The Combination Rifampin-Nitazoxanide, but Not Rifampin-Isoniazid-Pyrazinamide-Ethambutol, Kills Dormant Mycobacterium tuberculosis in Hypoxia at Neutral pH

The activities of rifampin, nitazoxanide, PA-824, and sutezolid were tested against dormant under conditions mimicking caseous granulomas (hypoxia at pH 7.3) in comparison with those of the combination rifampin-isoniazid-pyrazinamide-ethambutol (R-I-Z-E), which is used for human therapy. Mycobacteri...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2019-07, Vol.63 (7)
Main Authors: Iacobino, Angelo, Giannoni, Federico, Pardini, Manuela, Piccaro, Giovanni, Fattorini, Lanfranco
Format: Article
Language:English
Subjects:
Antitubercular Agents
Antitubercular Agents - pharmacology
Drug Combinations
Drug Therapy, Combination
Ethambutol - pharmacology
Humans
Hydrogen-Ion Concentration
Hypoxia
Isoniazid
Isoniazid - pharmacology
Mechanisms of Resistance
Microbial Sensitivity Tests
Mycobacterium tuberculosis
Mycobacterium tuberculosis - drug effects
Nitroimidazoles - pharmacology
Oxazolidinones - pharmacology
Pyrazinamide
Pyrazinamide - pharmacology
Rifampin
Rifampin - pharmacology
Tuberculosis - microbiology
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Summary:The activities of rifampin, nitazoxanide, PA-824, and sutezolid were tested against dormant under conditions mimicking caseous granulomas (hypoxia at pH 7.3) in comparison with those of the combination rifampin-isoniazid-pyrazinamide-ethambutol (R-I-Z-E), which is used for human therapy. Mycobacterial viability was monitored by CFU and regrowth in MGIT 960. As shown by lack of regrowth in MGIT, rifampin-nitazoxanide-containing combinations, but not R-I-Z-E, killed dormant cells in 28 to 35 days. These observations might be important in designing new tuberculosis therapies.
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.00273-19