colistin and Extensively-Drug-Resistant-Tuberculosis

Recently, paradoxical combinations of colistin with anti-Gram-positive bacterial agents were introduced as a treatment alternative for multidrug-resistant Acinetobacter baumannii (MDRAB) infection. We assessed the therapeutic efficacy of the colistin-linezolid combination regimen in vitro and in a murine model of Acinetobacter baumannii pneumonia. A multidrug-resistant clinical strain (MDRAB31) and an extensively drug-resistant clinical strain (XDRAB78) were used in this study. The survival rates of mice and bacterial counts in lung tissue were used to assess the effects of colistin-linezolid combination. The survival rates of colistin-linezolid combination groups significantly increased compared with colistin groups for MDRAB31 (72% versus 32%, P = 0.03) and for XDRAB78 (92% versus 68%, P = 0.031). The colistin-linezolid combination groups significantly reduced the bacterial counts in lung tissue compared with colistin groups for MDRAB31 and for XDRAB78 (P < 0.05). The colistin-linezolid combination had a bactericidal and synergistic effect compared with colistin alone in time-kill assay and in murine model of pneumonia. Our data demonstrated the synergistic effect of colistin-linezolid combination regimen as a treatment alternative for the severe pulmonary infection caused by MDRAB and XDRAB.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Antitubercular Agents; Colistin; Disease Models, Animal; Drug Synergism; Extensively Drug-Resistant Tuberculosis; Female; Linezolid; Lung; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Pneumonia, Bacterial; Time Factors; Tuberculosis, Multidrug-Resistant

Topics: Adult; Antitubercular Agents; Colistin; Diarylquinolines; Drug Synergism; Extensively Drug-Resistant Tuberculosis; Humans; Isoniazid; Male; Medication Adherence; Mycobacterium tuberculosis; Netherlands; Nitroimidazoles; Oxazoles; Patient Isolation; Phenotype; Trimethoprim, Sulfamethoxazole Drug Combination; United Kingdom