10.1 Introduction

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    When selecting or building a treatment regimen for multidrug-resistant tuberculosis (MDR-TB) and rifampicin-resistant tuberculosis (RR-TB), the following should be considered:

    10.1.1 Standard short regimens and individualized long regimens

    Patients should receive a standard short treatment regimen (STR) except if they do not meet the eligibility criteria for STRs, or do not tolerate STRs. In such cases, patients require an individualized long treatment regimen (LTR).

     

    It may be necessary to switch from an STR to an LTR, based on the latest drug-susceptibility test (DST) results and/or clinical evolution during treatment course (e.g. drug intolerance, persistence of a positive culture).

    10.1.2 Likely effective drugs

    Treatment is based on a combination of "likely effective" TB drugs.

     

    Table 10.1 – Definition of likely effective drugs (adapted from WHO [1] Citation 1. World Health Organization. Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis. Geneva. 2014.
    https://www.ncbi.nlm.nih.gov/books/NBK247420/pdf/Bookshelf_NBK247420.pdf         )

     

    DST

    Definition of a likely effective TB drug

    Available and reliable

    DST indicates susceptibility to the drug.

    Unavailable, unreliable, or result pending

    The following criteria should be met:

    • No resistance detected by DST to a drug with cross-resistance.
    • No resistance to the drug or to a drug with a cross-resistance to it detected by DST in the presumed source case.
    • No previous exposure (> 1 month) to the drug or to a drug with a cross-resistance.
    • The drug has not been widely used in the treatment of TB or drug resistance surveys indicate that drug resistance is rare in the area the patient comes from.

     

    When the criteria of a likely effective drug are not met:

    • If the strain of the patient (or the presumed source case) is resistant to clofazimine, bedaquiline can be used but not counted as a likely effective drug until DST demonstrates susceptibility to bedaquiline. The same applies to all drugs with known or potential cross-resistance (e.g. delamanid/pretomanid). For more information on drug resistance and cross-resistance, see Chapter 8.
    • If a drug has been widely used and there is no reliable DST for this drug (e.g. ethambutol, cycloserine, para-aminosalicylate sodium): it can be used but never counted as a likely effective drug.
    • If a drug has been widely used and there is a reliable DST for this drug (e.g. pyrazinamide): it can be used but not counted as a likely effective drug until DST demonstrates susceptibility.

    10.1.3 Other considerations

    The following should also be considered when choosing or building a treatment regimen:

    • Interactions and overlapping toxicities between TB drugs or other drugs the patient may take (see Appendix 10 for individual drugs and Appendix 19 for co-administration of TB drugs and antiretrovirals);
    • Comorbidities that can result in increased drug toxicity;
    • Absolute contraindications to any drug included in a regimen;
    • Pregnancy and breastfeeding (Appendix 11).

     

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