Efficacy and safety of tigecycline versus levofloxacin for community-acquired pneumonia

Abstract

Background: Tigecycline, an expanded broad-spectrum glycylcycline, exhibits in vitro activity against many common pathogens associated with community-acquired pneumonia (CAP), as well as penetration into lung tissues that suggests effectiveness in hospitalized CAP patients. The aim of the present study was to compare the efficacy and safety of intravenous (IV) tigecycline with IV levofloxacin in hospitalized adults with CAP.

Methods: In this prospective, double-blind, non-inferiority phase 3 trial, eligible patients with a clinical diagnosis of CAP supported by radiographic evidence were stratified by Fine Pneumonia Severity Index and randomized to tigecycline or levofloxacin for 7-14 days of therapy. Co-primary efficacy endpoints were clinical response in the clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure (Day 10-21 post-therapy).

Results: Of the 428 patients who received at least one dose of study drug, 79% had CAP of mild-moderate severity according to their Fine score. Clinical cure rates for the CE population were 88.9% for tigecycline and 85.3% for levofloxacin. Corresponding c-mITT population rates were 83.7% and 81.5%, respectively. Eradication rates for Streptococcus pneumoniae were 92% for tigecycline and 89% for levofloxacin. Nausea, vomiting, and diarrhoea were the most frequently reported adverse events. Rates of premature discontinuation of study drug or study withdrawal because of any adverse event were similar for both study drugs.

Conclusion: These findings suggest that IV tigecycline is non-inferior to IV levofloxacin and is generally well-tolerated in the treatment of hospitalized adults with CAP.

Trial registration: NCT00081575.

Figure 1

Flow diagram: disposition of patients. Patients randomized were included in the intent-to-treat (ITT) population. Those who received at least one dose of study drug comprised the modified ITT (mITT) population, and patients in the mITT population who had clinical evidence of CAP by meeting the minimal disease criteria made up the clinical modified ITT (c-mITT) population. The microbiologic modified intent-to-treat (m-mITT) population consisted of c-mITT subjects who had 1 or more baseline isolates identified. Patients in the c-mITT population were considered to be clinically evaluable (CE) if they satisfied inclusion and exclusion criteria, received no more than one dose of a non-once daily non-study antibacterial agent (single agent or combination therapy) to treat the current episode of CAP before the first dose of study drug, did not receive other concomitant systemic antimicrobial therapy unless a treatment failure, received at least 2 full days of study drug if clinical failure or 5 full days of study drug if clinical cure, were adherent with therapy (i.e., ≥ 80% but ≤ 120% of medication administered), had an assessment of cure or failure at the test-of-cure visit (10-21 days after the last dose of therapy), and the study blind was maintained. The microbiologically evaluable (ME) population included CE patients for whom at least one isolate was identified from the baseline culture that was susceptible to both test drugs and who had a microbiologic response that could be classified as eradication, persistence, or superinfection at the test-of-cure visit.