Of the Edwardsiella genus, E. tarda is the most commonly isolated species and the main species known to cause disease in humans (J Michael Janda and Abbott, 1993). These motile, facultative anaerobic gram-negative rod-shaped bacteria are often found in fresh and brackish water environments and among wildlife including reptiles, amphibians, and fish (J MichaelJanda and Abbott, 1993). Human infection caused by E. tarda is rare with septicemia comprising only 5% of infections (J MichaelJanda and Abbott, 1993). However, septicemia is a severe complication and can be associated with a high mortality rate of up to 40-50% (Nelson et al., 2009). Our case demonstrates the successful management of E. tarda septicemia and bacterial peritonitis in which there is no standardized treatment protocol.

A 20-year-old female with a complex past medical history of hemophagocytic lymphohistiocytosis, macrophage activation syndrome, idiopathic thrombocytopenic purpura, systemic juvenile idiopathic arthritis, chronic lung disease, pulmonary hypertension, adrenal insufficiency, portal hypertension, and congestive hepatopathy presented with fever of 102 degrees Fahrenheit. She reported abdominal pain localized to her lower abdomen, worsening of chronic abdominal distention, decreased oral intake, and hematochezia.

The patient had been hospitalized 2 weeks prior for a hemorrhage complication after percutaneous liver biopsy that required hepatic embolization by interventional radiology (IR). She was also previously receiving immunosuppressive medications for immune thrombocytopenia and remained on stress dose steroids after discharge from the hospital.

On physical exam, the patient was well-appearing and not in acute distress. She had a cushingoid appearance with moist mucous membranes. Breath sounds were clear to auscultation, and she had no signs of increased work of breathing. Her abdomen was severely distended, soft, with diffuse mild tenderness to palpation, and with normoactive bowel sounds. She had resolving ecchymoses along the extremities from the prior admission and pitting edema in the lower extremities to the mid-shin.

The patient’s treatment course is illustrated in Figure 1 .

In terms of laboratory testing, a complete blood count showed a white blood cell count 3.6x10³/uL, hemoglobin 11.1g/dL, and platelets 77 x10³/uL. A comprehensive metabolic panel showed alanine aminotransferase 28 U/L, aspartate aminotransferase 41 U/L, alkaline phosphatase 202 U/L, total bilirubin 3.6 mg/dL, direct bilirubin 2.8 mg/dL, total protein 4.6 g/dL, albumin 2.9 g/dL, lipase 37 U/L, lipase 37 U/L, INR 1.1, prothrombin time 14.2 seconds, c-reactive protein 0.9mg/dL, and lactate 17 mg/dL. Blood cultures were drawn prior to initial antibiotic dosing.

Diagnostic imaging included an abdominal x-ray with no significant colonic stool and hazy density overlying the abdomen suggestive of ascites; a chest x-ray showed no new consolidation or pleural effusion, persistent pulmonary vascular congestion, and stable enlarged cardio-mediastinal silhouette; a CT of abdomen and pelvis with and without contrast showed near complete resolution of the left upper quadrant hematoma seen on her previous admission, an evolving hemoperitoneum also seen in her previous admission but with no extravasation of contrast to suggest active bleeding, stable hepatic lesions seen on previous imaging; and an abdominal ultrasound (US) of the right upper quadrant showed moderate ascites and coarsened liver parenchyma with nodular contour, compatible with diffuse liver disease.

The initial differential was broad given the patient’s medical complexity and included bacteremia, recurrence of macrophage activation syndrome, a viral process in the presence of pancytopenia, and bacterial gastroenteritis given the history of hematochezia and abdominal pain. Spontaneous bacterial peritonitis (SBP) was also considered given the presence of ascites and fever.

Formally a member of the Enterobacteriaceae family and now part of the Hafniaceae family based on taxonomic and phylogenetics studies, E. tarda is an anaerobic gram-negative bacteria that ferments glucose but is unable to ferment lactose, sucrose, and mannitol (Jordan, 1969; Janda and Abbott, 2021). It is biochemically similar to Salmonella and is oxidase-negative with the ability to produce hydrogen sulfide; a key differentiating factor is its ability to degrade tryptophan into indole (Sakazaki, 2015). E. tarda is known to cause infections in aquatic birds and cultured fish, as well as marine mammals (Prymak et al., 1988; Miniero Davies et al., 2018). Infections in fish are often systemic, leading to ascites, hernia, exophthalmia, and lesions of the internal organs. Edwardsiellosis of cultured fish has led to massive economic losses in the aquaculture industry worldwide, and vaccine development to prevent disease in fish is an active area of research (Xu and Zhang, 2014). E. tarda virulence has been attributed to production of virulence factors, including catalases and contact-dependent hemolysins (J. M. Janda and Abbott, 1993), ability to invade epithelial cells, and resistance to phagocytic killing (Leung et al., 2012).

E. tarda can cause both localized and systemic infections in humans. The highest incidence rates occur in humid and subtropical climates and are likely related to dietary habits including raw food consumption.(J Michael Janda and Abbott, 1993; Hirai et al., 2015) The most common presentation in infected individuals is gastroenteritis, which amounts to 83% of reported cases and often resolves without antibiotic treatment (J Michael Janda and Abbott, 1993). Occupational and recreational exposures to fresh and brackish water environments also serve as potential seeding events for E. tarda. Wounds sustained in freshwater lakes, such as lacerations to the foot (Vartian and Septimus, 1990) and puncture wounds from catfish spines (Murphey et al., 1992; Hirai et al., 2015), have led to serious E. tarda skin and soft tissue infections (SSTIs). Several case reports have further described localized extraintestinal E. tarda infections, including liver abscesses, other intra-abdominal abscesses, genitourinary infections, and central nervous system infection (Sachs, 1974; J Michael Janda and Abbott, 1993; Wang et al., 2005; Takeuchi et al., 2009; Golub et al., 2010; Hirai et al., 2015; Suzuki et al., 2018; Bakirova et al., 2020).

