What do beta-lactams add to vancomycin or daptomycin in the treatment of patients with methicillin-resistant bacteraemia? A review.

Several studies have documented the synergy between vancomycin/daptomycin and various beta-lactams, and clinical studies have studied this combination therapy in humans. We review the published literature on this topic to know the utility of the combined treatment with beta-lactams in treating bacteraemia methicillin-resistant (MRSA) infections. Fifteen observational studies, three randomised clinical trials and three systematics reviews are analysed in this article. Observational studies used ceftaroline, cefazolin, piperacillin/tazobactam or cefepime among the beta-lactams. Clinical trials used cloxacillin or flucloxacillin as the most used beta-lactam in two trials and ceftaroline in one. Three systematic reviews are published. One of them only includes studies with vancomycin and included six studies. The other two systematic reviews include patients with daptomycin or vancomycin and included 15 and 9 studies, respectively. Adding a beta-lactam to vancomycin or daptomycin may help shorten bacteraemia and avoid recurrences in patients with MRSA bacteraemia. There is no evidence that combined therapy improves mortality. Nephrotoxicity in clinical trials precludes the use of combination therapy mainly with cloxacillin or flucloxacillin, but systematic reviews have not found a significant difference in this point in observational studies with other beta-lactams. The role of other beta-lactams such as ceftaroline should be thoroughly studied in these patients.