Daptomycin Plus Fosfomycin More Effective Than Daptomycin Monotherapy in MRSA Bacteremia

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SAN FRANCISCO—The combination of daptomycin with fosfomycin demonstrates increased efficacy in treating methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) compared with daptomycin alone, according to a study presented at ID Week 2018, held October 3 to 7, 2018, in San Francisco, California.

Animal models have shown the daptomycin/fosfomycin combination to be efficacious in the treatment of MRSAB via a synergistic, bactericidal mechanism. Because data are lacking in humans, investigators conducted an open-label clinical trial at 18 medical centers in Spain, with the primary endpoint of successful test of cure 6 weeks after treatment. From December 2013 to November 2017, 155 adults with MRSAB were randomly assigned, and 74 participants received either daptomycin plus fosfomycin (10 mg/kg intravenously daily and 2 g intravenously every 6 hours, respectively), whereas 81 participants received monotherapy of daptomycin (10 mg/kg intravenously daily) for 10 to 14 days in uncomplicated MRSAB, and 28 to 42 days for complicated MRSAB.

Researchers used an intention-to-treat analysis for data collected at a test-of-cure visit, 6 weeks posttreatment, which demonstrated cure of MRSAB in 54.1% of patients receiving combination therapy, vs 42.0% receiving monotherapy (absolute difference, 12.1%; 95% CI, 0%-27.0%). This visit also demonstrated a lower association with microbiologic failure in individuals receiving combination treatment when compared with participants receiving monotherapy (0 vs 9 participants; P =.009). However, there was a higher rate of adverse events, although nonsignificant, in the combination therapy group, likely because of the study medication leading to treatment failure and discontinuation of treatment (8.1% in the combination group vs 3.7% in the monotherapy group, P =.31). A noted secondary outcome at 7 days posttreatment initiation is that 93.2% of patients receiving combination treatment demonstrated MRSAB clearance, whereas 76.5% of patients receiving monotherapy achieved MRSAB clearance (absolute difference, 16.7%; 95% CI, 5.4%-27.7%).

On the basis of their accrued data and analysis, the study authors concluded, “[t]he combination of daptomycin plus fosfomycin was more effective than daptomycin alone in treating MRSAB.”

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Reference

Pujol M, Miro JM, Shaw E, et al. Daptomycin plus fosfomycin versus daptomycin monotherapy for methicillin-resistant Staphylococcus aureus bacteremia. a multicenter, randomized, clinical trial. Presented at: IDWeek 2018; October 4-8, 2018; San Francisco, CA. Poster LB 3.