Levofloxacin compared with imipenem/cilastatin followed by ciprofloxacin in adult patients with nosocomial pneumonia: A multicenter, prospective, randomized, open-label study

Background: Therapy of nosocomial pneumonia is usually empiric and includes greater than or equal to1 broad-spectrum antimicrobial agent. When considering the use of fluoroquinolones in these difficult-to-treat infections-in which drug delivery to the site of infection may be impaired or organisms with higher minimum inhibitory concentrations may be present-an agent should be chosen whose pharmacodynamics ensure maximal drug exposure. Use of the 750-mg dose of levofloxacin should enhance therapeutic benefit in patients with nosocomial pneumonia. Objective: The goal of this study was to compare the efficacy and safety of levofloxacin 750 mg and imipenem/cilastatin followed by ciprofloxacin in adult patients with nosocomial pneumonia. Methods: This was a multicenter, prospective, randomized, open-label trial conducted in North America. Patients were randomly assigned to I of 2 treatment arms: levofloxacin 750 mg QD given IV and then orally for 7 to 15 days or imipenem/cilastatin 500 mg to 1 g IV every 6 to 8 hours, followed by oral ciprofloxacin 750 mg every 12 hours for 7 to 15 days. Adjunctive antibacterial therapy was mandatory in patients with documented or suspected Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus infection. The primary predefined outcome measure was the clinical response (cure, improvement, failure, or unable to evaluate) in microbiologically evaluable patients 3 to 15 days after the end of therapy Results: The study enrolled 438 adult patients (315 men, 123 women; mean [SDI age, 55.7 [20.04] years). Two hundred twenty patients received levofloxacin, and 218 received the comparator regimen. Demographic and baseline clinical characteristics were similar in the intent-to-treat and clinically evaluable populations. In patients evaluable for microbiologic efficacy, clinical success (cure or improvement) was achieved in 58.1% (54/93) of patients who received levofloxacin, compared with 60.6% (57/94) of patients who received the comparator regimen (95% CI, -12.0 to 17.2). Similar clinical results were seen in patients evaluable for clinical efficacy and in the intent-to-treat population. In the 187 patients evaluable for microbiologic efficacy, eradication was achieved in 66.7% (62/93) of patients receiving levofloxacin and 60.6% (57/94) of patients receiving the comparator regimen (95% CI, -20.3 to 8.3). Conclusion: In this study, levofloxacin was at least as effective and was as well tolerated as imipenem/cilastatin followed by ciprofloxacin in adult patients with nosocomial pneumonia, as demonstrated by comparable clinical and microbiologic success rates. (Clin Ther 2003;25:485-506) Copyright (C) 2003 Excerpta Medica, Inc.