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

• Published in: Journal of antimicrobial chemotherapy Vol. 54; no. 6; pp. 1085 - 1091
• Main Authors: Montero, Abelardo, Ariza, Javier, Corbella, Xavier, Doménech, Alejandro, Cabellos, Carmen, Ayats, Josefina, Tubau, Fe, Borraz, Carmen, Gudiol, Francesc
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.12.2004; Oxford Publishing Limited (England)
• Subjects: A. baumannii; Acinetobacter baumannii; Acinetobacter baumannii - drug effects; Acinetobacter Infections - drug therapy; Acinetobacter Infections - microbiology; Animals; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; beta-Lactams - pharmacology; beta-Lactams - therapeutic use; Biological and medical sciences; Carbapenems - pharmacology; Colistin - pharmacology; Colistin - therapeutic use; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination - pharmacology; Drug Therapy, Combination - therapeutic use; experimental; Female; Humans; Medical sciences; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; multiresistant; Pharmacology. Drug treatments; Pneumonia, Bacterial - drug therapy; Pneumonia, Bacterial - microbiology; Rifampin - pharmacology; Rifampin - therapeutic use; Tobramycin - pharmacology; Tobramycin - therapeutic use; Lung disease; Animal model; Pneumonia; Respiratory disease; Neisseriaceae; Rodentia; Infection; Resistance; Vertebrata; Acinetobacter baumannii; Antibiotic; Carbapenem derivatives; Mammalia; Mouse; Bacteria; Micrococcales; Antibacterial agent
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkh485

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.