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Antimicrobial Agents and Chemotherapy, October 2009, p. 4298-4304, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00320-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

In Vitro Activity and In Vivo Efficacy of Clavulanic Acid against Acinetobacter baumannii{triangledown}

Alejandro Beceiro,1,{dagger} Rafael López-Rojas,2*,{dagger} Juan Domínguez-Herrera,2 Fernando Docobo-Pérez,2 Germán Bou,1 Jerónimo Pachón,2 the Spanish Network for Research in Infectious Diseases (REIPI)

Servicio de Microbiología-Unidad de Investigación, Complejo Hospitalario Universitario Juan Canalejo, 15006 La Coruña,1 Servicio de Enfermedades Infecciosas, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Seville, Spain2

Received 9 March 2009/ Returned for modification 11 May 2009/ Accepted 15 July 2009

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 ≤ 0.001), respectively, in the experiments with Ab11 and 2.42 and 2.28 log10 CFU/g (P ≤ 0.001), respectively, with Ab51. IPM significantly increased the sterility of blood cultures over that for the controls with both strains (P ≤ 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.

* Corresponding author. Mailing address: Servicio de Enfermedades Infecciosas, Hospitales Universitarios Virgen del Rocío, Avda. Manuel Siurot s/n, 41013, Seville, Spain. Phone: 34-955013651. Fax: 34-955013345. E-mail: rlopezrojas{at}hotmail.com

{triangledown} Published ahead of print on 27 July 2009.

{dagger} A.B. and R.L.-R. contributed equally to this work.

Antimicrobial Agents and Chemotherapy, October 2009, p. 4298-4304, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00320-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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