Rescue (XDR-TB) regimens
Introductory remarks Special considerations for persons on long regimens Introductory remarks Clients with RR-TB and suspected or confirmed resistance to linezolid, clofazimine, bedaquiline and pretomanid/delamanid need to be given a rescue regimen. All persons requiring treatment with a rescue regimen should have a specimen or sample sent for EDST. While awaiting the results of that DST, an empi
Special considerations for persons on long regimens
Introductory remarks
Clients with RR-TB and suspected or confirmed resistance to linezolid, clofazimine, bedaquiline and pretomanid/delamanid need to be given a rescue regimen. All persons requiring treatment with a rescue regimen should have a specimen or sample sent for EDST. While awaiting the results of that DST, an empiric rescue treatment regimen will be needed. Input should be sought from the NCAC.
The following principles should be used to design a rescue regimen [11]:
- Delamanid should be used if there is no history of previous exposure to it or to pretomanid.
- A carbapenem should be used if there is no history of previous exposure. Imipenem is the most widely available carbapenem, but both meropenem and ertapenem have been used to treat RR-TB. Carbapenems must be given with clavulanic acid; the only way to give clavulanic acid is in combination with amoxicillin. Thus amoxicillin-clavulanate should be administered (as per dosing tables) 30 minutes prior to the infusion or injection. Long-term IV access is usually needed to administer the carbapenems, although ertapenem can be given intramuscularly.
- Ethionamide may be used if there is a katG mutation (in the absence of inhA).
- Para-aminosalicylic acid may be used.
- Amikacin may be used if there is documented susceptibility to the medication and if formal hearing assessments can be done throughout treatment. Patients should be extensively counselled about the risk of amikacin use, including loss of hearing, and should give at least verbal informed consent to receive the medication. Therapeutic drug monitoring should be employed with use of amikacin.
- Groups A and B drugs should be added to the empiric regimen while awaiting DST results, based on an assessment of the risks and benefits of each individual drug. High-dose moxifloxacin (800 mg daily) could be considered with careful monitoring.
- Surgical consultation should be considered.
- Identify and address any contributing factors to treatment failure (e.g. poorly controlled diabetes, challenges with treatment adherence, high viral load on ART, substance use).
Special considerations for persons on long regimens
| Situation | Possible Actions |
| Persons not responding to treatment | - Careful assessment in any persons with a positive culture at month 3, clinical worsening or poor weight gain. - Review adherence, screen for any contributing factors that could relate to non-adherence (substance use, mental health, socio-economic factors), and ensure adherence support in place. - Confirm BDQ and LZD sensitivity. - Send extended DST request and perform chest X-ray. - Offer long individualized regimen. |
| Persons who are lost to follow up (LTFU) during treatment then return to care | - “Welcome back” counselling and additional adherence support. - Thorough assessment on reasons for LTFU (e.g. substance use, mental health, undisclosed adverse events, socioeconomic factors). - Send sputum for reflex testing and request extended DST. - Regimen selection to consider patient’s clinical status, extent of disease, comorbidities, bacteriologic status at time of LTFU (i.e. smear and culture status), length of therapy received, and length of time between LTFU and return to care. - In patients who have a microbiological/radiological and clinical picture confirming TB disease, an empiric long treatment regimen may be started while awaiting extended DST results, with input from PCAC/NCAC as needed. |
| Persons who have a history of previous treatment with BDQ, Pa, LZD | - Send sputum for ‘DR-TB reflex testing’ and request extended phenotypic DST. - Start on a long regimen including at least five drugs. - Contact NCAC for advice |
National Department of Health Clinical Management of Rifampicin-Resistant Tuberculosis, September 2023
Rescue (XDR-TB) regimens