title: Safety and efficacy of additional levofloxacin in tuberculous meningitis: A randomized controlled pilot study.
abstract: Levofloxacin is an effective bactericidal category III antitubercular drug. There is paucity of studies comparing the role of additional levofloxacin to standard antitubercular regimen in the patients with tuberculous meningitis (TBM).
  
  
  
  To compare the safety and efficacy of adding levofloxacin to standard four drug ATT regimen (RHZE).
  
  
  
  The patients with TBM diagnosed on the basis of clinical, cerebrospinal fluid (CSF) and MRI criteria were included. Children below 15 years, patients with pregnancy, seizures, liver failure, kidney failure and malignancy were excluded. The baseline clinical, CSF and MRI characteristics were noted and consciousness was evaluated by Glasgow Coma Scale (GCS). The patients were randomized to RHZE (rifampicin, isoniazid, pyrazinamide and ethambutol) and RHZEL (RHZE and levofloxacin) groups. Outcome was defined at 6 months. Primary outcome was death and secondary outcomes were disability as assess by Barthel Index score and adverse events.
  
  
  
  Out of 110 TBM patients screened, 57 fulfilled the inclusion criteria. Their median age was 35 (15-75) years. 29 patients received RHZEL and 28 RHZE. The baseline clinical, biochemical and MRI characteristics were similar in the two groups. At 6 months, 11 (19.3%) patients died, 38 (66.7%) had good and 7 (12.3%) poor outcome. There was insignificant survival benefit in RHZEL group compared to RHZE (HR-2.61, 95% CI 0.73-9.36, P = 0.14), 25% patients died in RHZE where as 13.8% in RHZEL group. The disability was not significantly different between the two groups. The composite side effects were also similar between the two groups except for a higher frequency of seizure in RHZEL group (5 Vs 0) which resulted in withdrawal of levofloxacin.
  
  
  
  There was insignificant survival benefit in RHZEL which was associated with high frequency of seizures.
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow 226014, Uttar Pradesh, India.
authors.forename: J
authors.initials: J
authors.lastname: Kalita
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow 226014, Uttar Pradesh, India.
authors.forename: S K
authors.initials: SK
authors.lastname: Bhoi
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow 226014, Uttar Pradesh, India.
authors.forename: S
authors.initials: S
authors.lastname: Betai
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow 226014, Uttar Pradesh, India. Electronic address: drukmisra@gmail.com.
authors.forename: U K
authors.initials: UK
authors.lastname: Misra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004185:Disability Evaluation; 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; D010865:Pilot Projects; D016016:Proportional Hazards Models; D011718:Pyrazinamide / Q000627:therapeutic use; D012293:Rifampin / Q000627:therapeutic use; D012640:Seizures / Q000139:chemically induced; D013997:Time Factors; D016896:Treatment Outcome; D014390:Tuberculosis, Meningeal / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D064704:Levofloxacin; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin
keywords: Immune reconstitution inflammatory syndrome; Levofloxacin; MRI; Outcome; Paradoxical response; Quinolone; Tuberculous meningitis