January 26, 2022
By A. Krishna Rao, MD, MS
Bloodstream infections (BSIs) are a major contributor to the significant morbidity and mortality resulting from methicillin-resistant Staphylococcus aureus (MRSA). While vancomycin is usually the initial treatment of choice, reduced vancomycin susceptibility and/or adverse drug reactions can occur, and failure rates exceed 30%. Daptomycin, the current agent with the most clinical evidence and Food and Drug Administration (FDA) approval for MRSA BSI, also results in treatment failures, and resistance is starting to become a concern. Ceftaroline has potent activity against MRSA, but comparative clinical data are limited, and it is not FDA-approved for MRSA BSI.
Zasowski et al. conducted a multicenter, retrospective, observational study on a cohort of adult patients from 2010-2017 with MRSA BSI treated with ceftaroline or daptomycin for ≥ 72 hours. Important exclusion criteria were pneumonia and clearing of cultures before study drug initiation. The primary outcome was a composite of 30-day mortality, BSI duration ≥ 7 days on the study drug, and 60-day MRSA BSI recurrence. These components individually constituted notable secondary outcomes along with length of stay.
The final cohort included 270 patients, 83 on ceftaroline and 187 on daptomycin, which exceeded the size calculated to have sufficient power for the prespecified 15% noninferiority margin. No significant difference in composite treatment failure was observed between daptomycin (39%) and ceftaroline (32.5%) patients (weighted risk difference, 7.0% [95% confidence interval, -5.0% to 19.0%]). This was also true of secondary outcomes, meeting the definition of noninferiority. Creatine phosphokinase elevation and rash were more common in the daptomycin and ceftaroline groups, respectively.
This study was well done and, within the limitations of a retrospective, observational study, addressed bias/confounding using best practices including inverse probability treatment weighting derived from a propensity score that compared well to the actual treatment assignments. Thus, this provides good, real-world clinical evidence that ceftaroline is noninferior to daptomycin for MRSA BSI. Of note, however, 33% of the daptomycin and 19% of the ceftaroline patients had the drug started as first-line therapy, and reasons for this are not provided. Guidelines and many hospitals still recommend vancomycin use initially, only switching to daptomycin or ceftaroline for failure to clear bacteremia or other signs of clinical progression after 4-5 days of treatment. However, these patients with vancomycin failure largely would have been excluded, so we cannot assume these results generalize to the context of salvage therapy after vancomycin failure, which deserves further study.