Guideline

WHO consolidated guidelines on tuberculosis: Module 4: Treatment - Drug-resistant tuberculosis treatment

Year of Publication

2020

Issuing Institution

World Health Organization

Links

WHO IRIS,WHO IRIS,Pubmed

Recommendations

38 included recommendations

In patients with confirmed rifampicin-susceptible, isoniazid-resistant tuberculosis (Hr-TB), treatment with rifampicin, ethambutol, pyrazinamide and levofloxacin is recommended for a duration of 6 months

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

In patients with confirmed rifampicin-susceptible, isoniazid-resistant tuberculosis, it is not recommended to add streptomycin or other injectable agents to the treatment regimen

Status

Maintained

Recommended against

Conditional

Certainty of evidence

Very low

In multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) patients on longer regimens, all three Group A agents and at least one Group B agent should be included to ensure that treatment starts with at least four TB agents likely to be effective, and that at least three agents are included for the rest of treatment if bedaquiline is stopped. If only one or two Group A agents are used, both Group B agents are to be included. If the regimen cannot be composed with agents from Groups A and B alone, Group C agents are added to complete it.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

Kanamycin and capreomycin are not to be included in the treatment of multidrug-resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB) patients on longer regimens

Status

Maintained

Recommended against

Conditional

Certainty of evidence

Very low

Levofloxacin or moxifloxacin should be included in the treatment of multidrug-resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB) patients on longer regimens.

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

Bedaquiline should be included in longer multidrug-resistant TB (MDR-TB) regimens for patients aged 18 years or more.

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

Linezolid should be included in the treatment of multidrug-resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB) patients on longer regimens

Status

Updated

Recommended in favor

Strong

Certainty of evidence

Moderate

Clofazimine and cycloserine or terizidone may be included in the treatment of multidrug-resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB) patients on longer regimens

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

Ethambutol may be included in the treatment of multidrug-resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB) patients on longer regimens

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

Delamanid may be included in the treatment of multidrug-resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB) patients aged 3 years or more on longer regimens

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Moderate

Pyrazinamide may be included in the treatment of multidrug-resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB) patients on longer regimens

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

Imipenem–cilastatin or meropenem may be included in the treatment of multidrug-resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB) patients on longer regimens

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

Amikacin may be included in the treatment of multidrug-resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB) patients aged 18 years or more on longer regimens when susceptibility has been demonstrated and adequate measures to monitor for adverse reactions can be ensured. If amikacin is not available, streptomycin may replace amikacin under the same conditions.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

Ethionamide or prothionamide may be included in the treatment of multidrug-resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB) patients on longer regimens only if bedaquiline, linezolid, clofazimine or delamanid are not used or if better options to compose a regimen are not possible

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

p-aminosalicylic acid may be included in the treatment of multidrug-resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB) patients on longer regimens only if bedaquiline, linezolid, clofazimine or delamanid are not used or if better options to compose a regimen are not possible

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

In multidrug-resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB) patients on longer regimens, a total treatment duration of 18–20 months is suggested for most patients;

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

In multidrug-resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB) patients on longer regimens, a treatment duration of 15–17 months after culture conversion is suggested for most patients; the duration may be modified according to the patient’s response to therapy.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

In multidrug-resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB) patients on longer regimens containing amikacin or streptomycin, an intensive phase of 6–7 months is suggested for most patients; the duration may be modified according to the patient’s response to therapy.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

A shorter all-oral bedaquiline-containing regimen of 9–12 months duration is recommended in eligible patients with confirmed multidrug- or rifampicinresistant tuberculosis (MDR/RR-TB) who have not been exposed to treatment with second-line TB medicines used in this regimen for more than 1 month, and in whom resistance to fluoroquinolones has been excluded.

Status

Updated

Recommended in favor

Conditional

Certainty of evidence

Very low

A treatment regimen lasting 6–9 months, composed of bedaquiline, pretomanid and linezolid (BPaL), may be used under operational research conditions in multidrug-resistant tuberculosis (MDR-TB) patients with TB that is resistant to fluoroquinolones, who have either had no previous exposure to bedaquiline and linezolid or have been exposed for no more than 2 weeks.

Status

Retired

Recommended in favor

Conditional

Certainty of evidence

Very low

In multidrug-resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB) patients on longer regimens, the performance of sputum culture in addition to sputum smear microscopy is recommended to monitor treatment response. It is desirable for sputum culture to be repeated at monthly intervals

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

Antiretroviral therapy is recommended for all patients with HIV and DR-TB requiring second-line antituberculosis drugs, irrespective of CD4 cell count, as early as possible (within the first 8 weeks) following initiation of antituberculosis treatment

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Very low

In patients with rifampicin-resistant tuberculosis (RR-TB) or multidrugresistant TB (MDR-TB), elective partial lung resection (lobectomy or wedge resection) may be used alongside a recommended MDR-TB regimen.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

Health education and counselling on the disease and treatment adherence should be provided to patients on tuberculosis (TB) treatment

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

A package of treatment adherence interventions may be offered to patients on TB treatment in conjunction with the selection of a suitable treatment administration option

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Low

One or more of the following treatment adherence interventions (complementary and not mutually exclusive) may be offered to patients on TB treatment or to health-care providers: tracers and/or digital medication monitor

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

One or more of the following treatment adherence interventions (complementary and not mutually exclusive) may be offered to patients on TB treatment or to health-care providers: material support to the patient

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Moderate

One or more of the following treatment adherence interventions (complementary and not mutually exclusive) may be offered to patients on TB treatment or to health-care providers: psychological support to the patient

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Low

One or more of the following treatment adherence interventions (complementary and not mutually exclusive) may be offered to patients on TB treatment or to health-care providers:staff education

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Low

The following treatment administration options may be offered to patients on TB treatment: Community- or home-based directly-observed treatment (DOT) is recommended over health facility-based DOT or unsupervised treatment

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Moderate

The following treatment administration options may be offered to patients on TB treatment: directly-observed treatment (DOT) administered by trained lay providers or healthcare workers is recommended over DOT administered by family members or unsupervised treatment

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

The following treatment administration options may be offered to patients on TB treatment: Video-observed treatment (VOT) may replace directly-observed treatment (DOT) when video communication technology is available, and it can be appropriately organized and operated by health-care providers and patients

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

Patients with multidrug-resistant tuberculosis (MDR-TB) should be treated using mainly ambulatory care rather than models of care based principally on hospitalization

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

A decentralized model of care is recommended over a centralized model for patients on multidrug-resistant tuberculosis (MDR-TB) treatment

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

Bedaquiline may also be included in longer multidrug-resistant tuberculosis (MDR-TB) regimens for patients aged 6–17 years

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

Longer regimens for multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB): Clavulanic acid should not be included in the treatment of MDR/RR-TB patients on longer regimens.

Status

Maintained

Recommended against

Strong

Certainty of evidence

Low

In patients with confirmed rifampicin-susceptible and isoniazid-resistant tuberculosis, treatment with rifampicin, ethambutol, pyrazinamide and levofloxacin is recommended for a duration of 6 months

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

In patients with confirmed rifampicin-susceptible and isoniazid-resistant tuberculosis, it is not recommended to add streptomycin or other injectable agents to the treatment regimen

Status

Maintained

Recommended against

Conditional

Certainty of evidence

Very low