Definitions of terms used in the 2023 Duke-ISCVID IE criteria for the diagnosis of infective endocarditis, with proposed changes in bold type

Major criteria

Microbiologic major criteria

Positive blood cultures

Microorganisms that commonly cause IE^* isolated from 2 or more separate blood culture sets (typical)^¶

Microorganisms that occasionally or rarely cause IE isolated from 3 or more separate blood culture sets (nontypical)^¶

Positive laboratory tests

Positive PCR or other nucleic acid-based technique^Δ for Coxiella burnetii, Bartonella species, or Tropheryma whipplei from blood

Coxiella burnetii antiphase I IgG antibody titer >1:800^◊, or isolated from a single blood culture

Indirect immunofluorescence assays (IFA) for detection of IgM and IgG antibodies to Bartonella henselae or Bartonella quintana with IgG titer ≥1:800^◊

Imaging major criteria

Echocardiography and cardiac computed tomography imaging

Echocardiography and/or cardiac CT showing vegetation^§, valvular/leaflet perforation^¥, valvular/leaflet aneurysm^‡, abscess^†, pseudoaneurysm^**, or intracardiac fistula^¶¶

Significant new valvular regurgitation on echocardiography as compared to previous imaging. Worsening or changing of pre-existing regurgitation is not sufficient.

New partial dehiscence of prosthetic valve as compared to previous imaging

[18F]FDG PET/CT imaging

Abnormal metabolic activity^ΔΔ involving a native or prosthetic valve, ascending aortic graft (with concomitant evidence of valve involvement), intracardiac device leads or other prosthetic material^◊◊,§§

Surgical major criteria

Evidence of IE documented by direct inspection during heart surgery neither major imaging criteria nor subsequent histologic or microbiologic confirmation^¥¥

Minor criteria

Predisposition

Previous history of IE
Prosthetic valve^‡‡
Previous valve repair^‡‡
Congenital heart disease^††
More than mild regurgitation or stenosis of any etiology
Endovascular CIED
Hypertrophic obstructive cardiomyopathy
Injection drug use

Fever

Documented temperature greater than 38.0 degrees centigrade (100.4 degrees Fahrenheit)

Vascular phenomena

Clinical or radiological evidence of arterial emboli, septic pulmonary infarcts, cerebral or splenic abscess, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions, purulent purpura

Immunologic phenomena

Positive rheumatoid factor, Osler nodes, Roth spots, or immune complex-mediated glomerulonephritis^***

Microbiologic evidence, falling short of a major criterion

Positive blood cultures for a microorganism consistent with IE but not meeting the requirements for major criterion^¶¶¶
Positive culture, PCR or other nucleic acid-based test (amplicon or shotgun sequencing, in situ hybridization) for an organism consistent with IE^¶¶¶ from a sterile body site other than cardiac tissue, cardiac prosthesis, or embolus; or a single finding of a skin bacterium by PCR on a valve or wire without additional clinical or microbiological supporting evidence

Imaging criteria

Abnormal metabolic activity as detected by [18F]FDG PET/CT within 3 months of implantation of prosthetic valve, ascending aortic graft (with concomitant evidence of valve involvement), intracardiac device leads or other prosthetic material

Physical examination criteria^ΔΔΔ

New valvular regurgitation identified on auscultation if echocardiography is not available. Worsening or changing of pre-existing murmur not sufficient.

CHD: coronary heart disease; CIED: cardiac implantable electronic device; CT: computed tomography; FDG PET/CT: F18-fluorodeoxyglucose positron emission tomography/CT; IE: infective endocarditis; IgG: immunoglobin G; IgM: immunoglobin M; NVE: native valve endocarditis; PCR: polymerase chain reaction; PVE: prosthetic valve endocarditis.

* Staphylococcus aureus; Staphylococcus lugdunensis; Enterococcus faecalis; all streptococcal species (except for S. pneumoniae and S. pyogenes), Granulicatella and Abiotrophia spp, Gemella spp, HACEK group microorganisms (Haemophilus species, Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae). In the setting of intracardiac prosthetic material, the following additional bacteria should be included as "typical" pathogens: coagulase negative staphylococci, Corynebacterium striatum and C. jeikeium, Serratia marcescens, Pseudomonas aeruginosa, Cutibacterium acnes, nontuberculous mycobacteria (especially M. chimaera), and Candida spp.

