Tigecycline versus levofloxacin for the treatment of community-acquired pneumonia: European experience.
Tigecycline (TGC), a first-in-class glycylcycline that has been approved for treating complicated skin and skin structure infections and complicated intra-abdominal infections, has an expanded spectrum of activity against Gram-positive, Gram-negative, anaerobic, and atypical bacteria, including resistant strains. The purpose of this study was to compare the efficacy and safety of TGC with levofloxacin (LEV) in adult hospitalised patients with community-acquired pneumonia (CAP) in a randomised, doubleblind, phase 3 multinational trial. This analysis evaluated TGC efficacy and safety in the European region. Hospitalised patients from 53 centres in 18 countries received 7-14 days of i.v. TGC (100-mg loading dose followed by 50 mg every 12 hours) or i.v. LEV (500 mg once or twice daily). Co-primary efficacy endpoints were clinical response in clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure (TOC). Results indicated that 358 patients received at least 1 dose of study medication (mITT: TGC 177, LEV 181), 245 were CE (TGC 125, LEV 120). Demographics were similar in both groups and the majority of patients had a Fine Pneumonia Severity Index of II to IV (84.4% TGC, 78.2% LEV, mITT). At TOC (CE), TGC cured 112/125 patients (89.6%; 95% CI 82.9, 94.3) and LEV cured 103/120 patients (85.8%; 95% CI 78.3, 91.5), absolute difference of TGC-LEV 3.8% (95% CI -5.3, 12.8; test for noninferiority p<0.001). For those CE patients with a Fine score of <III or III/IV, TGC cured 90.0% and 88.9%, and LEV cured 88.5% and 83.6%, respectively. In c-mITT, TGC cured 146/173 patients (84.4%; 95% CI 78.1, 89.5) and LEV cured 142/173 patients (82.1%; 95% CI 75.5, 87.5), absolute difference of TGC-LEV 2.3% (95% CI 6.1, 10.8; test for noninferiority p<0.001). In c-mITT patients with a Fine score of <III or III/IV, TGC cured 86.3% and 81.9%, and LEV cured 80.7% and 83.1%, respectively. Both regimens were generally well tolerated with only a few patients being withdrawn from the study because of any adverse event (3; 1.6% TGC versus 2, 1.1% LEV). The authors concluded that TGC was safe and efficacious in patients hospitalised with CAP, achieving similar efficacy to that of the comparator.
Dartois
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N
Wyeth Research, Paris, France. dartoin@wyeth.com
Castaing
N
N
Gandjini
H
H
Cooper
A
A
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017714:Community-Acquired Infections / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D006801:Humans; D007390:International Agencies; D064704:Levofloxacin; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008911:Minocycline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015242:Ofloxacin / Q000627:therapeutic use*; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D011446:Prospective Studies; D012449:Safety; D000078304:Tigecycline; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D000078304:Tigecycline; D015242:Ofloxacin; D008911:Minocycline