To monitor the treatment response in patients on longer MDR-TB regimens, it is strongly recommended that sputum culture be repeated at monthly intervals, in addition to sputum smear microscopy (38). The evidence used to explore the added value of culture over sputum smear microscopy alone was obtained from the IPD; it showed a higher sensitivity of monthly culture in predicting treatment outcomes when compared with monthly smear microscopy. Monthly culture increased the detection of patients with a true positive bacteriological result when compared with sputum smear microscopy alone; also, it reduced the proportion of patients with a false negative result.
Concomitant use of sputum smear microscopy and culture test results helps to identify patients whose bacteriology remains positive or reverts to positive following initial conversion to negative. This combined testing will help clinicians to identify patients whose treatment is likely to fail, and thus to plan alternative options and institute infection control measures in a timely manner. Additional benefits would be expected from reduced transmission and development of resistance, and from appropriate changes to treatment regimens. Regular microscopy and culture of sputum or other specimens remain important to ensure that treatment failure is detected early. Using smear microscopy or culture to assess conversion of bacteriological status is an important means of assessing response, and most patients are expected to have converted to a sputum negative status within the first few months of starting treatment. Persistence of culture positivity beyond that point, or close to the expected end of the intensive phase when injectable agents are in use, should trigger a review of the regimen and performance of DST. If DST to certain agents is not available, the strains should be stored for further investigations at the supranational TB reference laboratory. If the risk of resistance is high (e.g. after treatment failure in TB cases who are contacts of a drug-resistant TB case), sequencing methods may also provide valuable information. It is advisable to use culture to continue to monitor patients at 6 and 12 months after completion of treatment, to ensure sustained cure.
In children, smear and culture monitoring of the response to treatment may be challenging, for the same reasons it is difficult to obtain a bacteriological confirmation of the diagnosis. In children with a bacteriologically confirmed diagnosis, all reasonable efforts should be taken to demonstrate bacteriological conversion. Once cultures have become negative or in children who never had a confirmed diagnosis, repeated respiratory sampling may not be useful if the child is otherwise responding well clinically. Resolution of clinical symptoms and weight gain can be used as indicators of improvement. All children should have regular clinical follow-up, including weight and height monitoring. Drug dosages should be adjusted with weight gain, as needed.