In Vitro Antimicrobial Activities of Tigecycline, Eravacycline, Omadacycline, and Sarecycline against Rapidly Growing Mycobacteria
ABSTRACT Infections caused by rapidly growing mycobacteria (RGM) have increased globally. Chemotherapy against these infections is challenging due to the minimal antimicrobial choices available. The main aim of this study was to evaluate the in vitro susceptibilities of four tetracyclines against di...
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American Society for Microbiology
2023-02-01
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| Series: | Microbiology Spectrum |
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| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.03238-22 |
| _version_ | 1811164360211431424 |
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| author | Tingting Zhang Jian Du Lingling Dong Fen Wang Liping Zhao Junnan Jia Congli Wang Mengli Cheng Xia Yu Hairong Huang |
| author_facet | Tingting Zhang Jian Du Lingling Dong Fen Wang Liping Zhao Junnan Jia Congli Wang Mengli Cheng Xia Yu Hairong Huang |
| author_sort | Tingting Zhang |
| collection | DOAJ |
| description | ABSTRACT Infections caused by rapidly growing mycobacteria (RGM) have increased globally. Chemotherapy against these infections is challenging due to the minimal antimicrobial choices available. The main aim of this study was to evaluate the in vitro susceptibilities of four tetracyclines against different RGM species. The MICs of eravacycline (ERC), omadacycline (OMC), sarecycline (SAC), and tigecycline (TGC) against the reference strains of 27 RGM species and 121 RGM clinical isolates were determined by microtiter plate assay. The minimum bactericidal concentrations (MBCs) and cytotoxicities of these antibiotics were also tested. Except for SAC, the other three tetracyclines had MICs of ≤0.5 μg/mL against all 27 RGM reference strains. ERC generally presented the lowest MICs, with MIC90s against the clinical isolates of Mycobacterium abscessus subsp. abscessus, Mycobacterium abscessus subsp. massiliense, and Mycobacterium fortuitum of 0.25 μg/mL, 0.25 μg/mL, and 0.06 μg/mL, respectively. TGC and OMC also showed equivalent in vitro inhibitory activities against the isolates, while the TGC MIC90s for M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. fortuitum were lower than or equal to the OMC MIC90s (1, 1, and 0.25 μg/mL versus 1, 2, and 2 μg/mL). In addition, the MIC50s of three of the antibiotics for each species were always 2-fold lower than the corresponding MIC90s. MBC and cytotoxicity assays indicated that all four tetracycline antibiotics tested were bacteriostatic agents with low toxicity to the THP-1 cell line. Tetracycline antibiotics are efficacious in RGM infection treatment, with omadacycline showing the best promise for clinical application due to its potent antimicrobial activity, safety, and convenient administration route. IMPORTANCE The global rise in antibiotic-resistant nontuberculous mycobacteria has prompted the urgent need for new antimicrobials, especially oral antibiotics. Currently, adverse effects have limited the use of tetracycline-class antibiotics, particularly tigecycline (TGC), in the treatment of rapidly growing mycobacteria (RGM). However, several new tetracycline-class antibiotics might overcome the limitations of TGC. We assessed the in vitro antibiotic susceptibilities of four tetracyclines (eravacycline, omadacycline, sarecycline, and tigecycline) against reference RGM strains and clinical isolates of different RGM species. We showed that three of these antibiotics (tigecycline, eravacycline, and omadacycline) might be efficacious in M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. fortuitum treatment. Furthermore, omadacycline was more promising for clinical application for M. abscessus infections as an oral drug, whereas sarecycline, which had the best safety parameters, should be considered a potential antibiotic for M. abscessus infections caused by susceptible strains. Our work underscores the possible clinical applications of tetracycline-class antibiotics in the treatment of RGM infections. |
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| institution | Directory Open Access Journal |
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| language | English |
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| publisher | American Society for Microbiology |
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| series | Microbiology Spectrum |
