1522. Penicillin plus ceftaroline against Enterococcus faecalis blood isolates lacking ampicillin plus ceftriaxone activity

Abstract

Abstract Background Enterococcus faecalis infective endocarditis standard of care treatment, ampicillin plus ceftriaxone, unfortunately has been unable to decrease mortality rates and additionally increases patient risk for vancomycin-resistant enterococci (VRE). Recent data also demonstrates decreased ampicillin plus ceftriaxone activity in E. faecalis isolates with an elevated penicillin MIC of 4 mcg/mL. Penicillin plus ceftaroline is a promising alternative but limited data is available to support. Methods Seven E. faecalis clinical blood isolates and one wild-type E. faecalis isolate (i.e., JH2-2) were tested against penicillin plus ceftaroline utilizing 24-hour in vitro time-kill assays. All isolates were penicillin susceptible with minimum inhibitory concentrations (MIC) of either 2 (n=4) or 4 (n=4) mcg/mL, and ceftaroline MICs ranged from 1 to 8 mcg/mL. Penicillin and ceftaroline were tested at subinhibitory concentrations (0.25x and 0.5xMIC) as monotherapy and in combination. Antibacterial activity was described as bactericidal or bacteriostatic, defined as a ≥ 3-log10 colony-forming units (CFU)/mL or < 3-log10 CFU/mL decrease from initial inoculum, respectively. Synergy was defined as a ≥ 2-log10 decrease in CFU/mL at 24 hours from the most active single agent. Results Penicillin and ceftaroline monotherapy did not demonstrate any antibacterial activity, except for ceftaroline 0.5xMIC where four isolates demonstrated bacteriostatic activity (Table 1). Penicillin plus ceftaroline was synergistic in all isolates except JH2-2 (penicillin MIC of 2 mcg/mL) due to the bacteriostatic activity of ceftaroline alone. Synergistic and bactericidal activity was also more frequently observed in isolates with a penicillin MIC of 4 mcg/mL with penicillin plus ceftaroline than ampicillin plus ceftriaxone. Conclusion Penicillin plus ceftaroline demonstrates synergistic activity against clinical E. faecalis blood isolates including isolates with a penicillin MIC of 4 mcg/mL, where ampicillin plus ceftriaxone less frequently demonstrated synergy. Further research is warranted to support utilization in patients with E. faecalis infective endocarditis. Disclosures Jaclyn A. Cusumano, PharmD, BCIDP, Shionogi: Advisor/Consultant.