175 Persistent MRSA bacteremia 8 MRSAB, but the effect on mortality remains unclear [145–149]. Fortunately, a large, well-designed Phase 3 randomized clinical trial that tested ceftobiprole, another cephalosporin with efficacy against MRSA, has recently completed enrollment and reported positive topline results (discussed later). The emergence of possible alternatives for the treatment of MRSAB has an effect on the decisions that physicians make in clinical practice. In contrast to the situation in 2005, a second survey in 2017 showed that less than 20% of the surveyed American ID consultants would continue vancomycin and simply add another agent in case of persistent MRSAB on day 6. Instead, more than half of them would switch to another agent (either a single agent or daptomycin with a second agent) [150]. Although there is much (clinically unsubstantiated) debate about the most appropriate therapeutic modification in patients with persistent MRSAB, the single most important management component of these patients remains adequate source control. In the suggested management algorithm for MRSAB by Holland et al., a single positive follow-up blood culture represents a “worry point”, prompting reevaluation of potential sites of metastatic infection [21]. If blood cultures continue to be positive at the 3–5-day point despite appropriate antibiotic therapy, Holland et al. presume the patient has experienced monotherapy failure and recommend the addition of ceftaroline to vancomycin or a change of therapy to daptomycin plus a second antibiotic. The recommendation to add a second antibiotic to daptomycin or vancomycin, while unproven, is primarily to thwart the development of treatmentemergent daptomycin resistance rather than to improve efficacy based upon data using simulated vegetations [151]. The future There are a handful of clinical trials investigating future therapeutics for the treatment of MRSAB. Ceftobiprole is another fifth-generation cephalosporin currently under investigation with activity against MRSA [152,153]. Its safety and efficacy were recently evaluated in a landmark clinical trial. The ERADICATE trial is the largest clinical trial to evaluate a new antibiotic for complicated SAB and the first doubleblind, placebo-controlled Phase 3 ever conducted for that indication [154]. Results were presented at IDWeek2022. Topline data from the ERADICATE trial indicate that ceftobiprole met its primary efficacy endpoint without significant obvious toxicity concerns. Dalbavancin is approved for use in S. aureus bacterial skin infections, with the great advantage of having a uniquely long half-life [155]. A potential role of dalbavancin in endovascular infections has not yet been established [156]. The superiority of dalbavancin compared to standard parenteral antibiotic therapy for the completion of treatment is currently being studied in patients with complicated SAB in a phase
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