Daptomycin + Fosfomycin Compared to Daptomycin Monotherapy in MRSA Bacteremia

The combination of daptomycin plus fosfomycin was more effective than daptomycin alone for treating MRSAB.
The combination of daptomycin plus fosfomycin was more effective than daptomycin alone for treating MRSAB.
This article is part of MPR's coverage of IDWeek 2018, taking place in San Francisco, CA. Our on-site staff will be reporting on the latest breaking research and clinical advances in infectious diseases. Check back regularly for highlights from IDWeek 2018.

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 (10mg/kg intravenously daily and 2g intravenously every 6 hours, respectively), whereas 81 participants received monotherapy of daptomycin (10mg/kg intravenously daily) for 10 to 14 days in uncomplicated MRSAB, and 28 to 42 days for complicated MRSAB.

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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.