title: A pharmacodynamic simulation to assess tigecycline efficacy for hospital-acquired pneumonia compared with other common intravenous antibiotics.
abstract: A pharmacodynamic model was used to generate supportive data comparing tigecycline with other broad-spectrum agents against pathogens implicated in hospital-acquired pneumonia (HAP). A 5000 patient Monte Carlo simulation determined the probability of target attainment (PTA) of tigecycline (+/- ceftazidime) compared with imipenem, levofloxacin, and piperacillin/tazobactam (+/- vancomycin). PTA was calculated over MICs of current Gram-positive and Gram-negative bacteria collected from worldwide surveillance and weighted by the expected prevalence of these pathogens causing HAP. For monotherapy, the weighted PTA was imipenem (78.2%), piperacillin/tazobactam (73.3%), tigecycline (62.9%), and levofloxacin (62.5%). By pathogen PTA was greatest for tigecycline against Gram-positives, and ceftazidime or imipenem against Gram-negatives. Combination therapy increased PTA to 88.6%, 85.5%, 80.6%, and 69.8% for tigecycline, imipenem, piperacillin/tazobactam, and levofloxacin, respectively. Based on contemporary resistance data, tigecycline plus ceftazidime is predicted to achieve its pharmacodynamic targets similarly to combination therapy with imipenem plus vancomycin for the treatment of patients with HAP.
authors.affiliation: Center for Anti-Infective Research and Developement, Hartford Hospital, CT, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Kuti
authors.forename: M
authors.initials: M
authors.lastname: Dowzicky
authors.forename: D P
authors.initials: DP
authors.lastname: Nicolau
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D003428:Cross Infection / Q000188:drug therapy; D006801:Humans; D015378:Imipenem / Q000493:pharmacokinetics; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008954:Models, Biological; D009010:Monte Carlo Method; D015242:Ofloxacin / Q000493:pharmacokinetics; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D010878:Piperacillin / Q000493:pharmacokinetics; D000077725:Piperacillin, Tazobactam Drug Combination; D011014:Pneumonia / Q000188:drug therapy*; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D000077725:Piperacillin, Tazobactam Drug Combination; D064704:Levofloxacin; D000078304:Tigecycline; D015378:Imipenem; D010397:Penicillanic Acid; D015242:Ofloxacin; D008911:Minocycline; D010878:Piperacillin