1112. Ceftobiprole for the Treatment of Invasive Enterococcus faecalis Infections: Ampicillin, "Should I Stay or Should I Go?"

BACKGROUND: Enterococcus faecalis is responsible for many serious infections for which combination bactericidal therapy is required(1). A synergism between amoxicillin and cefotaxime against E. faecalis through partial saturation of penicillin-binding proteins (PBPs) 4 and 5 by amoxicillin and total saturation of PBPs 2 and 3 by cefotaxime has been demonstrated(2). Unlike cefotaxime, ceftobiprole binds with high affinity to PBP2, PBP3, PBP4 and PBP5(3,4,5), thus a potential role in the management of severe E. faecalis infections might be hypothesized. The availability of therapeutic drug monitoring (TDM) for ampicillin and ceftobiprole has been driving the choice of using the combination of ampicillin plus ceftobiprole (ABPR) for the treatment of life-threatening E. faecalis infections. METHODS: We retrospectively analyzed clinical features (Table1), and trough ceftobiprole and ampicillin plasmatic concentrations of 21 patients admitted to our hospital from January to December 2020 for serious infection due to E. faecalis (61% infective endocarditis and 39% complicated bacteremia) who underwent ABPR treatment. Bacterial killing kinetics were also investigated in vitro for all strains. Bactericidal activity was defined as a ≥3 log10 decrease in bacterial count at 24 h. Synergy was measured at 24 h and was defined as a ≥ 2 log10 decrease in CFU/mL by the combination compared with its most active constituent and a ≥ 2 log10 decrease in the CFU/mL below the starting inocula. [Figure: see text] [Figure: see text] RESULTS: High clinical success rate of 81% and elevated microbiological eradication rate of 86% were reported. The ratios among all patients total plasmatic ampicillin and ceftobiprole concentrations and the corresponding MIC of enterococcal isolates far exceeded the PK/PD targets of maximized bactericidal activity (6) ( >4-5) (Figure 1). Ceftobiprole MIC(50) and MIC(90) were 0.5 mg/l and 1 mg/l, respectively. Time-kill curve for one of the 21 studied E. faecalis isolates is reported in Figure 2. Ceftobiprole showed such a potent bactericidal activity at concentration four times the MIC that a synergistic effect with ampicillin was even not demonstrable (Figure 2). [Figure: see text] [Figure: see text] CONCLUSION: Ceftobiprole even alone or ABPR might represent a valuable option for the treatment of severe E. faecalis invasive infections. DISCLOSURES: All Authors: No reported disclosures