Technical Manual for Drug Susceptibility Testing of Medicines Used in the Treatment of Tuberculosis Geneva: World Health Organization; 2018
(2018; 52 pages)

Abrégé

This technical manual focuses on the available DST methods for both first- and second-line anti-TB agents. Culture-based phenotypic DST methods for certain anti-TB medicines are reliable and reproducible, but these methods are time-consuming, require sophisticated laboratory infrastructure, qualified staff and strict quality control. Only indirect DST procedures for anti-TB medicines are included in this document. The methods described are LJ, 7H10 and 7H11 agar and MGIT.

WHO recommends the use of rapid molecular DST tests as the initial tests to detect drug resistance prior to the initiation of appropriate therapy for all TB patients, including new patients and patients that require retreatment. If rifampicin resistance is detected, rapid molecular tests for resistance to isoniazid, fluoroquinolones and amikacin should be performed promptly to inform which second-line medicines should be used for the treatment of RR-TB and MDR-TB. Genotypic DST methods such as next generation sequencing are attractive alternatives to culture-based DST methods given the speed of performing molecular methods and the detailed sequence information that can be generated for multiple gene regions associated with drug resistance. However, until our knowledge of the molecular basis of resistance improves, culture-based DST for important second-line including bedaquiline, linezolid, and agents will need to be performed. Consider performing culture-based DST for the fluoroquinolones (FQ) and amikacin (AMK) when resistance is suspected despite the absence of previously identified genetic mutations associated with resistance. Commercially available rapid genetic methods such as the second-line line-probe assays detect approximately 85% of FQ or AMK resistant isolates.

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