Safety and efficacy of levofloxacin versus rifampicin in tuberculous meningitis: an open-label randomized controlled trial.

Abstract

OBJECTIVES:

We report the efficacy and safety of levofloxacin versus rifampicin in tuberculous meningitis (TBM).

PATIENTS AND 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: J Kalita, U K Misra, S Prasad, S K Bhoi
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 69 Issue 8 Pg. 2246-51 (Aug 2014) ISSN: 1460-2091 [Electronic] England
• PMID: 24752957 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Antitubercular Agents
• Pyrazinamide
• Levofloxacin
• Ethambutol
• Prednisolone
• Aspirin
• Isoniazid
• Rifampin

Topics

• Adolescent
• Adult
• Aged
• Antitubercular Agents (therapeutic use)
• Aspirin (therapeutic use)
• Drug Therapy, Combination
• Ethambutol (therapeutic use)
• Female
• Humans
• Isoniazid (therapeutic use)
• Levofloxacin (adverse effects, therapeutic use)
• Male
• Middle Aged
• Prednisolone (therapeutic use)
• Pyrazinamide (therapeutic use)
• Radiography
• Rifampin (adverse effects, therapeutic use)
• Treatment Outcome
• Tuberculosis, Meningeal (diagnostic imaging, drug therapy, mortality)
• Young Adult