RT Journal Article
T1 Is Once-Daily High-Dose Ceftriaxone plus Ampicillin an Alternative for Enterococcus faecalis Infective Endocarditis in Outpatient Parenteral Antibiotic Therapy Programs?
A1 Herrera-Hidalgo, Laura
A1 de Alarcon, Aristides
A1 Lopez-Cortes, Luis Eduardo
A1 Luque-Marquez, Rafael
A1 Lopez-Cortes, Luis Fernando
A1 Gutierrez-Valencia, Alicia
A1 Gil-Navarro, Maria Victoria
K1 Enterococcus faecalis
K1 OPAT
K1 ceftriaxone
K1 combination treatment
K1 endocarditis
K1 pharmacokinetics
AB Ceftriaxone administered as once-daily high-dose short infusion combined with ampicillin has been proposed for the treatment of Enterococcus faecalis infective 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. 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 h during 24 h followed by a 7-day wash-out. Then the participants received phase B, which consisted of a single dose of 4 g of ceftriaxone. Throughout both phases, each volunteer underwent intensive pharmacokinetic (PK) sampling over 24 h. Ceftriaxone total and unbound concentrations were measured. Twelve participants were enrolled and completed both phases. Mean ceftriaxone total and free concentrations 24 h after the administration of 2 g each 12 h were 86.44 ± 25.90 mg/liter and 3.59 ± 1.35 mg/liter, respectively, and after the 4-g single dose were 34.60 ± 11.16 mg/liter and 1.40 ± 0.62 mg/liter, respectively. Only 3 (25%) patients in phase A maintained unbound plasma concentrations superior to the suggested Cs = 5 mg/liter during 24 h, and none (0%) in phase B. No grade 3 to 4 adverse events or laboratory abnormalities were observed. Ceftriaxone optimal exposure combined with ampicillin to achieve maximal synergistic activity against E. faecalis required for the treatment of infective endocarditis remains unknown. However, the administration of a single daily dose of 4 g of ceftriaxone implies a reduction in the time of exposure to the proposed Cs. (This study has been registered in the European Union Drug Regulating Authorities Clinical Trials [EudraCT] database under identifier 2017-003127-29.).
PB American Society for Microbiology
YR 2020
FD 2020-12-16
LK http://hdl.handle.net/10668/16404
UL http://hdl.handle.net/10668/16404
LA en
NO Herrera-Hidalgo L, de Alarcón A, López-Cortes LE, Luque-Márquez R, López-Cortes LF, Gutiérrez-Valencia A, et al. Is Once-Daily High-Dose Ceftriaxone plus Ampicillin an Alternative for Enterococcus faecalis Infective Endocarditis in Outpatient Parenteral Antibiotic Therapy Programs? Antimicrob Agents Chemother. 2020 Dec 16;65(1):e02099-20.
DS RISalud
RD Apr 10, 2025