Pharmacokinetic/pharmacodynamic evaluation of sulbactam against Acinetobacter baumannii in in vitro and murine thigh and lung infection models

Int J Antimicrob Agents. 2014 Jun;43(6):547-52. doi: 10.1016/j.ijantimicag.2014.02.012. Epub 2014 Mar 30.


Acinetobacter baumannii is a pathogen that has become globally associated with nosocomial infections. Sulbactam, a potent inhibitor of β-lactamases, was previously shown to be active against A. baumannii strains in vitro and effective against A. baumannii infections. However, a pharmacokinetic/pharmacodynamic (PK/PD) analysis of sulbactam against A. baumannii infections has not yet been performed. This is necessary because optimisation of dosing regimens should be based on PK/PD analysis. Therefore, in vitro and in vivo PK/PD analyses of sulbactam were performed using murine thigh and lung infection models of A. baumannii to evaluate the pharmacokinetics and pharmacodynamics of sulbactam. Sulbactam showed time-dependent bactericidal activity in vitro against A. baumannii. The PK/PD index that best correlated with its in vivo effects was the time that the free drug concentration remained above the minimum inhibitory concentration (fT>MIC) both in the thigh (R(2)=0.95) and lung (R(2)=0.96) infection models. Values of fT>MIC for a static effect and 1, 2 and 3log10 kill, respectively, were 21.0%, 32.9%, 43.6% and 57.3% in the thigh infection model and 20.4%, 24.5%, 29.3% and 37.3% in the lung infection model. Here we report the in vitro and in vivo time-dependent activities of sulbactam against A. baumannii infection and demonstrate that sulbactam was sufficiently bactericidal when an fT>MIC of >60% against A. baumannii thigh infection and >40% against A. baumannii lung infection was achieved.

Keywords: Acinetobacter baumannii; Infection mouse model; Pharmacokinetic/pharmacodynamic; Sulbactam.

MeSH terms

  • Abscess / drug therapy
  • Acinetobacter Infections / drug therapy*
  • Acinetobacter baumannii / drug effects*
  • Animals
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Load
  • Disease Models, Animal
  • Female
  • Lung / pathology
  • Mice
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects
  • Plasma / chemistry
  • Pneumonia, Bacterial / drug therapy
  • Sulbactam / pharmacokinetics*
  • Sulbactam / pharmacology*
  • Sulbactam / therapeutic use
  • Thigh / pathology


  • Anti-Bacterial Agents
  • Sulbactam