Results of a multicenter, randomized, open-label efficacy and safety study of two doses of tigecycline for complicated skin and skin-structure infections in hospitalized patients.

BACKGROUND: Tigecycline is a broad-spectrum glycylcycline antibiotic being investigated for the treatment of serious infections in hospitalized patients. Tigecycline has been shown to be efficacious against serious infections in animals, and preliminary studies in healthy adults have shown that tigecycline has an acceptable tolerability profile. OBJECTIVE: This study compared the clinical and microbiological efficacy, pharmacokinetic properties, and tolerability of 2 doses of tigecycline in hospitalized patients with a complicated skin and skin-structure infection (cSSSI). METHODS: This Phase II, randomized, open-label study was conducted between September 1999 and March 2001 at 14 investigative centers across the United States. Patients were randomized to receive tigecycline 25 or 50 mg IV q12h for 7 to 14 days. The primary efficacy end point was the clinically observed cure rate among clinically evaluable (CE) patients at the test-of-cure visit. Secondary end points were the clinical cure rate at the end of treatment and bacteriologic response in microbiologically evaluable (ME) patients. Also, in vitro tests of susceptibility to tigecycline were performed for selected pathogens known to cause skin infections, including methicillin-resistant and methicillin-susceptible Streptococcus pyogenes, Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, and Enterococcus faecium. Tolerability assessments also were conducted. RESULTS: A total of 160 patients received > or =1 dose of tigecycline; 109 patients were CE, and 91 were ME. The majority of patients (74%) were men, and the mean (SD) age was 49.0 (14.8) years. At the test-of-cure visit, the clinical cure rate in the 25-mg group was 67% (95% CI, 53.3%-79.3%) and in the 50-mg group was 74% (95% CI, 60.3%-85.0%). In the 25-mg group, 56% of the patients had eradication (95% CI, 40.0%-70.4%) of the pathogens compared with 69% (95% CI, 54.2%-82.3%) in the 50-mg group. Values for the minimum concentration of tigecycline that is inhibitory for 90% of all isolates ranged from 0.06 to 0.50 microg/mL for the selected pathogens. Both tigecycline doses were generally well tolerated. Nausea and vomiting were the most common adverse events. CONCLUSIONS: In this study, tigecycline appeared efficacious and showed a favorable pharmacokinetic profile and an acceptable safety profile in the treatment of hospitalized patients with cSSSI. In patients who received 50-mg doses of tigecycline q12h, the clinical cure rates and microbial eradication rates were 74% and 70%, respectively, and were 67% and 56% in patients who received 25-mg doses.