OpiniãoThe recommendation would apply to any longer regimen, regardless of the number of Group A, B or C agents used and whether an injectable (intensive) phase was used or not. The GDG considered that the findings may apply to other key patient subgroups.
Patients aged below 15 years with MDR/RR-TB
Patients aged below 15 years with MDR/RR-TB comprised less than 2% of the IPD meta-analysis analysed for PICO question 11 (MDR/RR-TB, 2018). Younger children usually cannot produce sufficient sputum spontaneously to allow a bacteriological diagnosis (many are typically sputum smear microscopy negative). In these patients, culture may be a more sensitive way to detect viable TB bacilli even if very few organisms are present in the sputum or other samples that are below the detection threshold of direct microscopy. However, in children who are unable to expectorate, gastric aspirates or induced sputa may be possible, but the repetition of such tests at monthly frequency may not be acceptable.
Extrapulmonary disease
Extrapulmonary disease is commonly paucibacillary; therefore, biological specimens may contain few or no bacilli. In such situations, detection of persistent disease is more likely with culture, although collection of samples often poses problems. Direct microscopy should still be attempted because it may determine positivity much faster than culture.
HIV-negative individuals
HIV-negative individuals with TB typically have higher bacterial counts in the sputum and a greater likelihood of detection with smear microscopy. In such a situation, it might be expected that the difference in test sensitivity between smear and culture would be less extreme, because fewer patients would have subthreshold bacterial counts. However, past studies on datasets from multiple sites in which HIV positivity was low reported findings that led to the WHO recommendation, even in 2011, for joint use of both microscopy and culture, preferably every month.
Patients on the shorter MDR-TB regimen
Patients on the shorter MDR-TB regimen have a much shorter duration of intensive phase and total treatment. They receive seven drugs in the initial phase and, if fully compliant with the inclusion and exclusion criteria, usually have a more favourable prognostic outlook than other MDR-TB patients. Programmes may thus consider that patients on a shorter MDR-TB regimen may need less frequent or no culture to monitor treatment. Although the current analysis did not include patients treated with shorter regimens, the GDG proposes that programmes that implement this regimen should aim for more frequent culture testing, especially after the intensive phase, to confirm bacteriological cure in patients who complete treatment without signs of failure. Any sign of recurrence after termination of treatment should also be investigated using sputum smear microscopy, culture and DST.