WASHINGTON — Tigecycline, a novel broad-spectrum antibiotic, appears effective in treating a variety of serious infections, including those caused by resistant organisms, Evan Loh, M.D., said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
Wyeth's tigecycline, the first of the glycylcycline class, is a modification of the minocycline molecule designed specifically to overcome two major bacterial resistance mechanisms. It has activity against gram-positive, gram-negative, atypical, anaerobic, and antibiotic-resistant bacteria. Phase III data thus far demonstrate efficacy in the treatment both complicated intraabdominal infections and skin/skin structure infections, said Dr. Loh, vice president, cardiovascular/infectious disease, Wyeth Research, Collegeville, Pa.
“This agent offers a broad spectrum of activity that offers an exciting opportunity for physicians to consider as empiric therapy when individuals with serious infections present in the hospital setting,” he said in a symposium at the meeting.
In late-breaker poster presentations, Nathalie Dartois, M.D., of Wyeth Research in Paris reported data from two phase III clinical trials. Tigecycline monotherapy was compared with the combination imipenem/cilastatin (IMI/CIS) regimen (Primaxin) in 817 adult patients with a wide variety of complicated intraabdominal infections, including appendicitis with perforation and abscess (41%), cholecystitis with evidence of perforation or empyema (22%), postoperative intraabdominal abscess (11%), and intestinal perforation with abscess or fecal contamination (9%). The patients were predominantly white (88%) and male (59%), with a mean age of 49 years.
Of the total 523 microbiologically evaluable cases, 265 were treated with tigecycline in an initial intravenous dose of 100 mg, followed by 50 mg every 12 hours in 100 mL saline over 30 minutes, followed 6 hours later by 100 mL normal saline placebo infused over 30 minutes for an average duration of 7.7 days. The other 258 patients received IMI/CIS every 6 hours in a volume of 100 mL normal saline for a mean duration of 7.8 days.
Clinical cure, assessed at 12–44 days after the last dose, was achieved in 91% of the tigecycline subjects and 90% of the IMI/CIS group, Dr. Dartois reported.
Safety profiles were also similar between the two regimens, with adverse events reported by a total of 60% of the tigecycline and 59% of IMI/CIS subjects. Nausea was the most common, reported by 18% of the tigecycline group and 13% with IMI/CIS. Vomiting occurred in 13% and 9%, respectively. The findings demonstrate “noninferiority” to the combination regimen, she said.
In the other trial, tigecycline was compared with combination vancomycin/aztreonam (V/A) in 543 adults with skin and skin structure infections, including 324 with deep soft tissue infections, 308 with cellulitis (many had both), 157 with major abscesses, 44 with infected ulcers, and 17 with burns.
Tigecycline was given in an initial intravenous dose of 100 mg, followed by 50 mg every 12 hours in 250 mL normal saline over 60 minutes, then 100 mL normal saline placebo over 60 minutes. The V/A group received an initial 1-g intravenous vancomycin dose in 250 mL normal saline over 60 minutes, followed by 2 g aztreonam in 100 mL normal saline over 60 minutes every 12 hours.
Clinical cure at 14–90 days after the last dose was achieved in 90% of 223 tigecycline patients (ranging from 83% for the ulcers to 100% among the burns), compared with 94% of the 213 treated with V/A (92% of soft tissue infections to 100% ulcers and burns). Among the total 312 patients for whom results were microbiologically evaluable, the eradication rate was 85% for tigecycline and 93% for V/A, she said.
Adverse events were reported by 52% with tigecycline and 44% for V/A. Nausea and vomiting were significantly more frequent with tigecycline than V/A (25% and 12% vs. 5% and 2%), while rash was more common with V/A (4% vs. 1%).