Towards Improved Treatment Outcomes for Tuberculosis Meningitis - Rethinking the Regimen

Tuberculosis (TB) ranks as the second leading cause of death from an infectious disease worldwide. TB meningitis (TBM) is the most destructive extra-pulmonary form of TB. The current recommended treatment prevents death or disability in less than half of the patients. TB meningitis still represents an important problem by contributing to a huge number of years of life lost. The management of TBM remains a big challenge. In this context, this manuscript discusses anti TB drugs and treatment regimens that make a difference in the treatment outcomes of TBM considering the pharmacokinetics parameters of anti TB drugs with special reference to the Blood-Brain Barrier (BBB) which is unique to Central Nervous System (CNS). It was observed that generally the treatment outcomes are poor with the recommended regimens (mortality rate ranging from 6.3 to 48.1%). In view of the poor treatment outcomes with standard regimens, different studies were carried out to strengthen the regimen and improve the treatment outcomes by using different interventions. Most of the studies did not show a significant improvement in reducing mortality. There is an urgent need to rethink TBM treatment regimens and to strengthen it considering the following factors: PK parameters of the anti TB drugs including their ability to penetrate the BBB and drugs that achieve good CSF concentrations, drugs that achieve CSF concentrations above the MIC value, considering new drugs, retooling old drugs, using second line drugs for TBM as first line drugs, and modifying the host response. In the management of TBM we need clinical trials to evaluate the efficacy of regimens containing drugs like isoniazid, pyrazinamide, levofloxacin, linezolid, ethionamide, rifampicin and injectable aminoglycoside and trials are also needed to assess the optimum duration of treatment.