Comparison of tigecycline with imipenem/cilastatin for the treatment of hospital-acquired pneumonia.
To compare efficacy and safety of a tigecycline regimen with an imipenem/cilastatin regimen in hospital-acquired pneumonia patients, a phase 3, multicenter, randomized, double-blind, study evaluated 945 patients. Coprimary end points were clinical response in clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure. Cure rates were 67.9% for tigecycline and 78.2% for imipenem (CE patients) and 62.7% and 67.6% (c-mITT patients), respectively. A statistical interaction occurred between ventilator-associated pneumonia (VAP) and non-VAP subgroups, with significantly lower cure rates in tigecycline VAP patients compared to imipenem; in non-VAP patients, tigecycline was noninferior to imipenem. Overall mortality did not differ between the tigecycline (14.1%) and imipenem regimens (12.2%), although more deaths occurred in VAP patients treated with tigecycline than imipenem. Overall, the tigecycline regimen was noninferior to the imipenem/cilastatin regimen for the c-mITT but not the CE population; this difference appears to have been driven by results in VAP patients.
Freire
Antonio T
AT
Santa Casa de Misericórdia de Belo Horizonte, Santa Efigênia, Belo Horizonte-MG, Brazil.
Melnyk
Vasyl
V
Kim
Min Ja
MJ
Datsenko
Oleksiy
O
Dzyublik
Oleksandr
O
Glumcher
Felix
F
Chuang
Yin-Ching
YC
Maroko
Robert T
RT
Dukart
Gary
G
Cooper
C Angel
CA
Korth-Bradley
Joan M
JM
Dartois
Nathalie
N
Gandjini
Hassan
H
D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy; D015377:Cilastatin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000077728:Cilastatin, Imipenem Drug Combination; D003428:Cross Infection / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D004338:Drug Combinations; D017052:Hospital Mortality; D006801:Humans; D015378:Imipenem / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D011014:Pneumonia / Q000188:drug therapy* / Q000401:mortality; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy / Q000401:mortality; D000078304:Tigecycline; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D015377:Cilastatin; D000078304:Tigecycline; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D008911:Minocycline