Since the establishment of the Duke criteria for diagnosing infective endocarditis (IE) in 1994, with subsequent updates in 2000, the microbiological, epidemiological, diagnostic, and therapeutic landscapes have evolved significantly. The Infective Endocarditis Diagnostic Criteria Working Group of the International Society of Cardiovascular Infectious Diseases (ISCVID) has released a consensus document introducing the new diagnostic criteria: the 2023 Duke-ISCVID criteria.

COMMENTARY:

As this publication only highlights modifications relative to the previously used modified Duke criteria, many of which remain current, we will provide a summary of all the criteria, both new and pre-existing, that are currently utilized to establish a diagnosis of infective endocarditis:

Pathological Criteria:

The classical criteria included:

• Demonstration of microorganism presence through culture and/or histological examination of a cardiac vegetation, or one that has embolized, as well as histological analysis of a cardiac abscess specimen.
• Lesions, vegetations, or abscesses confirmed by histological examination consistent with IE.

In the new Duke criteria definition, compatible histological findings can now be detected not only in cardiac tissue but also in explanted prosthetic valves and prosthetic rings, vascular conduits from the ascending aorta (involving the aortic valve), and the intravascular portion of implantable electronic cardiac devices. Moreover, new genetic, molecular, and staining techniques are incorporated beyond histological analysis for diagnosis. The independent or combined use of 16S/18S rRNA gene PCR and fluorescence in situ hybridization has allowed up to a 30% increase in etiological identification for IE.

Clinical Criteria:

Traditionally, clinical criteria have been divided into two categories: major and minor. This classification remains in place, with new modifications incorporated into various components:

2.1 Major Clinical Criteria

2.1.1 Microbiological Criteria:

The previously required temporal criteria for drawing blood cultures from separate venipunctures have been removed. Isolating the microorganism in at least two independently drawn blood cultures is sufficient to meet the major criterion for typical pathogens; however, at least three cultures are needed for atypical pathogens. The updated criteria no longer require specific intervals between blood cultures, instead emphasizing the extraction of two independent samples if bacteremia is suspected. The list of typical IE agents has been expanded to include new species, such as Staphylococcus lugdunensis, Enterococcus faecalis, Streptococcus spp. (excluding S. pneumoniae and S. pyogenes), Granulicatella spp., Abiotrophia spp., and Gemella spp. Additionally, in prosthetic material samples, not from blood cultures, typical IE pathogens include coagulase-negative Staphylococcus, Corynebacterium striatum, Corynebacterium jeikeium, Serratia marcescens, Pseudomonas aeruginosa, Cutibacterium acnes, non-tuberculous Mycobacterium, and Candida spp.

Approximately 10% of patients with IE present with negative blood cultures. This may result from bacterial inhibition due to prior antibiotic treatment or a pathogen that cannot be isolated by traditional culture techniques. New criteria now consider positive PCR tests and other nucleic acid-based assays on blood samples for Coxiella burnetii, Bartonella spp., or Tropheryma whipplei as positive. For Coxiella burnetii, an IgG phase I antibody titer greater than 1:800 or detection in a single blood culture is sufficient. New indirect immunofluorescence criteria for detecting IgM and IgG antibodies against Bartonella henselae and Bartonella quintana with an IgG titer of 1:800 are also included.

2.1.2 Imaging Criteria:

Echocardiography remains the cornerstone of clinical diagnosis. Diagnostic criteria for IE will be established by identifying vegetations, perforations/ruptures of native or bioprosthetic leaflets, intracardiac/paravalvular abscesses, pseudoaneurysms, or intracardiac fistulas. Additionally, the presence of new regurgitation (native or prosthetic) is diagnostic, while worsening of a pre-existing regurgitation is insufficient in the absence of other findings. The presence of new paravalvular leakage within prosthetic valves is considered significant.

The new criteria introduce CT as a complementary imaging test due to its higher spatial resolution for detecting paravalvular lesions. It may supplement transesophageal echocardiography if doubts exist or serve as a substitute if contraindicated (e.g., in aortic endocarditis). The criteria for endocarditis findings are consistent with those described for echocardiography.

The PET-CT scan is also recognized as an imaging technique with high positive predictive value. The use of 18F-fluorodeoxyglucose (18-FDG) as a metabolic activity marker is accepted. Other techniques, such as Tc-99m-labeled leukocyte scintigraphy, commonly used in our setting, are not recognized. Intense, focal/multifocal, or heterogeneous uptake detected after 3 months from surgical implantation of intracardiac prosthetic material (valve, valvular conduit, and/or intracavitary electrodes) is classified as a major criterion. If the prosthetic implant is less than three months old, this finding is considered a minor criterion.

