SAN FRANCISCO — Tigecycline appeared to be comparable in efficacy and tolerability to levofloxacin in treating community-acquired pneumonia in two phase III studies of 891 hospitalized patients needing intravenous therapy, Dr. Gary Dukart reported in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
If approved, tigecycline would be the first glycylcycline available to treat pneumonia, said Dr. Dukart of Wyeth Research, Collegeville, Pa., and his associates. Wyeth markets the drug, which is approved in 40 countries including the United States, for treating complicated intra-abdominal infections and complicated skin and skin structure infections. Tigecycline is a broad-spectrum antibiotic with in vitro activity against gram-positive, gram-negative, anaerobic, and atypical bacteria, including some resistant strains.
A separate study of tigecycline therapy for hospital-acquired pneumonia is ongoing. Once that is complete, the company plans to apply in 2007 for approval of tigecycline to treat community or hospital-acquired pneumonias, he said.
Patients in the multicenter, double-blind studies of community-acquired pneumonia were randomized to 7–10 days of intravenous tigecycline (100 mg initially, then 50 mg every 12 hours) or intravenous levofloxacin. Levofloxacin dosages differed in the two trials: In one, patients received 500 mg every 24 hours; in the other, they got 500 mg every 12 or 24 hours at the discretion of the physician and based on local practice. In one trial, patients who showed improvements could be switched after at least 3 days of intravenous therapy to oral levofloxacin for the duration of therapy.
The mean duration of treatment in both groups was 10 days. The mean hospital stay in both groups was 6 days.
Among 846 patients who received at least one dose of medication (a modified intent-to-treat population), 81% on tigecycline and 80% on levofloxacin were considered cured. Among 574 “evaluable” patients assessed for cure between 7 and 23 days after the last dose of medication, 90% in the tigecycline group and 86% in the levofloxacin group were cured. The differences between groups were not significant.
Among 40 patients with pneumonia due to documented Streptococcus pneumoniae infection, tigecycline cured 20 (91%) of 22 patients and levofloxacin cured 13 (72%) of 18.
The rate of drug discontinuation because of side effects did not differ significantly between groups—6% with tigecycline and 8% with levofloxacin. Serious adverse events occurred in 10% with tigecycline and 11% with levofloxacin. In each group, 3% of patients died, but the deaths were not considered related to the drugs.
Drug-related adverse events affected 48% on tigecycline and 37% on levofloxacin, a significant difference. A significantly greater proportion of patients in the tigecycline group experienced nausea or vomiting (24% and 16%, respectively), compared with the levofloxacin group (6% and 3%). Patients in the tigecycline group were significantly less likely to have elevated ALT or AST levels (3% and 2%), compared with the levofloxacin group (6% and 6%).
Other common side effects were comparable between groups and included diarrhea, phlebitis, or headache in 3%–8% of patients.
The studies excluded patients needing ICU care at the time of randomization, patients hospitalized in the previous 2 weeks, residents of long-term care facilities for longer than 2 weeks, and patients with known or suspected Pseudomonas aeruginosa infection, active tuberculosis, or Legionella pneumonia.
About 6 million Americans get community-acquired pneumonia each year, leading to 1 million hospitalizations annually. About 12% of patients hospitalized for the disease die.
The conference was sponsored by the American Society for Microbiology.