Algorithm 3 is for further evaluation of patients with RR-TB or MDR-TB. In its most recent recommendations (57), WHO stresses the importance of DST before starting the preferred shorter all-oral BDQ-containing MDR-TB regimen, especially for medicines for which mWRDs are available. These medicines currently include RIF, INH and FQs. In addition, WHO stresses the need to scale up laboratory DST capacity for medicines for which there are accurate and reproducible phenotypic methods, including BDQ, LZD, clofazimine (CFZ) and DLM. As in any potentially life-saving situation, treatment for DR-TB should not be withheld from a patient because of a lack of complete DST results.
BDQ: bedaquiline; CFZ: clofazimine; DLM: delamanid; DST: drug-susceptibility testing; FQ: fluoroquinolone; INH: isoniazid; LC-aNAAT: low complexity automated NAAT; LZD: linezolid; MDR-TB: multidrug-resistant tuberculosis; MDR/RR-TB: multidrug- or rifampicin-resistant tuberculosis; NAAT: nucleic acid amplification test; PZA: pyrazinamide; RR-TB: rifampicin-resistant tuberculosis; SL-LPA: line-probe assay for second-line drugs; TB: tuberculosis; WHO: World Health Organization.
¹ Patients should be promptly initiated on an MDR-TB regimen in accordance with national guidelines and WHO recommendations. A shorter all-oral BDQ-containing treatment regimen of 9-12 months in duration is the preferred option for eligible MDR/RR-TB patients.
² If molecular and phenotypic testing are performed in the same laboratory, one specimen may be sufficient. If testing is performed in two laboratories, two specimens should be collected, and the molecular and phenotypic testing conducted in parallel.
³ WHO recommends getting the rapid DST results for FQs before the start of treatment, although this testing should not delay the start of treatment. Currently, LC-aNAAT and SL-LPA are the WHO-approved rapid molecular tests for detecting FQ resistance.
⁴ Phenotypic DST should be conducted for each of the drugs included in the treatment regimen for which there are accurate and reproducible methods. Reliable phenotypic DST methods when performed in a quality-assured laboratory are available for BDQ, FQ, CFZ, INH, PZA, DLM and LZD. A new molecular class of tests, the reverse hybridization high complexity NAAT, is available for PZA resistance detection on culture isolates. The initiation of treatment should not be delayed while awaiting the results of the phenotypic DST.
⁵ For more details regarding individualized regimens, see the WHO consolidated guidelines on drug-resistant tuberculosis treatment (58).
⁶ For FQ-resistant MDR/RR-TB, a specimen should be collected and submitted for phenotypic DST to the WHO Group A (BDQ and LZD), B and C drugs, if not already being done as described in note 4.
⁷ In settings with a high underlying prevalence of resistance to FQs or for patients considered at high risk of FQ resistance, a specimen should be referred for culture and phenotypic DST for FQs.
⁸ If resistance to an individual drug (e.g. BDQ) is suspected and DST for these drugs is not available in the country, laboratories will need to have mechanisms to store the isolate and ship it to a WHO supranational laboratory for DST.