January 03, 2020
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Earlier initiation of combination therapy is beneficial in MRSA bacteremia

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Warren E. Rose, PharmD, MPH
Warren E. Rose

Earlier initiation of treatment with a combination of daptomycin and ceftaroline for persistent MRSA bacteremia may make the treatment more effective, rather than delaying its use for salvage therapy, researchers reported in Open Forum Infectious Diseases.

“Guideline-recommended first-line therapy for [MRSA bacteremia] consists of vancomycin or daptomycin monotherapy, both of which have been associated with clinical failure,” Warren E. Rose, PharmD, MPH, associate professor in the School of Pharmacy at the University of Wisconsin-Madison, and colleagues wrote. “Options for salvage therapy after initial treatment failure include escalating daptomycin dose, switching to an alternative agent or using a combination of two or more antibiotics.”

According to Rose, there are ‘many unanswered questions’ regarding treatment in this setting.

“Updated treatment guidelines incorporating ceftaroline are lacking, and there are limited clinical data for use of salvage combinations earlier in infection courses, leaving many questions unanswered for optimal treatment,” he told Healio.

The researchers performed a multicenter, retrospective, matched cohort study to assess the clinical outcomes of patients who received daptomycin with ceftaroline (DAP-CPT) at any point in the treatment course compared with the standard-of-care (SOC) MRSA treatment, including empiric treatment with vancomycin or daptomycin and any other subsequent combination antibiotics, except for DAP-CPT.

The study population included 58 patients who received DAP-CPT and 113 matched patients who received SOC. Of those in the SOC group, 96% received vancomycin and 56% escalated therapy at least once throughout the treatment course.

Among patients who received DAP-CPT, 24 received treatment within 72 hours of an index culture. The researchers reported two deaths within 30 days from the DAP-CPT group compared with 16 deaths in the SOC group (P > .05).

Patients receiving DAP-CPT with a Charlson Comorbidity Index of 3 or more, an endovascular source and receipt of DAP-CPT therapy within 72 hours of index culture demonstrated numerically lower mortality, according to a subgroup analysis.

“Daptomycin combined with ceftaroline treatment is often delayed in MRSA bacteremia,” Rose said. “This combination may be more beneficial if initiated earlier, particularly in patients at higher mortality risk.”

The median duration of MRSA bacteremia was 9.3 days for DAP-CPT compared with 4.8 days for SOC. On average, DAP-CPT was started on day 6. After DAP-CPT was received, the duration of MRSA bacteremia was 3.3 days.

“This study is the only matched cohort to compare daptomycin plus ceftaroline combination therapy used as both initial (within 72 hours of index culture) and salvage therapy to standard of care for MRSA bacteremia,” Rose said. “The 58-patient cohort treated with daptomycin plus ceftaroline is the largest study of this combination.” – by Marley Ghizzone

Disclosures: Rose reports receiving speaking honoraria from Melinta. Please see the study for all other authors’ relevant financial disclosures.