In Vitro Synergism of Penicillin and Ceftriaxone against Enterococcus faecalis

Area of Science:

• Infectious Diseases
• Pharmacology
• Microbiology

Background:

• Enterococcus faecalis infective endocarditis (IE) is typically treated with intravenous ampicillin/ceftriaxone.
• Ampicillin's instability in continuous infusion limits its use in outpatient parenteral antibiotic therapy (OPAT).
• Benzylpenicillin has been proposed as an alternative to ampicillin in OPAT for IE.

Purpose of the Study:

• To evaluate the in vitro synergy of benzylpenicillin/ceftriaxone against clinical isolates of Enterococcus faecalis.
• To compare the synergistic effects of benzylpenicillin/ceftriaxone with ampicillin/ceftriaxone.
• To determine the influence of ceftriaxone minimum inhibitory concentrations (MICs) on the synergy of these combinations.

Main Methods:

• Checkerboard assays were performed on 28 clinical Enterococcus faecalis isolates and one laboratory strain.
• Fractional Inhibitory Concentration Index (FICI) was used to assess synergistic effects.
• Isolates were categorized based on ceftriaxone MICs (≤ 256 mg/L and ≥ 512 mg/L).

Main Results:

• Benzylpenicillin/ceftriaxone demonstrated synergy in 15/29 isolates, while ampicillin/ceftriaxone showed synergy in 22/29 isolates.
• For isolates with ceftriaxone MICs ≤ 256 mg/L, both combinations yielded comparable synergistic effects.
• For isolates with ceftriaxone MICs ≥ 512 mg/L, only ampicillin/ceftriaxone exhibited synergistic effects.

Conclusions:

• Benzylpenicillin/ceftriaxone may be suitable for OPAT of E. faecalis IE with ceftriaxone MICs ≤ 256 mg/L.
• For isolates with ceftriaxone MICs ≥ 512 mg/L, benzylpenicillin/ceftriaxone offers no advantage over benzylpenicillin monotherapy.
• Further research is needed to clarify the relationship between ceftriaxone susceptibility and penicillin/ceftriaxone synergy.