Modified Duke Criteria for Diagnosing Infective Endocarditis
Overview and Classification
The Modified Duke Criteria classify infective endocarditis into three categories—definite, possible, or rejected—with definite IE diagnosed by either pathological confirmation or specific combinations of clinical criteria: 2 major criteria, 1 major plus 3 minor criteria, or 5 minor criteria. 1
Pathological Criteria for Definite IE
- Microorganisms demonstrated by culture or histologic examination of a vegetation, embolized vegetation, or intracardiac abscess specimen confirms definite IE. 2, 1
- Histologic evidence of active endocarditis in a vegetation or intracardiac abscess also satisfies the pathological definition. 1
Clinical Criteria for Definite IE
Definite IE can be diagnosed clinically through the following combinations: 1
- Two major criteria
- One major criterion plus three minor criteria
- Five minor criteria
Major Criteria
Blood Culture Findings
Typical microorganisms from two separate blood cultures constitute a major criterion, including: 2, 1
- Viridans streptococci
- Streptococcus gallolyticus (formerly S. bovis)
- HACEK group organisms (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella)
- Staphylococcus aureus
- Community-acquired enterococci in the absence of a primary focus
Critical modification: Staphylococcus aureus bacteremia is now a major criterion regardless of whether it is nosocomial or community-acquired, reflecting that 13–46% of hospital-acquired S. aureus bacteremia cases progress to definite IE. 2, 1 This represents a key change from the original Duke criteria, which only considered community-acquired S. aureus as a major criterion. 2
Persistently positive blood cultures are defined as: 2, 1
- At least 2 positive cultures drawn >12 hours apart, OR
- All 3 cultures positive, OR
- A majority of ≥4 separate cultures positive with first and last drawn ≥1 hour apart
A single positive blood culture for Coxiella burnetii OR an anti-phase I IgG titer >1:800 meets a major criterion. 2, 1 This was upgraded from a minor to major criterion after studies demonstrated it reclassifies many culture-negative cases from possible to definite IE. 2, 1
Echocardiographic Evidence
Positive echocardiogram findings that constitute major criteria include: 2, 1
- Oscillating intracardiac mass on a valve or supporting structure, in the path of regurgitant jets, or on implanted material (without an alternative anatomic explanation)
- Abscess (perivalvular or myocardial)
- New partial dehiscence of a prosthetic valve
- New valvular regurgitation (worsening or changing of a pre-existing murmur is NOT sufficient)
Transthoracic echocardiography (TTE) should be performed first in all patients with suspected IE. 1, 3 Transesophageal echocardiography (TEE) is recommended for patients with prosthetic valves, those rated at least "possible IE" by clinical criteria, complicated IE with paravalvular abscess, or when optimal TTE windows cannot be obtained. 2, 3
Minor Criteria
The following constitute minor criteria: 1, 4
- Predisposition: Predisposing heart condition or injection drug use
- Fever: Temperature ≥38.0°C
- Vascular phenomena: Major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions
- Immunologic phenomena: Glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor
- Microbiological evidence: Positive blood culture that does not meet a major criterion OR serological evidence of active infection with an organism consistent with IE
Possible IE
Possible IE is diagnosed when: 1, 4
- One major criterion plus one minor criterion, OR
- Three minor criteria
Rejected IE
- A firm alternative diagnosis explains the findings, OR
- Resolution of the IE syndrome after ≤4 days of antibiotic therapy, OR
- Absence of pathological evidence at surgery or autopsy after ≤4 days of antibiotics, OR
- Failure to meet criteria for possible IE
Diagnostic Workflow and Key Recommendations
Obtain at least 3 sets of blood cultures from separate venipuncture sites before initiating antibiotics, with the first and last samples drawn at least 1 hour apart. 3 Blood cultures should be incubated under both aerobic and anaerobic conditions. 3
Blood cultures are positive in approximately 90% of IE cases when properly obtained; prior antibiotic administration is the most common cause of culture-negative IE. 3, 5 In one study, antibiotic treatment prior to blood culture was recorded in 63% of patients, contributing to a 71% rate of blood culture-negative IE. 5
If echocardiography is initially negative but clinical suspicion remains high, repeat echocardiography 7–10 days later, or earlier if S. aureus infection is suspected. 3
Critical Pitfalls and Caveats
The Duke criteria guide diagnosis but do not replace clinical judgment—clinicians may appropriately decide to treat regardless of whether criteria are met. 1, 3 This is particularly important because the Modified Duke Criteria have approximately 80% sensitivity, with lower diagnostic accuracy for early diagnosis, especially in prosthetic valve endocarditis and pacemaker/defibrillator lead IE. 3, 6
Failure to obtain adequate blood cultures before antibiotic administration is a major cause of culture-negative endocarditis. 4 For severely ill and unstable patients, perform 3 separate venipunctures over 1–2 hours and initiate empirical antibiotic therapy. 4 For non-acutely ill patients with negative cultures, withhold antibiotics for ≥48 hours to improve diagnostic yield. 4
For suspected culture-negative IE, specialized testing including serological testing for Coxiella burnetii, Bartonella spp., Brucella spp., Mycoplasma spp., and Legionella spp. should be pursued, along with consultation with a microbiology laboratory director or infectious disease specialist for guidance on molecular pathogen identification. 4, 3
The scarcity of classical Osler manifestations—bacteremia, fever, and peripheral stigmata—makes the diagnosis of IE a challenge in contemporary practice. 5 Low index of suspicion and inappropriate use of antibiotics have a great negative impact on diagnosis. 5