Source: Blood  |  Posted 5 years ago

By Paula Moyer

SAN FRANCISCO, CA -- October 4, 2006 -- Patients are hospitalized with community-acquired pneumonia have a cure rate of 89.7% when they are treated with tigecycline (Tygacil), according to investigators who presented their findings here at the 46[^]th[] Annual Meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

Noting that the cure rate is comparable to that for patients treated with levofloxacin (Levaquin), the investigators stressed the importance of identifying new agents to treat community-acquired pneumonia. Many strains are resistant to several antibiotics, noted principal investigator Gary Dukart, MD, clinical researcher, Wyeth Pharmaceuticals, Collegeville, Pennsylvania.

Tigecycline, the first glycylcycline approved for treating complicated skin and skin structure infections as well as intra-abdominal infections, had been shown in prior research to be active against Gram-positive, Gram-negative and anaerobic bacteria, as well as atypical bacteria, including several resistant strains, Dr. Dukart said.

Dr. Dukart and colleagues compare the safety and efficacy of tigecycline against the commonly used agent, levofloxacin, in two phase 3, multicenter, double-blind studies. His presentation on September 29[^]th[] combined the results of both studies.

The studies randomized hospitalized patients with community-acquired pneumonia to receive either tigecycline or levofloxacin intravenously. Tigecycline was initially started at 100 mg followed by 50 mg every 12 hours; levofloxacin was dosed at 500 mg daily or every 12 hours.

In one of the studies, physicians could switch patients to oral levofloxacin after at least 3 days of IV therapy.

The investigators wanted to determine the clinical response in clinically evaluable populations as well as in the clinical modified, intent-to-treat (c-mITT) populations as a way to test whether tigecycline was an effective cure. They also wanted to know, for the microbiologic efficacy and susceptibility to tigecycline of the bacteria that cause community-acquired pneumonia.

Of the 891 patients screened; 846 were in the c-mITT group, 424 in the tigecycline group and 422 in the levofloxacin group. Among these, 574 were clinically evaluable, 282 in the tigecycline group and 292 in the levofloxacin group.

Most patients had a baseline Fine Pneumonia Severity Index of II to IV, a severity range that encompassed 80.7% of those on tigecycline and 74.4% of those on levofloxacin in cm-ITT group.

Among the clinically evaluable patients, tigecycline cured 253 of 282 patients treated with it (89.7%); levofloxacin cured 252 of the 292 patients who received it (86.3%). The absolute difference between the two was 3.4%. This finding meant that the test for noninferiority was statistically significant for tigecycline ([]P[] < .001).

In the c-mITT group, tigecycline cured 81.0% of the 394 patients for whom data were available, and levofloxacin cured 79.7% of the 403 evaluable patients. As with the clinically evaluable group, the 1.3% absolute difference between the 2 agents' cure rates was negligible, a finding that meant the test for noninferiority was statistically significant for tigecycline ([]P[] < .001).

More patients in the tigecycline group experienced nausea than in the levofloxacin group (24.3% vs 8.3%, []P[] < .001). The tigecycline group was also more likely to experience vomiting than the levofloxacin group (16.0% vs 5.7%, []P[] < .001), as well as abdominal pain (5.7% vs 2.1%, []P[] < .05), leukocytosis (4.5% vs 1.7%, []P[] < .05).

Patients on levofloxacin were more likely to experience elevated hepatic enzymes []P[] < .01). Among these patients, 6.1% of those on tigecycline and 8.3% of those on levofloxacin discontinued due adverse events.

Wyeth Pharmaceuticals manufactures Tygacil and sponsored the study.

[Presentation title: Integrated Results of 2 Phase 3 Studies Comparing Tigecycline (TGC) With Levofloxacin (LEV) in Patients (Patients) With Community-Acquired Pneumonia. Abstract L-1450]