Outpatient parenteral antimicrobial therapy in Enterococcus faecalis infective endocarditis

Summary

What is known and objective

Enterococcus faecalis is the third most common causal agent of infective endocarditis. Currently, the treatment recommended is a combination of ampicillin (2 g/4 h) plus ceftriaxone (2 g/12 h), so patients must remain hospitalized for almost 6 weeks to receive the treatment. They are not generally included in outpatient parenteral antimicrobial therapy programs because 2 different electronic pumps are required to administer these 2 antibiotics. To enable the treatment of patients with E. faecalis IE at home, we designed a continuation combination regimen of ceftriaxone 4 g once daily in a short infusion plus ampicillin 2 g/4 h using a programmable pump.

Methods

We analyzed a cohort of patients attended in an outpatient parenteral antimicrobial therapy program that has been working since 2012 in 2 tertiary hospitals. We selected patients attended in this program for E. faecalis IE treated with a continuation regimen of ampicillin 12 g daily (2 g/4 h) and ceftriaxone 4 g every 24 hours between July 2012 and March 2017.

Results and discussion

Of the 720 patients included in the outpatient parenteral antimicrobial therapy program, 42 had infective endocarditis, and 4 (9.52%) were treated using the combination regimen described above. All patients were men, and all had left-sided native-valve infective endocarditis. All 4 patients received ampicillin 2 g every 4 hours and ceftriaxone 2 g every 12 hours in hospital, for a median duration of 25 days (IQR 15-32). Thereafter, in the program, they received the following regimen: a 30-minute infusion of ceftriaxone 4 g in 250 mL of saline solution, followed by ampicillin 12 g daily in 500 mL of saline solution delivered by a pump programmed to administer 2 g every 4 hours. Patients received this treatment at home for a median of 22.5 days (IQR 13-32). All patients achieved clinical and microbiological cure with no recurrences or complications after a lengthy follow-up period (median 365 days, IQR 221-406). No drug-related adverse events or problems with the pump system were reported.

What is new and conclusions

Use of ceftriaxone 4 g in a single dose yields a mean plasma concentration of 30 μg/mL. Ceftriaxone also has a high plasma protein binding capability, and once this binding is saturated, there is no reason to administer higher doses. Therefore, it seems reasonable to use a dose of 4 g of ceftriaxone once daily to have a synergist effect with ampicillin within the vegetation, and enable the treatment of patients with E. faecalis infective endocarditis at home. In conclusion, the administration of ampicillin (2 g/4 h) plus ceftriaxone (4 g/24 h) as a continuation regimen in an outpatient parenteral antimicrobial therapy program may be as effective and safe as the usual lengthy in-hospital regimen (ampicillin 2 g/4 h and ceftriaxone 2 g/12 h) in patients with E. faecalis infective endocarditis.

One of the most employed treatment for infective endocarditis due to E. faecalis is a combination of ampicillin (2 g/4 h) plus ceftriaxone (2 g/12 h), so patients must remain hospitalized for 6 weeks. We describe four cases treated with a continuation régimen of ampicillin 12 g daily (2 g/4 h) and ceftriaxone 4 g every 24 hours in an OPAT program in two Spanish tertiary hospitals. This strategy seems to be as effective and safe as the classic in-hospital régimen.

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