Introduction
Summary table of major guidelines changes The past five years have seen revolutionary changes in the diagnosis and management of rifampicin-resistant tuberculosis (RR-TB), including the use of new and repurposed drugs and novel therapeutic approaches [1] . South Africa has been a global leader in introducing innovation to the field of RR-TB and the work done in the country has had a signifi
Summary table of major guidelines changes
The past five years have seen revolutionary changes in the diagnosis and management of rifampicin-resistant tuberculosis (RR-TB), including the use of new and repurposed drugs and novel therapeutic approaches [1]. South Africa has been a global leader in introducing innovation to the field of RR-TB and the work done in the country has had a significant impact on global policy [2–6]. In May 2022, the WHO announced that 6-month BPaLM regimen, comprising bedaquiline, pretomanid, linezolid (600 mg), with or without moxifloxacin, may be used programmatically in place of 9-month or longer (≥18 months) regimens, in patients (aged ≥15 years) with multidrug-resistant (MDR)/RR-TB who have not had previous exposure to bedaquiline (BDQ), pretomanid or delamanid (DLM) and linezolid (LZD) (defined as >1 month exposure) [7].
Individuals who had more than 1 month exposure of second line drugs will be started on BPaL-L, resistance to bedaquiline and linezolid must be excluded. Treatment initiation must not be delayed pending results of resistance tests. This regimen may be used without levofloxacin (BPaL) in the case of documented resistance to fluoroquinolones (in patients with pre-extensively-drug-resistant (pre-XDR)-TB). Drug susceptibility testing (DST) to fluoroquinolones must be done, but DST should not delay treatment initiation. The short BPALM regimen showed up to 90% efficacy in clinical trial settings. There is accumulating evidence that this cure rate can be achieved in programmatic settings as well. Levofloxacin will be used in replacement of moxifloxacin in South Africa, although moxifloxacin may be used if levofloxacin is unavailable. LZD is the most toxic drug in the regimen. Healthcare providers must ensure careful monitoring to detect adverse events. Early detection of adverse events can be done at a primary care setting to prevent morbidity and even mortality. Confirmed resistance to any of the components except levofloxacin is a contraindication as is severe extrapulmonary TB.
Summary table of major guidelines changes
| Subject area | Major Policy Changes |
| Diagnosis | The Line Probe assay will be phased out and the GeneXpert XDR (Xpert MTB/XDR) cartridge will be used to detect fluoroquinolone and INH resistance. This test also detects resistance to ethionamide and the second line injectables (amikacin, kanamycin and capreomycin) in a single test. Phenotypic testing for linezolid and bedaquiline will be rolled out nationally for all patients who have RR-TB. This test can also be done at the clinician’s request. Pretomanid testing would be performed at the National TB reference laboratory for all isolates resistant to fluoroquinolones. Definitions of pre-XDR and XDR-TB have been updated in line with the latest WHO guidance. |
| Treatment | All persons with RR-TB will either be treated with a short, all-oral, 6- month regimen or with a long-individualized regimen. The previously recommended 9–11-month regimen is no longer included in these guidelines. Recommendations for treatment of RR-TB in children < 15 years of age have been updated. |
| Short (6-month) RR-TB regimen | The 6-month BPaL-L regimen, comprising bedaquiline, pretomanid, linezolid (600 mg) and levofloxacin, will be used programmatically in place of 9-month or longer (>18 months) regimens, in non-pregnant patients (aged ≥15 years) with MDR/RR-TB and Pre XDR-TB who have not had previous exposure to bedaquiline, pretomanid and linezolid (defined as >1 month exposure). Individuals who had more than 1 month exposure of second line drugs will be started on BPaL-L, but resistance to bedaquiline and linezolid must be excluded. Treatment initiation must not be delayed pending results of resistance tests. This regimen may be used without levofloxacin (BPaL) in the case of documented resistance to fluoroquinolones. Drug susceptibility testing (DST) to fluoroquinolones should be done using the GeneXpert XDR cartridge but this should not delay treatment initiation. All persons who are not responding to therapy will be identified early (i.e. based in part on month 3 culture status) and should be reviewed by the Provincial Clinical Advisory Committee (PCAC) or National Clinical Advisory Committee (NCAC) for a possible rescue regimen. |
| Individualized long regimen | This is to be offered to persons with documented resistance to pretomanid and/or BDQ and/or LZD. Prior exposure to pretomanid, linezolid and bedaquiline for more than a month is not an indication for a long-individualized regimen. Extended DST will be done on request by clinicians only to support individualized long regimen. The composition of the regimen will depend on the drug resistance pattern, prior drug exposure and toxicity. The long-individualized regimen can be offered to persons with RR-TB that have a high risk of resistance to BDQ and/or LZD. Please contact the NCAC for advice on the composition of the regimen. |
National Department of Health Clinical Management of Rifampicin-Resistant Tuberculosis, September 2023
Introduction