Listeria pericarditis in a lymphoma patient: Case report and literature review

Abstract

We present a case of pericarditis with pericardial effusion secondary to Listeria monocytogenes. A 56-year-old man presented with signs of acute pericarditis, but with prior chronic lymphocytic leukemia treated with stem cell transplantation, chronic graft-versus-host disease, and a recent diagnosis of untreated diffuse large B-cell lymphoma. He developed cardiac tamponade requiring pericardiocentesis. Blood and pericardial cultures grew Listeria monocytogenes. He responded to ampicillin but later died from gram-negative sepsis. A systematic review found 10 other published English-language cases of pericarditis caused by Listeria. The most common risk factors were cirrhosis and malignancy. Only three patients survived both the listeriosis and their underlying infections. Listeria monocytogenes is a rare and often fatal cause of pericarditis, typically occurring in immunocompromised patients. Cultures showing gram-positive bacilli in the context of pericarditis in an immunocompromised patient should prompt consideration of this rare cause.

Background

Pericarditis with pericardial effusion is a relatively common condition that is routinely managed by internists and cardiologists. The most common cause of acute pericarditis is a viral infection, typically with coxsackievirus and related viruses. However, in immunocompromised patients, the differential diagnosis is broader and must include otherwise rare infectious causes. We present a case of Listeria pericarditis with pericardial effusion in a patient with diffuse large B-cell lymphoma (DLBCL) whose infection initially responded to ampicillin, but who developed complications and ultimately died during admission.

Case Presentation

A 56-year-old man presented to his community hospital 5 days before his index admission, complaining of several days of malaise, fever, and positional chest pain. He had a history of chronic lymphocytic leukemia (CLL) treated with non-myeloablative allogeneic stem cell transplantation 2 years prior, which was followed by ibrutinib for recurrence and complicated by chronic graft-versus-host disease (GVHD) of the eyes, mouth, and skin. His GVHD was stable on prednisone 7.5 mg daily and cyclosporine 75 mg twice daily. He had also recently been diagnosed with DLBCL, which had not yet been treated, and he had an indwelling central line. On admission to the community hospital, he was diagnosed with acute pericarditis based on clinical and echocardiographic findings. He was discharged home a few days later on high-dose NSAIDs and colchicine, with symptoms stable.

However, once home, his fatigue and malaise worsened, with new and worsening exertional dyspnea and new loose bowel movements. He was seen in follow-up at his hematologist–oncologist appointment, where he was hypotensive and tachycardic and was admitted to hospital from clinic. His examination was notable only for mild confusion and fever (maximum 39.5ºC). His heart sounds, neurological examination, and abdominal examination were unremarkable. In the hospital, he was diagnosed with a large pericardial effusion causing cardiac tamponade based on echocardiography.

He was transferred to the intensive care unit (ICU) and underwent a pericardiectomy. Due to ongoing fevers, blood cultures were drawn from his central line, and pericardial fluid was sent for bacterial culture. A pericardiectomy was performed, and fluid was sent for cytology and culture. Intravenous vancomycin and piperacillin–tazobactam were started empirically for sepsis. Stool Clostridioides difficile testing was positive, and he was started on oral vancomycin 125 mg four times per day for a planned 14-day course. His blood cultures returned with gram-positive bacilli in 2 of 2 cultures, positive at 14 and 16 hours, drawn from both ports of his central line. Repeat cultures, including central and peripheral blood, were done 12 hours after admission, with both positive at 19 hours. His IV vancomycin was continued for the possibility of Bacillus or Corynebacterium central venous catheter infection. The piperacillin–tazobactam was changed to ceftriaxone, then both IV vancomycin and ceftriaxone were discontinued in favour of ampicillin 2 g IV every 4 hours on the second day of admission after blood cultures speciated to Listeria monocytogenes. Pericardial fluid cultures similarly grew Listeria, with cytology negative for malignant cells. Repeat blood cultures were negative. His fevers resolved within 12 hours of starting ampicillin. The frequency of his bowel movements improved. He stabilized and was transferred to the ward on the fifth day of admission.

Four days later, he developed new fevers and mild hypoxemia and had chest X-ray findings consistent with hospital-acquired pneumonia. Blood cultures grew Escherichia coli from central and peripheral lines at 7 hours. There was interval enlargement of a small pleural effusion, which was drained; the culture was negative, and chemistry could not be done. He was treated with meropenem, followed by piperacillin–tazobactam based on susceptibilities. Bloodwork drawn during his fever also showed a cytomegalovirus viral load that was positive at 2,005 IU/mL, for which he was started on pre-emptive foscarnet, chosen due to ongoing cytopenia. The following day, he developed seizures that were attributed to subdural hemorrhages, as seen on a computed tomography (CT) scan. He was readmitted to the ICU. Follow-up MRI showed acute hemorrhage with mass effect, but no evidence of abscess or rhomboencephalitis. There was one small area of the right frontal lobe of either motion artifact or encephalitis. He was too unstable for lumbar puncture. Despite aggressive treatment, he continued to deteriorate and developed multi-organ failure. After further discussion with the family, he transitioned to palliative care and died 26 days after admission.

Literature Review

Although endocarditis is a well-known complication of listeriosis, pericarditis is rare, and a systematic review was performed to assess the literature. MEDLINE was searched via PubMed for publications containing the terms Listeria or listeriosis as well as pericarditis, pericardial effusion, or tamponade. Of the 23 papers found on August 7, 2019, only 15 described cases of this disease in humans, and 10 of these were available in English. These 10 cases were reviewed qualitatively and summarized. Of note, although the earliest case in the English literature was in 1971, there appears to have been at least one case published in the Swedish language in 1961 (1). It was not included in this review.

