The long-awaited and much-needed update to the clinical guidelines on infective endocarditis (IE) has finally been published, driven by recent scientific evidence and the obsolescence of the previous 2015 guidelines.

If I had to highlight the most innovative contributions of these new guidelines, two fundamental aspects stand out. First, the long-anticipated reintroduction of antibiotic prophylaxis for procedures beyond dental interventions, reviving a practice that existed prior to the 2009 guidelines. The second highly significant change, paradigm-shifting after the POET clinical trial, is the possibility of oral antibiotic therapy starting from the tenth day of intravenous antibiotic treatment in selected cases, particularly after confirming the absence of complications with transesophageal echocardiography (TEE).

Main Updates

In addition to the above, the guideline introduces a series of highly interesting updates in almost all areas. It emphasizes the importance of a multidisciplinary team in managing complicated IE. Moreover, it provides new indications for prophylaxis and expands and modifies prophylactic antibiotic therapy. In the diagnostic field, it introduces innovations in advanced imaging techniques and presents highly useful algorithms for approaching suspected endocarditis. It underscores the relevance of early surgical intervention and updates embolism prevention strategies. Additionally, it addresses various other aspects, such as introducing recommendations for epicardial pacemaker implantation and proposing new guidelines for diagnostic tests in cases of spondylodiscitis. It also provides guidance on when to avoid preoperative coronary angiography and revises recommendations for surgical indications in endocarditis with right-sided chamber involvement, among other updates.

The core of this guideline lies in a scheme that illustrates, in detail, the patient’s flow from the moment IE is suspected until their medical discharge. At the heart of this process, especially for complicated IE, the fundamental role of the specialized multidisciplinary endocarditis team is highlighted. This team is responsible for making crucial decisions in managing the patient. Ideally, this team should operate from a referral center, ensuring the best care and follow-up.

1. Endocarditis Prophylaxis

The first recommendation of the guideline advocates the implementation of general prevention measures in patients at intermediate and high risk of developing IE. The identification of high-risk populations remains consistent with the 2015 guidelines. This includes patients with a history of endocarditis, those with cardiac prostheses (whether surgical or transcatheter), as well as patients with cyanotic congenital heart disease—whether unrepaired, repaired with a residual shunt, or completely repaired. For patients with complete repair, antibiotic prophylaxis is required only during the first six months. Notably, the recommendation class has been updated to Class I. Additionally, two new indications for antibiotic prophylaxis have been introduced:

1. Patients with ventricular assist devices, with a Class I recommendation.
2. Heart transplant recipients, with a Class IIb recommendation.

Regarding procedures requiring antibiotic prophylaxis, the recommendation for patients undergoing dental procedures involving gingival mucosa or the periapical region of the teeth has been upgraded to Class I B. A particularly significant innovation is the inclusion of other diagnostic and therapeutic procedures involving the respiratory, gastrointestinal, genitourinary, skin, and musculoskeletal systems, albeit with a slightly lower recommendation level of IIb C. Thus, antibiotic prophylaxis is no longer limited to dental procedures but extends to other types of interventions, reviving a practice that was in place before the 2009 guidelines. In a recent blog post, we anticipated that this extension was a much-needed measure, finally reflected in the new guidelines due to the abundant accumulated evidence.

For prophylactic antibiotic therapy in patients not allergic to beta-lactams, the recommendation to use amoxicillin or ampicillin is maintained. Options such as cefazolin or ceftriaxone are added. For patients allergic to beta-lactams, clindamycin has been excluded due to potential adverse effects and replaced with other antibiotics. It is important to note that the administration protocol remains a single dose given 30–60 minutes before the invasive procedure, primarily in the dental setting.

There is an emphasis on implementing general education measures for populations at high risk of endocarditis. This includes maintaining optimal oral health, proper skin hygiene, responsible use of antibiotics, and ensuring the patient is fully aware of the risk of endocarditis. It is crucial for the patient to recognize when antibiotic prophylaxis is necessary and to communicate it accordingly.

A Class I A recommendation for nasal screening for Staphylococcus aureus carriers prior to cardiac surgery or prosthetic implantation is retained. Additionally, the recommendation for perioperative antibiotic prophylaxis before any device implantation has been revised and elevated to Class I A. Significant new measures include the recommendation to apply skin antisepsis before device implantation and general aseptic measures when handling catheters in hemodynamic or electrophysiology labs. Directed antibiotic prophylaxis to cover common skin pathogens such as Staphylococcus aureusor Enterococcus is also proposed prior to transcatheter valve implantation, particularly transcatheter aortic valve implantation (TAVI).

