In a multicenter randomized trial across 23 US and Canadian hospitals, dalbavancin proved as effective as standard intravenous antibiotics for treating complicated S. aureus bacteremia in adults.
The primary endpoint was the desirability of outcome ranking (DOOR) at day 70, which integrated clinical success, infectious complications, safety events, mortality, and health-related quality of life. The probability of a more favorable outcome with dalbavancin compared with standard therapy was 48%, which showed no superiority.
Clinical efficacy at day 70—defined as survival without clinical failure, infectious complications, or death, as well as health-related quality of life—was similar between groups (73% for dalbavancin, 72% for standard therapy). Microbiologic success rates were also high in both groups.
Findings remained consistent across subgroups, regardless of site of infection, pathogen (MRSA or MSSA), duration of bacteremia, and whether patients had an immunosuppressed condition or whether they injected drugs, noted researchers.
Serious adverse events occurred in 40% of dalbavancin patients and 34% of standard therapy patients. Adverse events leading to discontinuation were less frequent with dalbavancin (3%) than with standard therapy (15%).
Common comorbidities included diabetes, chronic kidney disease, and heart failure. About one-third of infections were caused by MRSA. The most common infection sources were soft tissue, osteoarticular, endovascular, and pulmonary.
Median hospital stay after enrollment was 3 days for dalbavancin and 4 days for standard therapy. Although discharge location was not studied, dalbavancin’s dosing schedule eliminates the need for prolonged intravenous access, potentially reducing catheter-related infections and thrombosis. Pharmacokinetic data indicate drug levels remain adequate for up to 3 weeks after dosing.
"All treatments currently approved with an indication for bacteremia require prolonged intravenous access," the authors explained. "Switching from intravenous to oral therapy has proven successful in participants with bacterial endocarditis or osteomyelitis, but S aureus (especially MRSA) are underrepresented in existing trials with another large trial ongoing. ... Published observational data suggest high rates of clinical success with dalbavancin" as a nonintravenous option.
The trial enrolled 200 hospitalized adults with complicated S aureus bacteremia or right-sided endocarditis. All had documented clearance of S aureus from blood cultures after 72 hours to 10 days of initial antibiotic therapy.
Patients with central nervous system infection, retained infected prosthetic material, left-sided endocarditis, or severe immunosuppression were excluded. Participants were randomly assigned to either 2 doses of dalbavancin (1,500 mg on days 1 and 8) or 4 to 8 weeks of standard intravenous therapy—cefazolin or an antistaphylococcal penicillin for methicillin-susceptible strains, or vancomycin or daptomycin for methicillin-resistant strains.
Limitations included the modest sample size, exclusion of patients with more complex infections, and the open-label design, although a blinded review committee adjudicated outcomes.
Quality-of-life measures used in the DOOR analysis may not have fully captured possible advantages such as reduced caregiver burden or simpler outpatient care, though DOOR was "selected because it better reflects the full balance of efficacy, safety, and quality-of-life considerations clinicians and participants actually use to determine treatment," compared with binary clinical success or failure outcomes, the authors wrote,
They concluded: "When considered with other efficacy and safety outcomes, these findings may help inform use of dalbavancin in clinical practice."
Full disclosures can be found in the study.
Source: JAMA