Update after 2023 ESC Guidelines for the Management of Infective Endocarditis (IE) – Regarding the National IE Guideline of the German Society of Pediatric Cardiology

Introduction

In 2023, new guidelines of the European Society of Cardiology (ESC) for the management of infective endocarditis (IE) were published.[1] These new 2023 ESC Guidelines also include changes in the management of IE in pediatric and adult patients with congenital heart disease (CHD). Therefore, we intend to comment on changes in comparison with the national German IE Guideline of the German Society of Pediatric Cardiology from 2022[1] by incorporating the new ESC Guideline ^a(https://register.awmf.org/de/leitlinien/detail/023-024).

The preceding ESC Guidelines were published in 2015,[2] and the following reasons led to the remake of 2023:

• Increasing population at risk for IE

• New data on different clinical scenarios in patients with IE

• Increasing resistance of antibiotics for oral streptococci

• The impact of new diagnostic modalities, including CT/nuclear imaging techniques, especially for patients with prosthetic valves and implantable cardiac devices.

Within the new 2023 ESC Guidelines, a large number of revised or new recommendations (>20) were summarized in an extensive publication (>100 pages, >850 references), including an update on antibiotic treatment. A paradigm change opens perspective for new optional outpatient and oral antibiotic treatment following 2 weeks of intravenous antibiotic treatment in stable (adult) patients with IE due to non-difficult-to-treat microorganisms.[1]

Within this comment, the authors of the national German Guideline summarize and discuss the most important new or revised recommendations with a focus on IE in pediatric or adult patients with CHD.

Prevention of Infective Endocarditis

The 2023 ESC Guidelines define general prevention measures as recommended for individuals at high and intermediate risk of IE (Class 1, Level C).

The rationale of prevention of IE is based on the pathophysiology of IE, with the three main predisposing risk factors contributing to IE with (1) predisposing cardiac condition, (2) pathogens in the bloodstream, and (3) immune responses.

Implementing these predisposing risk factors, the overall incidence of IE was estimated at 13.8 cases per 100,000 persons per year in 2019. For adults with a moderate and high risk of IE, the calculated incidence is 280 to 497 cases per 100,000 persons per year.[3] Data for the overall incidence rate of IE among adults with congenital heart disease (ACHD) is 27 to 44 times higher than the rate of adults in the general population (1.33 cases per 1,000 persons per year). In children with CHD, the incidence is 0.41 cases per 1,000 persons per year.[4] [5]

Portals of entry of pathogens include the oral cavity, skin infections, direct inoculation in People Who Inject Drugs (PWID), and in unsafe unprotected vascular procedures, and health care exposure due to invasive diagnostic and therapeutic procedures, either transcatheter-based or surgical interventions.

Therefore, the ESC Task Force revised the risk categories for IE, strengthened the recommendation of antibiotic prophylaxis, clarified the population at risk, and considered the advances in transcatheter valve interventions, which are frequently used in ACHD.

Patients, including those with CHD, are divided into three categories related to their patient-individual risk, presenting with a high morbidity when developing IE.

The following individuals are defined as having a high risk of IE, and antibiotic prophylaxis is recommended ([Table 1]):

Table 1 Patients at high risk of infective endocarditis

1. Patients with previous I (Class I, Level B).

2. Patients with surgically implanted prosthetic valves, with transcatheter implanted prosthetic (aortic and pulmonary) valves, and with any material used for cardiac valve repair. Furthermore, patients after septal defect closure or left atrial appendage closure devices, vascular grafts, vena cava filter, central venous line systems, and ventriculoatrial shunts for 6 months (I, C).

3. Patients with congenital heart disease, that is, untreated cyanotic CHD, after surgery with prosthetic material, including valved conduits or systemic-to-pulmonary shunts (I, C).

4. Patients with ventricular assist devices as destination therapy (I, C).

Abbreviation: CHD, congenital heart disease.

