By Stan Deresinski, MD, FACP, FIDSA
Clinical Professor of Medicine, Stanford University
SYNOPSIS: Ceftaroline is an acceptable alternative therapy for treatment of methicillin-resistant Staphylococcus aureus bacteremia.
SOURCE: Zasowski EJ, Trinh TD, Claeys KC, et al. Multicenter cohort study of ceftaroline versus daptomycin for treatment of methicillin-resistant Staphylococcus aureus bloodstream infection. Open Forum Infect Dis 2022;9:ofab606.
Zasowski and colleagues performed a retrospective multicenter observational cohort study examining the relative efficacy of daptomycin and ceftaroline in the treatment of adults with bloodstream infection (BSI) due to methicillin-resistant Staphylococcus aureus (MRSA). Among the exclusions were receipt of an antibiotic with anti-MRSA activity for ≥ 96 hours prior to initiation of either daptomycin or ceftaroline and receipt of concomitant therapy for ≥ 24 hours after their initiation, as well as suspicion of the presence of pneumonia. The a priori noninferiority margin was set at 15%.
Among the 270 patients, the most frequent sources and/or foci of infection were endovascular (34.8%), bone/joint (31.1%), skin and soft tissue (20.4%), and intravenous catheter (11.9%). Approximately two-thirds of patients received vancomycin before daptomycin or ceftaroline, with little difference between the two cohorts; daptomycin and ceftaroline were first-line therapies in 33.2% and 19.2%, respectively. The ceftaroline dose was 600 mg in 68.7% with administration every eight hours in 42.2% and the daptomycin dose was ≥ 10 mg/kg in only 33.7%, while it was 6 mg/kg to 9 mg/kg in 63.6%.
There was no significant difference in composite treatment failure, the primary study endpoint, which was defined as 30-day mortality, BSI duration ≥ 7 days on study drug, and 60-day MRSA BSI recurrence: daptomycin 39%, ceftaroline 32.5%; weighted risk difference, 7.0% (95% confidence interval [CI], -5.0% to 19.0%). There also were no significant differences regarding the individual components of the composite.
The drugs were well tolerated, although creatine phosphokinase (CPK) elevation was significantly more frequent in daptomycin recipients (5.0% vs. 0%) and rash occurred more frequently in those receiving ceftaroline (10.8% vs. 1.1%). Two daptomycin recipients developed eosinophilic pneumonia. Seven (2.6%) patients overall developed Clostridioides difficile infection, and this was numerically more frequent in the ceftaroline group. No patient developed neutropenia.
COMMENTARY
While vancomycin remains the usual recommendation, the optimal therapy remains a matter of discussion. Among the alternatives are daptomycin and ceftaroline. While there is a relatively large amount of data supporting the use of daptomycin, this has not been true for the use of ceftaroline as monotherapy. Although the former has received Food and Drug Administration approval for use in treating S. aureus BSI and right-sided endocarditis, ceftaroline has not.
While this retrospective study has a number of drawbacks, its results are consistent with a conclusion that ceftaroline is noninferior to daptomycin in the treatment of MRSA BSI. Furthermore, it is well tolerated, although it caused skin rash in approximately one-tenth of recipients. Neutropenia, which is a known potential complication of prolonged administration of ceftaroline, did not occur. The occurrence of two cases of eosinophilic pneumonia among the 187 daptomycin recipients is noteworthy, as is the CPK elevation. One concern about ceftaroline use is that it is a broad-spectrum antibiotic while daptomycin is not, and, thus, its preferential use would violate an antibiotic use principle.
