Single dose formulations in the era of fixed dose combinations for TB: role in clinical trials

A recent article by Sotgiu et al. highlighted shortages in anti-TB drug supply, its impact on the TB treatment and implications for National TB programmes (NTPs).1 The authors raised various concerns, in-cluding unfavourable treatment outcomes, drug tox-icities, resistance and catastrophic costs.1 We address another aspect of the lack of availability of anti-TB drugs, which impacts TB research globally. The need for newer treatment regimens with different doses of the recommended drugs or newer drugs for the management of all forms of TB is being explored globally. This includes adjusting doses of recom- mended drugs, replacing drugs based on pharmaco- kinetics and available evidence, or due to the development of drug resistance. For example, evidence suggests that higher doses of rifampicin may improve treatment outcomes in drug-sensitive TB (DS-TB).2 The currently recommended drugs for severe forms of TB such as tuberculous meningitis (TBM) have varying cerebrospinal fluid (CSF) penetration. Isoni- azid and pyrazinamide achieve optimal therapeutic levels, whereas rifampicin and ethambutol achieve subtherapeutic levels in the brain.3 Drugs such as ethionamide and fluoroquinolones have demonstrated good CSF penetration. Mortality and morbidity as- sociated with TBM tend to be high despite treatment. We therefore need to evaluate the optimal regimen for fatal diseases like TBM. Currently, the role of inten- sified shorter regimens for various forms of TB is a key area of focus in TB research.