BOSTON — Daptomycin may be an effective option for difficult-to-treat gram-positive bloodstream infections, John Segreti, M.D., reported at the annual meeting of the Infectious Diseases Society of America.
In a retrospective study, 31 patients were treated with daptomycin (Cubicin) for bacteremia and/or infective endocarditis at two medical centers. Of these, 24 achieved clinical resolution of the life-threatening conditions, including all 11 patients with methicillin-resistant Staphylococcus aureus (MRSA) infection, 6 of 7 patients with methicillin-susceptible Staphylococcus aureus (MSSA) infection, and 5 of 11 patients with vancomycin-resistant enterococci (VRE).
These findings are particularly important in light of the increasing prevalence of serious infections involving gram-positive cocci and the increasing concern about antimicrobial resistance, especially in hospital intensive care units, said Dr. Segreti of Rush Medical College in Chicago. “Unfortunately, the gold standard for many serious gram-positive infections—vancomycin—is threatened. Its increased use for S. aureus infections leads to an increased risk for recurrent bacteremia and mortality.
“This may be a consequence of inadequate bactericidal activity of vancomycin, especially when treating some strains of S. aureus.” Daptomycin is a more rapidly bactericidal agent than vancomycin, “which is critical when treating bloodstream infections, especially in eradicating the vegetative mass associated with infective endocarditis,” he explained.
Between November 2003 and July 2004, 31 patients at Rush University Medical Center in Chicago and Fountain Valley (Calif.) Regional Hospital received 6 mg/kg daptomycin daily or every other day for bloodstream infections. Overall, 22 of the patients had been diagnosed with bacteremia only, 8 had culture-positive infective endocarditis, and 1 had culture-negative endocarditis. In 24 cases, the patients had received prior antibiotic therapy for their infections, including vancomycin in 18 patients and linezolid in 4, but they required a change because of limited success of the initial therapy or intolerable adverse effects.
The pathogens identified in the study population included MRSA in 11 patients, VRE in 11, MSSA in 7, and coagulase-negative staphylococcus in 1; 1 other patient had an infection of unknown etiology. An analysis of the patient records showed that daptomycin was effective for 18 of the 22 bacteremic patients without endocarditis and for 6 of the 9 patients with infective endocarditis. The seven patients for whom treatment was not successful died during hospitalization.
In general, daptomycin was safe and well tolerated, even for extended durations of therapy, Dr. Segreti said.
Currently, daptomycin is approved for the treatment of complicated skin and skin structure infections. A clinical trial is underway to assess the efficacy of higher dosages of the drug as well as the optimal dosage and duration of treatment and the long-term efficacy for these infections, he said.
The results of this study suggest that daptomycin “may provide an additional option for the treatment of bloodstream infections, not only for patients who fail prior antimicrobial therapy but also as initial therapy for patients at risk for drug-resistant gram-positive infections,” he concluded.
Dr. Segreti and his colleagues in this investigation reported no financial interest in the manufacturer of daptomycin, Cubist Pharmaceuticals Inc.
