title: Safety and efficacy of levofloxacin versus rifampicin in tuberculous meningitis: an open-label randomized controlled trial.
abstract: OBJECTIVE
  We report the efficacy and safety of levofloxacin versus rifampicin in tuberculous meningitis (TBM).
  
  
  METHODS
  In this open-label, randomized controlled trial from India, patients with TBM diagnosed on the basis of clinical, MRI and CSF findings were included. Patients with hepatic or renal dysfunction, organ transplantation, malignancy, pregnancy, lactation, allergy, seizure, age <15 years and antitubercular treatment ≥1 month were excluded. Sixty patients each were randomized to levofloxacin (10 mg/kg, maximum 500 mg) or rifampicin (10 mg/kg, maximum 450 mg). They also received isoniazid, pyrazinamide, ethambutol, prednisolone and aspirin. The primary outcome was death and secondary outcome measures were 6 month disability, repeat MRI changes and serious adverse events (SAEs).
  
  
  RESULTS
  The median age of the patients was 34.5 (16-75) years. The baseline clinical and MRI findings were similar between the two groups. At 6 months, 13 out of 60 (21.7%) patients in the levofloxacin arm and 23 out of 60 (38.3%) patients in the rifampicin arm had died (P = 0.07). On Cox regression analysis, survival in the levofloxacin group was significantly better than in the rifampicin group (hazard ratio 2.13, 95% CI 1.04-4.34, P = 0.04). The functional outcome (P = 0.47) was, however, not significantly different between the two groups. On intention-to-treat analysis, 10 out of 47 (21.3%) in the levofloxacin arm and 5 out of 37 (13.5%) in the rifampicin arm had poor recovery. Repeat MRI findings did not differ between the groups. Levofloxacin was discontinued more frequently than rifampicin due to SAEs (16 versus 4, P = 0.01).
  
  
  CONCLUSIONS
  Levofloxacin is superior to rifampicin in reducing 6 month death in TBM but not disability. Levofloxacin may be used in TBM especially in those patients with hepatotoxicity and without seizure.
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Lucknow, India.
authors.forename: J
authors.initials: J
authors.lastname: Kalita
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Lucknow, India drukmisra@rediffmail.com ukmisra@sgpgi.ac.in.
authors.forename: U K
authors.initials: UK
authors.lastname: Misra
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Lucknow, India.
authors.forename: S
authors.initials: S
authors.lastname: Prasad
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Medical Sciences, Lucknow, India.
authors.forename: S K
authors.initials: SK
authors.lastname: Bhoi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D064704:Levofloxacin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D011718:Pyrazinamide / Q000627:therapeutic use; D011859:Radiography; D012293:Rifampin / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014390:Tuberculosis, Meningeal / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D064704:Levofloxacin; D004977:Ethambutol; D011239:Prednisolone; D001241:Aspirin; D007538:Isoniazid; D012293:Rifampin
keywords: MRI; antitubercular drugs; corticosteroids; prognosis