Durham, NC - Daptomycin (Cubicin, Cubist Pharmaceuticals), a cyclic lipopeptide antibiotic approved for the treatment of skin and skin-structure infections, is not inferior to standard therapy for Staphylococcus aureus bacteremia and right-sided endocarditis, according to the results of a new study [1]. These findings, say investigators, provide support for another tool in their relatively thin armamentarium, particularly in the treatment of methicillin-resistant S aureus (MRSA).

"For methicillin-susceptible Staphylococcus aureus (MSSA), our drugs are pretty good," lead investigator Dr Vance Fowler (Duke University Medical Center, Durham, NC) told heartwire. "I don't think the role of daptomycin is to primarily replace existing antistaphylococcal penicillins. Those drugs work well; they're cheap and they're safe. The issue is MRSA. Antimicrobial resistance continues to grow, and there are S aureus strains isolated from clinics that are essentially resistant to all antibiotics. . . . It's really a perfect bacterial storm. Just as the need is growing with the increasing frequency of infections and a growing problem of resistance, the number of new drugs available to us has been diminishing."

The results of the study are published in the August 17, 2006 issue of the New England of Medicine.

Fowler told heartwire that there are limited data on treatment options for patients with bacteremia and endocarditis, primarily because the infections are difficult to study and patients are often too ill to be enrolled in a clinical trial. Moreover, there are often many confounding variables that influence findings. This particular study, he pointed out, was rigorously designed and examined the toughest infections encountered in clinical practice. In addition to every patient having undergone a transesophageal echocardiogram, a blinded adjudication committee established the clinical outcomes, he noted.

To assess whether daptomycin would be an effective alternative agent for S aureus bacteremia and endocarditis, investigators randomly assigned 124 patients with S aureus with or without endocarditis to receive 6 mg/kg of daptomycin intravenously daily and 122 patients to receive standard therapy with initial low-dose gentamicin plus either an antistaphylococcal penicillin or vancomycin. The primary efficacy end point was treatment success in the modified intention-to-treat population 42 days after the end of therapy.

Six weeks after therapy was completed in the modified intention-to-treat population, a successful outcome was documented in 44.2% of patients treated with daptomycin and 41.7% of patients treated with standard medical therapy, meeting the prespecified criteria for noninferiority. The success rates were similar in subgroups of patients with complicated bacteremia, right-sided endocarditis, and MSRA.

Fowler noted that the reasons for treatment failure differed in the two treatment groups, with more patients in the daptomycin-treatment arm likely to fail because of persistent or relapsing S aureus infection. In the comparator arm, the most common reason for treatment failure was adverse events, the most common of which was nephrotoxicity, likely due to gentamicin. When investigators compared outcomes according to reasons for failure, Fowler said, the outcomes remained "similar and robust."

"Daptomycin represents a new treatment option for S aureus bloodstream infections, as it was shown to be noninferior to standard therapy," said Fowler. "The study also emphasizes the critical need to debreed, and by that I mean the important role of adjunctive surgical therapy in the management of patients with S aureus bacteremia and endocarditis. Medicine alone, in the cases of established infection, is often not sufficient."

Fowler noted that of 19 patients with microbiologic failure in the daptomycin group, six had isolates with reduced susceptibility to daptomycin treatment. "This is not a panacea. It's not the perfect drug. I don't know if there is such a thing. Clinicians need to be vigilant. If they see persistent bacteremia or persistent positive cultures in patients with daptomycin, they need to repeat the susceptibility profiles on those isolates, and if the isolates are resistant to treatment, then they need to change the drug," he said.