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Early, intensified TB meningitis treatment decreases mortality risk
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Early and intensified medication improved survival in patients with isoniazid-resistant tuberculosis meningitis, according to researchers.
Their findings show that clinicians should quickly identify drug-resistant tuberculosis meningitis (TBM) and seek regimens to treat it, they wrote in Clinical Infectious Diseases.
“Early detection of drug-resistant TBM is key to improving outcomes,” study researcher A. Dorothee Heemskerk, MD, of the Oxford University Clinical Research Unit in Ho Chi Minh City, Vietnam, and colleagues wrote.
Their study — conducted between April 2011 and June 2014 — included 322 patients known to have drug-resistant TBM. The patients had been recruited at two hospitals in Ho Chi Minh City. Of those patients, 86 (26.7%) had isoniazid-resistant TBM, 15 (4.7%) had multidrug-resistant (MDR) TBM and one (0.3%) had rifampicin-resistant TBM. The other 220 patients (86.3%) had TBM susceptible to both isoniazid and rifampicin.
The patients were randomly assigned to receive either a standard or an intensified treatment regimen, the researchers said. Standard treatment included isoniazid (5 mg/kg/day), rifampicin (10 mg/kg/day), pyrazinamide (25 mg/kg/day) and either ethambutol (20 mg/kg/day) or streptomycin (20 mg/kg/day) for 3 months, then rifampicin and isoniazid in their original doses for 6 months.
Intensified treatment included the standard regimen with an additional 5 mg/kg/day of rifampicin and levofloxacin (20 mg/kg/day) for the first 8 weeks of treatment. Clinicians also adjusted regimens for certain types of TBM infections as needed.
In all, 90 patients (28%) died during a 9-month follow-up period. They included 27 of the 86 (31.4%) who had isoniazid-resistant TBM, 11 of 16 (68.8%) with MDR or rifampicin-resistant TBM and 52 of 220 (23.6%) with isoniazid- and rifampicin-susceptible TBM.
The researchers found that the following were independent predictors of death: HIV infection (HR = 2.6; P < .001), disease severity grade 2 compared with grade 1 (HR = 1.07), grade 3 compared with grade 1 (HR = 4.53; overall P < .001), and MDR infection (HR = 5.91; P < .001).
Intensified treatment significantly reduced the chance of death in patients with isoniazid-resistant TBM compared with standard treatment (HR = 0.45; P = .06). Intensified treatment was also more effective for those patients in avoiding the combined outcome of death or new neurological event — the occurrence of coma, deterioration of consciousness, seizures, cerebral herniation or other complications (HR = 0.60; P = .09), the researchers said.
Additionally, intensified treatment was more effective in HIV–uninfected patients with isoniazid-resistant TBM than in those with the virus. One of 22 (4.6%) HIV–uninfected patients undergoing intensified treatment died, compared with six of 17 (35.3%) in the standard treatment arm (HR = 0.11; P = .04).
Yet among patients with HIV, 10 of 23 (43.5%) in the intensified treatment arm died, compared with 10 of 24 (41.7%) in the standard treatment arm. – by Joe Green
Disclosure: The authors report no relevant financial disclosures.
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