Technical report on critical concentrations for TB drug susceptibility testing of medicines used in the treatment of drug-resistant TB
The End TB Strategy calls for early diagnosis and prompt treatment of all persons of all ages with any form of drug-susceptible or drug-resistant TB. The effective management of multi-drug and extensively-drug resistant TB (M/XDR-TB) relies upon the rapid diagnosis and treatment of resistant infections. Culture-based phenotypic drug susceptibility testing (DST) methods are currently the gold standard for drug resistance detection although these methods are time-consuming; require sophisticated laboratory infrastructure, qualified staff and strict quality assurance mechanisms.
DST uses critical concentrations of anti-TB agents to determine the susceptibility or resistance of a culture of Mycobacterium tuberculosis complex. The critical concentration is defined as the lowest concentration of an anti-TB agent in vitro that will inhibit the growth of 99% of phenotypically wild type strains of M. tuberculosis complex.
This technical report is based on a systematic review of available minimum inhibitory concentration (MIC) data for phenotypically wild type as well as phenotypically non-wild type strains, including associated sequencing data for relevant resistance genes. The medicines included in the review were the second-line injectable agents (kanamycin, amikacin and capreomycin), clofazimine and bedaquiline, cycloserine and terizidone, linezolid, delamanid, and the fluoroquinolones (ofloxacin, levofloxacin, gatifloxacin and moxifloxacin). The following media are considered: Löwenstein Jensen, Middlebrook 7H10/7H11 and BACTEC™ Mycobacterial Growth Indicator Tube™ 960.
In 2017, WHO convened a Technical Expert Group to review the evidence from the systematic review. The report presents new knowledge to inform TB practitioners and TB laboratory managers on revised critical concentrations for performing TB DST in different culture media. Evidence about what concentration of drug to test against M. tuberculosis strains in vitro provide the clinician with useful insights to improve care of MDR-TB patients. The report also informs how to interpret drug-susceptibility testing (DST) to make informed decisions on treatment.
The supplementary document and data files for this report can be downloaded here