The stability of antimycobacterial drugs in media used for drug susceptibility testing

Diagn Microbiol Infect Dis. 2018 Dec;92(4):305-308. doi: 10.1016/j.diagmicrobio.2018.06.015. Epub 2018 Jun 27.

Abstract

The emergence of drug-resistant tuberculosis and disease caused by nontuberculous mycobacteria has increased the need for accurate drug susceptibility testing of mycobacteria. The stability of the tested drugs in relevant test media have been understudied. We assessed the stability of isoniazid, rifampicin, clarithromycin, linezolid and amikacin in Middlebrook 7H9 medium and that of clarithromycin, amikacin and cefoxitin in the cation-adjusted Mueller Hinton broth. We used ultra-performance liquid chromatography (UPLC) methods for rifampicin and isoniazid and a microbiological assay for rifampicin, clarithromycin, amikacin, cefoxitin and linezolid. Rifampicin and isoniazid concentrations in Middlebrook 7H9 medium had decreased by 92% and 54% after 7 days. The microbiological assay revealed decreases in drug concentration of ≥75% (rifampicin, clarithromycin, cefoxitin) and 60% (linezolid) after 14 days. With the exception of amikacin, all antimycobacterial drugs were unstable during 14 days of incubation in the preferred media for DST. Drug stability may influence minimum inhibitory concentration measurements.

Keywords: Drug susceptibility testing; Mycobacteria; Rifampicin, clarithromycin; Stability.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Clarithromycin / pharmacology
  • Culture Media, Conditioned
  • Dose-Response Relationship, Drug
  • Drug Resistance, Bacterial
  • Drug Stability
  • Humans
  • Microbial Sensitivity Tests* / methods
  • Mycobacterium / drug effects*
  • Rifampin / pharmacology

Substances

  • Anti-Bacterial Agents
  • Culture Media, Conditioned
  • Clarithromycin
  • Rifampin