2023 Duke-International Society for Cardiovascular Infectious Diseases (ISCVID) Criteria

Major and Minor Criteria

Major Criteria: 

A. Microbiologic Major Criteria

1. Positive blood cultures
   i. Microorganisms  that commonly cause IE^a isolated from 2 or more separate blood culture sets (typical)^b
   or
   ii. Microorganisms that occasionally or rarely cause IE isolated from 3 or more separate blood culture sets (nontypical)^b

2. Positive laboratory tests
   i. Positive PCR or other nucleic acid-based technique^c for Coxiella burnetii, Bartonella species, or Tropheryma whipplei from blood
   or
   ii. Coxiella burnetii antiphase I IgG antibody titer >1:800^d, or isolated from a single blood culture
   or
   iii. Indirect IFA for detection of IgM and IgG antibodies to Bartonella henselae or Bartonella quintana with IgG titer ≥1:800^d

B. Imaging Major Criteria

1. Echocardiography and cardiac CT imaging
   i. Echocardiography and/or cardiac CT showing vegetation,^e valvular/leaflet perforation,^f valvular/leaflet aneurysm,^g abscess,^h pseudoaneurysm,ⁱ or intracardiac fistula^j
   or
   ii. Significant new valvular regurgitation on echocardiography as compared with previous imaging. Worsening or changing of preexisting regurgitation is not sufficient.
   or
   iii. New partial dehiscence of prosthetic valve as compared with previous imaging

2. [18F]FDG PET/CT imaging
   Abnormal metabolic activity^k involving a native or prosthetic valve, ascending aortic graft (with concomitant evidence of valve involvement), intracardiac device leads, or other prosthetic material^l,m

C. Surgical Major Criteria

• Evidence of IE documented by direct inspection during heart surgery without meeting major imaging criteria or subsequent histologic or microbiologic confirmationⁿ

Minor Criteria:

A. Predisposition

• Previous history of IE

• Prosthetic valve^o

• Previous valve repair^o

• Congenital heart disease^p

• More than mild regurgitation or stenosis of any etiology

• Endovascular CIED

• Hypertrophic obstructive cardiomyopathy

• Injection drug use

B. Fever with a documented temperature >38.0°C (100.4°F)

C. Vascular phenomena, including clinical or radiological evidence of arterial emboli, septic pulmonary infarcts, cerebral or splenic abscess, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions, or purulent purpura

D. Immunologic phenomena, including positive rheumatoid factor, Osler nodes, Roth spots, or immune complex-mediated glomerulonephritis^q

E. Microbiologic Evidence, Falling Short of a Major Criterion 

1. Positive blood cultures for a microorganism consistent with IE but not meeting the requirements for major criterion^r

2. Positive culture, PCR, or other nucleic acid-based test (amplicon or shotgun sequencing, in situ hybridization) for an organism consistent with IE^r from a sterile body site other than cardiac tissue, cardiac prosthesis, or arterial embolus; or a single finding of a skin bacterium by PCR on a valve or wire without additional clinical or microbiological supporting evidence

F. 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

G. Physical Examination Criteria^s

• New valvular regurgitation identified on auscultation, if echocardiography is not available. Worsening or changing of a preexisting murmur is not sufficient.

^aStaphylococcus aureus; Staphylococcus lugdunensis; Enterococcus faecalis; all streptococcal species (except for Streptococcus pneumoniae and Streptococcus 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 Corynebacterium jeikeium, Serratia marcescens, Pseudomonas aeruginosa, Cutibacterium acnes, nontuberculous mycobacteria (especially M. chimaerae), and Candida spp.  

^b“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.  

^cAmplicon (16S or 18S) or metagenomic (shotgun) sequencing.  

^dOr equivalent titer results on other methodologies.  

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

^fInterruption of valvular endocardial tissue continuity.  

^gElongation with saccular outpouching of valvular tissue.  

^hPerivalvular (or perigraft) soft tissue lesion with variable degrees of evolution to an organized collection.  

ⁱPerivalvular cavity communicating with the cardiovascular lumen.  

^jCommunication between 2 neighboring cardiac chambers through a perforation.  

^kFor prosthetic valve endocarditis (PVE), intense, focal/multifocal, or heterogeneous FDG uptake patterns; for native valve endocarditis and cardiac device leads, any abnormal uptake pattern.  

^lPerformed at least 3 months after prosthetic valve surgical implantation.  

^mSome prosthetic valves may have intrinsic, non-pathological 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.  

ⁿAddition of this major criterion should not be interpreted as permission to omit sending appropriate samples for histopathology and microbiological studies.  

^oPlaced either by open-heart surgical or transcatheter approach.  

^pIncludes 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.  

^qDefined as either: 

(1) Unexplained presence of either acute kidney injury (AKI, defined later) or acute-on-chronic kidney injury (defined later) 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); 

or 

(2) 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 1 ordinal level of function: e.g., 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 30–59 mL/min/1.73 m²; severely decreased 15–29 mL/min/1.73 m²; kidney failure <15 mL/min/1.73 m².

^rExcludes single positive blood cultures or sequencing-based assays for microorganisms that commonly contaminate blood cultures or rarely cause IE.  

^sApplicable only when echocardiography is unavailable. Based on expert opinion.