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"Ceftriaxone administered as once-daily high-dose short infusion combined with ampicillin has been proposed for the treatment Enterococcus faecalis infectious endocarditis in outpatient parenteral antibiotic therapy programs (OPAT)" Herrera-Hidalgo et al (2020).

Abstract:

Background: Ceftriaxone administered as once-daily high-dose short infusion combined with ampicillin has been proposed for the treatment Enterococcus faecalis infectious endocarditis in outpatient parenteral antibiotic therapy programs (OPAT). This combination requires synergistic activity, but the attainment of ceftriaxone synergic concentration (Cs) with the regimen proposed for OPAT has not been studied.

Methods: This Phase II pharmacokinetic study enrolled healthy adult volunteers, who underwent two sequential treatment phases. During Phase A volunteers received 2 g of ceftriaxone each 12 hours during 24 hours followed by 7-day washout. Then, the participants received Phase B, which consisted on 4 g single dose of ceftriaxone. Throughout both phases each volunteers underwent intensive pharmacokinetic (PK) sampling over 24 h. Ceftriaxone total and unbound concentrations were measured.

Results: Twelve participants were enrolled and completed both phases. Mean ceftriaxone total and free concentration 24 hours after the administration of 2 g each 12 hours were 86.44±25.90 mg/L and 3.59±1.35 mg/L and after 4 g single dose 34.60±11.16 mg/L and 1.40±0.62 mg/L, respectively. Only 3 (25%) patients in phase A maintained unbound plasma concentrations superior to the suggested Cs=5 mg/L during 24 hours, and none (0%) in phase B. No grade 3-4 adverse events or laboratory abnormalities were observed.

Conclusions: Ceftriaxone optimal exposure combined with ampicillin to achieve maximal synergistic activity against E. faecalis required for the treatment of infective endocarditis remains unknown. Whereas, the administration of a single daily dose 4 g of ceftriaxone implies a reduction in the time of exposure to the proposed Cs.

Herrera-Hidalgo L, de Alarcón A, López-Cortes LE, Luque-Márquez R, López-Cortes LF, Gutiérrez-Valencia A, Gil-Navarro MV; Grupo para el Estudio de las Infecciones Cardiovasculares de la Sociedad Andaluza de Enfermedades Infecciosas. Is once-daily high-dose ceftriaxone plus ampicillin an alternative for Enterococcus faecalis infective endocarditis in OPAT? Antimicrob Agents Chemother. 2020 Oct 12:AAC.02099-20. doi: 10.1128/AAC.02099-20. Epub ahead of print. PMID: 33046488.