BOSTON — Daptomycin may effectively treat gram-positive bone and joint infections and may be less likely than standard antimicrobials to cause drug resistance as a consequence of long-term therapy, Michael S. Finney, M.D., said at the annual meeting of the Infectious Diseases Society of America.
In a retrospective study, daptomycin (Cubicin) eradicated infections in 9 of 10 patients with gram-positive osteomyelitis, septic joint infection, septic arthritis infection, and/or bacteremia. The patients were treated at two medical centers between November 2003 and April 2004.
“Eight of the patients were infected with methicillin-resistant Staphylococcus aureus [MRSA], and enterococcus and streptococcus were isolated from two patients,” said Dr. Finney of Fountain Valley (Calif.) Regional Hospital, where six of the patients were treated. The remaining four patients were treated at Rush University Medical Center in Chicago.
Daptomycin was effective in seven of the eight MRSA-infected patients and both of the non-MRSA patients. Of the 10 patients, 4 had osteomyelitis only and 6 had some combination of osteomyelitis, septic joint infection, septic arthritis infection, and/or bacteremia.
Nine had undergone prior unsuccessful treatment with one or more antibiotics: Eight received vancomycin, three received linezolid, and three received quinupristin/dalfopristin. Among the patients successfully treated with daptomycin were seven who had failed or could not tolerate vancomycin, which is often a first-line treatment for osteomyelitis.
The daptomycin treatment duration averaged 30 days, with a range from 21 to 42 days. “In general, the therapy was well tolerated, even for the longer treatment durations,” he said.
The one patient in the case series whose infection was not resolved had a relapse during daptomycin therapy, “possibly as a result of underdosing,” he said. Because of renal insufficiency, the septic arthritis patient was started on alternate-day vs. daily dosing and was not adjusted to daily dosing once renal function improved. During treatment, the patient developed an epidural abscess from MRSA with reduced susceptibility to daptomycin.
Bone and joint infections are notoriously difficult to resolve, require prolonged treatment, and are associated with a high risk of recurrence. “Effective treatment requires the antibiotic to penetrate the site of infection at an adequate concentration to effectively kill the causative pathogen,” Dr. Finney noted. Because gram-positive organisms, particularly S. aureus, are the predominant cause of these infections, the possibility of drug resistance further complicates treatment.
Vancomycin, a standard treatment for bone and joint infections, is not highly active against some gram-positive organisms, including S. aureus. In fact, he said, “studies have shown an increased risk of recurrence with vancomycin treatment for S. aureus osteomyelitis.” Bacteriostatic antimicrobials such as vancomycin, which merely inhibit the growth of bacteria, may have a higher risk of causing drug resistance during therapy than do bactericidal agents such as daptomycin.
Daptomycin is approved for treating complicated skin and skin structure infections. The findings suggest that further studies are warranted to determine the agent's role in treating gram-positive bone and joint infections, and to determine optimal dosing, Dr. Finney said.
He and his colleagues in the study reported having no financial interest in the manufacturer of daptomycin, Cubist Pharmaceuticals Inc.