Background: Treatment regimens requiring multiple daily dosing for enterococcal endocarditis are challenging to deliver in the outpatient setting. Continuous-infusion benzylpenicillin via a 24 h elastomeric infusor, combined with either once-daily gentamicin or ceftriaxone, requires only one nursing encounter daily and is commonly used in New Zealand. Objectives: To assess the therapeutic success and adverse antibiotic effects of these regimens. Methods: A retrospective observational case series from multiple hospitals of patients aged 15 years or over with enterococcal endocarditis diagnosed between July 2013 and June 2019 who received at least 14 days of outpatient continuous-infusion benzylpenicillin combined with either gentamicin or ceftriaxone for synergy. Results: Forty-three episodes of enterococcal endocarditis in 41 patients met inclusion criteria. The primary synergy antibiotic was gentamicin in 20 episodes and ceftriaxone in 23 episodes. For the 41 initial treatment courses, 31 (76%) patients were cured, 3 (7%) patients developed relapsed endocarditis during or following antibiotic treatment and 7 (17%) patients continued with long-term suppressive oral amoxicillin following IV antibiotic treatment. There was no difference in the relapse rate between the two groups (P = 0.59). Seven (35%) adverse antibiotic effects were documented in the gentamicin group and none in the ceftriaxone group (P < 0.01). Two deaths (5%) occurred within the 6 month follow-up period. Conclusions: Outpatient treatment of enterococcal endocarditis with continuous-infusion benzylpenicillin combined with either once-daily gentamicin or ceftriaxone following a period of inpatient treatment is usually effective. A significantly higher rate of adverse effects was seen with gentamicin, favouring ceftriaxone as the initial synergy antibiotic.

Enterococcus faecalis infective endocarditis is commonly treated with intravenous ampicillin/ceftriaxone combination therapy. Ampicillin, however, is unsuitable for outpatient parenteral antibiotic therapy (OPAT) regimens due to its instability in 24 h continuous infusors, and has been successfully replaced by benzylpenicillin used together with ceftriaxone in a few small case series. Since in vitro synergy data of penicillin/ceftriaxone against E. faecalis are still lacking, checkerboard assays were performed for 28 clinical E. faecalis isolates and one laboratory standard strain. Synergistic effects (both lowest and median FICI) were observed for penicillin/ceftriaxone in 15/29 isolates, while ampicillin/ceftriaxone exhibited synergism in 22/29 isolates. For isolates with ceftriaxone MICs ≤ 256 mg/L, the addition of free ceftriaxone trough concentrations to penicillin or ampicillin resulted in comparable synergistic effects for both combinations. In contrast, for isolates with ceftriaxone MICs ≥ 512 mg/L free ceftriaxone trough concentrations were only sufficient to exhibit synergistic effects in combination with ampicillin, but not penicillin. This study suggests that benzylpenicillin/ceftriaxone would be expected to be suitable for the OPAT treatment of enterococcal endocarditis for E. faecalis isolates with ceftriaxone MICs ≤ 256 mg/L. However, combination therapy would be expected to provide no advantage over benzylpenicillin monotherapy for isolates with ceftriaxone MICs ≥ 512 mg/L. Further investigation is required to analyse the relationship between ceftriaxone susceptibility and penicillin/ceftriaxone synergy, especially for isolates with ceftriaxone MICs of 64 to 512 mg/L.

Background: In the 1970s, there were 2 reports of a late-onset adverse reaction during bolus infusions of benzyl penicillin, characterized by short-lived symptoms, most commonly abdominal pain. The mechanism is not known. We set out to further characterize this reaction. Methods: We conducted a prospective observational study of all adult patients receiving bolus intravenous (IV) beta-lactam antibiotics under the care of our Outpatient IV Antibiotic Service from 1 August 2007 to 31 January 2010, focusing on those who developed infusion-related symptoms. Results: During the 30-month study, 11 of the 163 patients (7%) treated with bolus IV beta-lactam antibiotics developed a late-onset infusion-related adverse reaction. Six of 30 patients (20%) treated with benzyl penicillin developed this adverse reaction compared to 5 of 133 (4%) treated with any other beta-lactam antibiotic (p = 0.006). The median duration of beta-lactam antibiotic before reaction onset was 25 days. Abdominal pain occurred in 9 patients (82%), fever in 3 (27%), and rash in 5 (45%). Seven patients (64%) developed a combination of thrombocytopenia, neutropenia, and/or lymphopenia and 6 (55%), elevated liver enzymes. Conclusions: This adverse reaction, occurring late during prolonged IV bolus beta-lactam treatment, is most often characterized by short-lived abdominal pain occurring at the time of infusion and is more common in patients receiving benzyl penicillin. It is frequently associated with cytopenias and elevated liver enzymes. It may have both immunological and non-immunological mechanisms.

Many patients with Enterococcus faecalis endocarditis are clinically stable and able to leave hospital before completing antibiotic treatment, but data are lacking regarding some outpatient treatment options. To assess the outcomes for adults with E. faecalis endocarditis receiving outpatient parenteral antimicrobial therapy (OPAT) with continuous infusion IV benzylpenicillin plus bolus/continuous infusion IV ceftriaxone. We retrospectively reviewed adults who received at least 2 weeks duration of OPAT for E. faecalis endocarditis with the above treatment regimen in the Auckland and Christchurch regions between July 2019 and September 2022. Forty-four patients met inclusion criteria. Fifteen were female (34%). The median age was 80 (IQR 71.5 to 84) years. Twenty-two (50%) had prosthetic valve (PV), 15 (34%) native valve (NV), 3 (7%) NV and/or cardiac implantable electronic device (CIED) infection, 3 (7%) PV and/or CIED infection, and 1 (2%) repaired valve endocarditis. Patients received a median of 16.5 days inpatient and 28 days OPAT antibiotic treatment. The 12 month outcome was cure (n = 25; 57%), antibiotic suppression (n = 9; 20%), relapse (n = 2; 5%; both possible) or death (n = 8; 18%). Compared with a historical cohort treated with OPAT continuous infusion IV benzylpenicillin plus bolus IV gentamicin, there was no difference in the relapse rate. This study adds to the accumulating evidence supporting the treatment of E. faecalis endocarditis with OPAT continuous infusion IV benzylpenicillin plus bolus/continuous infusion IV ceftriaxone. This is an option for patients requiring further antibiotic treatment at the time of hospital discharge.

We conducted a prospective cohort study of patients with newly acquired extended-spectrum beta-lactamase-producing Enterobacterales (ESBLPE) intestinal col