Efficacy of rifampin, in monotherapy and in combinations, in an experimental murine pneumonia model caused by panresistant Acinetobacter baumannii strains

• Published in: European journal of clinical microbiology & infectious diseases 2011-07, Vol.30 (7), p.895-901
• Main Authors: Pachón-Ibáñez, M. E., Docobo-Pérez, F., Jiménez-Mejias, M. E., Ibáñez-Martínez, J., García-Curiel, A., Pichardo, C., Pachón, J.
• Format: Article
• Language: English
• Subjects: Acinetobacter baumannii; Acinetobacter baumannii - drug effects; Animals; Anti-Bacterial Agents - administration & dosage; Antibacterial agents; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacterial Load; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Disease Models, Animal; Drug dosages; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination - methods; Experiments; Female; Imipenem - administration & dosage; Imipenem - pharmacology; Infections; Infectious diseases; Internal Medicine; Lung - microbiology; Medical Microbiology; Medical sciences; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Microbial Viability - drug effects; Pharmacology. Drug treatments; Pneumology; Pneumonia; Pneumonia, Bacterial - drug therapy; Respiratory system : syndromes and miscellaneous diseases; Ribosomal DNA; Rifampin - administration & dosage; Rifampin - pharmacology; Rodent Diseases - drug therapy; Sterilization; Sulbactam - administration & dosage; Sulbactam - pharmacology; Treatment Outcome
• ISSN: 0934-9723; 1435-4373
• DOI: 10.1007/s10096-011-1173-6

The objective of this work was to evaluate the efficacy of rifampin, and its combinations with imipenem or sulbactam, in an experimental pneumonia model caused by two panresistant Acinetobacter baumannii strains (HUVR99 and HUVR113). Minimum inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) (μg/ml) of the strains were rifampin 128/>128 for both strains, imipenem 128/>256 and 256/>256 for HUVR99 and HUVR113, respectively, and sulbactam >256/>256 for both strains. In time–kill studies, at MICs, rifampin was bactericidal for both strains and sulbactam against the HUVR99 strain. Rifampin plus imipenem or sulbactam, at the MIC or mice C max , were synergistic. In vivo, against HUVR99 and HUVR113, rifampin (73% and 40%) and its combinations improved the survival with respect to the control group (20% and 0%, p