Rifampicin tolerance and growth fitness among isoniazid-resistant clinical Mycobacterium tuberculosis isolates from a longitudinal study.

Autor:	Vijay S; Oxford University Clinical Research Unit, Ho Chi Minh, Viet Nam.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Theoretical Microbial Ecology, Institute of Microbiology, Faculty of Biological Sciences, Friedrich Schiller University, Jena, Germany.; Cluster of Excellence Balance of the Microverse, Friedrich Schiller University Jena, Jena, Germany., Bao NLH; Oxford University Clinical Research Unit, Ho Chi Minh, Viet Nam., Vinh DN; Oxford University Clinical Research Unit, Ho Chi Minh, Viet Nam., Nhat LTH; Oxford University Clinical Research Unit, Ho Chi Minh, Viet Nam., Thu DDA; Oxford University Clinical Research Unit, Ho Chi Minh, Viet Nam., Quang NL; Oxford University Clinical Research Unit, Ho Chi Minh, Viet Nam., Trieu LPT; Oxford University Clinical Research Unit, Ho Chi Minh, Viet Nam., Nhung HN; Oxford University Clinical Research Unit, Ho Chi Minh, Viet Nam., Ha VTN; Oxford University Clinical Research Unit, Ho Chi Minh, Viet Nam., Thai PVK; Pham Ngoc Thach Hospital, Ho Chi Minh, Viet Nam., Ha DTM; Pham Ngoc Thach Hospital, Ho Chi Minh, Viet Nam., Lan NH; Pham Ngoc Thach Hospital, Ho Chi Minh, Viet Nam., Caws M; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom., Thwaites GE; Oxford University Clinical Research Unit, Ho Chi Minh, Viet Nam.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Javid B; Division of Experimental Medicine, University of California, San Francisco, San Francisco, United States., Thuong NT; Oxford University Clinical Research Unit, Ho Chi Minh, Viet Nam.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2024 Sep 09; Vol. 13. Date of Electronic Publication: 2024 Sep 09.
DOI:	10.7554/eLife.93243
Abstrakt:	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. Competing Interests: SV, NB, DV, LN, DT, NQ, LT, HN, VH, PT, DH, NL, MC, GT, BJ, NT No competing interests declared (© 2024, Vijay, Bao et al.)
Databáze:	MEDLINE
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