For patients with transcatheter-implanted prosthetic (mitral and tricuspid) valves, data are limited, but antibiotic prophylaxis should be considered (IIa, C). For patients after heart transplantation, antibiotic prophylaxis may be considered (IIb, C). This has not been mentioned in the national German Guideline. Also, new in the 2023 ESC guidelines are patients with ventricular assist devices being used as destination therapy, where antibiotic prophylaxis is recommended as a patient-individual decision.

While patients with an intermediate risk of IE were not considered to receive antibiotic prophylaxis, this recommendation was adapted in 2023. For individuals with an intermediate risk of IE, antibiotic prophylaxis is not routinely recommended, but may be considered on an individual basis ([Table 2]):

Table 2 Patients at intermediate risk of infective endocarditis

1. Patients with rheumatic heart disease.

2. Patients with non-rheumatic degenerative valve disease.

3. Patients with congenital valve abnormalities, including a bicuspid aortic valve

4. Patients with cardiovascular implanted electronic devices

5. Patients with hypertrophic cardiomyopathy

This intermediate risk category is new in the 2023 ESC Guideline, and has not been mentioned in the national German Guideline, but it was pointed out that the use of transvenous pacemaker leads in children and adolescents should be avoided in favor of using epicardial systems.

General prevention measures other than antibiotic prophylaxis are recommended for patients with high and intermediate risk of IE ([Table 3]):

Table 3 General prevention measures for patients at high and intermediate risk of infective endocarditis

1. Tooth cleaning twice daily.

2. Professional dental cleaning twice yearly.

3. Strict cutaneous care and hygiene.

4. Desinfections of wounds.

5. Curative antibiotics for any focus of bacterial infection, no self-medication.

6. Strict infection control measures for any high-risk procedures.

7. Discouraging piercing and tattooing.

8. Limitations of infusion catheters and invasive procedures.

9. Strict adherence to care bundles for central and peripheral cannula.

Basic measures are given a higher relevance. Any patients at risk of IE should be educated to maintain good dental and skin hygiene, look out for signs of infection, and, in case of fever, report to their physicians on their risk of IE and screening for IE (blood cultures before initiating antibiotics).

For patients with low risk of IE, antibiotic prophylaxis is not recommended (III, C).

Antibiotic prophylaxis is recommended for high-risk individuals undergoing at-risk dental procedures. At-risk dental procedures include dental extractions, oral surgery procedures, and dental procedures with manipulation of the gingival or periapical region of teeth (scaling, root canal procedures) (I, B). The main target of antibiotic prophylaxis is oral streptococci. A single dose of amoxicillin is recommended with a low risk of adverse fatal/non-fatal events. Alternative regimens in patients with allergy to penicillin/ampicillin are given, while clindamycin is not further recommended due to a higher risk for adverse fatal/non-fatal events.

New in the 2023 ESC Guidelines: Antibiotic prophylaxis for high-risk individuals for non-dental medical procedures may be considered for invasive diagnostic or therapeutic procedures of the respiratory, gastrointestinal, genitourinary tract, skin, and musculoskeletal system (new: Class IIb, C). Of note, the evidence for this recommendation is limited and was not included in the national German Guideline.

Perioperative antibiotic prophylaxis is recommended for all patients undergoing cardiac procedures, including implantation of prosthetic valves (I, B), prosthetic graft (I, B), occluder device (I, B), or cardiovascular-implanted electronic devices (I, B) against the most frequent microorganisms, that is, coagulase-negative staphylococci and Staphylococcus aureus. This includes preoperative screening for nasal carriage of S. aureus before elective cardiac surgery or transcatheter valve implantation (I, A) and treating carriers using local chlorhexidine. Furthermore, elimination of potential sources of sepsis, including dental origin, should be considered at least 2 weeks before cardiac procedure, except for urgent procedures (IIa, C). Antibiotic prophylaxis covering for common skin flora, including Enterococcus spp. and S. aureus, should be considered before transcatheter valvular procedures (IIa, C). But systematic skin or nasal decolonization without screening for S. aureus is not recommended (III, C).

