January 2004 - A clinical trial involving 371 patients in eight countries shows that linezolid, a new antibiotic, is at least as effective as two older therapies for treating diabetic foot infections. The drug may be an important new agent for doctors treating infections that are increasingly caused by bacteria resistant to standard antibiotics, and that in severe cases may require amputation. The study, led by a Department of Veterans Affairs (VA) physician and conducted at 30 U.S. and 15 European sites, appears in the current issue of Clinical Infectious Diseases.
Foot infections are among the most serious complications of diabetes, and a leading cause of diabetes-related hospitalizations. The infections typically occur when pathogens--usually gram-positive bacteria--infect foot ulcers. These sores develop because of diabetes-related nerve damage and loss of feeling in the feet. Amputation may be needed when infections fail to respond to therapy. People with diabetes account for about two-thirds of the 134,000 lower-limb amputations performed each year in the United States.
"The complication of diabetes that patients fear most is leg amputation, and infection is often the final pathway that leads to this tragic, if often preventable, outcome," said lead author Benjamin A. Lipsky, director of the General Internal Medicine and Antibiotic Research clinics at the VA Puget Sound Health Care System and professor of medicine at the University of Washington School of Medicine in Seattle.
Linezolid, sold as Zyvox (Pfizer, Inc.), was approved by the Food and Drug Administration (FDA) in 2000 to treat a variety of infections, including some caused by bacteria resistant to the drug methicillin. Methicillin-resistant Staphylococcus aureus (MRSA) has become a major cause of infections--including diabetic foot infections--both in hospitals and communities. For years the antibiotic vancomycin had been a last line of defense against infections caused by MRSA and other antibiotic-resistant "superbugs," but now vancomycin-resistant infections have been reported.
Because of the growing problem of MRSA and vancomycin-resistant enterococci (VRE), new agents have been developed. Linezolid is among the first new treatments for MRSA infections since vancomycin was introduced in the 1950s. Based on the results of the new trial, the FDA has now specifically extended the drug's use to most diabetic foot infections.
Unlike other newer antibiotics for MRSA and VRE, linezolid can be given orally, as well as intravenously, making it suitable for outpatient use.
"The approval of this drug for appropriately selected diabetic foot infections is important because it may reduce the need to hospitalize patients and the risk of IV-related complications," said Lipsky.
In the study, patients with diabetic foot infections were randomly assigned to receive either linezolid or one of two standard combination treatments, consisting of an aminopenicillin and a betalactamase inhibitor, a drug that blocks an enzyme that inactivates penicillin. Vancomycin could be added to the regimen for patients in the non-linezolid group if their infection was caused by MRSA.
Linezolid produced a clinical cure for 81 percent of patients, while the comparator combination was effective for 71 percent of patients. Statistically, the overall results for the two groups were about equal. However, linezolid outperformed the aminopenicillin treatments in the largest subgroup: patients with an infected ulcer, as opposed to cellulitis, osteomyelitis, or other less common types of diabetic foot infections.
Lipsky's results were presented in part at the Oct. 2002 annual meeting of the Infectious Diseases Society of America. The study was supported by VA and Pharmacia, now part of Pfizer, the maker of linezolid. Lipsky has served as a consultant and speaker for Pharmacia and Pfizer.
Source: VA Research Communications Service