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. 2009 Oct;53(10):4298-304.
doi: 10.1128/AAC.00320-09. Epub 2009 Jul 27.

In vitro activity and in vivo efficacy of clavulanic acid against Acinetobacter baumannii

Alejandro Beceiro  1 , Rafael López-Rojas, Juan Domínguez-Herrera, Fernando Docobo-Pérez, Germán Bou, Jerónimo Pachón; Spanish Network for Research in Infectious Diseases (REIPI)
Affiliations

In vitro activity and in vivo efficacy of clavulanic acid against Acinetobacter baumannii

Alejandro Beceiro et al. Antimicrob Agents Chemother. 2009 Oct.

Abstract

Clavulanic acid (CLA) exhibits low MICs against some Acinetobacter baumannii strains. The present study evaluates the efficacy of CLA in a murine model of A. baumannii pneumonia. For this purpose, two clinical strains, Ab11 and Ab51, were used; CLA MICs for these strains were 2 and 4 mg/liter, respectively, and the imipenem (IPM) MIC was 0.5 mg/liter for both. A pneumonia model in C57BL/6 mice was used. The CLA dosage (13 mg/kg of body weight given intraperitoneally) was chosen to reach a maximum concentration of the drug in serum similar to that in humans and a time during which the serum CLA concentration remained above the MIC equivalent to 40% of the interval between doses. Six groups (n = 15) were inoculated with Ab11 or Ab51 and were allocated to IPM or CLA therapy or to the untreated control group. In time-kill experiments, CLA was bactericidal only against Ab11 whereas IPM was bactericidal against both strains. CLA and IPM both decreased bacterial concentrations in lungs, 1.78 and 2.47 log10 CFU/g (P < or = 0.001), respectively, in the experiments with Ab11 and 2.42 and 2.28 log10 CFU/g (P < or = 0.001), respectively, with Ab51. IPM significantly increased the sterility of blood cultures over that for the controls with both strains (P < or = 0.005); CLA had the same effect with Ab51 (P < 0.005) but not with Ab11 (P = 0.07). For the first time, we suggest that CLA may be used for the treatment of experimental severe A. baumannii infections.

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Figures

FIG. 1.
FIG. 1.
Time-kill curves of CLA and IPM against strains Ab11 and Ab51. The control has no antibiotic.
FIG. 2.
FIG. 2.
CLA concentrations during the time-kill curves with strains Ab11 and Ab51. The control has no bacteria and 8 mg of CLA/liter.
FIG. 3.
FIG. 3.
Serum CLA and IPM concentrations. CLA was administered at 13 mg/kg, and IPM was administered at 30 mg/kg.
FIG. 4.
FIG. 4.
Effect of antibiotic therapy with CLA or IPM on the clearance of A. baumannii from mouse lungs. *, P ≤ 0.001 relative to the control group (by ANOVA and Tukey and Dunnett post hoc tests).
See this image and copyright information in PMC

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