Cefazolin and Ertapenem Salvage Therapy Rapidly Clears Persistent Methicillin-Susceptible Staphylococcus aureus Bacteremia

Abstract

Cefazolin and ertapenem combination therapy was used successfully to salvage 11 cases (6 endocarditis) of persistent methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, including immediate clearance (≤24 hours) in 8 cases. While in vitro synergy was modest, cefazolin plus ertapenem exhibited synergistic action in a rat model of MSSA endocarditis. The combination of cefazolin and ertapenem provides potent in vivo activity against MSSA beyond what is predicted in vitro and warrants further clinical study in the treatment of refractory MSSA bacteremia and endocarditis.

Oxacillin plus ertapenem combination therapy leads to rapid blood culture clearance and positive outcomes among patients with persistent MSSA bacteraemia: a case series

“…Importantly, decisions regarding initiating dual β-lactam therapy for endocarditis patients were made by a multidisciplinary endocarditis team. 13 Taken together, our data extend those recently presented by Ulloa and colleagues 7 who showed positive clinical outcomes among 11 patients with persistent MSSA bacteraemia treated with cefazolin and ertapenem. Here, oxacillin plus a carbapenem was prioritized, suggesting that combination β-lactam therapy can be successfully employed with either an antistaphylococcal penicillin or cefazolin in combination with ertapenem.…”

“…Mechanisms supporting the utility of β-lactam combination therapy have been proposed to include use of two agents with complementary binding of PBP sites that target multiple steps in cell wall synthesis, thereby providing enhanced bacterial killing. 7 Ertapenem and cefazolin demonstrate strong affinity for PBP1 and PBP2, respectively. Alternatively, most patients in our study were treated with oxacillin plus ertapenem.…”

“…Our median FIC index was comparable to those previously reported against the combination of ertapenem with cefazolin or nafcillin. 7 Meropenem may also be considered as an alternative for patients with hypoalbuminaemia where ertapenem exposures are suboptimal. 12 …”

“…Overall, our data are consistent with earlier reports of encouraging patient outcomes and are the first to demonstrate the efficacy of oxacillin and ertapenem against MSSA bacteraemia. 7 , 9 These studies provide a basis for future investigation, and in particular a randomized clinical trial comparing the efficacy for standard-of-care treatment versus β-lactam combination therapy for patients with persistent MSSA bacteraemia. A pragmatic design may also provide an opportunity to compare combination regimens and the duration of combination therapy, for which few data currently exist.…”

“…Recent reports have documented encouraging outcomes for patients with persistent MSSA bacteraemia treated with cefazolin and ertapenem combination therapy. 7 , 9 Here, we report our experience in managing 10 consecutive cases of MSSA bacteraemia treated with dual β-lactam combination therapy, prioritizing oxacillin in combination with a carbapenem.…”