In vitro activity of bedaquiline and imipenem against actively growing, nutrient-starved, and intracellular mycobacterium abscessus
| Autor: | Eric L. Nuermberger, Amit Kaushik, Jin Lee, Kelly E. Dooley, Olumide Martins, Nicole C. Ammerman |
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| Přispěvatelé: | Medical Microbiology & Infectious Diseases |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Drug
Imipenem Tuberculosis media_common.quotation_subject Drug resistance Mycobacterium abscessus Pharmacology chemistry.chemical_compound SDG 3 - Good Health and Well-being medicine polycyclic compounds Pharmacology (medical) Experimental Therapeutics Cefoxitin media_common biology business.industry medicine.disease biology.organism_classification bacterial infections and mycoses Infectious Diseases chemistry Bedaquiline business Bacteria medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy, 65(12):e01545-21. American Society for Microbiology Antimicrob Agents Chemother |
| ISSN: | 0066-4804 |
| Popis: | Mycobacterium abscessus lung disease is difficult to treat due to intrinsic drug resistance and the persistence of drug-tolerant bacteria. Currently, the standard of care is a multidrug regimen with at least 3 active drugs, preferably including a β-lactam (imipenem or cefoxitin). These regimens are lengthy and toxic and have limited efficacy. The search for more efficacious regimens led us to evaluate bedaquiline, a diarylquinoline licensed for treatment of multidrug-resistant tuberculosis. We performed in vitro time-kill experiments to evaluate the activity of bedaquiline alone and in combination with the first-line drug imipenem against M. abscessus under various conditions. Against actively growing bacteria, bedaquiline was largely bacteriostatic and antagonized the bactericidal activity of imipenem. Contrarily, against nutrient-starved persisters, bedaquiline was bactericidal, while imipenem was not, and bedaquiline drove the activity of the combination. In an intracellular infection model, bedaquiline and imipenem had additive bactericidal effects. Correlations between ATP levels and the bactericidal activity of imipenem and its antagonism by bedaquiline were observed. Interestingly, the presence of Tween 80 in the media affected the activity of both drugs, enhancing the activity of imipenem and reducing that of bedaquiline. Overall, these results show that bedaquiline and imipenem interact differently depending on culture conditions. Previously reported antagonistic effects of bedaquiline on imipenem were limited to conditions with actively multiplying bacteria and/or the presence of Tween 80, whereas the combination was additive or indifferent against nutrient-starved and intracellular M. abscessus, where promising bactericidal activity of the combination suggests it may have a role in future treatment regimens. |
| Databáze: | OpenAIRE |
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