Integrated Results of 2 Phase III Studies Comparing Tigecycline with Levofloxacin in Patients with Community‐Acquired Pneumonia (CAP)

Background:

TGC, a first‐in‐class glycylcycline approved for treating complicated skin, skin structure, and intra‐abdominal infections, has an expanded spectrum of activity against gram‐positive, gram‐negative, anaerobic, and atypical bacteria, including some resistant strains. The primary objective of the study was to compare tigecycline (TGC) efficacy and safety with levofloxacin (LEV) in patients with community‐acquired pneumonia (CAP).

Methods:

In 2 phase 3, multicenter, double‐blind studies, hospitalized patients with CAP were randomized to IV TGC (100 mg initially followed by 50 mg every 12 hours) or intravenous (IV) LEV (500 mg daily or every 12 hours). In 1 study, patients could be switched to oral LEV after 3 days IV. Coprimary efficacy end points were clinical response in clinically evaluable (CE) and clinical modified intent‐to‐treat (c‐mITT) populations at test of cure (TOC). Secondary end points were microbiologic efficacy and susceptibility to TGC for bacteria that cause CAP. Safety evaluations included vital signs, lab tests, ECGs, and adverse events (AEs).

Results:

Eight hundred and ninety‐one patients were screened: 846 mITT (TGC 424, LEV 422), 574 CE (TGC 282, LEV 292). The majority of patients had a Fine Pneumonia Severity Index score of II‐IV (80.7% TGC, 74.4% LEV, mITT). At TOC (CE), TGC cured 253 of 282 patients (89.7%), LEV cured 252 of 292 patients (86.3%), with an absolute difference TGC‐LEV of 3.4% (95% CI: 2.2, 9.1, test for noninferiority [NI] P < .001). In c‐mITT, TGC cured 319 of 394 patients (81.0%), LEV cured 321 of 403 patients (79.7%), with an absolute difference TGC‐LEV of 1.3% (95% CI: 4.5, 7.1, test for NI P < .001). In ME with S. pneumoniae bacteremia, TGC cured 20 of 22 patients (90.9%), LEV cured 13 of 18 patients (72.2%), with an absolute difference TGC‐LEV of 18.7% (95% CI: 8.8, 45.6, test for NI P < .001). In m‐mITT with S. pneumoniae bacteremia, TGC cured 22 of 27 patients (81.5%), LEV cured 15 of 23 (65.2%), with absolute difference TGC‐LEV of 16.3% (95% CI: 10.5, 41.4, test for NI P < .001). For atypical pathogens, clinical cures at TOC assessments for TGC and LEV were reported for 100% (10 of 10) and 100% (6 of 6) of patients, respectively, in ME with Legionella spp.; for 94.9% (37 of 39) and 91.7% (44 of 48) of patients, respectively, in ME with Mycoplasma pneumoniae; and for 94.7% (18 of 19) and 96.3% (26 of 27) of patients, respectively, in ME with Chlamydia pneumoniae. For CE patients ≥ 65 years, TGC cured 73 of 83 patients (88%), LEV cured 77 of 94 patients (81.9%), with an absolute difference TGC‐LEV of 6.0% (95% CI: 5.7, 17.2, test for NI P < .001). The number of discontinuations because of adverse events were low, and the safety profile was similar to that seen in other tigecycline studies.

Conclusions:

TGC appeared safe and achieved cure rates similar to LEV in hospitalized patients with CAP

Author Disclosure:

G. Dukart, Wyeth Research, employee of Wyeth Research; N. Dartois, Wyeth Research, employee of Wyeth Research; C.A. Cooper, Wyeth Research, employee of Wyeth Research; H. Gandjini, Wyeth Research, employee of Wyeth Research.