Native valve emphysematous enterococcal endocarditis: expanding the differential diagnosis

Abstract

Introduction

Emphysematous endocarditis is caused by the gas-forming organisms Citrobacter koseri, Escherichia coli, Clostridium species, and Finegoldia magna. We report the first case of emphysematous endocarditis caused by Enterococcus faecalis.

Case report

An 82-year-old man presented with fever and rapidly progressive shortness of breath. He was found to be in atrial fibrillation with rapid ventricular rates. Two-dimensional transthoracic echocardiography demonstrated severe mitral regurgitation. Subsequent two- and three-dimensional transesophageal echocardiogram revealed a large, highly mobile vegetation on the atrial surface of the anterior mitral leaflet with aneurysmal destruction of the lateral scallop requiring mitral valve replacement. Sequencing of the vegetation revealed Enterococcus faecalis, an anaerobic gram-positive coccus that, in rare cases, produces gas using a heme-dependent catalase. Histopathological analysis of the infected valve suggested interstitial gas accumulation, leading to the diagnosis of emphysematous endocarditis.

Conclusions

E. faecalis-associated emphysematous endocarditis should be included in the differential diagnosis of valvular vegetation in patients with a rapidly progressing clinical course. When possible, histopathological analysis should be used alongside other imaging techniques to confirm the diagnosis of emphysematous endocarditis. This case also highlights the importance of collecting blood cultures prior to initiating antibiotic treatment.

Introduction

Infective endocarditis is a challenging infection to treat due to its various clinical presentations, potential embolic events, and vast number of causative organisms. Mortality rates for patients who develop infective endocarditis are as high as 20-40%.¹ Infective endocarditis is generally caused by gram positive bacteria such as streptococci and staphylococci. In very rare cases, the gas-forming organisms Citrobacter koseri, Escherichia coli, Clostridium species, and Finegoldia magna have also been reported.^2,4 Metabolic gas production by these organisms results in interstitial gas accumulation (i.e., emphysematous endocarditis). The accumulated gas can rapidly lead to complications such as valve damage, embolization, and metastatic infections.^3-5 This study presents the first case of gas-forming Enterococcus faecalis-associated infective endocarditis.

Case report

An 82-year-old man presented to the emergency department with fever, infrequent palpitations, shortness of breath, orthopnea, paroxysmal nocturnal dyspnea, and New York Heart Association (NYHA) class IV symptoms of acute heart failure progressing rapidly over a period of three days. He had a history of hypertension, obesity, obstructive sleep apnea, chronic kidney disease, renal calculi, and alcohol use (2-3 drinks, three times a week). Daily medications included telmisartan 80 mg, allopurinol 100 mg, and aspirin 81 mg. He was febrile (38.2°C/100.8°F) on admission. His heart rate was irregular at 127 bpm, blood pressure 95/58 mmHg, respiratory rate 20 breaths per minute, and oxygen saturation 92% on room air. He weighed 113 kg (BMI = 36 kg/m²). Physical exam revealed irregular heart sounds with a 3/6-holosystolic murmur (in the cardiac apex with radiation to the axilla), bilaterally diminished breath sounds, and 1+ pedal edema. An electrocardiogram revealed atrial fibrillation with rapid ventricular rates.

He was admitted with a diagnosis of congestive heart failure with mitral regurgitation and atrial fibrillation. Admission labs included a complete blood count with normocytic anemia (hemoglobin 11.2 g/dL, mean corpuscular volume 82 fL) and a comprehensive metabolic panel with an elevated but stable serum creatinine (1.54 mg/dL, creatinine clearance 57 mL/min). Urinalysis was positive for nitrite with moderate leukocytes and trace blood, and the patient was started on oral ciprofloxacin 250 mg every 12 hours for a possible urinary tract infection. Serum troponin I was normal. A transthoracic echocardiogram showed severe mitral regurgitation with normal left ventricular size and function (65%). A subsequent two- and three-dimensional transesophageal echocardiogram revealed a large, highly mobile vegetation (9.6 × 6.9 mm) on the atrial surface of the anterior mitral leaflet with aneurysmal destruction of the lateral scallop (Figure 1A-C). Three sets of blood cultures were drawn, as infective endocarditis was the dominant differential diagnosis. However, the patient was afebrile at this time and these cultures were drawn 5 days after ciprofloxacin was started.

Figure 1.

A-F. Two- (A) and three- (B) dimensional transesophageal echocardiogram showing aggregated vegetations (white arrow) on the atrial surface of the highly mobile anterior mitral leaflet with aneurysmal destruction of the lateral scallop leading to severe mitral regurgitation. (C) Color Doppler revealing severe mitral regurgitation that fills up almost the entire left atrial cavity. (D) Gram stain showing both single and clustered gram-positive cocci (white arrow) aggregated at the endocardial surface (1000×, oil). (E; 250×, F; 400×) Hematoxylin and eosin stain showing ovoid empty spaces marginated by macrophages (yellow arrowheads) and Langhans giant cells (black arrowheads).

