Management of DR-TB Treatment interruptions

Management of treatment interruptions and lost to follow-up

• All efforts must be made to ensure that the DR-TB patients do not interrupt treatment or are not LTFU.
• Action should be taken to promptly retrieve patients who fail to come for their daily dose by the treatment supporter/ supervisor. 
• All possible efforts should be made to support the patient and manage the adverse events to ensure uninterrupted treatment and intake of all medicines in the regimen; however, when severe toxicity occurs, the medicine should be stopped.

The following strategies are applicable for patients who interrupt treatment:

Patients who miss doses

• All missed doses during IP (wherever applicable) must be completed prior to switching the patient to CP. Similarly, all missed doses during CP must be administered prior to ending treatment.

Patients who interrupt treatment for less than 9 weeks

When the patient returns to resume treatment, the treatment will be continued, and the duration of treatment will be extended to complete the regimen. The follow-up smear or cultures will be done as per the schedule.

1. Consecutive treatment interruption (of all medicines in the regimen) of up to two weeks needs to be made up and added to the treatment duration. 
2. Non-consecutive missed doses of all medicines in the regimen up to a cumulated total of four weeks need to be made up and added to the treatment duration. 

• In case of tolerances is exceeded for anyone of the above two conditions, general guidance is to consider clinical review and switch to an individualized longer oral M/XDR-TB regimen.
• An additional culture may be considered if the DR-TB patient returns between four to nine weeks of treatment and has clinically deteriorated. If the culture is positive, repeat FL/SL LPA and LC DST need to be done as per the integrated algorithm. 
• If additional resistance is detected to any component drugs, the outcome will be declared as ‘treatment failed’, the patient will be sent to NDR-TB centre for clinical, radiological and microbiological review and be switched to an individualized longer oral M/XDR-TB regimen with a fresh PTE.

Patients who interrupt treatment continuously for 9 weeks or more and return for treatment

• Such patients will be given an outcome of LTFU. The patient would be revaluated as per the integrated algorithm to restart with appropriate treatment.
• If there are signs of impending treatment failure for any MDR/RR-TB patient with or without additional resistance to SLDs, the patient should be switched to an individualized longer oral M/XDR-TB regimen and evaluated further to modify appropriately based on DST results if required.

For patients who interrupt Bdq during the first two weeks of the Bdq course and return to resume the treatment

• If the interruption is up to seven days, Bdq will be continued to complete the doses, and the duration of treatment will be extended to complete first two weeks of loading dose and the compensation to be done before starting Bdq 200mg thrice weekly. Follow-up cultures will be done as per the revised schedule.
• If the interruption is more than seven consecutive days, the Bdq course will be reloaded (started afresh with a new bottle and the old bottle sent for reconstitution after adjusting for the additional tablets required for reloading). And a fresh specimen collected for culture and the culture isolate must be stored for Bdq DST in the future. Follow-up cultures will be done as per the revised schedule.

Patients who interrupt Bdq during 3-26 weeks of the Bdq course and return to resume treatment

During the maintenance phase of Bdq dosing, Bdq can be reinitiated with the loading dose if the interruption if any, is up to nine weeks. If Bdq is interrupted for

i.  less than two consecutive weeks, no reloading is required. Resume the thrice-weekly dosing schedule and complete the treatment duration.

ii. more than two weeks (but less than eight weeks), Bdq should be reloaded at the higher daily dose of 400 mg for seven days before resuming the thrice-weekly dosing schedule.

iii. more than eight consecutive weeks, then declare the outcome as ‘LTFU’ and the patient and treatment plan should be reassessed to consider an individualized longer oral M/XDR-TB regimen