| spelling | doaj.art-4674f7c856214792a0538c2951cb39202023-02-14T14:15:49ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-02-0111110.1128/spectrum.03238-22In Vitro Antimicrobial Activities of Tigecycline, Eravacycline, Omadacycline, and Sarecycline against Rapidly Growing MycobacteriaTingting Zhang0Jian Du1Lingling Dong2Fen Wang3Liping Zhao4Junnan Jia5Congli Wang6Mengli Cheng7Xia Yu8Hairong Huang9National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, ChinaNational Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, ChinaNational Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, ChinaNational Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, ChinaNational Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, ChinaNational Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, ChinaNational Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, ChinaNational Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, ChinaNational Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, ChinaNational Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, ChinaABSTRACT Infections caused by rapidly growing mycobacteria (RGM) have increased globally. Chemotherapy against these infections is challenging due to the minimal antimicrobial choices available. The main aim of this study was to evaluate the in vitro susceptibilities of four tetracyclines against different RGM species. The MICs of eravacycline (ERC), omadacycline (OMC), sarecycline (SAC), and tigecycline (TGC) against the reference strains of 27 RGM species and 121 RGM clinical isolates were determined by microtiter plate assay. The minimum bactericidal concentrations (MBCs) and cytotoxicities of these antibiotics were also tested. Except for SAC, the other three tetracyclines had MICs of ≤0.5 μg/mL against all 27 RGM reference strains. ERC generally presented the lowest MICs, with MIC90s against the clinical isolates of Mycobacterium abscessus subsp. abscessus, Mycobacterium abscessus subsp. massiliense, and Mycobacterium fortuitum of 0.25 μg/mL, 0.25 μg/mL, and 0.06 μg/mL, respectively. TGC and OMC also showed equivalent in vitro inhibitory activities against the isolates, while the TGC MIC90s for M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. fortuitum were lower than or equal to the OMC MIC90s (1, 1, and 0.25 μg/mL versus 1, 2, and 2 μg/mL). In addition, the MIC50s of three of the antibiotics for each species were always 2-fold lower than the corresponding MIC90s. MBC and cytotoxicity assays indicated that all four tetracycline antibiotics tested were bacteriostatic agents with low toxicity to the THP-1 cell line. Tetracycline antibiotics are efficacious in RGM infection treatment, with omadacycline showing the best promise for clinical application due to its potent antimicrobial activity, safety, and convenient administration route. IMPORTANCE The global rise in antibiotic-resistant nontuberculous mycobacteria has prompted the urgent need for new antimicrobials, especially oral antibiotics. Currently, adverse effects have limited the use of tetracycline-class antibiotics, particularly tigecycline (TGC), in the treatment of rapidly growing mycobacteria (RGM). However, several new tetracycline-class antibiotics might overcome the limitations of TGC. We assessed the in vitro antibiotic susceptibilities of four tetracyclines (eravacycline, omadacycline, sarecycline, and tigecycline) against reference RGM strains and clinical isolates of different RGM species. We showed that three of these antibiotics (tigecycline, eravacycline, and omadacycline) might be efficacious in M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. fortuitum treatment. Furthermore, omadacycline was more promising for clinical application for M. abscessus infections as an oral drug, whereas sarecycline, which had the best safety parameters, should be considered a potential antibiotic for M. abscessus infections caused by susceptible strains. Our work underscores the possible clinical applications of tetracycline-class antibiotics in the treatment of RGM infections.https://journals.asm.org/doi/10.1128/spectrum.03238-22antimicrobial activityeravacyclineomadacyclinesarecyclinetigecyclinerapidly growing mycobacteria |
| spellingShingle | Tingting Zhang Jian Du Lingling Dong Fen Wang Liping Zhao Junnan Jia Congli Wang Mengli Cheng Xia Yu Hairong Huang In Vitro Antimicrobial Activities of Tigecycline, Eravacycline, Omadacycline, and Sarecycline against Rapidly Growing Mycobacteria Microbiology Spectrum antimicrobial activity eravacycline omadacycline sarecycline tigecycline rapidly growing mycobacteria |
| title | In Vitro Antimicrobial Activities of Tigecycline, Eravacycline, Omadacycline, and Sarecycline against Rapidly Growing Mycobacteria |
| title_full | In Vitro Antimicrobial Activities of Tigecycline, Eravacycline, Omadacycline, and Sarecycline against Rapidly Growing Mycobacteria |
| title_fullStr | In Vitro Antimicrobial Activities of Tigecycline, Eravacycline, Omadacycline, and Sarecycline against Rapidly Growing Mycobacteria |
| title_full_unstemmed | In Vitro Antimicrobial Activities of Tigecycline, Eravacycline, Omadacycline, and Sarecycline against Rapidly Growing Mycobacteria |
| title_short | In Vitro Antimicrobial Activities of Tigecycline, Eravacycline, Omadacycline, and Sarecycline against Rapidly Growing Mycobacteria |
| title_sort | in vitro antimicrobial activities of tigecycline eravacycline omadacycline and sarecycline against rapidly growing mycobacteria |
| topic | antimicrobial activity eravacycline omadacycline sarecycline tigecycline rapidly growing mycobacteria |
| url | https://journals.asm.org/doi/10.1128/spectrum.03238-22 |
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