Patients who receive a shorter MDR-TB treatment regimen need to be monitored during treatment using schedules of relevant clinical and laboratory testing, which have been successfully applied in previous studies of shorter regimens under field conditions and in the programmatic setting in South Africa.
The GDG emphasized the need to strengthen and increase access to DST, and the need to monitor and undertake surveillance for emerging drug resistance, including for bedaquiline and for all second-line medicines in the shorter regimen for which reliable DST is available.
The schedule of bacteriological monitoring in South Africa included both smear and culture, carried out monthly. Therefore, the response to treatment should be monitored by using monthly sputum smear microscopy, and culture (ideally at the same frequency). This is similar to the schedule of bacteriological monitoring recommended for the longer regimens (Section 3). If feasible, it is also important to follow up patients 12 months after the completion of treatment, for possible relapse, including with sputum culture and smear.
Based on guidance in current literature and collective experience, the panel advised the following with regard to monitoring and evaluation of the safety and effectiveness of the 9-month regimens:
- the implementation of both regimens requires the use of routine DST, not only for patient selection but also to monitor the acquisition of resistance (collection of strains for sequencing should be considered);
- although the data assessed did not unearth any major signals of risk, aDSM systems must be functional to conduct rigorous active monitoring of adverse events and to detect, manage and report suspected or confirmed drug toxicities in a timely manner;
- programmes need to have access to reliable DST for bedaquiline and linezolid when no bacteriological conversion is seen at the end of the fourth month of treatment and following the 2 months of prolongation – in an ideal situation, the DST for all second-line medicines in these regimens would be available; and
- wider applicability of the 9-month regimens highlights the importance of paediatric formulations. Programmes and their partners need to address the sustained availability of modern paediatric formulations to ensure smooth implementation in this subgroup of patients.