Endocarditis Team

The importance and benefits of an Endocarditis Team have already been highlighted in previous recommendations. The 2023 ECS Guidelines again strongly recommend establishing such an expert team, as it has led to an earlier diagnosis of endocarditis and an earlier initiation of adequate therapy. In addition, decision-making for surgical interventions is optimized, all of this leading to an improved outcome for patients with infective endocarditis.

In the new 2023 ECS Guidelines, the role of the Endocarditis Team has been emphasized, and the recommendation to create a team of multidisciplinary specialists, depending on the local conditions and availability, is clearer than before. The setting of the team has also been defined, including core members (cardiologist, cardiovascular surgeon, infectious disease specialist, and microbiologist) and adjunct members (radiologists/nuclear medicine specialists, neurologists/neurosurgeons, intensive care specialists, geriatricians, and nephrologists), and the role of the team in the management of IE is explained in greater detail. The Endocarditis Team should meet regularly to discuss patient management and communicate closely with referring centers concerning the management of complicated cases. Given the increased emphasis on imaging techniques in the new ECS Guideline for the diagnosis and management of infective endocarditis, the input of cardiologists, radiologists, and nuclear medicine specialists from the Endocarditis Team is being brought into focus.

Adults with Congenital Heart Disease

While there are no changes in the specific recommendations for ACHD patients, the other changes in general principles, such as antibiotic prophylaxis, antibiotic therapy, or multimodality imaging, which are addressed in the previous and following paragraphs, also apply to our ACHD patients. It is important to note that the evidence regarding these recommendations is weak for the ACHD population.

Update on Diagnostic Approach

Diagnosis of IE is based on clinical suspicion, consistent microbiological data, and imaging results showing IE-related cardiac lesions.

Baseline clinical assessment remains crucial for clinical suspicion of infective endocarditis. The diagnosis of definite infective endocarditis relies heavily on the modified Duke criteria, which, however, were initially meant to equalize patient groups for research studies.[6] In practice, the modified Duke criteria have proven to be essential for IE diagnosis. The 2023 ECS Guidelines have been adapted due to the fact that newer imaging techniques have made considerable advances in confirming IE diagnosis when suspected. A large body of evidence is supplied in the data concerning nuclear imaging for the diagnosis and management of IE.[1]

Laboratory investigations remain as recommended or facilitating invasive risk stratification and monitoring the response to antibiotic therapy. No new biomarker has proven sufficient accuracy for endocarditis.

Blood cultures remain the cornerstone of IE diagnosis. In accordance with the previous guidelines, ESC recommends that at least three sets of blood cultures should be obtained, independent of the presence of fever.

Transthoracic echocardiography (TTE) remains the first-line imaging modality utilized to visualise endocarditis-related morphological and functional changes. The 2023 ECS Guidelines broaden the use of transesophageal echocardiography (TOE) in addition to TTE due to superior image resolution, with a sensitivity of about 90% and a specificity of >90%.[7] [8] Therefore, TOE is recommended in patients with suspected IE, even in cases with positive TTE, in left-sided native valve endocarditis (NVE), prosthetic valve endocarditis (PVE), or cardiac implantable electronic device (CIED)-related endocarditis. Performance of three-dimensional echocardiography or intracardiac echocardiography can be useful in right-sided endocarditis as well as in patients with PVE when TOE remains unclear.

However, in the presence of PVE and CIED-related IE, sufficient TTE and TOE imaging is often limited, so that other imaging techniques are strongly recommended.

Computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine imaging have been advanced with improved specificity and sensitivity.[7] [9] Therefore, in case of negative or inconclusive echocardiographic imaging, nuclear imaging is recommended to be performed, especially in PVE and CIED-IE. CT is recommended in patients with a high suspicion of NVE and negative or equivocal echocardiography. In patients with right-sided IE, whole-body CT can detect embolic complications, such as the presence of pulmonary infarctions and abscesses. CT is superior in diagnosing paravalvular and periprosthetic complications, abscesses, pseudoaneurysms, and fistulae compared to TOE. [¹⁸F]FDG-PET/CT(A) has become increasingly important in detecting IE, and, therefore, it is recommended to show metabolic activity associated with inflammation or abscesses in possible PVE and is useful in possible CIED-related IE to confirm the diagnosis and related complications ([Fig. 1]).

Fig. 1 Role of advanced imaging in the assessment of patients with infective endocarditis.[1] [19] ^aTOE is recommended in patients with suspected IE, even in cases with positive TTE, except in isolated right-sided native valve IE with good quality TTE examination and unequivocal echocardiographic findings (Class I, C); ^bsuspected paravalvular complications and TOE inconclusive or to detect pocket and lead infections and pulmonary embolism in CIED. CIED, cardiac implantable electronic device; [¹⁸F]FDG-PET, ¹⁸F-fluorodeoxyglucose positron emission tomography; CT, computed tomography; CTA, computed tomography angiography; IE, infective endocarditis; MRA, magnetic resonance angiography; MRI, magnetic resonance imaging; NVE, native valve endocarditis; PET, positron emission tomography; PVE, prosthetic valve endocarditis; TTE, transthoracic echocardiography; WBC SPECT/CT, white blood cell single photon emission tomography/computed tomography.

Brain and whole body assessment (CT, [¹⁸F]FDG-PET/CT, and MRI) is recommended in symptomatic patients with NVE and PVE to detect peripheral lesions and add to minor diagnostic criteria. MRI can detect subclinical brain embolization in the majority of patients with left-sided IE.[10] Compared to CT, the benefit of MRI is often limited in the diagnosis of IE and cardiac complications due to lower spatial resolution and artefacts from implants or increased blood flow. In asymptomatic patients, these imaging modalities may be considered for peripheral screening for NVE and PVE. White blood cell single photon emission tomography/computed tomography (WBC SPECT/CT) is often more specific in identifying active infection and may be more reliable for localizing IE in PVE, and it may be more helpful in detecting distant or subtle manifestations of IE, such as abscesses or emboli. It should also be considered when PET/CT is not available.[11]

2023 Duke-European Society of Cardiology Criteria and Diagnostic Algorithms

The major criteria of the modified Duke Criteria have been updated.[6] The microbiology, epidemiology, diagnostics, and treatment of infective endocarditis have undergone significant changes since the Duke Criteria were developed in 1994 and modified in 2000.[12] [13] The national German Guideline of the German Society of Pediatric Cardiology had already included enterococci species as typical IE microorganisms in 2022.[1] Due to the higher incidence of Enterococcus faecalis as a causative organism of IE, this organism has been specifically included by ESC as consistent with infective endocarditis in the major criteria.

An important novel part is the definite inclusion of all new nuclear imaging modalities as a major criterion, equally to echocardiography. In addition to the national German Guidelines, all imaging techniques are taken into account as relevant imaging methods for patients where echocardiography is inconclusive. Minor Duke Criteria remained unchanged by ESC 2023.

In addition to a modification of the diagnostic criteria, the 2023 ECS Guidelines provide new specific diagnostic algorithms for NVE, PVE, as well as for IE after implantation of a CIED. Pathways to diagnose NVE, PVE, and CIED-related IE support decision-making and reflect the use and sequencing of newer imaging methods to aid in diagnosing definite endocarditis and the detection of possible complications.