Characteristics of the 11 cases, present case included, are shown in Table 1. Heart failure was the most common presentation. Pericardial rubs are frequently found, though they are not universal, and in some cases developed after presentation. Most patients had an underlying immunocompromised state, although one patient did not (2). The most common underlying diseases were cirrhosis (3–5) and malignancy (6–8). Other risk factors included renal failure requiring hemodialysis (9), rheumatoid arthritis on low-dose prednisone (6), HIV infection with low CD4 (10), and recent delivery in the post-partum period (11).

Table 1:

Summary of published cases of Listeria pericarditis

Ref	Year	Presentation	Comorbidities	Sites of infection	Positive cultures	Antibiotics	Outcome
(2)	1971	61-year-old man with heart failure and fever	None	Pericarditis with pericardial effusion	Blood	Penicillin for 6 weeks	Resolution
(3)	1979	52-year-old man with fevers and dyspnea	Cirrhosis	Pericarditis with pericardial effusion	Pericardial fluid	Oxacillin and gentamicin	Death; post-mortem diagnosis
(9)	1984	54-year-old woman with fevers and bilateral shoulder pain	Hemodialysis for chronic glomerulone-phritis	Pericarditis with pericardial effusion	Blood and pericardial fluid	Cefazolin for 2 weeks, followed by erythromycin for 4 weeks following recurrence	Recurrence then resolution
(6)	1990	58-year-old woman with heart failure	Rheumatoid arthritis on prednisone 7.5 mg daily	Myocarditis with pericardial effusion	Pericardial fluid	None	Post-mortem diagnosis				Poorly-differentiated squamous cell carcinoma
(10)	1993	37-year-old man with chest pain and confusion	HIV infection with CD4 count 51	Pancarditis and meningitis	Blood	Ampicillin	Death
(11)	1995	25-year-old post-partum woman with dyspnea and low-grade fevers	Recent cesarean delivery	Pericarditis	Pericardial fluid only	None	Death
(4)	1997	65-year-old man with fever and confusion	Cirrhosis from hemochro- matosis	Meningitis, endocarditis, and pericarditis	Blood and pericardial fluid	Ampicillin and tobramycin	Death
(5)	2011	60-year-old man with anorexia and dyspnea	Cirrhosis	Pericardial effusion	Pericardial fluid only	Meropenem, followed by ampicillin for 5 weeks with gentamicin for the first week	Resolution
(7)	2012	61-year-old woman with dyspnea and edema	Remote, cured Hodgkin lymphoma	Pericarditis and pleural effusion	Pericardial fluid only	Amoxicillin and cotrimoxazole	Death from candidemia
(8)	2014	71-year-old woman with subacute fever and malaise	Metastatic breast cancer on chemotherapy	Pericardial effusion, endocarditis, and pleural effusion	Blood	Ampicillin for 6 weeks with gentamicin for first 4 weeks	Relapse then resolution, then death from underlying disease
This study	2019	56-year-old man with dyspnea and diarrhea	Chronic lymphocytic leukemia	Pericarditis	Blood and pericardial fluid	Ampicillin	Death
			Allogeneic stem cell transplant
			Graft-versus-host disease
			Diffuse large B-cell lymphoma

Two cases had concomitant endocarditis, one with native tricuspid valve involvement and the other with right atrial septal involvement (4,8). Two had myocarditis on pathology (6,10). Two had evidence of concomitant meningitis, suggesting disseminated disease (4,10). Penicillin or ampicillin was the most common antibiotic used (2,4,5,7,8,10), often with the addition of an aminoglycoside (4,5,8) or cotrimoxazole (7). One case reported successful treatment with an aminoglycoside alone (9). The duration of treatment, when reported, ranged from 4 to 6 weeks. In the described cases, mortality from Listeria was 54% (6/11), with 2 patients dying from another cause and only 3 patients (27%) recovering. Death, when it occurred due to Listeria, was generally within the first 2 weeks.

Discussion

Listeria can cause a number of infectious syndromes. The most well-known is meningitis, though endocarditis is also well-described. Here, we have added another case to the relatively short list of patients with the rare presentation of Listeria pericarditis. Around the time our patient became ill, there was a national outbreak of listeriosis associated with frozen cooked chicken; it is unknown whether our patient was exposed. As with the majority of cases, our patient had an underlying disease causing an immunocompromised state. The case also highlights the possibility of disseminated disease that involves the heart and brain, which portends a poorer prognosis. Our patient died, as did half of the other patients found in the English-language medical literature. The high mortality is likely due to a combination of the severity of the pericardial infection, dissemination to multiple sites of infection, and the severity of their underlying illness.

Unfortunately, the optimal treatment is not well-defined. In the cases reviewed, neither the specific antibiotics nor the duration appeared to correlate well with the outcome, though the sample size was small. Treating with ampicillin, with consideration for concurrent aminoglycoside for the first few weeks, is common and seems reasonable. Optimal duration is unclear, though most patients were treated for 6 weeks.

Listeria is a rare cause of purulent pericarditis and should be considered in high-risk patients who present with heart failure and either gram-positive bacillus bacteremia or concomitant meningoencephalitis. Given the high mortality, prompt treatment is important.

Funding:

No funding was received for this work.

Disclosures:

The authors have nothing to disclose.

Informed Consent:

Informed consent was obtained from the patients.

Peer Review:

This manuscript has been peer reviewed.

Animal Studies:

N/A.