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

Abstract

Objectives: To evaluate the effectiveness of ceftaroline vs. vancomycin or daptomycin in the treatment of methicillin-resistant Staphylococcus aureus bloodstream infections (BSIs) (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 ≥72 hours within the first week of BSI onset; the standard-of-care (SOC) group included patients who received vancomycin or daptomycin ≥72 hours 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 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 Sequential Organ Failure Assessment 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 propensity-score 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 (hazard ratio [HR], 1.05; 95% CI, 1.03-1.07) and Sequential Organ Failure Assessment 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 the SOC group (p < 0.01). Most AEs occurred when ceftaroline was used in combination vs. monotherapy (17.2% vs. 2.2%; p 0.01).

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

Keywords: Bloodstream infection; Ceftaroline; Combination therapy; MRSA; Mortality; Staphylococcus.