Alternative and Experimental Therapies of Mycobacterium abscessus Infections
Abstract
:1. Introduction
1.1. Clofazimine
1.2. Bedaquiline
1.3. Rifabutin
1.4. Novel β-Lactamase Inhibitors
1.5. Dual β-Lactams
1.6. Vancomycin/Clarithromycin
1.7. Novel Antimicrobials
1.8. Inhaled Nitric Oxide
1.9. Phage Therapy
2. Discussion
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
NTM | Non-tuberculous mycobacteria |
BDQ | Bedaquiline |
BLAMAB | β lactamase inhibitor of Mycobacterium abscessus, Ambler-Class A |
CFZ | Clofazimine |
CLR | Clarithromycin |
AMK | Amikacin |
TIG | Tigecycline |
VAN | Vancomycin |
RFB | Rifabutin |
NO | Nitric oxide |
FDA | U.S. Food and Drug Administration |
References
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Therapy (Route of Administration) | In Vitro Evidence | In Vivo Models | Published Clinical Experience |
---|---|---|---|
Clofazimine (PO) | Synergy with CLR, AMK, TIG and BDQ [11,12] | Treatment of M. abscessus in GKO−/− and SCID mice with a combination of CFZ and BDQ was effective [13]. | Retrospective study of 42 patients [15], Cohort study in immune-compromised patients. [16] |
BlaMab inhibitors Avibactam Relebactam Vaborbactam (IV) | Active against reference and clinical isolates when combined with β-lactams [17,18,19]. | Avibactam combinations effective in macrophage, Zebrafish and Galleria mellonella models [20,21]. | N/A |
Dual β-lactams | Synergy of two β-lactams shown in reference and clinical strains [22] | Synergy in a murine model of chronic pulmonary infection [23] | N/A |
Bedaquiline (PO) | Activity in vitro in clinical strains [24] Possible antagonism with β-lactams [21] | Effect of CFZ/BDQ in GKO−/− and SCID mice [13]. No effect in nude mice [25], Protective effect in zebrafish [24]. | Report of 10 patients, favorable tolerability [20] |
VAN/CLR combination | Synergy of VAN and CLR in reference and clinical strains, questionable effect in strains with acquired CLR resistance [26]. | N/A | N/A |
Rifabutin (PO) | Activity against clinical and reference strains, including CLR resistant strains [27,28] Synergy with CLR, suppresses CLR induced resistance [29]. | Effect in a macrophage model [30], improved survival in a zebrafish model [30], effect similar to CLR in a NOD SCID mouse model [31]. | N/A |
Omadacycline (PO/IV), Eravacycline (PO/IV) | omadacycline [32,33] and eravacycline [34,35] have activity against reference and clinical strains | N/A | Report of one patient—noted clinical improvement [36] |
Tedizolid (PO/IV) | Tedizolid has in vitro alone and combined with CLR and AMK [37,38] | Intracellular effect in a macrophage model [19]. | Report of one immune-compromised patient [39] |
Delpazolid (PO/IV) | Active against reference strain and 8 clinical strains. Noted spontaneous resistance to delpazolid [40] | Intracellular effect in a macrophage model [40] Comparable effect of delpazolid to linezolid in a murine model [40]. | |
VXc-486 | Active against multiple strains of M. abscessus | N/A | N/A |
PIPD1 | Activity against clinical strains [41] | Intracellular effect in macrophages, effective in a zebrafish model [41]. | N/A |
Indole-carboxamides | Activity against clinical strains [42] Synergy with imipenem and cefoxitin [43] | Intracellular effect in macrophages [42], effect in a murine model [44]. | N/A |
Inhaled NO | N/A | N/A | Report of 2 patients with cystic fibrosis showed reduction in sputum bacterial-loads [45]. Report of 9 patients had limited effect [46]. |
Phage therapy | Profound use in mycobacterial laboratory research | N/A | Treatment of disseminated infection in one patient [47] |
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Meir, M.; Barkan, D. Alternative and Experimental Therapies of Mycobacterium abscessus Infections. Int. J. Mol. Sci. 2020, 21, 6793. https://doi.org/10.3390/ijms21186793
Meir M, Barkan D. Alternative and Experimental Therapies of Mycobacterium abscessus Infections. International Journal of Molecular Sciences. 2020; 21(18):6793. https://doi.org/10.3390/ijms21186793
Chicago/Turabian StyleMeir, Michal, and Daniel Barkan. 2020. "Alternative and Experimental Therapies of Mycobacterium abscessus Infections" International Journal of Molecular Sciences 21, no. 18: 6793. https://doi.org/10.3390/ijms21186793