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

Diagnostic Microbiology and Infectious Disease
Esther L M SchoutropJakko van Ingen

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.

Citations

Jul 3, 2019·Antimicrobial Agents and Chemotherapy·Mike Marvin RuthJakko van Ingen
May 24, 2019·The Journal of Antimicrobial Chemotherapy·Rana JajouDick van Soolingen
Mar 7, 2020·Frontiers in Microbiology·Jérémy JaffréUNKNOWN CNR-MyRMA (Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux)
Feb 13, 2021·Infection and Drug Resistance·Maria Carolina SiscoRafael Silva Duarte
Mar 23, 2021·Clinical Pharmacokinetics·Jan-Willem AlffenaarCharles A Peloquin
May 12, 2021·Antimicrobial Agents and Chemotherapy·Vidhisha V SonawaneJakko van Ingen

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