Integrated results of 2 phase 3 studies comparing tigecycline and levofloxacin in community-acquired pneumonia.
Tigecycline (TGC), a glycylcycline, has expanded activity against Gram-positive and Gram-negative, anaerobic, and atypical bacteria. Two phase 3 studies were conducted. Hospitalized patients with community-acquired pneumonia (CAP) were randomized to intravenous (IV) TGC (100 mg followed by 50 mg bid) or IV levofloxacin (LEV) (500 mg bid). In 1 study, patients could be switched to oral LEV after at least 3 days intravenously. The coprimary efficacy end points were as follows: clinical response in clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure (TOC). The secondary end points were as follows: microbiologic efficacy and susceptibility to TGC for CAP bacteria. Safety evaluations were included. Eight hundred ninety-one were patients screened: 846 mITT (TGC 424, LEV 422), 574 CE (TGC 282, LEV 292). Most patients had Fine Pneumonia Severity Index II to IV (80.7% TGC, 74.4% LEV, mITT). At TOC (CE), TGC cured 253/282 patients (89.7%) and LEV cured 252/292 patients (86.3%); the absolute difference of TGC-LEV was 3.4% (95% confidence interval [CI], -2.2 to 9.1, noninferior [P < 0.001]). In c-mITT, TGC cured 319/394 patients (81.0%) and LEV cured 321/403 patients (79.7%); the absolute difference of TGC-LEV was 1.3% (95% CI -4.5 to 7.1, noninferior [P < 0.001]). The drug-related adverse events (AEs) of nausea (20.8% TGC versus 6.6% LEV) and vomiting (13.2% TGC versus 3.3% LEV) were significantly higher in TGC; elevated alanine aminotransferase (2.8% TGC versus 7.3% LEV) and aspartate aminotransferase (2.6% TGC versus 6.9% LEV) were significantly higher in LEV. Discontinuations for AEs were low (TGC, 26 patients [6.1%]; LEV, 34 patients [8.1%]). TGC appeared safe and achieved cure rates similar to LEV in hospitalized patients with CAP.
Department of Internal Medicine, St. Pantelimon Clinical Emergency Hospital, Bucharest OP 22, Romania. cristina.tanaseanu@gmail.com
Cristina
C
Tanaseanu
Carlos
C
Bergallo
Osvaldo
O
Teglia
Abel
A
Jasovich
Maria Eugenia
ME
Oliva
Gary
G
Dukart
Nathalie
N
Dartois
C Angel
CA
Cooper
Hassan
H
Gandjini
Rajiv
R
Mallick
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017714:Community-Acquired Infections / Q000188:drug therapy*; D005260:Female; D016905:Gram-Negative Bacterial Infections; D006192:Haemophilus Infections / Q000188:drug therapy; D006801:Humans; D064704:Levofloxacin; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015242:Ofloxacin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011008:Pneumococcal Infections / Q000188:drug therapy; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D000078304:Tigecycline; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D000078304:Tigecycline; D015242:Ofloxacin; D008911:Minocycline