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

Abstract

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 Staphylococcus aureus (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.

Synergistic Combinations of FDA-Approved Drugs with Ceftobiprole against Methicillin-Resistant Staphylococcus aureus

“…1g ; ∑FIC min = 0.6). Ceftobiprole-vancomycin synergy has previously been observed ( 39 ), and several clinical studies of β-lactam combinations with vancomycin have been reported and recently reviewed ( 40 ). Floxuridine, which demonstrated strong synergy with cefoxitin in a prior study ( 37 ), demonstrated effectively no synergy with ceftobiprole ( Fig.…”

Clinical characteristics and antibiotic resistance profile of invasive MRSA infections in newborn inpatients: a retrospective multicenter study from China

“…Combination therapy with vancomycin plus beta-lactams for MRSA bacteremia showed lower clinical failure rates, and the combination exposures significantly suppresses the development of VISA [ 28 , 29 ]. Several studies have documented that adding a beta-lactam to vancomycin or daptomycin may help shorten bacteremia and avoid recurrences in patients with MRSA bacteremia [ 30 ]. Daptomycin is not routinely used in neonates because of a scarcity of literature on its efficacy and safety in infants.…”