Time to abandon ampicillin plus gentamicin in favour of ampicillin plus ceftriaxone in Enterococcus faecalis infective endocarditis? A meta-analysis of comparative trials

Abstract

Background Current guidelines recommend either ampicillin plus ceftriaxone (AC) or amoxicillin/ampicillin plus gentamicin (AG) with an equivalent class IB recommendation in Enterococcus faecalis endocarditis. However, previous observational studies suggest that AC might be favourable in terms of adverse events. Objectives To investigate whether AC is non-inferior to AG, and if it is associated with less adverse events. Methods In June 2021, a systematic literature search using the databases PubMed/MEDLINE, CDSR, CENTRAL, CCAs, EBM Reviews, Web of Science and LILACS was conducted by two independent reviewers. Studies were considered eligible if (P) patients included were ≥ 18 years of age and had IE with E. faecalis, (I) treatment with AC was compared to (C) treatment with AG and (O) outcomes on in-hospital mortality, nephrotoxicity and adverse events requiring drug withdrawal were reported. Odds ratios and 95% confidence intervals were calculated using random-effects models with the Mantel–Haenszel method, the Sidik–Jonkman estimator for τ2 and the Hartung–Knapp adjustment. Results Treatment with AC was non-inferior to AG, as depicted by no significant differences in-hospital mortality, 3-month mortality, relapses or treatment failure. Furthermore, AC was associated with a lower prevalence of nephrotoxicity (OR 0.45 [0.26–0.77], p = 0.0182) and drug withdrawal due to adverse events (OR 0.11 [0.03–0.46], p = 0.0160) than AG. Conclusions Treatment with AC was non-inferior to treatment with AG, and it was associated with a reduced prevalence of nephrotoxicity and drug withdrawal due to adverse events. Thus, combination therapy with AC appears favourable over AG in patients with E. faecalis IE. Graphical abstract

Infective Endocarditis in the Elderly: Challenges and Strategies

“…Accordingly, therapeutic drug monitoring is essential in this population, especially when using narrow therapeutic index antibiotics [ 100 , 101 , 102 ]. A reduction in aminoglycoside use, recommended in the latest guidelines (no longer recommended in Staphylococcus aureus native-valve IE and shortened to 2 weeks in Enterococcus faecalis and streptococci with penicillin MIC > 0.125 μg/mL) [ 9 ], as well as aminoglycoside replacement by ceftriaxone in E. faecalis treatment [ 103 , 104 , 105 , 106 ], should be preferential in older people [ 107 , 108 ]. Despite recent efforts to improve vancomycin drug monitoring [ 100 , 101 , 109 , 110 ], daptomycin has shown a lower risk of clinical failure and treatment-limiting AEs than vancomycin [ 111 , 112 , 113 , 114 ] and should be preferentially used when available.…”

Guidelines for Diagnosis and Management of Infective Endocarditis in Adults

“…Most WikiGuidelines authors suggest against routine use of adjunctive aminoglycosides because of a lack of evidence of benefit with a demonstrable risk of harm (discussed in eAppendix 3 in Supplement 1). Options for definitive intravenous therapy by organism are presented in Table 2, with nuanced discussions in eAppendix 3 in Supplement 1 …”

“…Options for definitive intravenous therapy by organism are presented in Table 2, with nuanced discussions in eAppendix 3 in Supplement 1. [54][55][56][57][58][59][60] Question 3: Can Oral Antimicrobial Therapy Be Used to Treat IE? (Clear Recommendation)…”

“…If used, 2 weeks of gentamicin may provide most of the benefit while mitigating toxic effects [57][58][59]. The combination of ampicillin and ceftriaxone is associated with similar cure rates and fewer adverse events 60. It is not known whether ampicillin is as effective.…”

Impact of Enterococcus faecalis Endocarditis Treatment on Risk of Relapse

“…This dual therapy has the disadvantage of a high risk of acute kidney injury (25% of patients) and loses its synergistic effect against isolates with high-level aminoglycoside resistance (HLAR) [ 10 , 11 ]. The combination of ampicillin and ceftriaxone has shown synergistic activity in vitro against E. faecalis, and retrospective studies have shown that this combination had a similar clinical cure rate for EFIE as the A-G combination, with a better safety profile [ 10 , 12 , 13 ].…”