2023 Duke-International Society of Cardiovascular Infectious Diseases Criteria

In addition to the 2023 ECS Guideline, the International Society of Cardiovascular Infectious Diseases (ISCVID) published an actualized version of the Duke Criteria, also in 2023.[6]

ISCVID introduced distinct versions of the Duke Criteria reflecting significant advancements in microbiology and imaging techniques over the past decade. The 2023 Duke-ISCVID made substantial modifications to the microbiological major criteria by expanding the typical endocarditis pathogens with Streptococcus agalactiae and Streptococcus dysgalactiae alongside Streptococcus bovis group and viridans streptococci (with the exception of Streptococcus pneumoniae), as these pathogens are categorized as having a moderate risk for IE . In addition, a number of pathogens considered typical only in the presence of intracardiac prostheses are included. The requirements for timing and separate venipunctures for blood cultures were removed. Changes are proposed to the major criteria by including new microbiology diagnostic methods (enzyme immunoassay for Bartonella species, polymerase chain reaction [PCR], amplicon/metagenomic sequencing, in situ hybridization). As a new major criterion, intraoperative inspection and the identification of microorganisms by pathological criteria (PCR, amplicon or metagenomic sequencing, in situ hybridization) is suggested.

Similar to the Duke-ESC criteria, imaging by [¹⁸F]FDG-PET/CT (>3 months after cardiac surgery) and cardiac CT gets its place as a major clinical criterion.

Minor criteria have been more specified by clarifying three more conditions as predispositions: Transcatheter valve implantation, previous IE, and CIED.

New diagnostic methods were added as minor microbiological criteria, and [¹⁸F]FDG-PET/CT (<3 months after cardiac surgery) as a minor imaging criterion.

Several studies have observed an improvement in the sensitivity with the 2023 Duke-ISCVID and 2023 Duke-ESC compared to the 2015 Duke-ESC clinical criteria in different populations, such as patients with suspected IE, patients with bacteremia, or only those without IE, especially for streptococcal IE.[14]

Although the two 2023 versions differ in other aspects, changes in the microbiological criterion drove the superior performance of the 2023 Duke-ISCVID. These changes had a minor impact on specificity, which experienced a slight decrease.

Antibiotic Treatment

The standard antibiotic therapy of IE has not changed fundamentally from the guidelines in 2015. New is the inclusion of recommendations regarding the use of outpatient therapy, both as outpatient parenteral antibiotic therapy (OPAT) and as oral therapy.[15] Main reason for oral therapy was to get the older age population mobilized and out of the hospital, as long-term hospitalization led to immobility and secondary illness.

A novel strategy of potential oral antibiotic treatment is included in the ESC 2023 Guidelines and is based on a positive experience in an adult non-CHD population. This new recommendation for outpatient therapy parenteral antibiotic treatment should be considered in patients with left-sided IE caused by Streptococcus spp., E. faecalis, S. aureus, or CoNS who have received appropriate intravenous antibiotic treatment for at least 10 days (or at least 7 days after cardiac surgery), are clinically stable, and who do not show signs in TOE of complications such as abscess formation or valve abnormalities requiring surgery.

Outpatient parenteral antibiotic treatment is not recommended in patients with IE caused by highly difficult-to-treat microorganisms, heart failure, neurological involvement, renal impairment, liver cirrhosis (Child-Pugh B or C), untreated large extracardiac abscesses, heart valve complications, or other severe conditions requiring surgery, severe postsurgical complications, malabsorption, and in PWID-related IE.

If outpatient antibiotic therapy is planned, performance of a TOE is recommended before discharge to exclude a new indication for surgery.

If OPAT is considered possible, the new guidelines include a recommendation for the use of Dalbavancin, although the dosing regimen has not been clearly defined, and the new medication has not yet been approved in all countries at that point. A possible dosing regimen of 1.5 g as a loading dose followed by 0.5 to 1 g weekly until completing 6 weeks of antibiotic treatment has been suggested.

