Impact of early vs delayed initiation of dual antimicrobial salvage therapy on clinical outcomes in MRSA bacteremia

ABSTRACT Our retrospective observational cohort study investigated the effect of the timing of escalation to dual salvage therapy utilizing ceftaroline with vancomycin or daptomycin for the treatment of persistent methicillin-resistant Staphylococcus aureus bacteremia on patient outcomes. Eligibility criteria included age ≥18 years old, at least one positive blood culture for methicillin-resistant Staphylococcus aureus , and receipt of salvage therapy consisting of ceftaroline in combination with either vancomycin or daptomycin for any duration during their bloodstream infection within our health system over a 10-year period. This resulted in the inclusion of 189 adult patients. Patients were stratified by the timing of ceftaroline initiation: ≤5 days (early initiation) versus >5 days (late initiation) from index positive culture. The study populations were similar, although there was a higher prevalence of persons who inject drugs started on early salvage therapy (36.0% versus 18.0%, P = 0.005) and fewer patients with type II diabetes (25.8% versus 41.0%, P = 0.028). Analysis revealed no statistically significant differences between 90-day all-cause mortality or readmission rates in either group; however, there was less 90-day microbiologic recurrence in the early initiation group (3.4% versus 11.0%, P = 0.046). Patients started on early salvage therapy also had fewer total days of bacteremia (7.0 versus 10.5 days, P < 0.001), fewer metastatic foci of infection (61.8% versus 82.0%, P = 0.002), and a shorter duration of treatment (46.0 versus 50.0 days, P = 0.013). IMPORTANCE Treatment of methicillin-resistant Staphylococcus aureus bacteremia remains a challenge due to its high morbidity and mortality. Ceftaroline has been studied for off-label utilization in dual salvage therapy with daptomycin or vancomycin in these patients, although current data regarding the optimal timing for its addition are limited. We sought to address this knowledge gap with our retrospective review of patient outcomes at our hospital system who received ceftaroline for this indication. Overall, earlier initiation of ceftaroline-based dual therapy was beneficial, as evidenced by reduced microbiologic recurrence, shorter duration of bacteremia, reduced metastatic disease, and subsequent shorter duration of therapy if patients were escalated to dual salvage therapy with ceftaroline within 5 days of the index culture.