In Vitro Activity and In Vivo Efficacy of Clavulanic Acid against Acinetobacter baumannii
Open Access
- 1 October 2009
- journal article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 53 (10), 4298-4304
- https://doi.org/10.1128/aac.00320-09
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.This publication has 50 references indexed in Scilit:
- False extended-spectrum -lactamase detection in Acinetobacter spp. due to intrinsic susceptibility to clavulanic acidJournal of Antimicrobial Chemotherapy, 2007
- Attributable mortality of Acinetobacter baumannii: no longer a controversial issueCritical Care, 2007
- A review of the antimicrobial activity of clavulanateJournal of Antimicrobial Chemotherapy, 2003
- Impact of co-amoxiclav on polymorphonuclear granulocytes from chronic hemodialysis patientsAmerican Journal of Kidney Diseases, 2001
- Cloning, Nucleotide Sequencing, and Analysis of the Gene Encoding an AmpC β-Lactamase in Acinetobacter baumanniiAntimicrobial Agents and Chemotherapy, 2000
- In vitro activity of β-lactamase inhibitors against clinical isolates of Acinetobacter speciesDiagnostic Microbiology and Infectious Disease, 1995
- Penetration of amoxycillin/clavulanic acid into bronchial mucosa with different dosing regimens.Thorax, 1994
- Acinetobacterin Denmark: II. Molecular studies of theAcinetobacter calcoaceticus-Acinetobacter baumanniicomplexAPMIS, 1993
- Comparative activities of amoxycillin, amoxycillin/clavulanic acid and tetracycline against Chlamydia trachomatis in cell culture and in an experimental mouse pneumonitisJournal of Antimicrobial Chemotherapy, 1991
- Experimental Infection with Streptococcus pneumoniae in Mice: Correlation of in Vitro Activity and Pharmacokinetic Parameters with in Vivo Effect for 14 CephalosporinsThe Journal of Infectious Diseases, 1986