title: Evaluation of a pharmacokineticpharmacodynamic approach using software to optimize the carbapenem antibiotic regimen.
abstract: OBJECTIVE
  Meropenem (MEPM) and doripenem (DRPM), whose antipseudomonal activity is more potent than that of other carbapenem antimicrobials, were used in the study. Monte Carlo simulation of drug concentrations was performed to develop an administration plan for MEPM and DRPM that takes into account the pharmacokinetics (PK)-pharmacodynamics (PD) of MEPM and DRPM and the renal function of each patient. Drug administration plans were proactively applied to patients with pneumonia to determine the usefulness of the method by assessing treatment efficacy and safety.
  
  
  METHODS
  Patients with healthcareassociated pneumonia and an indication for MEPM or DRPM chemotherapy underwent drug administration in accordance with the MEPM and DRPM treatment plan developed by the PK-PD software applications. The primary efficacy endpoints were the clinical and bacteriological efficacy of the drugs agains pneumonia. The safety of the antimicrobials was assessed based on abnormal laboratory findings and the seizure disorders in accordance with the criteria for safety evaluation of antimicrobial agents.
  
  
  RESULTS
  This study examined 12 and 11 patients in the MEPM and DRPM group, respectively; however, 3 DRPM patients were excluded due to the administration of anti-methicillin-resistant Staphylococcus aureus drugs after the initiation of DRPM treatment. MEPM and DRPM drug administration was determined to be safe and effective in all patients.
  
  
  CONCLUSIONS
  The present results suggest that the Monte Carlo simulation-based PK-PD software is an effective tool for planning individualized antimicrobial chemotherapy with carbapenem in accordance with the PK-PD theory of antimicrobials. It is also possible to propose safe and effective drug administration plans for patients with healthcare-associated pneumonia.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ishihara
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishimura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tamaki
authors.forename: Fumi
authors.initials: F
authors.lastname: Karino
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Miura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Isobe
authors.forename: Kazuro
authors.initials: K
authors.lastname: Ikawa
authors.forename: Norifumi
authors.initials: N
authors.lastname: Morikawa
authors.forename: Kohji
authors.initials: K
authors.lastname: Naora
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D015780:Carbapenems / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D003198:Computer Simulation; D000077726:Doripenem; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D016903:Drug Monitoring; D004360:Drug Therapy, Computer-Assisted / Q000379:methods*; D005260:Female; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008954:Models, Biological; D009010:Monte Carlo Method; D018410:Pneumonia, Bacterial / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D011446:Prospective Studies; D012984:Software; D013845:Thienamycins / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D013845:Thienamycins; D000077726:Doripenem; D000077731:Meropenem