ABSTRACT

Blood culture-negative endocarditis is often severe and

difficult to diagnose. It is necessary to emphasize the
importance for the early diagnosis and accurate treatment of
blood culture-negative endocarditis. Here, we described the
relevant clinical information of a blood culture-negative but
clinically diagnosed infective endocarditis complicated by
multiple septic emboli and non hemorrhagic infarct. This
patient was a 72-year-old man with a 2-month history of
intermittent fever and died in the end for the progressive
neurological deterioration. Although the blood culture is
negative, this patient was clinically diagnosed as infective
endocarditis according to Duke criteria.. The clinical findings
of this patient suggest that the confirmatory microbiology is
essential for the treatment of blood culture-negative infective
endocarditis. One should be aware of the detriment of blood
culture-negative infective endocarditis for its multiple
complications may occur in one patient. The delayed
etiological diagnosis and insufficient treatment may aggregate
the clinical outcome of blood culture-negative infective
endocarditis.
CASE REPORT
A 72 year old man k/c/o Type 2 DM and Hypertension with
one and half month history of high grade fever with chills,
pain abdomen, dyspnoea and right great toe ulcer admitted in
our institution. Physical examination revealed decreased air
entry at bases with few rhonchi, oedema both lower limbs and
a fever of 38.5 degree C. After withdrawing sample for blood
culture, he was started on broad spectrum antibiotics and
supportive management. Lab investigations suggestive of
hyponatremia, hypoalbuminemia, anaemia, septicemia and
high glucose levels. On day 2 he developed weakness,
numbness and pain in right arm. On examination, radial pulse
was not well felt and prompted for further evaluation of
thrombo embolic phenomenon. A transthoracic
echocardiogram revealed an approximate 1.5x0.8 cm size
mobile mass (?vegetation) attached to tip of atrial aspect of
anterior mitral valve leaflet, mild mitral regurgitation,
eccentric jet, moderate pericardial effusion, ejection fraction
65%. CT abdomen was done which revealed thrombo-
occlusion of common hepatic, left gastric, superior mesenteric
and splenic arteries with splenic infarct and splenic abscess
and bilateral pleural effusion. Blood culture revealed no
growth after 72 hours of incubation. He had intermittent
spikes of fever during coarse of admission and was managed
with i/v fluids, antibiotics, antipyretics, anticoagulants
(enoxaparin) and regular insulin. Blood culture testing was
done 3 times after admission but produced negative results.
Infective endocarditis was diagnosed clinically according to
the Duke criteria (one major and three minor). The major
criteria for thois patient were eviodence of endocardial
involvement with positive echocardiogram, and the monor
criteria were the following: predisposing factor(prior
antibiotic therapy), fever more than 38 degree C, and
embolism evidence. Patient continued to receive antibiotic
treatment with i/v teicoplanin and meropenem. In due coarse
he underwent right upper and lower limb venous/arterial
Doppler which revealed thrombus in right radial and ulnar
arteries. A repeat transthoracic echocardiogram revealed a
mobile mass (1.10x1.03 cm) attached to atrial surface of AML
(?vegetation), concentric LVH, mild mitral and tricuspid
regurgitation, early diastolic dysfunction, moderate pericardial
effusion, ejection fraction 60%. A cardiologist opinion was
takeb for surgical intervention and thrombolectomy was
planned but refused by attenders. He was discharged in stable
condition on oral antibiotics, antifungal, newer anti coagulant
and supportive therapy. After a week he was re admitted with
complaints of irrelevant talking, confusion since 3-4 days. On
examination he was conscious, dull and drowsy, had left limb
weakness and memory loss.In view of above findings A CT
scan was done which revealed well defined hypodensity in
right occipital region suggestive of an acute non-hemorrhagic
infarct in right PCA territory. On day of admission in evening
patient was dull, drowsy, febrile and had tachycardia. Further
examination revealed irregularly irregular pulse suggestive of
atrial fibrillation confirmed by ECG. He was managed with
i/v fluids , antibiotis, antipyretics, calcium channel blocker,
anticoagulants. Lab investigations showed anaemia,
septicaemia and hyponatremia. After 2 days of admission, in
evening he had sudden onset ghabrahat, shortness of breath.
He was febrile, dull and drowsy, developed aphasia. GCS was
E3V1M4. A repeat CT scan was not done. He died in hospital
after 2 days of above episode.
INTRODUCTION
Infective endocarditis (IE), with mortality rates of 20% to
40%, is the most frequently encountered endocarditis.
However, many cases of IE are clinically silent and are
recognized in only 2-10% of patients with eventual diagnosis
of infective endocarditis. Neurological complications of IE,
occurring in 20-40% of cases, can be classified into the
following categories: meningitis-encephalopathy, ischemic
complications, cerebral hemorrhage, and brain abscess [1].
Moreover, most complications occur in blood culture-positive
infective endocarditis, and most patients only experience one
or two neurological events during the IE episode [1]. Previous
reports have indicated that blood culture-negative endocarditis
is not common, and few studies have reported the correlation
between blood culture-negative IE and neurological
complications. Here, we report a blood culture-negative but
clinically diagnosed patient with IE complicated by
neurological and peripheral complication.
DISCUSSION
Blood culture-negative IE refers to endocarditis without
etiology after three blood samples incubated on standard
media. The Duke criteria may be inadequate for blood culture-
negative endocarditis due mainly to preceding antibiotic
administration or to fastidious slow-growing organisms.
Intracellular bacteria or autoimmunity also contributes to
occurrence of culture-negative IE.This patient who previously
received intermittent antibiotic therapy was clinically
diagnosed with blood culture-negative IE. This report
suggests that even when blood cultures are negative on initial
examination, careful history-taking, blood tests, and other
auxiliary examination are crucial for diagnosis before
histopathological examination.
Neurological complications are common manifestations of IE.
They develop in 25% of cases and lead to a higher mortality
rate, especially when vegetation size is ≥3 cm. Septic
embolization may cause ischemic stroke, mycotic aneurysm,
intracranial hemorrhage, meningitis, and brain abscess. This
patient manifested with multiple septic emboli. Ischemic
events are the most frequent neurologic complications of IE,
accounting for about 42% of all neurologic complications, and
are the first sign of IE in 47% of episodes . Recurrent cerebral
embolization has been rarely observed in previous reports. In
addition to the difficulty in diagnosis, the treatment for these
complications does not yet have defined protocols, especially
when occurring in combination. Early antimicrobial treatment
and cardiac surgery can reduce the risk of cerebral embolism.
Although previous report suggested that there was no
difference in in-hospital mortality or long-term survival
between culture-negative and culture-positive endocarditis
patients, the delayed etiological diagnosis may increase the
mortality of culture-negative endocarditis patients. Absence of
microbiological diagnosis may be a predictor for the poor
prognosis of blood culture-negative endocarditis. Early
diagnosis and empiric antibiotic treatment is important for the
prognosis of blood culture-negative endocarditis.