Ampicillin plus ceftriaxone (AC) is a well-recognized inpatient regimen for Enterococcus
faecalis infective endocarditis (IE). In this regimen, ceftriaxone is usually administered 2 g every 2 h
(AC12). The administration of AC in outpatient parenteral antibiotic treatment (OPAT) programs
is challenging because multiple daily doses are required. AC regimens useful for OPAT programs
include once-daily high-dose administration of ceftriaxone (AC24) or AC co-diluted and jointly
administered in bolus every 4 h (ACjoined). In this retrospective analysis of prospectively collected
cases, we aimed to assess the clinical effectivity and safety of three AC regimens for the treatment
of E. faecalis IE. Fifty-nine patients were treated with AC combinations (AC12 n = 32, AC24 n = 17,
and ACjoined n = 10). Six relapses occurred in the whole cohort: five (29.4%) treated with AC24
regimen and one (10.0%) with ACjoined. Patients were cured in 30 (93.3%), 16 (94.1%), and eight
(80.0%) cases in the AC12, AC24 and ACjoined groups, respectively. Unplanned readmission occurred
in eight (25.0%), six (35.3%), and two (20.0%) patients in the AC12, AC24 and ACjoined groups,
respectively. The outcome of patients with E. faecalis IE treated with AC in OPAT programs relies
on an optimization of the delivery of the combination. AC24 exhibit an unexpected rate of failures,
however, ACjoined might be an effective alternative which clinical results should corroborate in
further studies