Journal Article

Association between Mycobacterium tuberculosis Complex Phylogenetic Lineage and Acquired Drug Resistance

Cegielski, J. Peter, Kurbatova, Ekaterina V., Cavanaugh, J. Sean, Click, Eleanor S., Yuen, Courtney M.

2013

Overview

Development of resistance to antituberculosis drugs during treatment (i.e., acquired resistance) can lead to emergence of resistant strains and consequent poor clinical outcomes. However, it is unknown whether Mycobacterium tuberculosis complex species and lineage affects the likelihood of acquired resistance. We analyzed data from the U.S. National Tuberculosis Surveillance System and National Tuberculosis Genotyping Service for tuberculosis cases during 2004-2011 with assigned species and lineage and both initial and final drug susceptibility test results. We determined univariate associations between species and lineage of Mycobacterium tuberculosis complex bacteria and acquired resistance to isoniazid, rifamycins, fluoroquinolones, and second-line injectables. We used Poisson regression with backward elimination to generate multivariable models for acquired resistance to isoniazid and rifamycins. M. bovis was independently associated with acquired resistance to isoniazid (adjusted prevalence ratio = 8.46, 95% CI 2.96-24.14) adjusting for HIV status, and with acquired resistance to rifamycins (adjusted prevalence ratio = 4.53, 95% CI 1.29-15.90) adjusting for homelessness, HIV status, initial resistance to isoniazid, site of disease, and administration of therapy. East Asian lineage was associated with acquired resistance to fluoroquinolones (prevalence ratio = 6.10, 95% CI 1.56-23.83). We found an association between mycobacterial species and lineage and acquired drug resistance using U.S. surveillance data. Prospective clinical studies are needed to determine the clinical significance of these findings, including whether rapid genotyping of isolates at the outset of treatment may benefit patient management.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acquired immune deficiency syndrome / Adolescent / Adult / Aged / AIDS / Analysis / Antitubercular agents / Antitubercular Agents - therapeutic use / Bacteria / Bacterial Typing Techniques / Child / Child, Preschool / Data processing / Disease control / Disease prevention / Drug development / Drug resistance / Drugs / Epidemiological Monitoring / Female / Fluoroquinolones / Fluoroquinolones - therapeutic use / Genotype & phenotype / Genotyping / Hepatitis / HIV / Homeless people / Homelessness / Human immunodeficiency virus / Humans / Infant / Infant, Newborn / Isoniazid / Isoniazid - therapeutic use / Male / Medical diagnosis / Medical screening / Microbial drug resistance / Microbial Sensitivity Tests / Middle Aged / Multivariate Analysis / Mycobacterium bovis - drug effects / Mycobacterium bovis - genetics / Mycobacterium bovis - isolation & purification / Mycobacterium tuberculosis / Mycobacterium tuberculosis - classification / Mycobacterium tuberculosis - drug effects / Mycobacterium tuberculosis - genetics / Mycobacterium tuberculosis - isolation & purification / Phylogenetics / Phylogeny / Poisson density functions / Prevalence / Regression analysis / Rifamycins / Rifamycins - therapeutic use / Species / Statistical analysis / Surveillance / Systematic review / Tuberculosis / Tuberculosis, Multidrug-Resistant - drug therapy / Tuberculosis, Multidrug-Resistant - epidemiology / Tuberculosis, Multidrug-Resistant - microbiology / United States - epidemiology