There are several subgroups to be considered for these recommendations:

• The recommendations are based on the evidence of diagnostic accuracy in sputum of adultswith bacteriologically confirmed pulmonary TB, with or without rifampicin resistance.
• The recommendations are extrapolated to adolescents and children, based on thegeneralization of data from adults.
• The recommendations apply to people living with HIV (studies included a varying proportionof such individuals); data stratified by HIV status were not available.
• The recommendations are extrapolated to people with extrapulmonary TB, and testing ofnon-sputum samples was considered appropriate, which affects the certainty. The panel didnot evaluate test accuracy in non-sputum samples directly, including in children; however,extrapolation was considered appropriate given that WHO has recommendations for similartechnologies for use on non-sputum samples (e.g. Xpert MTB/RIF and Xpert Ultra).
• Recommendations for detection of resistance to amikacin and ethionamide are only relevantfor people who have bacteriologically confirmed pulmonary TB and resistance to rifampicin.

Implementation considerations Factors to consider when implementing low complexity automated NAATs for detection of resistance to isoniazid and second-line anti-TB agents are as follows:

• local epidemiological data on resistance prevalence should guide local testing algorithms, whereas pretest probability is important for the clinical interpretation of test results;
• the cost of a test varies depending on parameters such as the number of samples in a batch and the staff time required; therefore, a local costing exercise should be performed;
• low, moderate and high complexity tests have successive increase in technical competency needs (qualifications and skills) and staff time, which affects planning and budgeting;
• availability and timeliness of local support services and maintenance should be considered when selecting a provider;
• laboratory accreditation and compliance with a robust quality management system (including appropriate quality control) are essential for sustained service excellence and trust;
• training of both laboratory and clinical staff will ensure effective delivery of services and clinical impact;
• use of connectivity solutions for communication of results is encouraged, to improve efficiency of service delivery and time to treatment initiation;
• rapid and early testing for the detection of fluoroquinolone resistance is essential before starting treatment with the all-oral MDR/RR-TB shorter regimen (i.e. 6–9 months); this may also become relevant (depending on the epidemiological context) if new shorter drugsusceptible TB regimens that include fluoroquinolones are introduced;
• these tests can be used to rule in ethionamide resistance, but not to rule out resistance, because mutations conferring resistance to ethionamide are not limited to the inhA promoter region – they also include ethA, ethR and other genes;
• culture-based phenotypic DST may still be required, particularly among those with a high pretest probability of resistance when the low complexity automated NAATs does not detect drug resistance; in addition, culture-based phenotypic DST:
• remains important to determine resistance to other anti-TB agents, particularly the new and repurposed medicines, and to monitor the emergence of additional drug resistance;
• does not apply to ethionamide because it is unreliable and poorly reproducible;
• for second-line injectable drugs, the panel evaluated the performance in detecting resistance to amikacin only because both kanamycin and capreomycin are no longer recommended for the treatment of DR-TB; and
• culture-based phenotypic DST may be important to confirm amikacin susceptibility in situations where it is appropriate to use this medicine, to balance risk and benefit.