title: Pharmacodynamic evaluation of i.v. antimicrobials against Pseudomonas aeruginosa samples collected from U.S. hospitals.
abstract: OBJECTIVE
  Selected i.v. antimicrobials were evaluated against Pseudomonas aeruginosa isolates collected from U.S. hospitals to predict the likelihood of achieving maximal bactericidal activity.
  
  
  METHODS
  The pharmacodynamic profiles of ceftazidime, doripenem, imipenem-cilastatin, levofloxacin, meropenem, and piperacillin-tazobactam were simulated for 5000 adult patients using pharmacokinetic data from infected patients with the minimum inhibitory concentrations of 6142 P. aeruginosa isolates in U.S. hospitals collected during 2009. The probability of achieving bactericidal activity in this population, referred to as the cumulative fraction of response (CFR), was calculated for each antimicrobial. An optimal regimen was defined as achieving a CFR of ≥90%.
  
  
  RESULTS
  The majority of isolates were collected from male inpatients who were not in an intensive care unit (ICU) and were over age 65 years. Standard dosing for all antimicrobials failed to achieve optimal CFRs, regardless of hospital location. While high-dose prolonged infusions improved the CFRs for the β-lactams, optimal exposures were only attained by doripenem (2 g every 8 hours infused over 1 hour; 0.5-2 g every 8 hours infused over 4 hours) and meropenem (2 g every 8 hours infused over 0.5 and 3 hours) for all isolates. Non-ICU isolates had approximately 5-10% higher CFRs compared with those collected in the ICU. Lower-respiratory-tract isolates had a lower predicted CFR than did isolates from the blood and skin or wounds.
  
  
  CONCLUSIONS
  Simulated pharmacodynamic profiles of i.v. antimicrobials commonly used to treat P. aeruginosa indicated that higher dosages and prolonged infusion times are needed to achieve optimal exposure for bactericidal activity.
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, CT 06102, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Keel
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Kuti
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Sahm
authors.forename: David P
authors.initials: DP
authors.lastname: Nicolau
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D005260:Female; D006761:Hospitals; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D014481:United States
chemical_list: D000900:Anti-Bacterial Agents