A cardiothoracic surgical consultation was obtained. Given the severity of mitral regurgitation, the size of vegetation, the rapidly progressing congestive heart failure, and the ensuing atrial fibrillation, the patient underwent mitral valve replacement with a bioprosthetic valve (Magna 27 mm pericardial tissue valve). A diagnostic cardiac catheterization revealed obstructive disease in the left coronary circulation necessitating concomitant three vessel bypass surgery (left internal mammary artery to left anterior descending (LAD) and saphenous vein grafts to the diagonal branch of LAD and obtuse marginal branch of the circumflex artery). Intraoperatively, there was evidence of destruction of the anterior leaflet of the mitral valve with prolapse of the A1 segment due to rupture of the chords attached to A1 and P1 scallops.

The resected valvular specimen showed gram-positive cocci (Figure 1D) surrounded by macrophages and Langerhans giant cells, aggregated at the endocardial surface. The histopathology showed interstitial gas consistent with pneumatosis (Figure 1E and 1F). His blood cultures remained negative, likely due to their collection post ciprofloxacin administration. Sequencing by PCR revealed the organism to be Enterococcus faecalis. The histopathological examination of the valve leaflet did not show signs of myxomatous degeneration. A diagnosis of emphysematous Enterococcus faecalis endocarditis of the mitral valve was made (Figure 2). Following mitral valve replacement, the patient was treated with 2 grams of intravenous ampicillin every 6 hours and 2 grams of intravenous ceftriaxone every 12 hours for six weeks and the patient’s condition improved. The patient’s post-operative course was notable for requiring intravenous hemodynamic support until post-operative day 4. He also required BiPAP and high flow nasal canula. A post-operative echo showed no acute changes. He underwent a peripherally inserted central catheter (PICC) line placement on post-operative day 5 for prolonged ampicillin and ceftriaxone administration. The patient was stable for discharge on post-operative day 10 and sent home on aspirin 325 mg daily, atorvastatin 40 mg daily, metoprolol 25 mg twice daily, furosemide 40 mg twice daily, and ampicillin and ceftriaxone as aforementioned. The patient was advised to follow up with cardiology, nephrology, and infectious disease and has not had further complications in over five years.

Figure 2.

Aggregated, raised, soft, pink-tan vegetations were present on the atrial surface of the mitral valve leaflet, which extended onto the chordae tendinea (black arrowheads).

Pathology results

Two recognizable pieces of tan-yellow, pliable mitral valve leaflets were received in formalin fixative. The larger, 4.6 cm × 2.5 cm × 0.3 cm, bore numerous 1.5-2.5 cm thread-like 0.2 cm chorda tendineae. Several 0.25-0.5 cm soft, pink-tan elevations grossly resembling infective vegetations were scattered on the atrial surface of the valve leaflet. Similar vegetations were present near the insertional ends of some of the chorda tendineae. A grossly unremarkable, 1.75 cm × 2 cm × 0.3 cm, piece of mitral valve leaflet which bore a single chorda tendineae was also submitted (Figure 2). Microscopically, numerous single and clustered gram-positive cocci were present within the fibrinous vegetations and the immediate subjacent matrix of the mitral leaflet. Within the latter, conspicuous ovoid empty spaces were marginated by macrophages and Langerhans giant cells (Figure 1D). We recognize the difficulty in distinguishing interstitial gas from lipid; however, the empty spaces were devoid of the signet ring of cytoplasm and solitary nucleus which would categorize adipocytes. Neither foam cells, formation of granulomata, nor degenerating adipocytes were identified. In this setting of acute bacterial endocarditis due to a gas-forming organism, absence of intact and degenerating adipocytes, and the macrophage and giant cell reaction at the edges of the empty spaces (well-documented in the gas spaces of pneumatosis cystoides intestinalis), the diagnosis of emphysematous endocarditis in our patient was supported (Figure 1E and 1F).

Discussion

Emphysematous endocarditis is an exceedingly rare presentation of infective endocarditis. This disease was first noted in 1967 when a study of 3029 fatal Clostridium infections found nine patients who displayed myonecrosis with myocardial gaseous cysts.⁶ Clostridium spp. were the only reported organisms associated with myocardial gas accumulation until van der Vliet et al. identified gas forming Escherichia coli to be a cause of myocardial interstitial emphysema in 2004.⁹ Since then, there have been three additional reports of Escherichia coli-associated emphysematous endocarditis.^2,5,8 In 2016, Citrobacter koseri and Finegoldia magna were also identified as causes.^3,4 This study documents emphysematous endocarditis caused by Enterococcus faecalis.

