General approach to antimicrobial therapy for infective endocarditis

Antimicrobials for infective endocarditis must be given intravenously to ensure adequate drug concentrations, except in rare cases (eg infective endocarditis caused by Coxiella burnetii).

Beta lactams frequently form the basis of treatment for infective endocarditis. When beta-lactam antibiotics are recommended as first-line therapy, using vancomycin instead can be less effective and is associated with the selection of antimicrobial resistance and an increased risk of toxicity.

For patients who report penicillin hypersensitivity, verify their allergy. In some patients it may be appropriate to directly delabel their allergy by taking an extensive allergy history (see Clinical history for initial assessment of patients reporting penicillin hypersensitivity). In patients whose penicillin allergy has been delabeled, a penicillin-based regimen should be used. For patients with a verified hypersensitivity reaction to a penicillin that is:

• nonsevere (immediate or delayed), a cephalosporin-based regimen can be used (if appropriate for the type of endocarditis)
• severe immediate¹, treatment usually requires expert advice. Options that an infectious diseases physician or clinical microbiologist may use include:
  • using a cephalosporin (if appropriate for the type of endocarditis) if a beta-lactam antibiotic is strongly preferred (eg in a critical situation) – for considerations, see Severe immediate hypersensitivity: Implications of cross-reactivity between penicillins and cephalosporins
  • performing desensitisation
  • using a non–beta-lactam antibiotic
• severe delayed², a non–beta-lactam regimen should be used.

Avoid clindamycin, lincomycin and teicoplanin because rates of treatment failure with these drugs are unacceptably high for all types of infective endocarditis.

Particular attention should be given to therapeutic drug monitoring in endocarditis. Recommended dosages are for initial treatment only and may need to be modified according to the plasma concentrations attained (see Monitoring antimicrobial blood concentrations).

Treatment of infective endocarditis usually involves 4 to 6 weeks of intravenous therapy. The duration of therapy may be altered by valve surgery (see Duration of therapy after valve surgery for endocarditis). Once medically stable (usually after at least 1 to 2 weeks of inpatient treatment), some patients are suitable for Ambulatory antimicrobial therapy for endocarditis.

Studies on oral therapy for endocarditis (including the POET trial [Partial Oral Versus Intravenous Antibiotic Treatment of Endocarditis])Iversen, 2019Pries-Heje, 2022 have suggested that partial oral therapy may be safe in some highly selected adults with uncomplicated left-sided endocarditis. However, it has been questioned whether this approach is generalisable, given that a large number of cases in the POET trial were due to highly susceptible streptococcal species, in which shorter course combination therapy is routinely used (see Streptococcal endocarditis). In addition, the studies did not consider the outcomes relative to ambulatory antimicrobial therapy for endocarditis, which is well established in the Australian healthcare setting. Given the serious nature of endocarditis and the general availability and good outcomes with ambulatory antimicrobial therapy for endocarditis, the Antibiotic Expert Group recommends that partial oral therapy should only be considered in patients who meet strict stability criteria and are managed by an endocarditis team who have expertise in antimicrobial pharmacokinetics and have access to regular and timely therapeutic drug monitoringBoucher, 2019Brown, 2020Bundgaard, 2019Chowdhury, 2021Kobayashi, 2019Lauter, 2019Musher, 2019Perica, 2019Tattevin, 2019Verkaik, 2019Vroon, 2021Zimhony, 2019.