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

Abstract Background: Therapy of nosocomial pneumonia is usually empiric and includes ≥ 1 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 1 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 [SD] 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.