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Vijay, Srinivasan, Bao, Nguyen Le Hoai, Vinh, Dao Nguyen, Nhat, Le Thanh Hoang, Thu, Do Dang Anh, Quang, Nguyen Le, Trieu, Le Pham Tien, Nhung, Hoang Ngoc, Ha, Vu Thi Ngoc, Thai, Phan Vuong Khac, Ha, Dang Thi Minh, Lan, Nguyen Huu, Caws, Maxine 
ORCID: https://orcid.org/0000-0002-9109-350X, Thwaites, Guy E, Javid, Babak and Thuong, Nguyen Thuy
(2024)
'Rifampicin tolerance and growth fitness among isoniazid-resistant clinical Mycobacterium tuberculosis isolates from a longitudinal study'. eLife, Vol 13, p. 93243.
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Abstract
Antibiotic tolerance in Mycobacterium tuberculosis reduces bacterial killing, worsens treatment outcomes, and contributes to resistance. We studied rifampicin tolerance in isolates with or without isoniazid resistance (IR). Using a minimum duration of killing assay, we measured rifampicin survival in isoniazid-susceptible (IS, n=119) and resistant (IR, n=84) isolates, correlating tolerance with bacterial growth, rifampicin minimum inhibitory concentrations (MICs), and isoniazid-resistant mutations. Longitudinal IR isolates were analyzed for changes in rifampicin tolerance and genetic variant emergence. The median time for rifampicin to reduce the bacterial population by 90% (MDK90) increased from 1.23 days (IS) and 1.31 days (IR) to 2.55 days (IS) and 1.98 days (IR) over 15–60 days of incubation, indicating fast and slow-growing tolerant sub-populations. A 6 log10-fold survival fraction classified tolerance as low, medium, or high, showing that IR is linked to increased tolerance and faster growth (OR = 2.68 for low vs. medium, OR = 4.42 for low vs. high, p-trend = 0.0003). High tolerance in IR isolates was associated with rifampicin treatment in patients and genetic microvariants. These findings suggest that IR tuberculosis should be assessed for high rifampicin tolerance to optimize treatment and prevent the development of multi-drug-resistant tuberculosis.
| Item Type: | Article |
|---|---|
| Subjects: | QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 252 Antifungal agents. Antifungal antibiotics WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General) |
| Faculty: Department: | Clinical Sciences & International Health > Clinical Sciences Department |
| Digital Object Identifer (DOI): | https://doi.org/10.7554/elife.93243 |
| SWORD Depositor: | JISC Pubrouter |
| Depositing User: | JISC Pubrouter |
| Date Deposited: | 26 Sep 2024 14:12 |
| Last Modified: | 26 Sep 2024 14:12 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/25312 |
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