¶ "Blood culture set" is defined as a simultaneously drawn pair of 1 aerobic and 1 anaerobic bottle. "Positive" blood culture set is defined as microbial growth from at least 1 of the bottles. Blood cultures from separate venipuncture sites are strongly recommended whenever possible for evaluating suspected IE.

Δ Amplicon (16S or 18S) or metagenomic (shotgun) sequencing.

◊ Or equivalent titer results on other methodologies.

§ Oscillating intracardiac mass on valve or other cardiac tissue, endovascular CIED, or other implanted material in the absence of an alternative anatomic explanation.

¥ Interruption of valvular endocardial tissue continuity.

‡ Elongation with saccular outpouching of valvular tissue.

† Perivalvular (or perigraft) soft tissue lesion with variable degree of evolution to an organized collection.

** Perivalvular cavity communicating with the cardiovascular lumen.

¶¶ Communication between 2 neighboring cardiac chambers through a perforation.

ΔΔ For PVE, intense, focal/multifocal or heterogeneous FDG uptake patterns; for NVE and cardiac device leads, any abnormal uptake pattern.

◊◊ Performed at least 3 months after prosthetic valve surgical implantation.

§§ Some prosthetic valves may have intrinsic nonpathological FDG uptake. An isolated FDG-PET positive generator pocket in the absence of intracardiac infection, does not qualify as a major criterion. PET/CT can be useful in detecting extracardiac foci of infection.

¥¥ Addition of this major criterion should not be interpreted as giving license to not send appropriate samples for histopathology and microbiological studies.

‡‡ Placed either by open-heart surgical or transcatheter approach.

†† Includes cyanotic CHD (tetralogy of Fallot, univentricular heart, complete transposition, truncus arteriosus, hypoplastic left heart); endocardial cushion defects; ventricular septal defect; left-sided lesions (bicuspid aortic valve; aortic stenosis and insufficiency, mitral valve prolapse, mitral stenosis and insufficiency); right-sided lesions (Ebstein anomaly, anomalies of the pulmonary valve, congenital tricuspid valve disease); patent ductus arteriosus; and other congenital anomalies, with or without repair.

*** Defined as either:

Unexplained presence of either acute kidney injury (AKI, defined below) or acute on chronic kidney injury (defined below) plus 2 of the following: hematuria, proteinuria, cellular casts on inspection of urinary sediment, or serologic perturbations (hypocomplementemia, cryoglobulinemia, and/or presence of circulating immune complexes);

Renal biopsy consistent with immune complex-mediated renal disease. AKI: new unexplained reduction of estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². Acute on chronic kidney injury: reduction by at least one ordinal level of function: eg, from "moderately decreased" to "severely decreased"; or from "severely decreased" to "kidney failure." Interpretive ranges for eGFR: Normal ≥60 mL/min/1.73 m²; moderately decreased 30 to 59 mL/min/1.73 m²; severely decreased 15 to 29 mL/min/1.73 m²; kidney failure <15 mL/min/1.73 m².

¶¶¶ Excludes single positive blood cultures or sequencing based assays for microorganisms that commonly contaminate blood cultures or rarely cause IE.

ΔΔΔ Applicable only when echocardiography is unavailable. Based on expert opinion.

From: Vance G Fowler, Jr, et al. 'The 2023 Duke-International Society for Cardiovascular Infectious Diseases Criteria for Infective Endocarditis: Updating the Modified Duke Criteria.' Clinical Infectious Diseases (77) 4 (2023): 518-526, https://doi.org/10.1093/cid/ciad271. Reproduced by permission of Oxford University Press on behalf of the Infectious Diseases Society of America.

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Definitions of terms used in the 2023 Duke-ISCVID IE criteria for the diagnosis of infective endocarditis, with proposed changes in bold type