Randomized phase 2 trial to evaluate the clinical efficacy of two high-dosage
tigecycline regimens versus imipenem-cilastatin for treatment of
hospital-acquired pneumonia.
Author(s): Ramirez J(1), Dartois N, Gandjini H, Yan JL, Korth-Bradley J, McGovern PC.
Affiliation(s): Author information:
(1)University of Louisville, Louisville, Kentucky, USA. j.ramirez@louisville.edu
Publication date & source: 2013, Antimicrob Agents Chemother. , 57(4):1756-62
In a previous phase 3 study, the cure rates that occurred in patients with
hospital-acquired pneumonia treated with tigecycline at the approved dose were
lower than those seen with patients treated with imipenem and cilastatin
(imipenem/cilastatin). We hypothesized that a higher dose of tigecycline is
necessary in patients with hospital-acquired pneumonia. This phase 2 study
compared the safety and efficacy of two higher doses of tigecycline with
imipenem/cilastatin in subjects with hospital-acquired pneumonia. Subjects with
hospital-acquired pneumonia were randomized to receive one of two doses of
tigecycline (150 mg followed by 75 mg every 12 h or 200 mg followed by 100 mg
every 12 h) or 1 g of imipenem/cilastatin every 8 h. Empirical adjunctive therapy
was administered for initial coverage of methicillin-resistant Staphylococcus
aureus and Pseudomonas aeruginosa infection, depending on the randomization
regimen. Clinical response, defined as cure, failure of treatment, or
indeterminate outcome, was assessed 10 to 21 days after the last day of therapy.
In the clinically evaluable population, clinical cure with tigecycline 100 mg
(17/20, 85.0%) was numerically higher than with tigecycline 75 mg (16/23, 69.6%)
and imipenem/cilastatin (18/24, 75.0%). No new safety signals with the high-dose
tigecycline were identified. A numerically higher clinical response was observed
with the 100-mg dose of tigecycline. This supports our hypothesis that a higher
area under the concentration-time curve over 24 h in the steady state divided by
the MIC (AUC/MIC ratio) may be necessary to achieve clinical cure in patients
with hospital-acquired pneumonia. Further studies are necessary. (The
ClinicalTrials.gov identifier for this clinical trial is NCT00707239.).
|