Our patient was treated with mitral valve replacement and a combination of ampicillin and ceftriaxone. While the addition of gentamicin is often used for the first 3 to 5 days to accelerate the treatment of enterococcal endocarditis, gentamicin was avoided in this patient due to its associated drug-induced nephrotoxicity and the patient’s chronic kidney disease. Gentamicin is excreted by glomerular filtration and may cause tubular necrosis, especially of the proximal segment.⁹ Of the reported cases of emphysematous endocarditis (summarized in Table 1), two patients were treated with mitral valve replacement. These are the only two patients who recovered from the acute phase of the disease. The first patient to recover was infected by C. koseri and continues to have mild cognitive deficits, left-sided weakness, and dysphagia.³ The second patient was infected by E. coli and made a complete recovery.⁵ Our patient is the third example of emphysematous endocarditis successfully treated with mitral valve replacement. The patients that did not survive only received antibiotic treatment. These patients died due to cardiac complications within five weeks of admission (Table 1). Surgical intervention with combination antibiotics appears to be the most successful treatment for emphysematous endocarditis. Notably, unlike previously reported cases of emphysematous endocarditis^{2-4, 8} (Table 1), no evidence of emphysema was observed on echocardiogram. Our diagnosis was only possible by surgical pathology, highlighting the importance of histopathological analysis alongside imaging to aid in the diagnosis.

Table 1.

Summary of reported cases of emphysematous endocarditis

Organism	Diagnostic tools	Presentation	Treatment	Outcome	Author
E. coli	Non-contrast enhanced chest CT Transthoracic echocardiogram	Air bubbles surrounding mitral annulus Hyperechogenic mass on posteromedial side of mitral annulus 2 eccentric mitral jets	Meropenem Surgery was advised but was declined by the patient	The patient died 5 weeks after initial presentation	Kim et al. (2018)2
E. coli	Contrast enhanced CT angiogram Head CT Transesophageal echocardiogram	Gas-containing vegetation in left atrium and posterior mitral annulus Gas-containing embolus completely occluding left femoral artery Right occipital abscess	Mitral valve replacement and left femoral embolectomy Amoxicillin therapy following mitral valve replacement	After completing the amoxicillin treatment, the patient followed up with recurrent fevers. Head CT revealed a right occipital lobe abscess which was treated with ceftriaxone for 28 days. The patient had a good recovery.	Law D, Thomas M (2020)5
E. coli	Thoracic CT Cardiac ultrasound	Dehydration and high fever Multiple splenic abscesses Signs of left sided heart failure Left ventricular inferoposterior wall motion abnormalities	Antibiotic treatment	The patient died due to ventricular fibrillation	van der Vliet HJ, Niessen HW, Perenboom RM (2004)7
E. coli	Chest X-ray Non-contrast enhanced head CT Pulmonary angiography CT	Hypodense foci in both centrum semiovali Air containing lesion around mitral valve Mobile hyperechoic mass in anterior mitral valve leaflet Mild mitral regurgitation	Ceftriaxone was used empirically Piperacillin was used after E. coli confirmation	The patient died 4 days after initial presentation due to ventricular arrythmia	Al Dhali AS, Al-Umairi R, Elkadi O (2021)8
C. koseri	Chest and abdomen CT Transesophageal echocardiogram	Air in left ventricle and within renal collecting system Increased echogenic density of anterior papillary muscle Echo-dense vegetation in the anterior and posterior mitral leaflets Severe mitral regurgitation and pulmonary hypertension	Mitral valve replacement	Complete recovery of kidney function The patient continues to have mild cognitive deficits, left-sided weakness, and dysphagia	Kesler S et al. (2016)3
F. magna	Non-contrast head and chest CT Transthoracicechocardiogram	Atrial fibrillation with rapid ventricular response Air found in the posterior mitral annulus, left ventricular wall, aorta, and right anterior frontal lobe of the brain Upon autopsy, gas bubbles and clusters of bacteria were found in areas of myocardial necrosis	Vancomycin, levofloxacin, aztreonam, metronidazole were used empirically Vancomycin, meropenem, rifampin, and gentamicin were used for presumed embolic endocarditis	The patient died from cardiac arrest 3 days after initial presentation	Cohen M et al. (2016)4
Clostridium	Autopsy				Roberts W, Berard C. (1967)6

The literature search for this study was conducted using PubMed. Non-MeSH terms included “emphysematous endocarditis”, “enterococcal endocarditis”, “infective endocarditis”, “interstitial”, “gas”, “air”, “heart”, and “myocardial”.

Conclusions

Emphysematous endocarditis secondary to E. faecalis infection should be included in the differential diagnosis of infective endocarditis. Echocardiography did not reveal interstitial gas accumulation in the infected heart valve of our patient, which suggests that histopathological analysis should be performed in the work-up of complicated IE when possible. This case also highlights the importance of collecting blood cultures prior to initiating antibiotic treatment.