A 26-year-old gentleman with a history of epilepsy on Levetiracetam and a remote history of a gunshot wound to his abdomen was transferred to our hospital for acute liver failure after a two-day stay at an outside facility. The patient noted sore throat, productive cough, periumbilical abdominal pain, watery diarrhea, nausea, and vomiting, subjective fevers along with progressive jaundice for seven days before presentation at the outside hospital. The patient indicated that he took acetaminophen (three tablets of acetaminophen 500 mg at different times) for his abdominal pain. He was incarcerated twelve days before admission for one week at a local county jail. His illness began three days after his release. His COVID-19 test was negative while in jail. The patient history was negative for new medications, ingestions, exposures, IV drug use, smoking, sick contacts, travel, animals, water or hiking activity, tuberculosis and hepatitis. The patient reported using marijuana daily and drank half a pint of brandy once weekly. He reported being sexually active with one female partner with frequent condom use. The patient lived in Arkansas, where he had grown up, with no recent travel.
The patient had a blood pressure of 140/74 mmHg on arrival to the outside hospital with a heart rate of 106 BPM, respiratory rate of 22 breaths/min, and oxygen saturation of 98 % on room air. Physical examination was remarkable for scleral icterus. The patient had a crusted lesion on his right lateral oral commissure. His left eye showed a small subconjunctival hemorrhage. He had no evidence of oropharyngeal exudate. Chest examination showed regular rate and rhythm, no murmurs, rubs, or gallops, and lungs that were clear to auscultation bilaterally with distant breath sounds. An abdominal exam revealed mild diffuse abdominal tenderness, but he did not demonstrate any stigmata of chronic liver disease.
Laboratory workup showed leukocytosis, anemia, hyponatremia, cholestatic liver injury, acute kidney injury (Table 1), and a negative respiratory pathogen panel. Arterial blood gas revealed primary anion gap metabolic acidosis. Chest X-ray demonstrated patchy interstitial and alveolar opacities throughout the right and left lung that was concerning for multifocal pneumonia. Computed tomography (CT) scan of the chest, abdomen, and pelvis showed bilateral lung parenchymal ground glass consolidative lesions with central cavitation; no abnormalities were noted in the abdomen (Fig. 1). A panel of tests including an autoimmune workup (C3, C4, ANCA), blood cultures, Histoplasma and Blastomyces urine antigens, Cryptococcus antigen, 1,3 Beta D-Glucan, TB-PCR from sputum samples, Leptospira PCR, and Lyme serologies were sent. Serologies for Francisella tularensis, Ehrlichia chaffeensis (in addition to PCR) and Rickettsia rickettsii were also sent. Transthoracic echocardiography showed reduced left ventricular function with global hypokinesis and no valve lesions, although the views were limited.
The patient received vancomycin, cefepime, and metronidazole and due to fulminant liver failure, was transferred to our tertiary care facility as noted. His course was complicated by hypothermia, shock, and encephalopathy. He also developed acute renal failure requiring continuous renal replacement therapy and respiratory failure requiring mechanical ventilation.
Bronchoscopy with bronchoalveolar lavage (BAL) was performed, which revealed a neutrophilic predominance with negative GMS and AFB stains and negative cytology. The patient's right lip exudate was swabbed and returned positive for HSV 1 through NAAT testing. Complete etiological workup for other causes of encephalopathy (Brain CT scan), acute liver injury workup including Anti-LKM, Mitochondrial Antibody IgG, Smooth muscle Antibody IgG, A1AT levels, Salicylates, acetaminophen levels, ethanol levels, ceruloplasmin, HIV, Hepatitis Screen, EBV PCR, CMV PCR, and urine drug screen were sent and were all negative. Ammonia level was elevated. Hemophagocytic lymphohistiocytosis (patient had high ferritin reaching > 40,000 ng/mL) workup was ordered and was negative. Amylase and Lipase were also negative.
Thirteen hours after collection of blood cultures, one out of two blood cultures sets was positive with a Gram stain showing gram-positive cocci and gram-positive bacilli. At 23 h after collection, four out of four blood culture bottles were positive. The Gram-positive Bacilli were elongated and tapered on one end. BAL cultures were subsequently positive as well. Using Matrix-assisted laser desorption ionization-time of flight Mass spectrometry (MALDI-TOF) for identification, Arcanobacterium haemolyticum was identified in both Blood and BAL cultures. The patient's antimicrobial therapy was narrowed from Vancomycin and Cefepime to Ampicillin-Sulbactam. Due to concern for an oropharyngeal source of Arcanobacterium septicemia, a CT scan of the neck was obtained, which showed a 1.4 cm right palatine tonsillar abscess (Fig. 2), prominence of nasopharyngeal adenoids, cervical lymphadenopathy in the bilateral anterior and posterior triangles, mediastinal fat stranding, and sinusitis; furthermore, the visualized portion of the lungs demonstrated the development of multiple abscesses and loculated pleural effusions. The internal jugular veins did not show a thrombus or occlusion. Otolaryngology assessed the patient and deemed the abscess too small for drainage. A dedicated CT chest was performed, which showed bilateral pleural fluid collections concerning for empyema, requiring multiple pigtail catheters to be placed. Chest tubes returned bloody purulent drainage, and eventually, the patient required surgical thoracotomy with evacuation of the hemothorax and pulmonary decortication. Other infectious and autoimmune workup remained negative. He had a Trans-esophageal echocardiogram which didn't show any oscillating echo-densities. There was, however, mild tricuspid, mitral and pulmonary valve regurgitation. There was mention of a tiny, delayed right to left shunt with the Bubble study that was suggestive of a pulmonary AVM. A percutaneous tracheostomy was performed, and the patient slowly improved. The previously mentioned infectious workup was all negative.
The patient's multi-organ failure and septicemia were determined to be due to Arcanobacterium haemolyticum infection likely originating from initial pharyngitis. This pathogen was repeatedly isolated from cultures from various body culture sites while the other infectious workup remained negative. Susceptibilities were obtained from the outside hospital, and the organism was penicillin-sensitive. The patient completed an antibiotics therapy course for six weeks with Ampicillin-Sulbactam covering five weeks of that duration. This was associated with clinical improvement. Chest and tracheostomy tubes were removed, and he no longer required renal replacement therapy. He was discharged home after an inpatient stay of over a month. The patient had recovered fully at his two-month post-discharge follow-up.