Diagnosis of culture negative endocarditis: novel strategies to prove the suspect guilty.

The diagnosis of infective endocarditis with its multiple clinical and morphological manifestations remains a challenging task. The von Reyn criteria, published in 1981, focused mainly on clinical and pathological findings in combination with positive blood culture to diagnose infective endocarditis. They were helpful to standardise diagnostic criteria, but their positive and negative predictive values remained unacceptably low, especially in the absence of positive blood culture results. With the introduction of transoesophageal echocardiography for the diagnosis of infective endocarditis, and the implementation of this method into the diagnostic criteria by Durack and colleagues, sensitivity and specificity of the diagnosis was significantly increased. Yet, in culture negative cases, sensitivity of these Duke criteria remains limited. 6 In most cases, there are two reasons for negative blood cultures: (1) patients received antibiotics before blood cultures are taken due to systemic infection or suspected diagnosis of a bacterial infection; and (2) the causative microorganisms have no, or limited proliferation in conventional blood cultures, or the diagnosis of the causative microorganisms requires special media or cell culture conditions. Negative blood cultures occur in 2.5–31% of all cases of infective endocarditis, which often delays diagnosis and onset of treatment with profound impact on the clinical outcome. The difficulties arising from culture negativity in cases of suspected endocarditis may be illustrated by a recent example from our institution. In November 2001, a 68 year old man was submitted to our department after syncope of unclear origin. The patient had undergone aortic valve replacement (Saint Jude 29.0 mm) in April 1999. Transthoracic and subsequent transoesophageal echocardiography yielded an oscillating structure of 3.8 mm length and 3.0 mm width at the aortic valve (fig 1). There was no concomitant valvar insufficiency and left ventricular (LV) function was normal. The patient had no clinical signs or symptoms of inflammation and routine blood cultures were negative. Since the anticoagulation management in this patient appeared inadequate, we diagnosed a thrombus at the aortic valve, and started intravenous anticoagulation with heparin and additional acetylsalicylic acid. After three weeks the control echocardiography showed no residual structure at the aortic valve, so the patient was switched to oral anticoagulation treatment and discharged. Six months later, the patient was readmitted to our intensive care unit with severe dyspnoea (New York Heart Association functional class IV) and a new diastolic murmur. Echocardiography showed aortic insufficiency grade III caused by paravalvar leakage, a dilated LV with a reduced systolic function, and a relative mitral insufficiency grade II. This time the patient displayed moderate leucocytosis and C reactive protein elevation. Immediately, empiric antibiotic treatment was initiated, and the patient was submitted to urgent aortic valve re-replacement. Intraoperatively a perivalvar abscess was found at the aortic valve, and aortic root reconstruction was performed with pericardial patching and implantation of a Carpentier Edwards Perimount 27 mm prothesis. Under empiric antibiotic treatment, blood culture results and cultures of the aortic valve remained negative. However, inflammatory parameters returned to normal and the patient recovered quickly and was discharged after six weeks of antibiotic treatment. Retrospectively, we suggest that the initially observed “thrombus” at the aortic valve represented already an endocarditic vegetation at the mechanical valve. In the following months, the inflammatory process then spread into the perivalvar tissue, with abscess formation and subsequent severe perivalvar insufficiency. The above case illustrates that echocardiography can provide crucial diagnostic information. In fact, transoesophageal echocardiography appears essential for the diagnosis of culture negative endocarditis when the Duke criteria are applied.