Polymicrobial native valve endocarditis due to Bacillus cereus and Cardiobacterium hominis

Abstract

We present a case of polymicrobial subacute bacterial endocarditis and bacteremia with Bacillus cereus and Cardiobacterium hominis in a 72-year-old man with pre-existing mitral valve disease and prior mitral valve repair who presented with renal failure and glomerulonephritis. Bacillus is often a contaminant in blood cultures but has been rarely implicated in patients with invasive infections such as endocarditis. Intravenous drug use, prosthetic heart valves, valvular heart disease and venous catheters are the most frequently described risk factors for Bacillus bacteremia and endocarditis in the medical literature. Management is challenging as Bacillus is resistant to penicillin and cephalosporin antibiotics due to production of beta-lactamase. Polymicrobial endocarditis is uncommon and when it occurs typically involves Staphylococcal species. To our knowledge, this is the first reported case of polymicrobial endocarditis in which both Bacillus and a HACEK organism are implicated.

Background

The isolation of Bacillus cereus from blood cultures is frequently viewed as a result of contamination, but systemic infections can occur. Endocarditis is decidedly rare and when present, is often associated with intravenous drug abuse. Rarer still is polymicrobial bacteremia with B. cereus and Cardiobacterium hominis in a patient with subacute bacterial endocarditis.

Case presentation

A 72-year-old man was admitted for evaluation of worsening renal failure. Seven months prior to admission his creatinine had been reported to be normal at 0.9 mg/dL. Eight months prior to admission he underwent repair of mitral valve prolapse with regurgitation. For several months following this procedure he experienced chills, but these resolved spontaneously without any medical intervention. He reported recent fatigue but denied any fever or other complaints. The patient denied any history of intravenous drug use, trauma, sinus disease or gastrointestinal symptoms in the past several months. On admission he was afebrile, appeared non-toxic and had a holosystolic heart murmur best heard at the apex.

Investigations

His white blood cell count was 5780 cells/mm³ with 69% neutrophils, creatinine was 7.6 mg/dL and had microscopic haematuria on urinalysis. Antinuclear antibody (ANA) titers, antiglomerular basement membrane antibodies, anti-double stranded DNA antibodies, hepatitis serology, HIV test and complement levels were all unremarkable; an antineutrophil cytoplasmic antibody-proteinase 3 (pANCA) was positive. A scheduled renal biopsy was postponed when he developed a temperature of 39°C. Blood cultures obtained at the time of his fever grew both gram-negative and gram-positive bacilli (figure 1) which were subsequently identified as B. cereus and C. hominis via matrix-assisted laser desorption ionisation time of flight mass spectrometry (MALDI-TOF). Although we did recognise that B. cereus was often a contaminant, it grew on blood cultures from days 2, 3, 4, 5, 7 and 10 of hospitalisation and Cardiobacterium was identified on days 1 and 4 of hospitalisation. In this setting, we regarded both organisms as true pathogens. Blood cultures eventually cleared on hospital day 11.

Figure 1.

Gram stain of blood cultures showing Cardiobacterium hominis (left) and Bacillus cereus (right).

Treatment

Despite initial therapy with vancomycin and piperacillin/tazobactam repeat blood cultures grew C. hominis for 4 days and B. cereus for 10 days. A transthoracic echocardiogram revealed an 8 mm vegetation on his mitral valve. Due to his renal impairment, he was transitioned from vancomycin to meropenem based on susceptibility testing via the Kirby-Bauer method (table 1) for a total of 6 weeks of antibiotic treatment with resolution of bacteremia but minimal improvement in his creatinine.

Table 1.

Susceptibility testing for Bacillus cerues

Drug	Bacillus cereus
	KB zone (Kirby-Bauer)
Ceftriaxone	12.00 mm
Ciprofloxacin	28.00 mm
Clindamycin	22.00 mm
Imipenem	35.00 mm
Linezolid	30.00 mm
Meropenem	29.00 mm
Trimethoprim/sulfamethoxazole	6.00 mm
Vancomycin	19.00 mm (c)

