OpiniãoA stepwise approach guides the design of longer MDR-TB regimens (Table 6.1).
The selection of medicines follows a priority order based on the revised classification of regimen components, and a fully oral regimen is preferred. At least four drugs must be selected, starting from Group A and then from Group B. Group C drugs are usually included in a longer regimen if it cannot be composed with Group A and B agents alone. The choice of drugs from Group C is usually determined by the order in which the medicines are ranked, and by the individual circumstances of the patient and the setting. A recent review of the observational data found no additional safety concerns when bedaquiline was used for longer than 6 months; however, no clear evidence was available to indicate whether longer use added efficacy (1). The clinicians may therefore consider continuing bedaquiline for longer than 6 months and adding some flexibility for regimen design and the number of effective drugs.
In the case of longer treatment regimens, an individual approach is needed. Therefore, apart from the drug classification, it is crucial to optimize drug selection according to the patient’s clinical condition and the drug-resistance pattern. Considerations include:
- the clinical history of drugs taken in the past by the patient or the index case, or according to local resistance epidemiology in the country or region;
- the DST results – where available, is it of utmost importance to guide the drug selection using phenotypic or genotypic DST; in patients with extensive patterns of resistance, whenever possible, it is advised to perform whole genome sequencing; and
- selecting drugs according to their special features – in addition to susceptibility, key drug features and clinical particularities of the patient that may boost survival must be considered (e.g. likelihood of effectiveness, CNS penetration, drug–drug interaction profile, tolerance and patient preference, oral absorption and bioavailability).
Most anti-TB drugs are used once daily to achieve a high peak serum concentration that increases the bactericidal and sterilizing effect and to support adherence (to avoid missed or partial doses). The doses of anti-TB drugs by weight bands are outlined in the Annex. The essential information about TB medicines used in MDR/RR-TB treatment is described in detail in Web Annex 1.
Many patients may have comorbidities and adverse events that need to be addressed separately. Hospitalization, surgery and other adjuvant treatment may be needed at certain stages of treatment. Comprehensive monitoring and treatment adherence support are important to ensure a favourable treatment experience. Access to palliative and end-of-life care services may be needed, with a patientcentred approach to relieve the suffering from the disease and its treatment (65). Respiratory infection control measures at the sites where the patient is being treated, contact tracing and counselling are important accompanying measures for clinical care and public health.
Table 6.2 summarizes some common situations that a clinician may face, and the decisions that could be taken to adjust the treatment regimen accordingly. The suggested regimens may vary based on the individual clinical circumstances and the availability of medicines. Table 6.2 is not exhaustive. Although it is recommended to use at least four effective agents initially, not all the regimens composed using this algorithm have been tested directly in either research or field conditions. Moreover, when Group C agents are included, the number of medicines in the regimen may exceed four, to reflect the uncertainty about the efficacy of some of these medicines. In such situations, the advice of a specialist is important to ensure the safest and most effective possible regimen.