In vitro activity of amoxicillin combined with oral cephalosporins against endocarditis-associated E. faecalis clinical isolates

Abstract

Objectives: Aminopenicillin associated with parenteral cephalosporins provides synergistic activity against Enterococcus faecalis. Oral consolidation treatment is an option for infective endocarditis E. faecalis (EFIE), but optimal oral regimen remains under debate. We aimed to assess the in vitro activity of combinations based on amoxicillin plus an oral cephalosporin, namely, cephalexin or cefixime, against E. faecalis strains.

Methods: MIC and MBC values were determined against 6 clinical isolates of endocarditis-associated E. faecalis. Time-kill (TK) experiments were performed using amoxicillin (½MIC) plus cephalexin or cefixime at different concentrations (Cmax, ½Cmax and Cmin). Comparator regimens were amoxicillin/cefazolin and amoxicillin/ceftriaxone. TK experiments were carried out at standard (∼5 × 105 cfu/mL) and high inoculum (∼108 cfu/mL).

Results: Using amoxicillin combined with Cmax, ½Cmax or Cmin of oral cephalosporin at standard inoculum, synergy or additivity was observed in 66, 33 and 0% of E. faecalis isolates with adjunctive cephalexin; and in 83, 50 and 33% of isolates with adjunctive cefixime, respectively. In comparator regimens, synergy was found in all isolates at standard inoculum. At high inoculum, amoxicillin/cefixime at Cmax had similar efficacy to amoxicillin/ceftriaxone, showing synergy in 50% of E. faecalis isolates, while amoxicillin/cephalexin at Cmax and amoxicillin/cefazolin only achieved synergy in 17% of isolates.

Conclusions: The combination of amoxicillin/cefixime exhibits synergy in most E. faecalis strains at standard inoculum. Cefixime could represent an interesting adjunctive therapy to amoxicillin for oral consolidation treatment of EFIE.