Ceftaroline for bloodstream infections caused by methicillin-resistant Staphylococcus aureus: a multicentre retrospective cohort study

Clin Microbiol Infect. 2024 Nov 22:S1198-743X(24)00551-2. doi: 10.1016/j.cmi.2024.11.022. Online ahead of print.

Abstract

Objectives: To evaluate the effectiveness of ceftaroline vs. vancomycin or daptomycin in the treatment of methicillin-resistant Staphylococcus aureus bloodstream infections (MRSA-BSIs).

Methods: This multicentre retrospective study conducted in 15 Spanish hospitals, included data from the first MRSA-BSIs of adult patients between January-2019 and December-2022. The ceftaroline group included patients who received ceftaroline for ≥72h within the first week of BSI onset; the standard of care (SOC) group included patients who received vancomycin or daptomycin ≥72h after BSI onset. Primary outcome was 30-day all-cause mortality; secondary outcomes included 90-day mortality and incidence of adverse events (AEs). Propensity-score (PS) matching and Cox proportional-hazards analyses were performed.

Results: A total of 429 MRSA-BSIs were included: 133 in the ceftaroline group and 296 in the SOC group. More patients in the ceftaroline group had a SOFA score>2 (51.1% vs. 36.5%; p<0.01), complicated-BSI (66.2% vs. 42.2%; p<0.01), infective endocarditis (18.8% vs. 6.4%; p<0.01) and prescribed in combination treatment (65.4% vs. 11.5%; p<0.01), with no statistically significant differences in 30-day mortality: 23.3% ceftaroline (95%CI 16.1%-30.5%) vs. 16.2% SOC (95%CI 12.0%-20.4%), p=0.08. There were no statistically significant differences in 90-day mortality (33.1% ceftaroline vs. 26.7% SOC; p=0.17). After PS matching, 105 patients treated with ceftaroline were matched with 105 controls: the 30-day mortality rates were 21.9% and 16.2% (p=0.38). Cox-regression analysis of the entire cohort (n=429) revealed that age (HR 1.05, 95%CI 1.03-1.07) and SOFA score>2 (HR 2.34, 95%CI 1.50-3.65) were associated with 90-day mortality risk, although ceftaroline treatment did not demonstrate a significant effect (HR 1.00, 95%CI 0.97-1.02). Incidence of AEs was 12.0% in ceftaroline vs. 4.4% in SOC group (p<0.01). Most AEs occurred when ceftaroline was used in combination vs. monotherapy (17.2% vs. 2.2%; p=0.01).

Conclusions: Ceftaroline was an effective treatment for MRSA-BSIs but was commonly prescribed in combination showing a higher incidence of AEs.

Keywords: Bloodstream-infection; MRSA; Staphylococcus aureus; ceftaroline; combination therapy; mortality.