Consequences of Noncompliance for Therapy Efficacy and Emergence of Resistance in Murine Tuberculosis Caused by the Beijing Genotype of Mycobacterium tuberculosis
- 1 September 2012
- journal article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 56 (9), 4937-4944
- https://doi.org/10.1128/aac.00124-12
Abstract
Despite great effort by health organizations worldwide in fighting tuberculosis (TB), morbidity and mortality are not declining as expected. One of the reasons is related to the evolutionary development of Mycobacterium tuberculosis , in particular the Beijing genotype strains. In a previous study, we showed the association between the Beijing genotype and an increased mutation frequency for rifampin resistance. In this study, we use a Beijing genotype strain and an East-African/Indian genotype strain to investigate with our mouse TB model whether the higher mutation frequency observed in a Beijing genotype strain is associated with treatment failure particularly during noncompliance therapy. Both genotype strains showed high virulence in comparison to that of M. tuberculosis strain H37Rv, resulting in a highly progressive infection with a rapid lethal outcome in untreated mice. Compliance treatment was effective without relapse of TB irrespective of the infecting strain, showing similar decreases in the mycobacterial load in infected organs and similar histopathological changes. Noncompliance treatment, simulated by a reduced duration and dosing frequency, resulted in a relapse of infection. Relapse rates were correlated with the level of noncompliance and were identical for Beijing infection and East African/Indian infection. However, only in Beijing-infected mice, isoniazid-resistant mutants were selected at the highest level of noncompliance. This is in line with the substantial selection of isoniazid-resistant mutants in vitro in a wide isoniazid concentration window observed for the Beijing strain and not for the EAI strain. These results suggest that genotype diversity of M. tuberculosis may be involved in emergence of resistance and indicates that genotype-tailor-made treatment should be investigated.This publication has 24 references indexed in Scilit:
- Importance of Confirming Data on the In Vivo Efficacy of Novel Antibacterial Drug Regimens against Various Strains of Mycobacterium tuberculosisAntimicrobial Agents and Chemotherapy, 2012
- Multidrug-Resistant Tuberculosis Not Due to Noncompliance but to Between-Patient Pharmacokinetic VariabilityThe Journal of Infectious Diseases, 2011
- Dynamics of interferon-gamma release assay and cytokine profiles in blood and respiratory tract specimens from mice with tuberculosis and the effect of therapyEuropean Journal of Clinical Microbiology & Infectious Diseases, 2011
- Mycobacterium tuberculosis Lineage Influences Innate Immune Response and Virulence and Is Associated with Distinct Cell Envelope Lipid ProfilesPLOS ONE, 2011
- Beijing Genotype of Mycobacterium tuberculosis Is Significantly Associated with High-Level Fluoroquinolone Resistance in VietnamAntimicrobial Agents and Chemotherapy, 2009
- Emergence of New Forms of Totally Drug-Resistant Tuberculosis Bacilli: Super Extensively Drug-Resistant Tuberculosis or Totally Drug-Resistant Strains in IranSocial psychiatry. Sozialpsychiatrie. Psychiatrie sociale, 2009
- The clinical consequences of strain diversity in Mycobacterium tuberculosisTransactions of the Royal Society of Tropical Medicine and Hygiene, 2008
- Evaluation of the GenoType MTBDRplus Assay for Rifampin and Isoniazid Susceptibility Testing of Mycobacterium tuberculosis Strains and Clinical SpecimensJournal of Clinical Microbiology, 2007
- The emergence of Beijing family genotypes ofMycobacterium tuberculosisand low-level protection by bacille Calmette–Guérin (BCG) vaccines: is there a link?Clinical and Experimental Immunology, 2006
- Beijing/W GenotypeMycobacterium tuberculosisand Drug ResistanceEmerging Infectious Diseases, 2006