Editorials

Diagnosis of infective endocarditis

Echocardiography and microbiological tests have improved the diagnosis

Since Osler's description of the classical signsbeloved of medical students, postgraduates, and their examinersinfective endocarditis has remained a clinical diagnosis.¹ But despite improved preventive strategies, rational prescribing of antibiotics, advances in imaging, and increasing use of lifesaving cardiac surgery at an early stage the incidence and mortality of the condition remain high. Current estimates suggest an incidence of 1.7-6.2 per 100 000 person years in the United States.² Mortality varies according to the infecting organism (viridans streptococci 4-16%, Staphylococcus aureus 25-47%, fungal infections over 50%) and is higher when infection affects a prosthetic valve or is complicated by congestive heart failure, abscess formation, or a neurological event. ^{2 3} Infective endocarditis often presents in an occult fashion, and early diagnosis depends on a high index of clinical suspicion especially in patients with congenital heart disease, prosthetic valves, or previous infective endocarditis. Sadly, clinical experience shows that the sickest patients are often referred late for imaging, specialist care, or surgery, even when the diagnosis has been clear for days or weeksalbeit in hindsight.⁴ Conversely, echocardiography departments are universally swamped with imaging requests for patients in whom the diagnosis is unlikely.

The failures of modern medicine to have an impact on an antiquarian diagnosis are highlighted in the June 2002 issue of Infectious Disease Clinics of North America, which contains articles on the current diagnosis and management of infective endocarditis. The original diagnostic criteria for infective endocarditis proposed by von Reyn, based on clinical and microbiological features, have now been superseded by the Duke criteria, which emphasise the role of echocardiography, the key imaging tool for both diagnosis and assessing prognosis.^5-7 Transthoracic echocardiography is a rapid and non-invasive investigation with high specificity (98%) but low sensitivity (60%) for the detection of vegetations. Imaging may be inadequate in up to 20% of patients, and transthoracic echocardiography is poor in the assessment of prosthetic valves and complications such as formation of abscesses, perforation of leaflets, and destruction of tissue. Thus, although good quality transthoracic echocardiography may exclude the diagnosis in patients at low risk, a negative study does not exclude infective endocarditis or its complications if these are strongly suspected.

The sensitivity and specificity of transoesophageal echocardiography are far superior owing to improved spatial resolution and image quality. It is therefore recommended in patients who are difficult to image, in patients with intermediate or high diagnostic probability and a normal transthoracic echocardiogram, in those with infective endocarditis affecting a prosthetic valve, and in patients with suspected complications such as abscess formation. Serial imaging may be required in patients with an initially normal study in whom diagnostic suspicion persists.⁸

Blood cultures are persistently negative in 5-10% of patients who satisfy diagnostic criteria for infective endocarditis. Failed culture may stem from inadequate microbiological techniques, infection with fastidious bacteria or non-bacterial organisms, or, most importantly, prior antibiotic administration. Commonly implicated organisms include the HACEK group, (Haemophilus aphrophilus, H paraphrophilus, H influenzae, H parainfluenzae, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella species), Coxiella burnetii, Bartonella, nutritionally variant streptococci (Abiotrophia species), Brucella, Legionella, and yeasts, including Aspergillus, Candida, and Cryptococcus. Improved diagnostic yields may be obtained by prolonged culture (although the risk of contamination increases), subculture under specialised conditions according to the suspected organism, and, for intracellular bacteria, inoculation of samples in shell vials and use of novel tissue cell lines.⁹

Serological assay can detect Coxiella, Brucella, Bartonella, or Chlamydia, and polymerase chain reaction to recover specific DNA or RNA from blood, urine, or surgically excised tissue has specific application when the potential pathogen is slow growing or non-culturable by conventional methods and when phenotypic characterisation is essential after two or more organisms are isolated in separate cultures. The latter happens most commonly after contamination with skin commensals during sampling or in case of polymicrobial infection in injecting drug users.¹⁰ These and other novel diagnostic techniques, such as specific fluorescent labelled antibody staining and electron microscopy, should now be considered in all cases where cultures have tested negative for infective endocarditis. Revised wording of the Duke criteria to take these into account has been proposed, although formal evaluation is awaited.¹¹

To date definitive studies of infective endocarditis have been difficult to perform because of the heterogeneous nature of the condition and because most data derive from case reports or case series from single centreslarge case control studies and randomised controlled trials are scant. The International Collaboration on Endocarditis has been conceived recently to develop a large global database of patients whose clinical, echocardiographic, and microbiological findings have been characterised by using standard methodology. The associated network of investigators and organisational infrastructure will provide the platform for large randomised trials to test therapeutic strategies.¹² This resource offers the opportunity for major advances in our understanding and treatment of infective endocarditis over the next two decades and provides a model on which global collaboration in other disease areas is likely to be based.

Bernard D Prendergast, consultant cardiologist. 

Department of Cardiology, North-West Regional Cardiothoracic Centre, Wythenshawe Hospital, Manchester M23 9LT (Bernard.Prendergast{at}smuht.nwest.nhs.uk)

Footnotes

Competing interests: None declared.