If a patient starts the 9-month all-oral MDR/RR-TB regimen but is later found to be ineligible following detection of M. tuberculosis resistance to fluoroquinolones, the patient must switch to a different regimen. Such patients might be eligible for a 6-month BPaL regimen if their prior exposure to bedaquiline and linezolid was for less than 1 month and there is no demonstrated resistance to any components of the BPaL regimen. The BPaL regimen may only be considered if the patient meets the eligibility criteria and the regimen is available and feasible in the setting. In cases where an eligible patient starts the 9-month all-oral MDR/RR-TB regimen but additional resistance is detected later in treatment (after initial DST indicated susceptibility to Group A and B drugs), it can be assumed that further acquisition of resistance may have emerged during that period of drug exposure; such patients should be considered for a treatment outcome of failure and should not continue with the 9-month regimen. The 6-month BPaL regimen should not be offered to these patients because amplification may have occurred to linezolid and bedaquiline, key drugs in the BPaLM/BPaL regimen. The patient should switch to a longer individualized regimen, with repeated phenotypic DST to guide the composition of the longer regimen.
Patients who start a 6-month BPaLM/BPaL regimen may switch to the 9-month all-oral regimen, if required, provided they meet the necessary eligibility criteria for the 9-month regimen. This may be warranted when toxicity to linezolid develops early in the BPaLM/BPaL regimen and necessitates a linezolid-sparing regimen, such as the 9-month regimen with ethionamide.
Patients who start on a longer regimen but are subsequently found to be eligible for the 9-month all-oral regimen may switch to the 9-month regimen if this is done within the first month of starting treatment. There is little experience in switching from longer to shorter regimens in this way; hence, clinical monitoring and adequate data collection are important to inform future treatment recommendations.
Patients who are lost to follow-up after starting the 9-month all-oral regimen are likely to have had more than 1 month of exposure to key drugs within the 9-month regimen. Should such patients return to care and require MDR/RR-TB treatment in future, the 9-month all-oral regimen may still be considered as a treatment option if resistance to bedaquiline, fluoroquinolones, clofazimine, and ethionamide or linezolid (whichever is considered for inclusion in the regimen) is ruled out and all other relevant eligibility criteria are met. In such cases, DST for the key drugs in this regimen is likely to take some time; therefore, patients may have to initiate a longer individualized regimen while awaiting DST results.