Impact of heteroresistance on treatment outcomes of people with drug-resistant TB.

Autor:	Crowder R; Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA.; Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA., Kato-Maeda M; Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA.; Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA., Schwem B; University of the Philippines, National Institutes of Health, Manila, Philippines., Dela Tonga A; University of the Philippines, National Institutes of Health, Manila, Philippines., Geocaniga-Gaviola DM; Philippines Department of Health, Manila, Philippines., Lopez E; Philippines Department of Health, Manila, Philippines., Valdez CL; Philippines Department of Health, Manila, Philippines., Lim AR; Philippines Department of Health, Manila, Philippines., Hunat N; National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa, Philippines., Sedusta AG; National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa, Philippines., Sacopon CA; National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa, Philippines., Atienza GAM; National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa, Philippines., Bulag E; National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa, Philippines., Lim D; National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa, Philippines., Bascuña J; National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa, Philippines., Shah K; Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA.; Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA., Basillio RP; National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa, Philippines., Berger CA; Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA.; Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA., Lopez MCDP; University of the Philippines, National Institutes of Health, Manila, Philippines., Sen S; Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA., Allender C; Pathogen and Microbiome Division, Translational Genomics Research Institute, Flagstaff, AZ, USA., Folkerts M; Pathogen and Microbiome Division, Translational Genomics Research Institute, Flagstaff, AZ, USA., Karaoz U; Ecology Department, Lawrence Berkeley National Laboratory, Berkeley, CA, USA., Brodie E; Ecology Department, Lawrence Berkeley National Laboratory, Berkeley, CA, USA., Mitarai S; Research Institute for Tuberculosis, Tokyo, Japan., Garfin AMC; Philippines Department of Health, Manila, Philippines., Ama MC; National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa, Philippines., Engelthaler DM; Pathogen and Microbiome Division, Translational Genomics Research Institute, Flagstaff, AZ, USA., Cattamanchi A; Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA.; Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA.; Division of Pulmonary Diseases and Critical Care Medicine, University of California Irvine, Irvine, CA, USA., Destura R; University of the Philippines, National Institutes of Health, Manila, Philippines.
Jazyk:	angličtina
Zdroj:	IJTLD open [IJTLD Open] 2024 Oct 01; Vol. 1 (10), pp. 466-472. Date of Electronic Publication: 2024 Oct 01 (Print Publication: 2024).
DOI:	10.5588/ijtldopen.24.0343
Abstrakt:	Background: Poor treatment outcomes among people with drug-resistant TB (DR-TB) are a major concern. Heteroresistance (presence of susceptible and resistant Mycobacterium tuberculosis in the same sample) has been identified in some people with TB, but its impact on treatment outcomes is unknown. Methods: We used targeted deep sequencing to identify mutations associated with DR-TB and heteroresistance in culture samples of 624 people with DR-TB. We evaluated the association between heteroresistance and time to unfavorable treatment outcome using Cox proportional hazards regression. Results: The proportion of drug-resistant isolates with a known mutation conferring resistance was lower for streptomycin (45.2%) and second-line injectables (79.1%) than for fluoroquinolones (86.7%), isoniazid (93.2%) and rifampin (96.5%). Fifty-two (8.3%) had heteroresistance, and it was more common for fluoroquinolones (4.6%) than rifampin (2.2%), second-line injectables (1.4%), streptomycin (1.7%), or isoniazid (1.3%). There was no association between heteroresistance and time to unfavorable outcome among people with multidrug-resistant TB (adjusted hazard ratio [aHR] 1.74, 95% CI 0.39-7.72) or pre-extensively DR-TB (aHR 0.65, 95% CI 0.24-1.72). Conclusions: Heteroresistance was relatively common (8.3%) among people with DR-TB in the Philippines. However, we found insufficient evidence to demonstrate an impact on unfavorable treatment outcomes. Competing Interests: Conflicts of interest: none declared. (© 2024 The Authors.)
Databáze:	MEDLINE
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