Standard regimen for endocarditis caused by enterococci susceptible to penicillin but with high-level resistance to gentamicin
Gentamicin has no role in the treatment of endocarditis caused by enterococci susceptible to penicillin but with high-level gentamicin resistance, since synergistic killing is not achieved. Alternative regimens should be considered and cardiac surgery may be required. Some strains (approximately 10%) remain susceptible to streptomycin – seek expert advice1.
For adults and children with native or prosthetic valve Enterococcus faecalis endocarditis susceptible to penicillin, amoxicillin or ampicillin, but with either high-level aminoglycoside resistance, or relevant contraindications or precautions that preclude the use of gentamicin, as a 2-drug regimen, use:
1amoxicillin 2 g (child: 50 mg/kg up to 2 g) intravenously, 4-hourly for 6 weeks. For dosage adjustment in adults with kidney impairment, see amoxicillin dosage adjustment amoxicillin amoxicillin amoxicillin
OR
1ampicillin 2 g (child: 50 mg/kg up to 2 g) intravenously, 4-hourly for 6 weeks. For dosage adjustment in adults with kidney impairment, see ampicillin dosage adjustment ampicillin ampicillin ampicillin
OR
1benzylpenicillin 2.4 g (child: 60 mg/kg up to 2.4 g) intravenously, 4-hourly for 6 weeks. For dosage adjustment in adults with kidney impairment, see benzylpenicillin dosage adjustment benzylpenicillin benzylpenicillin benzylpenicillin
PLUS with one of the above drugs
ceftriaxone 2 g (child 1 month or older: 50 mg/kg up to 2 g) intravenously, 12-hourly for 6 weeks. ceftriaxone ceftriaxone ceftriaxone
Amoxicillin- or ampicillin-based regimens are supported by several nonrandomised observational clinical studies and are based on the in vitro synergistic effect of amoxicillin and broad-spectrum cephalosporins against E. faecalisFernandez-Hidalgo, 2013Leone, 2016Peterson, 2017Ramos-Martinez, 2020. This mechanism of synergy suggests high-dose benzylpenicillin is likely to have a similar effect (assuming proven susceptibility) if amoxicillin or ampicillin cannot be used, although supporting clinical data are limitedBeganovic, 2018Briggs, 2021Freeman, 2022Koehler, 2019Tritle, 2020. Twice-daily dosing of ceftriaxone is needed to maintain synergistic concentrationsHerrera-Hidalgo, 2021.
Parenteral ampicillin is inherently less stable than benzylpenicillin and its use in ambulatory antimicrobial therapy may pose a logistical challenge compared with using benzylpenicillinMaher, 2016 Suzuki, 2020. Switching to benzylpenicillin may be appropriate for continuation therapy for patients receiving ambulatory antimicrobial therapy for infective endocarditis – seek expert adviceBaddour, 2015Habib, 2015.
For patients with native or prosthetic valve endocarditis caused by other species of enterococci (including Enterococcus faecium), a synergistic effect with a penicillin and a broad-spectrum cephalosporin has not been shown. For penicillin-susceptible isolates, use monotherapy with benzylpenicillin, amoxicillin or ampicillin (see dosage above) and seek expert advice.