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JAC Advance Access originally published online on November 16, 2004
Journal of Antimicrobial Chemotherapy 2004 54(6):1085-1091; doi:10.1093/jac/dkh485
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JAC vol.54 no.6 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved

Antibiotic combinations for serious infections caused by carbapenem-resistant Acinetobacter baumannii in a mouse pneumonia model

Abelardo Montero1,*, Javier Ariza1, Xavier Corbella1, Alejandro Doménech1, Carmen Cabellos1, Josefina Ayats2, Fe Tubau2, Carmen Borraz2 and Francesc Gudiol1

1 Laboratory of Experimental Infection, Infectious Disease Service;; 2 Microbiology Department, Hospital de Bellvitge, University of Barcelona, C/Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain

* Correspondence address. C/Diputació 89–91, 4° 4a, 08015 Barcelona, Spain. Tel: +34-93-2607625; Fax: +34-93-2607637; Email: amontero{at}gencat.net

Objectives: Successful therapy of carbapenem-resistant Acinetobacter baumannii strains has been reported with colistin, but recently we argued against its use as monotherapy because of the poor results obtained in a mouse pneumonia model. Our aim was to identify antibiotic combinations that were valid therapeutic alternatives in the same model.

Methods: We used two carbapenem-resistant A. baumannii strains (D and E; MICs of imipenem, 8 and 512 mg/L, respectively). MICs of tobramycin, rifampicin and colistin for both strains were 8, 8 and 0.5 mg/L, respectively.

Results: In infections caused by strain D, lung bacterial counts (log10 cfu/g, mean ± S.D.) were: controls (10.86±0.25), imipenem (5.99±0.59, P < 0.05 versus controls), and colistin (10.43 ± 1.09); imipenem + tobramycin was the most active combination (5.46±0.62, P < 0.05 versus controls). In infections caused by strain E, results were: controls (10.82±0.33), rifampicin (5.62±0.26, P < 0.05 versus controls), colistin (8.38±1.22, P < 0.05 versus controls), and imipenem (11.01±0.2); rifampicin + imipenem (3.79±0.99) and rifampicin + tobramycin (3.96±0.30) were the most active combinations (P < 0.05); results with rifampicin + colistin (5.59±1.17) were similar to those with rifampicin alone.

Conclusions: Our data indicate that imipenem can still be the best alternative for carbapenem-resistant A. baumannii infections with moderate levels of imipenem resistance, preferably combined with aminoglycosides. For strains highly resistant to imipenem, a combination of rifampicin with imipenem, tobramycin or colistin may be useful, if resistance to rifampicin is only moderate.

Keywords: multiresistant , A. baumannii , experimental , animals


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