %CFR of > 88. While, %PTA and %CFR > 90 were achieved with fosfomycin 24g/day prolonged infusion in combination with carbapenem.
  
  
  CONCLUSIONS
  Prolonged infusion of fosfomycin 16 - 24g combined with extended carbapenem infusion could be used in non-MDR PA treatment with CRPA.
authors.affiliation: Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand.
authors.forename: O
authors.initials: O
authors.lastname: Asuphon
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
authors.forename: P
authors.initials: P
authors.lastname: Montakantikul
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
authors.forename: J
authors.initials: J
authors.lastname: Houngsaitong
authors.affiliation: Department of Microbiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: P
authors.initials: P
authors.lastname: Kiratisin
authors.affiliation: Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand. Electronic address: paveenasonthi@hotmail.com.
authors.forename: P
authors.initials: P
authors.lastname: Sonthisombat
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015780:Carbapenems / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016638:Critical Illness / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005578:Fosfomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D013785:Thailand
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D005578:Fosfomycin
keywords: Monte Carlo simulation; Pseudomonas aeruginosa; fosfomycin; pharmacokinetics/pharmacodynamics