Advancing the chemotherapy of tuberculous meningitis: a consensus view

Abstract

Tuberculous meningitis causes death or disability in approximately 50% of affected individuals and kills approximately 78 200 adults every year. Antimicrobial treatment is based on regimens used for pulmonary tuberculosis, which overlooks important differences between lung and brain drug distributions. Tuberculous meningitis has a profound inflammatory component, yet only adjunctive corticosteroids have shown clear benefit. There is an active pipeline of new antitubercular drugs, and the advent of biological agents targeted at specific inflammatory pathways promises a new era of improved tuberculous meningitis treatment and outcomes. Yet, to date, tuberculous meningitis trials have been small, underpowered, heterogeneous, poorly generalisable, and have had little effect on policy and practice. Progress is slow, and a new approach is required. In this Personal View, a global consortium of tuberculous meningitis researchers articulate a coordinated, definitive way ahead via globally conducted clinical trials of novel drugs and regimens to advance treatment and improve outcomes for this life-threatening infection.

Figure 1. Potential regimens based on individual drug rankings.

B = bedaquiline, H = isoniazid, L = linezolid, M = moxifloxacin, O = DprE1 inhibitor, Pa = pretomanid, Rb = rifabutin, S = sutezolid, AlpE = alpibectir/ethionamide, Z = pyrazinamide, R = rifampicin (high dose), Fq = fluoroquinolone, E = ethambutol. Coloured cells relate to individual drug scores on the ranking system, indicated in Table 3: green ≥ 12; orange 9 – 11; yellow < 9; red not currently manufactured.