2.1.3 Surgical Criterion

A new surgical section has been added to the major clinical criteria. It is defined as intraoperative evidence of IE documented through direct inspection during surgery. This becomes a new major criterion without requiring prior microbiological or pathological confirmation. This criterion supports the management of cases requiring emergent intervention before culture/laboratory results or intraoperative pathological analysis are available, thereby allowing diagnosis and initiation/maintenance of antibiotic therapy.

2.2 Minor Clinical Criteria

In this heterogeneous section, many previous criteria are retained, some are modified, and others are added. They can be categorized as follows:

• Predisposition: The presence of prosthetic material for valve replacement or repair is retained, but intracavitary electrodes and prosthetic material for transcatheter valve repair or implantation are now included. A history of prior IE is also added. Criteria for congenital heart disease (any, not necessarily cyanotic), valvular insufficiency (more than mild), stenosis (any degree), hypertrophic obstructive cardiomyopathy, and intravenous drug use remain unchanged.
• Fever: The criterion for documented temperature >38ºC during the clinical course is retained.
• Vascular Phenomena: The criterion for evidence of septic arterial emboli causing pulmonary infarction, cerebral or splenic abscesses/infarcts (now included), mycotic aneurysms, intracranial hemorrhage, conjunctival hemorrhage, Janeway lesions, and septic purpura is retained.
• Immunological Phenomena: Criteria for the presence of positive rheumatoid factor, Osler’s nodes, Roth spots, and immune-complex-mediated glomerulonephritis are retained.
• Incomplete Major Criteria: This category, where most changes have been made, includes clinical findings that are significant but insufficient to define a major criterion. Among these:
  • Positive blood cultures that do not meet the requirements for a major criterion (<2 cultures for typical organisms, <3 cultures for atypical organisms).
  • A new criterion is added for the presence of positive cultures, PCR, or other nucleic acid-based tests (e.g., AMPLICON, shotgun sequencing, in situ hybridization) for IE-causing organisms in cardiac tissue, prosthetic material, or emboli without prior clinical or microbiological criteria to support them. This criterion appears to cover intraoperative samples of incidental findings that allow re-evaluation of preoperative diagnosis.
  • The finding of new valvular regurgitation identified by auscultation is downgraded to a minor criterion if echocardiography is unavailable. Worsening or changes in a pre-existing murmur are insufficient. This criterion was previously considered major. It remains useful for diagnosis in settings with limited resources (developing countries) or without direct access to echocardiography (primary care, first-level hospitals).
  • Pathological 18-FDG uptake in PET-CT within the first three months after prosthetic implantation, as previously indicated.

With the criteria outlined above, IE diagnosis is established based on the number of criteria met, unchanged from the previous version:

• Definite endocarditis: 1 pathological criterion or 2 major clinical criteria or 1 major + 3 minor clinical criteria or 5 minor clinical criteria
• Possible endocarditis: 1 major clinical + 1 minor criterion or 3 minor clinical criteria

However, the new document updates two of the three rejection criteria for IE:

1. An alternative diagnosis exists for the signs or symptoms, requiring three conditions: bacteremia due to an atypical pathogen, rapid resolution of bacteremia, and absence of IE evidence on imaging.
2. A new criterion for absence of recurrent bacteremia despite antibiotic therapy for less than 4 days. This expands the classic criterion of no autopsy or pathological findings compatible with IE despite antibiotic therapy for less than 4 days.
3. Failure to meet the criteria for definite or possible IE mentioned above.

In summary, most of the included criteria adapt the diagnosis to current resources and practices, which is welcome. However, one main limitation of these new criteria is the requirement for three blood cultures to meet the microbiological criterion for atypical pathogens. In an emergency or inpatient setting, two blood cultures are the norm. This could be problematic for diagnosing such pathogens. Nonetheless, blood culture requirements are simplified compared to previous temporal criteria for venipuncture extractions, which were rarely adhered to.

In conclusion, the Duke criteria emerged three decades ago to standardize the diagnosis of a complex condition like IE. These types of updates are essential for integrating technological and therapeutic advances into clinical practice.

REFERENCE:

Fowler VG, Durack DT, Selton-Suty C, Athan E, Bayer AS, Chamis AL, et al. The 2023 Duke-ISCVID Criteria for Infective Endocarditis: Updating the Modified Duke Criteria. Clin Infect Dis. 2023 May 4. doi: 10.1093/cid/ciad271.