OU PHYSICIAN FINDS PROMISE IN STUDY OF NOVEL INJECTABLE ANTIBIOTIC

Results in Treatment of Hospital Patients with Complicated Skin Infections Reported in Clinical Therapeutics

An antibiotic, currently being tested in clinical trials, produced a 74 percent cure rate for hospitalized patients with possibly life-threatening, complicated skin and skin structure infections (cSSSI). Tigecycline, a candidate antibiotic drug, produced these promising results in a study led by Russell G. Postier, M.D., OU Physicians Chairman of Surgery and John A. Schilling Professor of Surgery at the University of Oklahoma College of Medicine.

"Tigecycline displayed promising efficacy against a wide spectrum bacteria commonly related to complicated skin infections, with an acceptable safety profile. These data warrant further investigation in blinded comparator clinical trials, said Postier, John A. Schilling Professor and chairman of surgery, OU Physicians and the study’s principle investigator. Results of the multicenter, phase 2 will be published in the May 2004, issue of Clinical Therapeutics.

In the study, 85 percent of patients who received 50-milligram (mg) doses of tigecycline were cured at the end of their seven- to 14-day treatment, and 74 percent were cured at the test-of-cure visit (the study’s primary outcome measure), about 21 days after their initial dose of tigecycline. Similarly, 78 percent of patients on the 25-mg doses were cured at the end of treatment, and 67 percent at the test-of-cure visit. The decline in rates directly resulted from patients receiving either additional antibiotics or surgery between the end of their treatments and their test-of-cure visits.
The 50 mg group also had a higher overall bacterial eradication rate at the end of therapy, 74 percent, than the 62 percent rate of the 25 mg group. At the test-of-cure visit, the rates were 70 and 56, respectively. Additionally, the trial used laboratory tests to document tigecycline activity against particular bacterial strains found in patients at the study start, including strains of Staphylococcus aureus that are resistant or susceptible to the antibiotic methicillin, MRSA and MSSA, respectively, as well as Escherichia coli, Enterococcus faecalis and Enterococcus faecium. This study was sponsored by Wyeth Pharmaceuticals, the developer of tigecycline. Phase 3 clinical trials using tigecycline for this indication will finish in 2004.
Virtually all important bacteria have developed resistance to one or more classes of antibiotics, which has critical public health consequences, Postier explains. Future antibiotics will need to be active broadly, not just against the usual "suspects" –frequently seen disease-causing bacteria--but also against new strains, particularly those with resistance.

Bacterial-caused cSSSI can result in death rates of up to 75 percent. Many bacterial strains infect skin, and the most common are Staphylococcus and Streptococcus, but less common bacterial strains can cause cSSSI, particularly in hospitalized patients. In the trial, the investigators tested tigecycline in hospitalized cSSSI patients. Their infections involved deeper soft tissue or required significant surgery and included infected ulcers (35 percent), burns, or bites; major abscesses (31 percent); and superficial infections or abscesses with a high risk of infection by anaerobic or gram-negative bacteria.

In previous laboratory studies, tigecycline demonstrated effectiveness in treatments for disease-causing bacteria, including MRSA and MSSA strains, E. coli, E. faecalis and E. faecium. Tigecycline, a novel glycylcycline, acts by inhibiting protein synthesis and cell growth in bacteria.

Postier’s coinvestigators include Stephen L. Green, M.D., of Hampton Roads Medical Specialists in Virginia; Stanley R. Klein, M.D., of the Harbor-University of California Los Angeles Medical Center; and Evan Loh, M.D., and E. J. Ellis-Grosse, Ph.D., of Wyeth Research. The trial was funded by Wyeth, which is conducting phase 3 trials of tigecycline for patients with complicated skin and skin structure infections, complicated intra-abdominal infections, multidrug resistant pathogens and pneumonia infections.