Ceftaroline as a Treatment Option for MRSA-Induced Sepsis?
A recently published study by a team of authors from several American institutions focused on comparing the efficacy and safety of the 5th generation cephalosporin ceftaroline with the standard of care in the treatment of sepsis caused by methicillin-resistant Staphylococcus aureus (MRSA).
Options for Treating MRSA-Induced Sepsis
For decades, the antibiotic of choice for MRSA-induced sepsis has been vancomycin. However, treatment failure occurs in up to 1/3 of cases. With the increasing prevalence of strains with reduced sensitivity to vancomycin and adverse reactions to its administration, the need for additional therapeutic options is growing. An alternative to vancomycin for MRSA-induced sepsis with the most extensive clinical evidence is daptomycin.
Ceftaroline
Ceftaroline is a 5th generation cephalosporin with strong activity against Gram-positive bacteria, including MRSA and strains showing reduced sensitivity to vancomycin. In the EU, it is approved for treating complicated skin and soft tissue infections and community-acquired pneumonia. Observational data suggest its efficacy in MRSA-induced sepsis, but a comparison with the standard of care was lacking. Recently, results were published from a multicentric observational retrospective study comparing ceftaroline with daptomycin in adult patients for this indication.
Study Methodology and Monitored Parameters
Patients treated with one of the compared drugs from 2010 to 2017 were included in the study. The condition was the use of ceftaroline or daptomycin for at least 72 hours, and the source of sepsis could not be pneumonia.
The primary composite monitored parameter was treatment failure, defined as death within 30 days, duration of sepsis while receiving the evaluated drug for ≥ 7 days, and recurrence of MRSA-induced sepsis within 60 days. Secondary monitored parameters included the individual components of the primary monitored parameter, rehospitalization due to MRSA-induced sepsis, duration of sepsis, and length of hospitalization after the initiation of the evaluated treatment. A 15% difference in the weighted risk of the primary monitored parameter was set as the noninferiority margin.
Findings
The average age of the 270 patients included was 58 years. Eighty-three used ceftaroline, and 187 used daptomycin. Approximately 2/3 from each therapeutic group had used vancomycin before the evaluated treatment. The most common dose of ceftaroline was 600 mg every 12 or 8 hours; the median dose of daptomycin was 600 mg. Patients frequently had comorbidities - 40% had kidney diseases (20% on hemodialysis), 39% had diabetes, 24% had heart failure, and 21% had liver disease. The most common sources of MRSA sepsis were intravascular (35%), followed by bone/joint infections (31%), skin/soft tissue infections (20%), and intravenous catheters (19%).
Treatment failure occurred in 37% of patients: 11.9% died within 30 days, 18.5% had sepsis lasting ≥ 7 days, and 14% experienced MRSA sepsis recurrence within the next 60 days. Ceftaroline demonstrated noninferiority to daptomycin regarding the primary composite parameter, which occurred in 39% of patients with daptomycin and 32.5% with ceftaroline (weighted risk difference 7%; 95% confidence interval [CI] ‐5 to 19%). No statistically significant difference was found between therapeutic groups in terms of secondary monitored parameters either. The 30-day mortality was 14.5% for ceftaroline and 10.7% for daptomycin; sepsis duration ≥ 7 days was observed in 16.9% and 19.3% of patients, respectively; recurrence within 60 days happened in 8.4% and 16.6% of patients, respectively, and rehospitalization within 60 days due to MRSA sepsis occurred in 7.2% and 9.1% of patients, respectively. The median sepsis duration (4 days with ceftaroline and 3 days with daptomycin; p = 0.134) and length of hospitalization (median 13 days with ceftaroline and 11 days with daptomycin; p = 0.095) did not significantly differ between the groups.
Regarding treatment safety, increased creatine phosphokinase levels were more common in the daptomycin group (5.3 vs. 0%; p = 0.034), while rash was more frequent in the ceftaroline group (10.8 vs. 1.1%; p = 0.001). The incidence of all other monitored safety parameters was comparable.
Conclusion
These results support future evaluations of ceftaroline as a primary treatment for MRSA-induced sepsis and its use as an alternative to vancomycin and daptomycin when needed.
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Sources:
1. Zasowski E. J., Trinh T. D., Claeys K. C. et al. Multicenter cohort study of ceftaroline versus daptomycin for treatment of methicillin-resistant Staphylococcus aureus bloodstream infection. Open Forum Infect Dis 2021 Dec 23; 9 (3): ofab606, doi: 10.1093/ofid/ofab606.
2. SPC Zinforo. Available at: www.ema.europa.eu/en/documents/product-information/zinforo-epar-product-information_cs.pdf
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