Yersinia enterocolitica Pneumonia in a Heart Transplant Recipient

Dear Editor, Yersiniosis is a human diarrheal zoonotic infection caused by either Yersinia enterocolitica or Yersinia pseudotuberculosis. Despite the usual presentation of self-limiting gastroenteritis in immunocompetent hosts, both intestinal and extra-intestinal manifestations of the disease have been described in immunocompromised individuals. Here, we report a rare case of Y. enterocolitica pneumonia presenting as a focal lung mass in a heart transplant recipient. A 73-year-old male farmer, native and resident of the northeastern area of the United States presented to our hospital with 2 weeks of cough, diarrhea, fevers, and weight loss. Fifteen months prior to admission, he underwent an orthotopic heart transplant (Epstein-Barr virus [EBV] serostatus donor negative/receptor positive) for severe non-ischemic cardiomyopathy. He had significant contact with horses on his farm and did not consume raw or undercooked meat. On arrival, he had a heart rate of 100 bpm, a temperature of 100.2 F, and his lungs were clear to auscultation. Immunosuppression included prednisone 5 mg daily, sirolimus 1.5 mg daily, and tacrolimus 3.5 mg twice daily (goal trough 5–7 ng/mL). He had a white blood cell count of 10,240/uL with elevated neutrophils at 8420/uL. His iron and ferritin levels were not suggestive of iron overload. A computed tomography (CT) of the chest revealed a solid 1.6-cm right upper lobe nodule with surrounding ground glass opacities (Figure 1A). Initial investigations included HIV testing, blood cultures, nasopharyngeal polymerase chain reaction (PCR) respiratory viral panel, serum cryptococcal antigen, 1-3-beta-D-glucan, and galactomannan, all of which were negative. Owing to the intermittent nature of his diarrhea, stool testing was not performed. A transthoracic echocardiogram showed adequate graft function without vegetation. An expectorated sample of sputum was cultured with the growth of normal flora. Plasma EBV DNA was low detectable at 147 IU/mL. He was started on empiric intravenous cefepime with a resolution of fevers after 72 h. He was then switched to oral amoxicillin/clavulanate and was discharged home to complete a total of 10 days of antibiotics with plans for repeat imaging. One week after completing therapy, a repeat CT chest was performed which showed a stable-sized nodule with persistent surrounding ground glass opacities (Figure 1B). Ten days after discharge, he was re-admitted electively for an abdominal hernia repair. He had persistent symptoms of cough, malaise, and now frequent diarrhea. A repeat chest CT (Figure 1C) 16 days after finishing antibiotics revealed an enlarging 5.5-cm mass-like right upper lobe lung nodule. Intravenous cefepime and liposomal amphotericin B were started. A sputum culture was obtained which grew Y. enterocolitica. A stool culture was negative for Y. enterocolitica. Plasma EBV DNA increased at 1,270 IU/mL. A biopsy of the lung nodule demonstrated scattered EBV-positive B cells on a background of fibrosis, inflammation, and purulent necrosis suggestive of a bacterial infection with an accompanying reactive EBV+ process. Microbiological stains, including fungal, acid-fast bacilli, and Gram stain, were negative. Lung tissue culture grew moderate Yersinia. Due to concerns about post-transplant lymphoproliferative disorder (PTLD), immunosuppression was reduced by stopping sirolimus and decreasing the target level of tacrolimus to 3–5 ng/mL. He was then treated with intravenous ceftriaxone and transitioned to oral ciprofloxacin for a total of 14 days of antibiotics, which led to sustained clinical and radiological resolution (Figure 1D). There were no further changes to his immunosuppression and plasma EBV DNA decreased and has maintained at <35 IU/mL. He was given extensive counseling to avoid further infections from zoonotic pathogens while living and working on a farm. Y. enterocolitica is a motile Gram-negative rod-shaped facultatively anaerobic bacterium belonging to the family Yersiniaceae and order Enterobacterales [1]. It is present widely in nature, more prevalent in colder climates, and is present in the intestinal tracts of various wild mammals, including horses [2]. The most common form of the disease is gastroenteritis associated with the consumption of contaminated food (e.g., raw or undercooked pork, beef, or chicken) or water [3]. Immunocompetent patients typically experience a self-resolving illness lasting less than 7 days [4]. Extra-intestinal manifestations are rare, although acute pharyngitis, community-acquired pneumonia, and skin and soft tissue infection have all been attributed to Y. enterocolitica infection [5]. Pneumonia has been described in both immunocompetent and immunocompromised patients, typically in the setting of sepsis or positive culture data from blood or stool [5, 6]. Y. enterocolitica has also been described as causing an interstitial pneumonia pattern on chest imaging [7]. In one case report, this organism was thought to result in a focal dense consolidation noted on the CT chest in a kidney transplant recipient with growth of Y. enterocolitica on bronchoalveolar lavage sampling, although culture from tissue biopsy failed to yield Y. enterocolitica [8]. Risk factors for invasive Y. enterocolitica infection include iron overload and corticosteroid therapy [9]. Solid organ transplant recipients are at risk of severe disease [10]. Dendritic cells and T lymphocytes, which typically have impaired function after solid organ transplantation, are critical for immunity against Y. enterocolitica [11]. The use of highly sensitive molecular assays (i.e., Y. enterocolitica PCR on stool) is important [12]. Y. enterocolitica produces two chromosomal beta-lactamases (BlaA and BlaB) and is typically resistant to first-generation cephalosporins and most penicillins [13, 14]. Notably, failures of therapy with amoxicillin/clavulanate have been reported [15]. While Y. enterocolitica typically shows in vitro susceptibility to aminoglycosides, sulphonamides, tetracyclines, fluoroquinolones, and third-generation cephalosporins, recommended therapy for severe disease is a third-generation cephalosporin with or without an aminoglycoside [15, 16] The case presented highlights the differential diagnosis of an enlarging pulmonary mass in a solid organ transplant recipient which includes PTLD, malignancy, invasive fungal disease, mycobacterial infection, and nocardiosis. It also underscores the importance of early biopsy for histological and microbiological testing. Our patient had evidence of prior EBV infection and had a low but increasing quantitative EBV DNA in plasma raising concern for EBV-related PTLD. However, scattered EBV+ B cells on lung tissue specimens represented EBV reactivation in the presence of Y. enterocolitica infection. The subacute and mild nature of infection in our patient also warrants special mention. This could be explained either by recent receipt of antimicrobial therapy perhaps partially treating the infection, down-regulation of pro-inflammatory cytokines by immunosuppressive therapy, or infection with a less severe bioserotype. In conclusion, evaluation of a focal lung mass in a solid organ transplant recipient requires a detailed epidemiological history and can often involve the need for timely invasive diagnostic procedures including tissue biopsies to achieve a diagnosis. Carlos Alejandro Portales Castillo, Adam G. Stewart, and Camille N. Kotton participated in the writing, review, and editing of the paper. The authors declare no conflicts of interest. Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.