Summary:
The key updates include general prevention measures for patients at moderate and high risk of IE, new indications for prophylaxis, and the modification and expansion of prophylactic antibiotic therapy.

2. Diagnosis of Infective Endocarditis

The microbiological diagnostic algorithm presented in these guidelines does not differ significantly from the previous 2015 guidelines. However, innovations are observed in imaging techniques. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) remain the fundamental tests for diagnosing IE.

The following updates are noteworthy:

• The recommendation for TEE when IE is suspected, even if TTE results are positive, has been elevated to Class I. Exceptions include cases with isolated right-sided native valve vegetations or involvement, provided TTE findings are of good quality and unequivocal.
• A new Class I recommendation has been introduced to perform TEE prior to transitioning from intravenous to oral antibiotic therapy—one of the most significant innovations in these guidelines.
• Echocardiography is now recommended not only in cases of Staphylococcus aureus bacteremia but also for Enterococcus faecalis and Streptococcus bacteremia.

Regarding advanced imaging techniques:

• Cardiac computed tomography (CT) and positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) are recommended with a Class I designation for diagnosing IE in native valves, prosthetic valves, and paravalvular lesions.
• Techniques like technetium-99m-labeled white blood cell (99mTc-WBC) imaging are mentioned with lower levels of evidence and are primarily reserved for detecting complications (both cardiac and extracardiac) or identifying the source of bacteremia.

3. Diagnostic Criteria

The newly proposed diagnostic criteria in these guidelines do not significantly deviate from the modified Duke criteria previously outlined in the 2015 guidelines. The main addition is the inclusion of Enterococcus faecalis as a typical microorganism.

The true innovation lies in imaging techniques, although not in TTE or TEE, which remain the cornerstone tests for diagnosis. Instead, a multimodal imaging approach is promoted.

Key advancements include:

• PET/CT and SPECT no longer require waiting three months after prosthetic implantation to be considered a major criterion, as was stipulated in the 2015 guidelines. Current evidence supports their ability to differentiate between inflammation and infection during this early postoperative period. As a result, PET/SPECT can now be performed immediately when needed.
• Minor criteria remain largely unchanged, as does the classification of IE as definite, possible, or rejected.

New algorithms are presented to address suspected IE in native valves, prosthetic valves, and devices. In all these algorithms, Class I recommendations establish that the first-line diagnostic approach should consider clinical characteristics, blood cultures, TTE, and TEE.

For possible endocarditis, which may be the most relevant scenario:

• A Class I recommendation is made to repeat blood cultures if initial results are negative or inconclusive, repeat TTE/TEE within 5–7 days, and perform cardiac CT if there is suspicion of a lesion on a native valve.
• For prosthetic valves, it is recommended to perform cardiac CT or 18F-FDG PET/CT.
• Advanced imaging techniques for detecting minor criteria are reserved as a secondary option, with a Class IIa recommendation.

4. Antibiotic Therapy

No significant changes have been made to the therapeutic regimens established in previous guidelines, as no new evidence has emerged to support modifications. Most of the available evidence remains classified as Class I with B/C levels of evidence, maintaining stability in this area.

However, a pivotal modification in the therapeutic approach to IE arises from the POET study, published in January 2019. After overcoming the critical acute phase during the initial 10-day hospitalization with intravenous (IV) antibiotic therapy, transitioning to oral therapy in stable patients is now a possibility. This is translated into close outpatient follow-up, supported by a Class I recommendation for a prior TEE, once the critical hospital phase has been completed.

Criteria for Stability
Patients eligible for this transition must meet specific stability criteria, which include:

• Positive blood cultures for Staphylococcus aureus, Streptococcus, coagulase-negative staphylococci, or Enterococcus faecalis.
• Controlled infection, demonstrated by the absence of fever, normalization of C-reactive protein levels, and absence of leukocytosis.
• Completion of at least 10 days of IV antibiotic therapy or 7 days post-valve surgery.
• No new surgical indications following TEE.

This innovative approach with oral therapy is expected to reduce hospitalization duration, among other long-term benefits already demonstrated. The recommendation for this group of patients is classified as Class IIa A.

5. Surgical Treatment

The three basic pillars of surgical indication in the 2015 guidelines—heart failure, uncontrolled infection, and high embolic risk or established embolism—remain unchanged. Heart failure continues to be the primary surgical indication, with its classification, class, and level of evidence remaining unaltered, as is the case for uncontrolled infection.

Notable Updates in Embolism Prevention

• A new Class I recommendation introduces urgent surgery for patients with vegetations ≥10 mm and other surgical indications.
• A new Class IIb recommendation suggests urgent surgery for patients with aortic or mitral IE who have vegetations ≥10 mm, without severe valve dysfunction or clinical evidence of embolism, provided they are at low surgical risk.