The Supplementary Table S8 provides details regarding the criteria to be considered when OPAT or oral therapy is used as a stepdown regimen after a “stabilization phase” of a minimum 10 days of intravenous therapy has been completed and the patient has no contraindications.[1] Two major scenarios for each of NVE, PVE, and CIED-related IE are depicted: A “critical phase” in which, after 10 days of intravenous treatment, OPAT or oral therapy is possible for patients with IE due to susceptible oral streptococcal or Streptococcus gallolyticus; and a continuation phase beyond 2 weeks, in which the causative microorganism is expanded to include Streptococcus spp., E. faecalis, S. aureus, or CoNS.

OPAT can effectively be continued in the appropriate patient using the same antibiotics used in the stabilization phase for the total duration of the antibiotic therapy.

The Supplementary Table S9 provides the drugs and doses of the oral antibiotic agents (largely those used in the POET study,[15] but with the additional combination of fusidic acid plus amoxicillin, dicloxacillin, or linezolid).[1] No literature source for this combination is provided. The selection of patients suitable for oral therapy is determined by both patient-specific factors, such as compliance, home environment, and availability of follow-up, as well as the availability of an oral antibiotic with suitable pharmacodynamic/pharmacokinetic properties for the respective microorganism.

The evidence base for the treatment of IE with oral antibiotics is still small, and therefore, although the guidelines make a bold statement, caution should be encouraged, and careful patient selection and monitoring are probably essential for a good outcome. There is no evidence yet on whether oral continuation of antibiotic therapy is effective in CHD patients. Nevertheless, the oral stepdown treatment is a very attractive addition to the management of IE.

Surgical Treatment

The indications for surgical treatment have essentially remained unchanged. The empirically known survival benefits of surgical therapy, if indicated, have been confirmed in larger studies.[16] [17] [18] Also, the principles of cardiac surgery have remained the same. In repair—if possible—an attempt should be made to avoid synthetic material. For the aortic valve, replacement will frequently be necessary; the choice of procedure and implant must take the patient's characteristics into consideration. The Ross procedure remains a reasonable option despite its inherent complexity.

Conclusion

Recommendation of antibiotic prophylaxis for high-risk patients before non-dental medical procedures is questionable; French guidelines do not include this, data are scarce to support this, probably just for really high-risk patients in vulnerable general conditions. Guidelines open the evaluation for the need of antibiotic prophylaxis in intermediate-risk patients upon individual medical judgment. Whether this leads to a reduction in IE cases in patients with CHD needs to be further investigated. The removal of clindamycin in case of allergy (due to increased Clostridium infections) remains to be discussed. Doxycycline, as an alternative, is still off-label use until 8 years of age and not feasible for most patients due to the unavailable of intravenous products. Furthermore, as a potential side effect, photosensitization for children remains a relevant problem during summer.

The new ISCVID criteria are valuable in terms of their usefulness, and the arguments leading to these adjustments are also important for the population with CHD. Nevertheless, it remains questionable why the 2023 ECS Guideline committee has no microbiologist on board. The inclusion of additional evidence from imaging as a major Duke criterion is particularly valuable and welcome for the CHD population. Modern microbiological diagnostics are missing in the 2023 ECS Guideline and still remain important for the CHD population. The role of the included streptococci species, as mentioned in the ISCVID Duke Criteria, needs to be verified in the future.

Oral treatment, as suggested by the Danish group to mobilize the elderly population, has been verified for left-sided IE demanding clinical follow-up twice weekly, including echocardiography and revision of oral medication.[15] In addition to this, the Danish group also uses this scheme for right-sided IE and CHD patients, not been published or verified so far. Nevertheless, we believe that this strategy should be urgently implemented for stable patients with CHD.

Conflict of Interest

None declared.

^a Knirsch W, MacKenzie CR, Schäfers HJ, Heying B, Tutarel O, Rickers C. Infektiöse Endokarditis und Endokarditisprophylaxe. Leitlinie der DGPK (beschlossen 28.09.2022) http://www.kinderkardiologie.org/Leitlinien

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Publication History

Received: 03 April 2025

Accepted: 03 August 2025

Article published online:
23 December 2025