What Are the New Duke ISCVID Criteria?

April 11, 2024

Written by Clay Smith

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Yesterday, we covered an article demonstrating the superior diagnostic accuracy of the new Duke-International Society for Cardiovascular Infectious Diseases Diagnostic (Duke-ISCVID) criteria. Today, we cover what the new criteria actually are.

“Wow, Duke has sure made a simple diagnostic tool for IE!” …said no one ever
It’s not a simple scoring system. Given the extraordinarily nuanced nature, we are going to quote the new criteria here for your reference. The big changes were in the introduction of new microbiological diagnostic tools and imaging advancements. Hopefully, our friends at MDCalc will build a shiny new calculator soon! Until then, here are the criteria – quoted in full here.

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

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Changes are in bold.

I. DEFINITE ENDOCARDITIS

A. Pathologic Criteria

1. Microorganisms identified^a in the context of clinical signs of active endocarditis in a vegetation; from cardiac tissue; from an explanted prosthetic valve or sewing ring; from an ascending aortic graft (with concomitant evidence of valve involvement); from an endovascular intracardiac implantable electronic device (CIED); or from an arterial embolus…
   or
2. Active endocarditis^b (may be acute^c or subacute/chronic^d) identified in or on a vegetation; from cardiac tissue; from an explanted prosthetic valve or sewing ring; from an ascending aortic graft (with concomitant evidence of valve involvement); from a CIED; or from an arterial embolus

B. Clinical Criteria

1. 2 Major Criteria
   or
2. 1 Major Criterion and 3 Minor Criteria
   or
3. 5 Minor Criteria

II. POSSIBLE ENDOCARDITIS

• A. 1 Major Criterion And 1 Minor Criterion
  or
• B. 3 Minor Criteria

III. REJECTED ENDOCARDITIS

• A. Firm alternate diagnosis explaining signs/symptoms^e
  or
• B. Lack of recurrence despite antibiotic therapy for less than 4 d.
  or
• C. No pathologic or macroscopic evidence of IE at surgery or autopsy, with antibiotic therapy for less than 4 d or
• D. Does not meet criteria for possible IE, as above

Here are all the tiny footnotes:

• ^aBy culture, staining, immunologic techniques, polymerase chain reaction (PCR), or other nucleic acid–based tests including amplicon (16S, 18S, internal transcribed spacers) sequencing, metagenomic (shotgun) sequencing, or in situ hybridization on fresh or paraffin-fixed tissue. Molecular techniques and tissue staining (Gram stain, periodic acid–Schiff with diastase, Grocott, or silver stains such as Warthin-Starry, Steiner, or Dieterle) should be interpreted cautiously, particularly in patients with a prior episode of IE because such tests can remain positive for extended periods following successful treatment. Antibiotic therapy before tissue procurement may also significantly alter microorganism morphology and staining characteristics. Test specificity is influenced by several factors, and false positives can occur. Test interpretation should always be in the context of clinical and histological evidence of active endocarditis. A single finding of a skin bacterium by PCR on a valve or wire without additional clinical or microbiological supporting evidence should be regarded as Minor Criterion and not Definite IE [51].
• ^bActive endocarditis—vegetations, leaflet destruction, or adjacent tissue of native or prosthetic valves showing variable degrees of inflammatory cell infiltrates and healing. Many specimens demonstrate mixed features.
• ^cAcute endocarditis—vegetations or cardiac/aortic tissue lesions of native or prosthetic valves showing active inflammation without significant healing or organizational change.
• ^dSubacute/chronic endocarditis—vegetations or cardiac/aortic tissue lesions of native or prosthetic valves demonstrating evidence of healing or attempted healing: maturing granulation tissue and fibrosis showing variable mononuclear cell infiltration and/or calcification. Calcification can occur rapidly in injured tissue and vegetations or be part of the underlying valvular disease that was the original nidus for IE.
• ^eFirm alternate diagnosis explaining IE signs and symptoms consists of either microbiologic or nonmicrobiologic causes. Firm alternate microbiologic diagnosis includes (1) identifiable source for bloodstream infection with a nontypical IE pathogen, (2) rapid resolution of bloodstream infection, and (3) absence of evidence for IE on cardiac imaging. Firm alternate nonmicrobiologic diagnosis includes (1) presence of non-IE cause for cardiac imaging findings (eg, marantic or nonbacterial thrombotic endocarditis) and (2) absence of microbiologic evidence for IE.

Ah, yes but what are the Major and Minor Criteria? Fret not, gentle reader. We have them for you here! Changes are in bold.

I. 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 polymerase chain reaction (PCR) or other nucleic acid-based technique^c for Coxiella burnetii, Bartonella species, or Tropheryma whipplei from blood
  or
  ii. Coxiella burnetii antiphase I immunoglobulin G (IgG) antibody titer >1:800^d, or isolated from a single blood culture
  or
  iii. Indirect immunofluorescence assays (IFA) for detection of IgM and IgG antibodies to Bartonella henselae or Bartonella quintana with immunoglobulin G (IgG) titer ≥1:800^d
  
• B. Imaging Major Criteria
  (1) Echocardiography and cardiac computed tomography (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) Positron emission computed tomography with 18F-fluorodeoxyglucose ([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 neither Major Imaging Criteria nor subsequent histologic or microbiologic confirmationⁿ

II. 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 intracardiac implantable electronic device (CIED)
  – Hypertrophic obstructive cardiomyopathy
  – Injection drug use
  
• B. Fever – Documented temperature greater than 38.0 °C (100.4 °F)
  
• C. 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
  
• D. Immunologic – Phenomena 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
  or
  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 mo 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 preexisting murmur not sufficient

Here are all the footnotes…

• ^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 degree 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 [42, 56]. 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 [51, 57].
• ⁿAddition of this major criterion should not be interpreted as giving license to not send 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 [58–60].
• ^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 or chronic kidney injury: reduction by at least 1 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 30–59 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.

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How will this change my practice?
Well, I certainly won’t be memorizing these. However, when I clinically suspect IE, I will look up the new criteria here, so I can better communicate my concerns with the admitting team and make the diagnosis with greater accuracy.

Source
The 2023 Duke-International Society for Cardiovascular Infectious Diseases Criteria for Infective Endocarditis: Updating the Modified Duke Criteria. Clin Infect Dis. 2023 Aug 22;77(4):518-526. doi: 10.1093/cid/ciad271. Erratum in: Clin Infect Dis. 2023 Oct 13;77(8):1222.