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

Yuta Yokoyama, Kazuaki Matsumoto, Kazuro Ikawa, Erika Watanabe, Akari Shigemi, Yasuhiro Umezaki, Koyo Nakamura, Keiichiro Ueno, Norifumi Morikawa, Yasuo Takeda

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 (R2 = 0.96) infection models. Values of fT>MIC for a static effect and 1, 2 and 3 log10 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.

Original languageEnglish
Pages (from-to)547-552
Number of pages6
JournalInternational journal of antimicrobial agents
Volume43
Issue number6
DOIs
Publication statusPublished - 2014 Jun
Externally publishedYes

Keywords

  • Acinetobacter baumannii
  • Infection mouse model
  • Pharmacokinetic/pharmacodynamic
  • Sulbactam

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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