Clinical Outcomes Among Persons With Pulmonary Tuberculosis Caused by Mycobacterium tuberculosis Isolates With Phenotypic Heterogeneity in Results of Drug-Susceptibility Tests

Zetola, Nicola M.; Modongo, Chawangwa; Moonan, Patrick K.; Ncube, Ronald; Matlhagela, Keikantse; Sepako, Enoch; Collman, Ronald G.; Bisson, Gregory P.

doi:10.1093/infdis/jiu040

Cited by 49 publications

(39 citation statements)

References 34 publications

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“…Our results are in agreement with a previous study which have demonstrated that infections with heteroresistance can compromise treatment outcomes14. In contrast, Cohen et al .…”

Section: Discussionsupporting

confidence: 94%

Evaluation of the impact of polyclonal infection and heteroresistance on treatment of tuberculosis patients

Kamakoli

Sadegh

Farmanfarmaei

et al. 2017

Sci Rep

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Mixed strain infections of Mycobacterium tuberculosis make diagnosis, treatment, and control of tuberculosis (TB) more difficult. This study was aimed to evaluate the relationship between mixed infections, antibiotic resistance patterns and treatment of TB patients. In this study, among 2850 suspected TB clinical samples, a total of ninety-six clinical samples from 66 TB confirmed patients were subjected to the 24-locus variable-number tandem repeat method to evaluate the prevalence of mixed infections. For all studied strains, 288 colonies (three individual clones for each sample) were isolated from different colonies and separately analyzed by the Drug Susceptibility Test (DST). For all patients, follow up was done after 6 months of treatment. Based on direct 24 loci MIRU-VNTR, in the 66 TB patients, 53% (35/66) showed mixed infection. In the mixed samples, 45.71% (16/35) showed different antibiotic resistant patterns. Among the mixed infection patients, eight (22.9%; 8/35) showed treatment failure after six- month therapy. Six of these non-treated patients (75%; 6/8) had different antibiotic resistant patterns. We conclude that mixed infections, have a negative impact on treatment of TB patients especially when co-infecting M. tuberculosis strains display heteroresistance.

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“…Our results are in agreement with a previous study which have demonstrated that infections with heteroresistance can compromise treatment outcomes14. In contrast, Cohen et al .…”

Section: Discussionsupporting

confidence: 94%

Evaluation of the impact of polyclonal infection and heteroresistance on treatment of tuberculosis patients

Kamakoli

Sadegh

Farmanfarmaei

et al. 2017

Sci Rep

View full text Add to dashboard Cite

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“…These scenarios lead to so-called heteroresistance, which is encountered in 7-25% of patients with MDR tuberculosis, patients previously treated for tuberculosis, and those in whom first-line therapy failed. 70,205,206 Treatment with standard regimens or MDR tuberculosis regimens would lead to rapid selection of the drugresistant subpopulations, either on the basis of classic Luria-Delbrück considerations, or the antibiotic resistance process shown in figure 5. 207 Redefining drug resistance, MDR tuberculosis, and XDR tuberculosis by changing susceptibility breakpoints M tuberculosis is considered drug resistant when >1% of M tuberculosis cultures grow in the presence of critical drug concentrations.…”

Section: The Role Of Efflux Pumps In Antibiotic Resistancementioning

confidence: 99%

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

Dheda

Gumbo

Maartens

et al. 2017

The Lancet Respiratory Medicine

523

474

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“…While M. tuberculosis primarily causes lung infections, it can disseminate to extrapulmonary organs, particularly in subjects co-infected with HIV. Understanding how M. tuberculosis diversifies and spreads within individuals is crucial to outbreak tracing 11 , clinical diagnosis of resistance 12–14 , and designing strategies to minimize de novo emergence of antibiotic resistance 15–17 .…”

mentioning

confidence: 99%

Genomic diversity in autopsy samples reveals within-host dissemination of HIV-associated Mycobacterium tuberculosis

Lieberman

Wilson

Misra

et al. 2016

Nat Med

129

113

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Mycobacterium tuberculosis remains a leading cause of death worldwide, especially among individuals infected with HIV1. While phylogenetic analysis has revealed M. tuberculosis spread throughout history2–5 and in local outbreaks6–8, much less is understood about its dissemination within the body. Here, we report genomic analysis of 2693 samples collected postmortem from lung and extrapulmonary biopsies of 44 subjects in KwaZulu-Natal, South Africa who received minimal antitubercular treatment and most of whom were HIV seropositive. We found that purifying selection acted within individual patients, without the need for patient-to-patient transmission. Despite negative selection, mycobacteria diversified within individuals to form sub-lineages that co-existed for years. These sub-lineages, as well as distinct strains from mixed infections, were differentially distributed throughout the lung, suggesting temporary barriers to pathogen migration. As a consequence, samples taken from the upper airway often captured only a fraction of the population diversity, challenging current methods of outbreak tracing and resistance diagnostics. Phylogenetic analysis indicated that dissemination from the lungs to extrapulmonary sites was as frequent as between lung sites—supporting similar migration routes within and between organs, at least in subjects with HIV. Genomic diversity therefore provides a record of pathogen diversification and repeated dissemination across the body.

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Clinical Outcomes Among Persons With Pulmonary Tuberculosis Caused by Mycobacterium tuberculosis Isolates With Phenotypic Heterogeneity in Results of Drug-Susceptibility Tests

Abstract: Phenotypic DST heterogeneity among persons with HIV infection who are being treated for MDR tuberculosis is associated with poor outcomes and longer times to culture conversion.

Cited by 49 publications

References 34 publications

Evaluation of the impact of polyclonal infection and heteroresistance on treatment of tuberculosis patients

Evaluation of the impact of polyclonal infection and heteroresistance on treatment of tuberculosis patients

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

Genomic diversity in autopsy samples reveals within-host dissemination of HIV-associated Mycobacterium tuberculosis

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