Endocarditis Secondary to Microsporidia
Giant Vegetation in a Pacemaker User
A 60-year-old white man was admitted with a 2-week history of shivering and fever (38°C). He had had a dual-chamber pacemaker implanted in 1996 because of complete atrioventricular block, with an elective pulse generator replaced 3 months before admission. Medications taken on a daily basis included amiodarone for atrial fibrillation rhythm control and atenolol for hypertension. His blood pressure was normal; his heart rate was 80 bpm; and he was febrile (38.5°C). Chest auscultation revealed a systolic murmur at the left and right sternal borders with respiratory shifting in the heart sound, not previously described in this patient. ECG showed a normally functioning pacemaker (Figure 1). Chest x-ray was normal (Figure 2), as were renal function and differential white cell count.
Endocarditis was confirmed by a transesophageal echocardiography showing a large echogenic mass (3.4 cm in diameter) in the right atrium attached to the ventricle pacing lead that did not compromise the tricuspid valve but caused moderate insufficiency (Figure 3 and movies in the online Data Supplement). Subsequently, because of the pacemaker endocarditis diagnosis, he was started on empirical vancomycin and gentamicin. Blood cultures were all negative, and despite antibiotic treatment, a control echocardiogram revealed that the vegetation had enlarged, reaching 4.0 cm in the largest diameter 4 weeks after the initial diagnosis. Because of the vegetation size and the persistent bacteremia, open heart surgery was indicated. On opening of the heart, a 4×7-cm vegetation was disclosed in the right atrium without signs of endocarditis (Figure 4). After 1 week of temporary pacing, a new permanent endocardial atrioventricular pacemaker was implanted.
Histological examination of the removed vegetation revealed a fibrin mass with no whole inflammatory cells containing many foci of Gram-positive coccobacilli (Figure 5). Electron microscopy demonstrated many microorganisms with characteristics of microsporidial spore, characterized by oval structures with a thickened external wall, containing 1 or 2 electron-dense round bodies. These microbes ranged from 0.4 to 0.8 μm in diameter, were 1.5 μm long, and had an absence of mitochondria; many of them exhibited clear spaces in the middle of the electron-dense material (Figure 6). Peripherally to these foci, the microorganisms had no external membranes compatible with their proliferative forms.
The diagnosis was confirmed by polymerase chain reaction (PCR) technique. DNA extraction was performed according to the method of Joseph et al,1 and primers were designed according to sequences published by Fedorko et al.2 The PCR results are shown in Figure 7. Negative control containing a reaction mixture without DNA was used during amplification (lane 1). Lane 2 shows the patient sample, and lane 3 shows a positive control from a culture of the microsporidium Encephalitozoon cuniculi.
In the present case, electron microscopy was fundamental for the diagnosis of microsporidia, confirmed later by PCR technique; without it, this diagnosis would not have been suspected. Although microsporidia are considered Gram negative and intracellular microorganisms,3 in our case, they were Gram positive and restricted to the extracellular inside a fibrin mass. Microsporidia have also been described as Gram positive in a case of intense proliferation of E cuniculi in an immunosuppressed patient, different from our case, whose HIV serology was also negative.4
After 6 weeks of antibiotic therapy, the patient was discharged on antihypertensive agents. He remained completely asymptomatic for 16 months after surgery without any evidence of recurrent infection. To the best of our knowledge, this is the first report of microsporidia infection in an implantable cardiac device. It may be a cause of antibiotic-resistant endocarditis in pacemaker lead implantation. For this diagnosis, electron microscopy study is fundamental and should be complemented by PCR.
The online-only Data Supplement is available with this article http://circ.ahajournals.org/cgi/content/full/119/14/e386/DC1.
Joseph J, Sharma S, Murthy SI, Krishna PV, Garg P, Nutheti R, Kenneth J, Balasubramanian D. Microsporidial keratitis in India: 16S rRNA gene-based PCR assay for diagnosis and species identification of microsporidia in clinical samples. Invest Ophthalmol Vis Sci. 2006; 47: 4468–4473.
Fedorko DP, Nelson NA, Cartwright CP. Identification of microsporidia in stool specimens by using PCR and restriction endonucleases. J Clin Microbiol. 1995; 33: 1739–1741.