TB KaSPar
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When TB affects the CNS it leads to several additional problems. For example, the concentrations of some drugs in the CNS can be reduced owing to low penetration through the blood–brain barrier. Therefore, drugs need to be selected on the basis of both susceptibility and specific CNS penetration. Drugs with high CNS penetration should be used.
A longer treatment regimen may be more suitable in cases of severe extrapulmonary TB, owing to the high risk of negative outcomes including relapse. All such cases have in common the dispersion of M. tuberculosis through blood. Severe extrapulmonary TB is associated with lesions in multiple organs, potentially leading to multiorgan failure.
Currently, there are no specific changes in patients with diabetes; however, such patients may present cumulative risk factors for clinical complications, toxicities and drug–drug interactions. Good glycaemic control is considered essential while on TB treatment because such control optimizes the chance of cure and limits complications. The concomitant use of metformin at high doses and linezolid may increase the risk of lactic acidosis.
Dosing and safety data to support the optimal use of second-line TB medicines during pregnancy are generally sparse. There have been case reports and observational data reporting successful treatment and pregnancy outcomes among women who received treatment (including bedaquiline-containing regimens) for MDR/RR-TB during pregnancy and postpartum, but pregnant and lactating women are usually excluded from clinical drug trials and early access programmes.
WHO recommendations on longer MDR/RR-TB regimens apply to children as well as adults. Currently, there is no age restriction on the use of bedaquiline, so children of all ages should receive it in longer regimens unless there is a specific contraindication. Most medicines in longer regimens have been part of MDR/RR-TB regimens for many years, in similar combinations, for both adults and children. Second-line TB medicines are also available in child-friendly formulations.
A stepwise approach guides the design of longer MDR-TB regimens (Table 6.1).
When designing longer regimens, several basic principles need to be respected, in line with the best available evidence on composition of the regimens, as per the recommendations listed below.
Introducing the longer and shorter MDR-TB regimens entails a series of steps that are the same as those necessary when an NTP introduces a new MDR-TB treatment component. This chapter summarizes some key considerations for those steps.
With regard to HIV infection, a specific recommendation was made in 2011 on the use of ART in all patients with HIV and DR-TB (68, 115):
6.1. ART is recommended for all patients with HIV and drug-resistant TB requiring second-line anti-tuberculosis drugs irrespective of CD4 cell count, as early as possible (within the first 8 weeks) following initiation of anti-tuberculosis treatment (Strong recommendation, very low quality of evidence)