Impact of Heteroresistance on Treatment Outcomes of People with Drug-resistant TB

Overview

Journal IJTLD Open

Date 2024 Oct 14

PMID 39398438

Authors

R Crowder

M Kato-Maeda

B Schwem

A Dela Tonga

D M Geocaniga-Gaviola

E Lopez

C L Valdez

A R Lim

N Hunat

A G Sedusta

C A Sacopon

G A M Atienza

E Bulag

D Lim

J Bascuna

K Shah

R P Basillio

C A Berger

M C D P Lopez

S Sen

C Allender

M Folkerts

U Karaoz

E Brodie

S Mitarai

A M C Garfin

M C Ama

D M Engelthaler

A Cattamanchi

R Destura

Affiliations

Soon will be listed here.

Abstract

Background: Poor treatment outcomes among people with drug-resistant TB (DR-TB) are a major concern. Heteroresistance (presence of susceptible and resistant 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.

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