Mixed Mycobacterium tuberculosis–Strain Infections Are Associated With Poor Treatment Outcomes Among Patients With Newly Diagnosed Tuberculosis …
SS Shin, C Modongo, Y Baik, C Allender… - The Journal of …, 2018 - academic.oup.com
The Journal of infectious diseases, 2018•academic.oup.com
Abstract Background Heteroresistant Mycobacterium tuberculosis infections (defined as
concomitant infection with drug-resistant and drug-susceptible strains) may explain the
higher risk of poor tuberculosis treatment outcomes observed among patients with mixed-
strain M. tuberculosis infections. We investigated the clinical effect of mixed-strain infections
while controlling for pretreatment heteroresistance in a population-based sample of patients
with tuberculosis starting first-line tuberculosis therapy in Botswana. Methods We performed …
concomitant infection with drug-resistant and drug-susceptible strains) may explain the
higher risk of poor tuberculosis treatment outcomes observed among patients with mixed-
strain M. tuberculosis infections. We investigated the clinical effect of mixed-strain infections
while controlling for pretreatment heteroresistance in a population-based sample of patients
with tuberculosis starting first-line tuberculosis therapy in Botswana. Methods We performed …
Background
Heteroresistant Mycobacterium tuberculosis infections (defined as concomitant infection with drug-resistant and drug-susceptible strains) may explain the higher risk of poor tuberculosis treatment outcomes observed among patients with mixed-strain M. tuberculosis infections. We investigated the clinical effect of mixed-strain infections while controlling for pretreatment heteroresistance in a population-based sample of patients with tuberculosis starting first-line tuberculosis therapy in Botswana.
Methods
We performed 24-locus mycobacterial interspersed repetitive unit–variable number tandem-repeat analysis and targeted deep sequencing on baseline primary cultured isolates to detect mixed infections and heteroresistance, respectively. Drug-sensitive, micro-heteroresistant, macro-heteroresistant, and fixed-resistant infections were defined as infections in which the frequency of resistance was <0.1%, 0.1%–4%, 5%–94%, and ≥95%, respectively, in resistance-conferring domains of the inhA promoter, the katG gene, and the rpoB gene.
Results
Of the 260 patients with tuberculosis included in the study, 25 (9.6%) had mixed infections and 30 (11.5%) had poor treatment outcomes. Micro-heteroresistance, macro-heteroresistance, and fixed resistance were found among 11 (4.2%), 2 (0.8%), and 11 (4.2%), respectively, for isoniazid and 21 (8.1%), 0 (0%), and 10 (3.8%), respectively, for rifampicin. In multivariable analysis, mixed infections but not heteroresistant infections independently predicted poor treatment outcomes.
Conclusions
Among patients starting first-line tuberculosis therapy in Botswana, mixed infections were associated with poor tuberculosis treatment outcomes, independent of heteroresistance.
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