Penicillin plus Ceftriaxone versus Ampicillin plus Ceftriaxone Synergistic Potential against Clinical Enterococcus faecalis Blood Isolates

Penicillin plus ceftriaxone is a promising alternative to ampicillin plus ceftriaxone for the treatment of Enterococcus faecalis infective endocarditis. Limited data is available supporting the utilization of penicillin plus ceftriaxone. A total of 20 E. faecalis isolates; one wild-type strain (JH2-2) and 19 clinical blood strains were assessed for penicillin plus ceftriaxone and ampicillin plus ceftriaxone synergy using a 24-h time-kill experiment. Susceptibility was determined by broth microdilution. Differences in bactericidal, bacteriostatic, or inactivity, as well as synergy between treatments were assessed by chi-square or Fisher exact test. All E. faecalis isolates were considered susceptible to ampicillin and penicillin. Ampicillin plus ceftriaxone versus penicillin plus ceftriaxone similarly demonstrated synergy. Bactericidal activity was more commonly observed for ampicillin plus ceftriaxone versus penicillin plus ceftriaxone. Among isolates with a penicillin MIC of 4 μg/mL (n = 7), synergistic activity for both combinations was less common compared to isolates with a penicillin MIC ≤ 2 μg/mL (n = 13). Ampicillin plus ceftriaxone and penicillin plus ceftriaxone demonstrate similar synergistic potential against E. faecalis clinical blood isolates, but strains with higher penicillin and ceftriaxone MICs less frequently demonstrated synergy. Further research is warranted to determine the role of the penicillin plus ceftriaxone therapy and the penicillin MIC in clinical practice. IMPORTANCE Penicillin plus ceftriaxone demonstrates similar synergistic activity against Enterococcus faecalis to ampicillin plus ceftriaxone. Isolates with a penicillin MIC of 4 mg/L and a ceftriaxone MIC of 512 or higher, lack penicillin plus ceftriaxone synergy despite the penicillin susceptibility MIC breakpoint of 8 mg/L.