Timing of Surgical Interventions
The guidelines define timelines for these surgical indications:

• Emergent surgery: Performed within 24 hours.
• Urgent surgery: Carried out within 3–5 days.
• Non-urgent surgery: No specific timeframe is provided but must be performed before discharge during hospitalization.

A Class I C recommendation has been added for early surgical treatment involving valve replacement and complete debridement in cases of early prosthetic valve endocarditis (within six months of valve surgery).

Stroke Management and Surgical Indications
In the diagnostic and management algorithm proposed for IE, the type of stroke must first be determined:

• For ischemic stroke, surgery should not be delayed, with the recommendation upgraded to Class I.
• For hemorrhagic stroke, waiting for one month is ideal (Class IIa). However, in patients with hemorrhagic stroke who also present clinical instability due to heart failure, uncontrolled infection, or persistent high embolic risk, urgent or emergent surgery is considered, weighing the likelihood of neurological damage. This is also classified as Class IIa.

New recommendations include the use of mechanical thrombectomy and the contraindication of fibrinolysis in cases of embolic stroke.

Summary:
The guidelines emphasize the necessity of early surgical intervention. Surgery should not be delayed after ischemic stroke, while hemorrhagic stroke patients may undergo surgery under specific conditions. Early surgical treatment is recommended for IE on prosthetic valves, and surgical flexibility has been expanded to enhance thromboembolic prevention.

6. Device Implantation and Management

A Class I recommendation is established for the immediate removal of infected cardiovascular implantable electronic devices (CIEDs) once empirical antibiotic therapy has been initiated. This measure aims to reduce the risk of systemic complications and ensure effective infection control.

Additionally, a Class IIa recommendation suggests extending antibiotic therapy for 4–6 weeks after device removal in cases of septic embolism or when the patient has a prosthetic valve.

New Recommendations

• A Class IIa recommendation supports the implantation of epicardial pacemakers in patients with complete heart block who exhibit certain high-risk characteristics, such as:
  • Presence of Staphylococcus aureus.
  • Aortic root abscess.
  • Tricuspid valve involvement.
  • Prior valve surgery.

7. Musculoskeletal Complications

New recommendations, absent in previous guidelines, focus on musculoskeletal complications, particularly spondylodiscitis. The guidelines establish a Class I recommendation for the use of magnetic resonance imaging (MRI) or PET/CT in cases of suspected spondylodiscitis or vertebral osteomyelitis associated with IE.

8. Coronary Artery Assessment Before Cardiac Surgery

For patients with hemodynamic stability and aortic valve IE requiring cardiac surgery and at high risk of coronary artery disease (CAD), the guidelines recommend:

• High-resolution coronary CT angiography (CTA) with a Class I B recommendation.
• In cases where IE does not affect the aortic valve, coronary angiography remains the standard, with a Class I C recommendation.

9. Right-Sided Infective Endocarditis

The surgical indication for right-sided IE has been reviewed, and its recommendation has been elevated to Class I compared to previous guidelines. Surgery is considered in the following scenarios:

• Persistent vegetations >20 mm with recurrent pulmonary embolism.
• Right ventricular dysfunction secondary to severe tricuspid regurgitation, unresponsive to diuretics.
• Simultaneous involvement of left-sided structures.

New Recommendations:

• A Class IIa recommendation advises tricuspid valve repair whenever possible.
• Preventive placement of a pacemaker lead during tricuspid valve procedures is also recommended (Class IIa).

10. Patient-Centered Care

The guidelines conclude with a representation of contemporary medicine’s emphasis on individualized care. The patient plays an active role in decision-making regarding diagnostic tests and therapeutic options.

Preventive Measures:
Patients are encouraged to adopt general prevention measures, such as optimal oral health, early infection detection, and timely communication with healthcare providers about the need for antibiotic prophylaxis.

Final Highlights

The 2023 ESC guidelines will likely be remembered for two groundbreaking changes:

1. Reintroduction of antibiotic prophylaxis for invasive procedures beyond dental interventions, marking the first revision in nearly 15 years.
2. Incorporation of oral antibiotic therapy, a transformative approach to completing treatment for infective endocarditis.

REFERENCE:
Delgado V, Ajmone Marsan N, de Waha S, Bonaros N, Brida M, et al.; ESC Scientific Document Group. 2023 ESC Guidelines for the management of endocarditis. Eur Heart J. 2023 Aug 25:ehad193. doi: 10.1093/eurheartj/ehad193.