Activity of tigecycline alone and in combination with colistin and meropenem against carbapenemase (KPC)-producing Enterobacteriaceae strains by time-kill assay

Spyros Pournaras (1) , Georgia Vrioni (2) , Evangelia Neou (1) , John Dendrinos (2) , Evangelia Dimitroulia (2) , Aggeliki Poulou (3) , Athanassios Tsakris (2)

1 Department of Microbiology
2 Department of Microbiology
3 Department of Microbiology

Antibiotic combinations including tigecycline have not been studied against carbapenemase (KPC)-producing pathogens. Tigecycline alone and combined with colistin and meropenem was tested against eight genetically unrelated KPC-producing clinical strains of Enterobacteriaceae (four, two , one and one ) by time-kill assay. Tigecycline displayed a concentration-independent bacteriostatic activity in seven strains and bactericidal activity in one strain. Colistin showed bactericidal activity at 4× the minimum inhibitory concentration (MIC) in three strains and was bacteriostatic for the remaining strains and concentrations. Meropenem was bactericidal in three strains and bacteriostatic in five strains. The tigecycline+meropenem combination was not bactericidal against the four strains and was non-synergistic against all eight strains. Tigecycline+colistin was bactericidal against all strains at most time intervals and concentrations and was also synergistic at 1× and 2× MIC against most strains up to 4-8h and at 4× MIC up to 24h against all strains. These findings suggest that, at most drug concentrations, tigecycline, colistin and meropenem as single agents do not exhibit efficient bactericidal activity against most of the KPC-producing strains. Tigecycline alone might be a therapeutic option for infections caused by KPC-producers when bacteriostatic activity is adequate or combined with colistin when bactericidal activity is necessary. Additional in vivo tests are warranted to assess better the killing kinetics of tigecycline combinations against KPC-producers.

Mots clés: Class A carbapenemase; KPC; Tigecycline; Colistin; Meropenem; Time-kill; Bacteriostatic; Bactericidal; Synergistic

Domaines: Microbiologie et Parasitologie

Spyros Pournaras, Georgia Vrioni, Evangelia Neou, John Dendrinos, Evangelia Dimitroulia, et al.. Activity of tigecycline alone and in combination with colistin and meropenem against carbapenemase (KPC)-producing Enterobacteriaceae strains by time-kill assay. International Journal of Antimicrobial Agents, 2011, 37 (3), pp.244. ⟨10.1016/j.ijantimicag.2010.10.031⟩. ⟨hal-00671245⟩