Giuseppe
Emeritus
[Source: Antimicrobial Agents and Chemotherapy, full text: (LINK). Abstract, edited.]
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A Randomized Phase 2 Trial to Evaluate the Clinical Efficacy of Two High Tigecycline Dosage Regimens Versus Imipenem/Cilastatin in Hospital-Acquired Pneumonia
Julio Ramirez 1,*, Nathalie Dartois 2, Hassan Gandjini 2, Jean Li Yan 3, Joan Korth-Bradley 3 and Paul C. McGovern 3
Author Affiliations: <SUP>1</SUP>University of Louisville, Louisville, Kentucky <SUP>2</SUP>Pfizer Inc, Paris, France <SUP>3</SUP>Pfizer Inc, Collegeville, Pennsylvania
ABSTRACT
In a previous phase 3 study, lower cure rates occurred in patients with hospital-acquired pneumonia treated with tigecycline at the approved dose compared with those treated with 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 hours or 200 mg followed by 100 mg every 12 hours) or 1 gram of imipenem/cilastatin every 8 hours. Empiric adjunctive therapy was administered for initial coverage of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, depending on the randomization regimen. Clinical response, defined as cure, failure, 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 compared 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/MIC ratio may be necessary to achieve clinical cure in patients with hospital-acquired pneumonia. Further studies are necessary.
FOOTNOTES
*Corresponding author. Mailing address: Division of Infectious Diseases, University of Louisville Health Outpatient Center, 401 East Chestnut Street, Ste. 310, Louisville, KY 40202. Phone: (502) 852-5131. Fax: (502) 852-1147.E-mail: j.ramirez@louisville.edu.
Copyright ? 2013, American Society for Microbiology. All Rights Reserved.
-Julio Ramirez 1,*, Nathalie Dartois 2, Hassan Gandjini 2, Jean Li Yan 3, Joan Korth-Bradley 3 and Paul C. McGovern 3
Author Affiliations: <SUP>1</SUP>University of Louisville, Louisville, Kentucky <SUP>2</SUP>Pfizer Inc, Paris, France <SUP>3</SUP>Pfizer Inc, Collegeville, Pennsylvania
ABSTRACT
In a previous phase 3 study, lower cure rates occurred in patients with hospital-acquired pneumonia treated with tigecycline at the approved dose compared with those treated with 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 hours or 200 mg followed by 100 mg every 12 hours) or 1 gram of imipenem/cilastatin every 8 hours. Empiric adjunctive therapy was administered for initial coverage of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, depending on the randomization regimen. Clinical response, defined as cure, failure, 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 compared 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/MIC ratio may be necessary to achieve clinical cure in patients with hospital-acquired pneumonia. Further studies are necessary.
FOOTNOTES
*Corresponding author. Mailing address: Division of Infectious Diseases, University of Louisville Health Outpatient Center, 401 East Chestnut Street, Ste. 310, Louisville, KY 40202. Phone: (502) 852-5131. Fax: (502) 852-1147.E-mail: j.ramirez@louisville.edu.
Copyright ? 2013, American Society for Microbiology. All Rights Reserved.
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