Better treatments are needed for tuberculous meningitis (TBM), which leads to mortality in excess of 50%. Linezolid penetrates into cerebrospinal fluid and is effective against TB. Little is known about its use in often critically ill TBM patients.
Persons with HIV (PWH) with definite or suspected TBM were recruited from a rural hospital in southwestern Uganda. Participants were seen on day 2, weeks 1, 2, 4, 8, 12, 18, and 24 for symptom assessment, medication adherence, physical examination, visual testing, neuropathy screening, and/or safety labs.
Of 23 participants enrolled (52% women, mean age 37 years, 78% with moderate to severe TBM grade), 12 were allocated to linezolid. Median CD4 count was 150 cells/mm3, (IQR 81-331) and 7 were on anti-retroviral therapy (ART). Twelve serious adverse events (SAEs) occurred, 6 among those on linezolid. The six included, sepsis (n=2), aspiration pneumonia (n=1), ART-related Stevens-Johnson syndrome (n=1), dehydration (n=1), and hyponatremia (n=1). Seven participants died, 2 on linezolid. No SAE was determined to be related to linezolid. No participants required linezolid discontinuation or dose reduction. Three participants developed >grade 3 hyponatremia. No >grade 3 anemia, thrombocytopenia, or neutropenia occurred. Mild grade 1 or 2 neuropathy symptoms were reported, more commonly among linezolid recipients (55% versus 0%, p=0.025), but resolved after treatment ended.
In this preliminary analysis, linezolid was generally safe and well tolerated in TBM patients. Data from the completed trial will increase the power to determine if linezolid is safe to use with high and standard dose rifampin in PWH and TBM.