Recent Progress and Challenges for Drug-Resistant Tuberculosis Treatment
Abstract
1. Introduction
2. Progress
2.1. Fluoroquinolone
2.2. Rifamycin
2.3. Oxazolidinone
2.4. Nitroimidazole
2.5. Diarylquinoline
2.6. Benzothiazinone
2.7. Other Classes
2.8. Drug Repurposing for TB Treatment
2.9. Host-Directed Therapy
2.10. Tuberculosis (TB) Immunotherapy
3. Challenges
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Chemical Class | Compound | Progress | Mode of Action | Reference(s) |
---|---|---|---|---|
Fluoroquinolone | Levofloxacin | Phase 2 | DNA gyrase inhibitor | [102,103] |
Rifamycin | Rifampicin (high dose) | Phase 2 | RpoB inhibitor | [37] |
Oxazolidinone | Delpazolid | Phase 2 | Inhibition of protein synthesis | [104,105] |
Sutezolid | Phase 2 | Inhibition of protein synthesis | [47] | |
TBI-223 | Phase 1 | Inhibits the binding of N-formylmethionyl tRNA to ribosome | [106] | |
Nitroimidazole | Delamanid | Phase 3—approved | Inhibits cell wall synthesis | [107] |
Pretomanid | Phase 3—approved | Inhibits cell wall synthesis | [108] | |
Diarylquinoline | Bedaquiline | Phase 3—accepted | Inhibits mycobacterial ATP synthase | [109] |
TBAJ-587 | Preclinical trial | Inhibits mycobacterial ATP synthase and hERG potassium channel | [110] | |
TBAJ-876 | Preclinical trial | Inhibits mycobacterial ATP synthase | [73,111] | |
Benzothiazinone | Macozinone | Phase 2 | DprE1 inhibitor | [112,113] |
BTZ-043 | Phase 1 | DprE1 inhibitor | [74] | |
Other classes | Telacebec (imidazopyridine) | Phase 2 | QcrB inhibitor | [84] |
Nitazoxanide (nitrothiazolyl-salicylamide derivate) | Phase 2 | Disruption of membrane potential and pH homeostasis | [114,115] | |
SQ109 (ethylenediamine) | Phase 2 | MmpL3 inhibitor | [37,94] | |
TBA-7371 (1,4-azaindole) | Phase 2 | DprE1 inhibitor | [116] | |
OPC-167832 (3,4-dihydrocarbostyril derivate) | Phase 2 | DprE1 inhibitor | [117] | |
SPR-720 (ethyl urea benzimidazole) | Phase 1 | GyrB inhibitor | [98] | |
TBI-166 (riminophenazine) | Phase 1 | Membrane destabilization | [99] | |
Sanfetrinem (beta-lactam) | Preclinical trial | Inhibits peptidoglycan synthesis | [118] | |
Spectinamide-1810 (spectinamide) | Preclinical trial | Selective ribosomal inhibition | [100] |
Therapeutics | Composition | Target (Outcome) | References |
---|---|---|---|
Mycobacterium vaccae | Killed, interdermal | Meta-analysis of 54-studies on newly diagnosed pulmonary TB (improved sputum conversion and X-ray changes | [143,144] |
Capsule | Faster smear conversion | [143,145] | |
RUTI® | Detoxified cellular fragments of Mycobacterium tuberculosis | Phase I and II clinical trials on LTBI cases or healthy volunteers (immunogenic, reasonable tolerability) | [143,146,147] |
Autologous MSC | MSC | MDR or XDR patients (with radiologic improvement) | [143,148] |
V5 immunitor | Inactivated pooled blood | Re-treatment or proven MDR (higher rate of sputum conversion) | [143,149] |
Cytokines and cytokine inhibitors | IL-2 | MDR-TB patients (better sputum conversion rate), MDR-TB patients (decrease AFB smear counts with daily IL-2 compared to control or pulse IL-2), new TB patients (significant delays in culture conversion) | [143,150] |
IFN-γ | MDR-TB patients (all smear negative/improved, MDR-TB cases (no marked microbiologic effect), HIV-positive TB cases (more rapid culture conversion compared to historical control) | [143,151] | |
Drugs/compounds | High-dose steroid | HIV-positive TB cases (increased culture conversion at 1 month) | [143,152] |
Levamisole | Newly diagnosed pulmonary TB patients (improved radiology, but no effect on smear conversion) | [143,153] | |
Albendazole | New pulmonary TB patients (no effect on clinical, radiologic, and microbiologic outcome) | [143,154] | |
Thalidomide | HIV-positive (clinical improvement), HIV-positive (no clinical difference) | [143,155] |
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Stephanie, F.; Saragih, M.; Tambunan, U.S.F. Recent Progress and Challenges for Drug-Resistant Tuberculosis Treatment. Pharmaceutics 2021, 13, 592. https://doi.org/10.3390/pharmaceutics13050592
Stephanie F, Saragih M, Tambunan USF. Recent Progress and Challenges for Drug-Resistant Tuberculosis Treatment. Pharmaceutics. 2021; 13(5):592. https://doi.org/10.3390/pharmaceutics13050592
Chicago/Turabian StyleStephanie, Filia, Mutiara Saragih, and Usman Sumo Friend Tambunan. 2021. "Recent Progress and Challenges for Drug-Resistant Tuberculosis Treatment" Pharmaceutics 13, no. 5: 592. https://doi.org/10.3390/pharmaceutics13050592
APA StyleStephanie, F., Saragih, M., & Tambunan, U. S. F. (2021). Recent Progress and Challenges for Drug-Resistant Tuberculosis Treatment. Pharmaceutics, 13(5), 592. https://doi.org/10.3390/pharmaceutics13050592