Background and purpose

Infective endocarditis (IE) remains a serious syndrome in which timely diagnosis directs antimicrobial therapy, timing of surgery, and outcomes. Because IE is defined by a combination of microbiologic, imaging, and clinical findings, standardized criteria help teams classify cases as definite, possible, or rejected and communicate clearly across specialties. The 2023 Duke–ISCVID criteria update the widely used modified Duke framework to reflect advances in blood culture practice, molecular diagnostics, echocardiography, cardiac computed tomography (CT), and ¹⁸F-FDG PET/CT, while preserving the familiar major/minor structure.

These criteria are classification tools: they organize evidence and improve comparability in research and registries. In individual patients, results must always be integrated with pretest probability, response to therapy, procedural findings, and alternative diagnoses.

Overall classification logic (clinical criteria)

When pathologic criteria are not met, clinical IE is classified using counts of major and minor clinical criteria:

• Definite IE (clinical): any of (1) two major criteria; (2) one major criterion and three or more minor criteria; (3) five or more minor criteria.
• Possible IE (clinical): any of (1) one major criterion and one or more minor criteria; (2) three or more minor criteria when major criteria are not fulfilled.
• Rejected IE: assigned when specific exclusion scenarios apply (for example, a firm alternative explanation, failure to meet even "possible" criteria, or pathologic absence of IE after limited antimicrobial exposure as defined in the original publication). This determination relies on longitudinal clinical judgment rather than a single checklist pass.

Pathologic criteria (definite IE)

Pathologic definite IE is established independently of the clinical major/minor tally when any of the following apply, as specified in the 2023 Duke–ISCVID document:

• Histopathologic evidence of infective endocarditis on examination of resected valve tissue, embolic material, or other relevant specimens.
• Microbiologic demonstration of organisms by culture or molecular methods in material from a patient with clinical evidence of active IE, in accordance with the pathologic arm of the criteria.

When pathologic definite IE is present, the clinical major/minor counts are secondary for that "definite" label, though teams may still document imaging and culture data for completeness.

Major clinical criteria

Microbiology from blood

A major microbiologic criterion is satisfied by blood culture patterns that meet published thresholds for (a) organisms typical of IE with two or more separate positive blood culture sets, or (b) organisms that rarely or only occasionally cause IE with three or more separate positive sets. The formal manuscript distinguishes "typical" versus other organisms; calculators and bedside tools should defer to that list rather than informal assumptions about virulence.

Another major microbiologic pathway involves special pathogens: nucleic acid detection of Coxiella burnetii, Bartonella species, or Tropheryma whipplei from blood, or serologic/microbiologic results that meet predefined thresholds (including specified IgG titers and indirect immunofluorescence patterns for Bartonella and criteria for C. burnetii). These entries acknowledge culture-negative and slow-growing presentations that are disproportionately important in prosthetic and epidemiologically exposed populations.

Structural imaging: echocardiography and cardiac CT

Major imaging findings include vegetations; valvular or leaflet perforation or aneurysm; perivalvular or intracardiac abscess; pseudoaneurysm; or intracardiac fistula on echocardiography and/or cardiac CT when those modalities meet definitional requirements.

Valvular regurgitation counts as a major criterion only when echocardiography demonstrates a significant new regurgitant lesion. Worsening or changing of a preexisting regurgitant jet without meeting the "new" standard does not satisfy this item—an important safeguard against overcalling hemodynamic progression unrelated to acute infection.

For prosthetic valves, new partial dehiscence compared with prior imaging is a major criterion, reflecting a specific mechanical complication pattern linked to IE in appropriate clinical context.

¹⁸F-FDG PET/CT (major timing window)

FDG PET/CT has a dedicated major-criterion pathway when abnormal metabolic activity involves a native or prosthetic valve, ascending aortic graft with concomitant valve involvement, intracardiac device leads, or other specified prosthetic material, provided the timing relative to implantation meets the major-criterion definition (notably, for valves, activity at least three months after implantation in the qualifying pattern described in the source criteria). Early post-implant inflammatory uptake can mimic infection; the criteria therefore separate time-dependent PET findings into major versus minor roles.

Direct surgical observation

Intraoperative inspection that demonstrates infective endocarditis is a major criterion, aligning operative diagnosis with the schema used for multidisciplinary endocarditis teams and surgical planning.

Minor clinical criteria

Minor criteria aggregate clinical context and supportive—but not sufficient—evidence. In the Duke structure, each category below contributes at most one minor criterion when any element in that category is present.

Predisposition

Predisposing cardiac or behavioral factors include prior IE, prosthetic valve, previous valve repair, congenital heart disease, more-than-mild valvular stenosis or regurgitation from any cause, endovascular intracardiac implantable electronic devices, hypertrophic obstructive cardiomyopathy, and injection drug use. The minor criterion reflects elevated baseline risk rather than proof of infection.

Systemic inflammation

Fever (temperature ≥38.0°C, 100.4°F) is a minor criterion when documented, recognizing that immunosuppression, prior antipyretics, or renal failure may blunt this finding.

Vascular phenomena

Major arterial emboli, septic pulmonary infarcts, abscesses of the brain or spleen, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions, and purulent purpura—when clinically or radiologically confirmed—fall in this minor category. These findings raise suspicion and often trigger imaging but still require integration with microbiology and valve imaging.

Immunologic phenomena

Immune complex glomerulonephritis, Osler nodes, Roth spots, and rheumatoid factor constitute immunologic minor criteria. They are neither sensitive nor specific in isolation, yet they contribute to the pattern recognition that IE shares with other immune-complex states.

Microbiology not meeting major thresholds

Findings that are consistent with IE but fall short of major microbiologic criteria receive a minor criterion. This includes specified single positive cultures or molecular results and positive cultures or nucleic acid tests from select sterile sites other than cardiac tissue or embolic material, as detailed in the primary source. Teams must avoid double-counting the same culture line of evidence as both major and minor.

¹⁸F-FDG PET/CT (minor timing window)

When PET/CT shows abnormal uptake at a qualifying site within the early post-implant interval (for native or prosthetic valves, within three months of implantation in the qualifying pattern), it may fulfill a minor imaging criterion rather than a major one. This distinction reduces false positives from postoperative inflammation while retaining PET as a useful adjunct in selected cases.

Physical examination when echocardiography is unavailable

If echocardiography cannot be obtained, auscultatory evidence of new valvular regurgitation may serve as a minor criterion. As with the imaging major criterion, worsening or changing of a prior murmur without a new regurgitant lesion does not qualify.

Practical application in modern practice

Endocarditis evaluation is iterative. Early blood cultures (before antibiotics when safe), repeated cultures when clinically appropriate, and coordinated TTE/TEE remain central. Cardiac CT can clarify perivalvular complications when acoustic windows are poor. PET/CT is most valuable in prosthetic valve and device-related suspicion when timing and interpretation are aligned with the criteria. Multidisciplinary discussion (infectious diseases, cardiology, cardiac surgery, microbiology) is especially important when classification is borderline, when surgical indication is considered, or when intravenous drug use, healthcare exposure, or zoonotic exposures change the pathogen differential.

Clinicians should document which major and minor categories are satisfied, the dates of implantation for device and valve imaging interpretation, and why alternative diagnoses (septic thrombophlebitis, nonbacterial thrombotic endocarditis, malignancy, autoimmune mimics) are less compelling when IE remains possible or definite.