E. tarda septicemia is a rare and severe complication with a high mortality rate. It is thought that E. tarda septicemia first develops through initial colonization or infection of the gastrointestinal tract. Our patient had ingested raw fish and raw oysters 5 days prior to clinical presentation. The genomic similarity of the blood isolate recovered from our patient to an isolate originally recovered from a false killer whale further demonstrates the environmental niche of E. tarda and its link to aquatic and marine animals.

E. tarda septicemic presentations tend to occur in patients with underlying hepatobiliary disease, diabetes mellitus, malignancy, and iron overload states, such as sickle cell disease (J Michael Janda and Abbott, 1993; Wang et al., 2005). Healey and colleagues recently described a rapidly fatal case of E. tarda bacteremia in a patient with advanced lung cancer, pulmonary hypertension, hepatitis C virus, and liver cirrhosis, acquired after the ingestion of raw oysters a day prior to presentation (Healey et al., 2021). Our patient had portal hypertension and congestive hepatopathy that may have contributed to her presenting with bacteremia and SBP.

Molecular and immunochromatographic assays for E. tarda detection have been developed for use in the aquaculture industry (Savan et al., 2004; Xie et al., 2013; Liu et al., 2015). Yet, the clinical diagnosis of human E. tarda infection still relies on recovery of the pathogen from microbiological culture. E. tarda can be easily identified in the clinical microbiology laboratory, as the organism grows readily on routinely used laboratory culture media (5% sheep blood agar, MacConkey agar) and displays a characteristic biochemical profile: indole-positivity and hydrogen sulfide production. In addition to manual biochemical testing, species identification can occur through use of kit-based commercial systems (i.e., bioMérieux API 20E or Vitek GNI Plus card) or MALDI-TOF mass spectrometry. Recovery of E. tarda from fecal specimens can be aided by use of selective and differential media including Hektoen enteric (HE) agar and xylose-lysine-deoxycholate (XLD) agar.

Most E. tarda strains are known to be susceptible to commonly administered therapeutic agents. The empiric treatment for E. tarda can begin with antimicrobials that typically target gram negative organisms, and in vitro studies have shown susceptibility to beta-lactams, cephalosporins, aminoglycosides, and oxyquinolones (J Michael Janda and Abbott, 1993). Historically, the greatest resistance has been to polymyxin B and colistin (Reinhardt et al., 1985) and more recently, E. tarda has been shown to have resistance to macrolides, lincosamides, streptogramins, glycopeptides, rifampin, and fusidic acid (Stock and Wiedemann, 2001). E. tarda is known to express beta-lactamase; however, it is likely only expressed in low levels and has not been shown to confer resistance to beta-lactams (J Michael Janda and Abbott, 1993; Stock and Wiedemann, 2001). For this patient, she was started on meropenem given her medical complexity, a broad-spectrum empirical treatment, and was narrowed to ampicillin after susceptibilities returned (TABLE).

Immunocompetent patients with gastroenteritis secondary to E. tarda do not typically require antibiotics, though severe infections benefit from treatment. In the immunocompromised or patients with significant underlying disease who have extraintestinal disease, prognosis is related to the extent of infection and the ability for source control. For patients with E. tarda bacteremia, liver cirrhosis is an independent risk factor for death (Hirai et al., 2015). In the pediatric population, there have been a few reported cases of E. tarda infection in immunocompromised patients. These include cases of patients who had a renal transplant with acute gastroenteritis, Cushing’s syndrome secondary to adrenal gland hyperplasia with liver abscess and sepsis, Crohn’s disease with gastroenteritis and an inflammatory bowel disease flare, and X-linked chronic granulomatous disease with osteomyelitis (Spencer et al., 2008; Kawai et al., 2011; John et al., 2012; Li et al., 2019). Fortunately, though these patients had weakened immune systems from their disease state or from medications, they all recovered. For some, discontinuing immunosuppressive therapy or finding the source of immunosuppression facilitated recovery (Spencer et al., 2008; John et al., 2012). For our patient who was on stress dose hydrocortisone due to adrenal insufficiency, the steroids could not be discontinued, but were gradually weaned.

In conclusion, though an infection secondary to E. tarda is uncommon, the organism should be considered in patients with underlying illness and with food-borne or environmental exposures. For most immunocompetent patients, intestinal disease is common and does not frequently require antibiotic treatment. Conversely, for immunocompromised patients, extra-intestinal manifestations of the disease can occur, and initiating treatment with a beta-lactam will frequently provide sufficient empiric coverage.

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/genbank/, SRR25388894.

Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article. Written informed consent was obtained from the participant/patient(s) for the publication of this case report.

LA: Conceptualization, Investigation, Visualization, Writing – original draft, Writing – review & editing. JC: Conceptualization, Formal Analysis, Investigation, Visualization, Writing – review & editing. MN: Conceptualization, Investigation, Writing – original draft, Writing – review & editing. SY: Formal Analysis, Investigation, Supervision, Writing – review & editing. JD: Conceptualization, Supervision, Writing – review & editing.