Earlier Initiation of Daptomycin-Ceftaroline for MRSA Bacteremia May Improve Outcomes


Earlier initiation of DAP-CPT combination therapy may be beneficial, despite a tendency to use the therapy after initial treatment failure.

Vancomycin or daptomycin monotherapy are the recommended first-line treatments for Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. It is known that these treatments are associated with high failure rates, but greater clarity is needed when it comes to alternatives and salvage therapies following initial treatment failure.

Daptomycin and ceftaroline (DAP-CPT) combination therapy is one of the frequent salvage therapies for persistent MRSA bacteremia, but there have been few comparison studies involving the treatment. Results from a retrospective, matched cohort study published in Open Forum Infectious Diseases demonstrate that although DAP-CPT treatment is often delayed in MRSA bacteremia, the therapy may be beneficial if initiated earlier.

The study took place among patients with MRSA bacteremia at 4 hospitals in the United States.

Patients who received DAP-CPT for >72 hours at any point during therapy were matched 2:1 if possible, or otherwise 1:1, to standard of care. Patients were matched by infection source, then age, and then by renal function.

A total 171 of patients were included. The total study population consisted of 58 patients who received DAP-CPT and 133 matched patients who were treated with standard of care therapy. Standard of care was defined as empiric treatment with vancomycin or daptomycin, as well as any subsequent combination antibiotics except for DAP-CPT.

Of the 133 standard of care patients, 96% received vancomycin. Therapy was escalated at least once for 56% of the standard of care group.

Over a 30 day period, investigators reported 16 deaths in the standard of care group and 2 deaths in the DAP-CPT group. Median MRSA bacteremia duration was 4.8 days for standard of care and 9.3 for DAP-CPT.

Approximately 42% of patients in the DAP-CPT group were treated with the combination therapy within 72 hours of an index culture. This prompt treatment (along with a Charlson Comorbidity Index of 3 or more and an endovascular source) was associated with lower mortality.

In the combination therapy group, 1 patient received DAP-CPT for the full treatment course. Of the 57 other patients in the combination therapy group, 29 received DAP-CPT as a second line therapy, 26 as a third line therapy, and 2 as a fourth line therapy.

A total of 32 patents completed treatment on DAP-CPT. Of the rest, 15 were deescalated to daptomycin monotherapy, 6 were deescalated to ceftaroline monotherapy, and 5 to vancomycin monotherapy.

Due to the biases inherent to the retrospective analyses where treatment is not randomized, investigators recommend future blinded, randomized, prospective studies for a fuller picture of how DAP-CPT measures against standard of care.

They did, however, express that treatment guidelines incorporating ceftaroline were lacking, leaving open questions for clinicians. Their results present a step forward in clarifying those questions.

“Despite the DAP-CPT group having a higher baseline mortality risk and statistically less source control, the overall mortality rates were still similar to SOC [standard of care]. Receiving DAP-CPT early in the infection course may be more beneficial for survival as opposed to its use as salvage therapy, especially in patients with endovascular sources or at high risk of death,” study authors wrote.

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