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5.5.1.5 Infective endocarditis classification Infective endocarditis classification has been added to the 2023 ESC criteria. Possible IE cases include the combination of 1 major and 1 or 2 minor criteria. Infective endocarditis classification should be applied by the Endocarditis Team at admission and later at follow-up, taking into account the complete clinical, microbiology, imaging, and surgical information to establish the final diagnosis. It is important to acknowledge that these new criteria should be prospectively validated. 5.5.2 The new 2023 European Society of Cardiology diagnostic algorithms The diagnosis of IE is based on clinical suspicion, blood cultures, and imaging findings. Echocardiography is usually the first imaging technique to diagnose IE, although the use of other techniques, either for the diagnosis of cardiac involvement (cardiac CT, [18F]FDG-PET/CT, or WBC SPECT/CT), or for the diagnosis of distant lesions (cerebral MRI, wholebody CT, and/or PET/CT), is encouraged. In the presence of prosthetic valves and CIED, echocardiography is particularly limited and the aforementioned imaging techniques are strongly recommended. Adapted diagnostic algorithms for suspected IE in NVE, PVE, and CIED are displayed in Figures 5–7, respectively. 6 Prognostic assessment at admission The in-hospital mortality rate of patients with IE has remained largely unchanged over the past two decades, ranging from 15% to 30%.5,145,250,251 Several patient characteristics, often occurring simultaneously, have been shown to confer an increased risk of death in IE. The rapid identification of patients at the highest risk may offer the opportunity to change the course of the disease (i.e. with urgent or emergency surgery) and improve prognosis. Predictors of poor outcome on admission of patients with IE are specified in the Supplementary data online, Section S3.1; Table S7. 7 Antimicrobial therapy: principles and methods 7.1 General principles Successful treatment of IE relies on microbial eradication by antimicrobial drugs. Surgery contributes by removing infected material. Bactericidal regimens are more effective than bacteriostatic therapy, both in animal experiments and in humans.252–254 Aminoglycosides synergize with cell wall inhibitors (i.e. beta-lactams and glycopeptides) for bactericidal activity and are useful for shortening the duration of therapy (e.g. oral streptococci) and eradicating problematic organisms. However, the side effects of aminoglycosides should be taken into consideration and currently the combination of ampicillin with ceftriaxone has demonstrated effective in treating IE caused by E. faecalis irrespective of the presence of high-level aminoglycoside resistance (HLAR) and minimizing the risk of nephrotoxicity.255,256 One major hindrance to drug-induced killing is bacterial antibiotic tolerance. Tolerant microbes are not resistant (i.e. they are still susceptible to growth inhibition by the drug) but escape drug-induced killing and may resume growth after treatment discontinuation. Slow-growing and dormant microbes display phenotypic tolerance towards most antimicrobials (except rifampin to some extent). They are present in vegetations and biofilms (complex communities of bacteria residing within an exopolysaccharide matrix that adheres to a surface, e.g. in PVE),257 and justify the need for prolonged therapy to fully sterilize infected heart valves. Some bacteria carry mutations rendering them tolerant during both active growth and stationary (dormant) phases.258,259 Bactericidal drug combinations are preferred to monotherapy against tolerant organisms (e.g. the combination of ampicillin and ceftriaxone in IE caused by E. faecalis). Drug treatment of PVE should last longer (≥6 weeks) than that of NVE (2–6 weeks) but is otherwise similar. In staphylococcal PVE, the regimen should include rifampin whenever the strain is susceptible, even if some recent data have shown no differences in outcomes between patients with PVE treated with rifampin vs. those treated without.260,261 In NVE needing valve replacement by a prosthesis during antibiotic therapy, the post-operative antibiotic regimen should be that recommended for NVE, not for PVE. In both NVE and PVE, the duration of treatment is based on the first day of effective antibiotic therapy (negative blood culture in the case of initial positive blood culture), not on the day of surgery. A new full course of treatment should only start if valve cultures are positive. Finally, there are important considerations in these recommendations: (i) Only published antibiotic efficacy data from clinical trials and cohort studies in patients with IE (or bacteraemia if there are no IE data) have been considered in these guidelines. Data from experimental IE models have not been taken into account. A recent systematic review evaluating the existing evidence about clinical benefits and harms of different antibiotic regimens used to treat patients with IE has shown that there is limited and low- to very low-quality evidence to make strong conclusions on the comparative effects of different antibiotic regimens on cure rates or other relevant clinical outcomes and, therefore, there is not enough evidence to support or reject any regimen of antibiotic therapy for the treatment of IE.262,263 (ii) These guidelines have adopted the MIC breakpoints included in the 2022 EUCAST clinical breakpoint tables.42 The EUCAST breakpoints are used to categorize results into three susceptibility categories: • Susceptible, standard dosing regimen: a microorganism is categorized as such, when there is a high likelihood of therapeutic success using a standard dosing regimen of the agent. • Susceptible, increased exposure: a microorganism is categorized as such when there is a high likelihood of therapeutic success because exposure to the agent is increased by adjusting the dosing regimen or by its concentration at the site of infection. • Resistant: a microorganism is categorized as such when there is a high likelihood of therapeutic failure even when there is increased exposure. The term exposure is defined as a function of how the mode of administration, dose, dosing interval, infusion time, as well as distribution and excretion of the antimicrobial agent, will influence the infecting organism at the site of infection. The local laboratories are responsible for the use of appropriate methods and interpretative criteria and quality control of the test results (MIC) while the clinicians are responsible for adjusting the level of exposure by modifying the dosing strategy ESC Guidelines 3975 Downloaded from academic.oup.com/eurheartj/article/44/39/3948/7243107 by guest on 07 October 2026