Wild-type Distributions of Seven Oral Second-Line Drugs Against Mycobacterium Tuberculosis

Int J Tuberc Lung Dis. 2011 Apr;15(4):502-9. doi: 10.5588/ijtld.10.0238.

Abstract

Objectives: To determine wild-type minimum inhibitory concentration (MIC) distributions for Mycobacterium tuberculosis, as the background data for defining susceptibility breakpoints are limited.

Methods: We determined wild-type MIC distributions of M. tuberculosis using a 96-stick replicator in Middlebrook 7H10 (7H10) medium for ethionamide (ETH), prothionamide, thiacetazone, cycloserine, rifabutin (RFB), clofazimine and linezolid in consecutive susceptible clinical isolates (n = 78).

Results: Tentative epidemiological wild-type cut-offs (ECOFF) were determined for all investigated drugs where World Health Organization recommended critical concentrations for 7H10 are lacking, except for ETH. As the ECOFF was closely related to the non-wild-type strains for ETH and thiacetazone, the use of an intermediary (I) category in drug susceptibility testing could increase reproducibility. The cross-resistance between ETH and isoniazid was 21%. Applying 0.5 mg/l as a breakpoint for RFB classified two non-wild type and rpoB mutated isolates as susceptible for RFB and resistant against rifampicin.

Conclusions: We propose that wild-type MIC distributions should be used as a tool to define clinical breakpoints against second-line drugs. This is increasingly important considering the rapid emergence of drug resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Drug Resistance, Multiple, Bacterial
  • Humans
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / isolation & purification
  • Reproducibility of Results
  • Tuberculosis / drug therapy*
  • Tuberculosis / microbiology
  • Tuberculosis, Multidrug-Resistant / drug therapy
  • Tuberculosis, Multidrug-Resistant / microbiology
  • World Health Organization

Substances

  • Antitubercular Agents