Outcome and follow-up

Our patient was seen in our office for multiple visits 2 months following discharge. He initially had improving renal function but 1 month after discharge had developed pancytopenia, lower extremity rash and worsening kidney function while on meropenem. This was presumed to be from acute interstitial nephritis. He was switched to ciprofloxacin to complete his 6-week treatment course. He was also treated with prednisone 60 mg by his nephrologist but developed rising blood urea nitrogen (BUN) and creatinine and was admitted for renal biopsy and haemodialysis. His biopsy showed 80% glomerulosclerosis which was attributed to endocarditis-related glomerulonephritis and significant interstitial fibrosis with no evidence of active interstitial nephritis. He had three haemodialysis sessions while inpatient and elevated BUN was thought to be secondary to steroids. He was discharged home with prednisone taper and remains of off haemodialysis. He has ongoing follow-up with nephrology and is being treated to stage 5 chronic kidney disease. His most recent creatinine is 5.28 mg/dL with glomerular filtration rate of 10–12. Although he continues to remain off dialysis, he is undergoing evaluation for peritoneal dialysis catheter should the need arise and is being evaluated for kidney transplant.

Discussion

Bacillus species are gram positive, aerobic, spore forming rods that are most commonly associated with a gastrointestinal illness.¹ Injection drug users appear to be at particular risk for the development of invasive B. cereus infections such as endophthalmitis. There are also reports of B. cereus catheter-related bloodstream infections in patients with haematological malignancies and other chronic diseases.² The finding of Bacillus in blood cultures is most frequently the result of contamination. However, besides intravenous drug use, the presence of indwelling central venous catheters can predispose to bacteremic illness. Endocarditis is a distinctly uncommon sequela of Bacillus infection but is more common in men and appears to have a predilection for the mitral valve.

B. cereus is typically resistant to beta-lactam antibiotics, and the mainstay of treatment is vancomycin until susceptibilities are available. Imipenem, chloramphenicol, gentamicin and ciprofloxacin are also typically effective against this organism. B. cereus secretes a beta-lactamase enzyme which confers resistance to cephalosporins and pencillins.^{3 4} Prosthetic heart valves and pre-existing valvular heart disease are risk factors for Bacillus endocarditis, in addition to intravenous drug use, and in a review of 26 cases of B. cereus endocarditis by Gopinathan et al, most prosthetic valve cases were treated with a combination of surgery and antimicrobial therapy whereas, in most cases, native valve infection was cured with antimicrobials alone.⁴

Our patient had glomerulonephritis believed to be secondary to his subacute endocarditis with renal injury and microscopic haematuria, which can be associated with subacute endocarditis. Similar findings have been described by Nallaraja et al in a patient with B. cereus endocarditis.¹ In a biopsy-based study of 49 patients, over 80% of patients with infective endocarditis had a focal, segmental or diffuse proliferative glomerulonephritis. Hypocomplementemia was found in 56% of patients and antineutrophilic cytoplasmic antibody (ANCA) in 28% of patients.⁵ In a report by Wang et al, IgA vasculitis was seen in a patient with a bioprosthetic pulmonary valve and subacute C. hominis endocarditis.⁶ C. hominis is a pleomorphic, facultatively anaerobic, gram negative bacilli.⁷ It is a member of the Hemophilus, Aggregatibacter, Cardiobacterium, Eikenella and Kingella group (HACEK), which are recognised as being uncommon pathogens in patients with endocarditis. In a review from Das et al, 58% of patients with infective endocarditis from the HACEK group had pre-existing structural cardiac disease and 27% of patients had prosthetic valves.⁸

Polymicrobial endocarditis as seen in our patient is extremely rare. In a review of 1011 patients with endocarditis, 5.9% were diagnosed with polymicrobial infections, although nearly 50% of those were coinfected with coagulase-negative staphylococci raising the question of contamination versus actual infection.⁹

In our patient, the aetiology of the patient’s polymicrobial bacteremia was difficult to ascertain. Our patient had pre-existing mitral valve disease but lacked other risk factors associated with B. cereus endocarditis in other published cases such as immunodeficiency, prosthetic valves, indwelling venous catheters or intravenous drug use. His initial mitral valve repair may have been the portal of entry. The concomitant C. hominis makes this case unique in the medical literature.

Learning points.

• Bacillus is often a contaminant in blood cultures but can cause invasive infections including endocarditis. B. cereus is the species most commonly associated with bacteremia and endocarditis.

• Intravenous drug use, prosthetic heart valves, valvular heart disease and venous catheters are risk factors for Bacillus bacteremia and endocarditis.

• Bacillus is resistant to penicillin and cephalosporin antibiotics due to production of beta-lactamase; vancomycin is the preferred empiric treatment.

• Polymicrobial endocarditis is uncommon, accounting for approximately 6% of all endocarditis cases.

Ethics statements

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