Edwardsiella tarda Causing Fishbone Injury Cellulitis Leading to Sepsis in a Case of Hematological Malignancy—A Rare Report and Review of Literature

Key Message

Appropriate supplemented media and a reliable detection system should be used to identify these fastidious organisms. Clinicians should be aware of the pathogenic potential of Edwardsiella tarda to initiate appropriate therapy in time to prevent fatal extraintestinal manifestations.

Introduction

The genus Edwardsiella first described by Ewing et al in 1965 is a member of the family Enterobacterales consisting of three species such as Edwardsiella hoshinae, E. ictaluri, and E. tarda. Their usual habitat is freshwater and marine environments thus commonly pathogenic to cold-blooded vertebrates such as reptiles, amphibians, and fish especially those who are associated with these ecological niches.^[1] Among the three, E. tarda is the only species known to cause human infections. Among them, more than 80% are gastroenteritis presenting as acute watery diarrhea resembling that produced by other toxigenic enteropathogens. Extraintestinal and systemic infections like wound infections meningitis, osteomyelitis, cholecystitis, and septicemia are rarely caused and can lead to potentially life-threatening conditions with a 50% risk of mortality.^[2] Exposure to aquatic environments/exotic animals, people with underlying illnesses, including liver disease, and the ingestion of raw fish are the major risk factors associated with E. tarda. Other factors that increase the risk of getting E. tarda infection are prolonged contact with water, high iron concentration, and very young or old age.^[3]

Case Report

A 71-year-old male with a known case of diffuse large B cell lymphoma (activated B cell type, stage IIIB with national comprehensive cancer network-international prognostic index prognostic score 4) presented to the outpatient department of medical oncology and hematology for the fifth cycle of intravenous rituximab, cyclophosphamide, doxorubicin, vincristine, and oral prednisolone (R-CHOP) chemotherapy. Chemotherapy was started after reviewing the physical and laboratory parameters (serum creatinine, renal function, liver function, complete blood count) to be completely normal. On the next day, he complained of pain and swelling of the right hand that extended moderately up to the lower forearm over the next 4 to 6 hours and developed a fever.

The patient's physical and systemic examinations were unremarkable except he was febrile(38°C). On further interrogation, he gave the history of prick by a raw fishbone over the left thumb 4 days back. Local examination revealed erythema, swelling, tenderness, and local rise of temperature of left hand and forearm including wrist sparing the elbow. There was no loss of movement, sensation, and vascularity. A scanty amount of serosanguinous collection could be aspirated from the swollen area and sent for gram stain and culture. Gram stain revealed few epithelial cells, 10 to 15 polymorphonuclear cells/low power field, fibrinous debris, and few gram-negative bacilli. Initial blood investigations revealed an absolute neutrophil count of 12,510/cu.mm, a high white blood cell count (14. 3₈ × 10³/μL) with polymorphic predominance (87.8%), platelet count: 2,45,000/mm³, hemoglobin: 8.5 g/dL, C-reactive protein: 178.4 mg/L. There was no remaining fishbone on the affected finger as confirmed by radiographic imaging. Left upper limb venous Doppler also showed no abnormality. Blood was sent for automated culture and sensitivity before starting empirical therapy of intravenous meropenem 1 g three times daily + linezolid 600 mg twice daily along with local conservative management of the swelling. Prophylactic acyclovir and cotrimoxazole were also continued with the R-CHOP regimen. Automated blood culture came positive on day 2 (gram-negative bacilli), and yielded pure growth of small nonlactose fermenting colonies (0.5–1 mm) on MacConkey agar (►Fig. 1). Phenotypic identification was done by putting up a panel of biochemical tests. The isolate was gram-negative motile bacilli, catalase positive, oxidase negative, fermenting only glucose and maltose, negative for nitrate reduction, citrate utilization, Voges Proskauer, phenylpyruvic acid, and urease test. Methyl red, indole, ornithine, and lysine decarboxylase were positive, triple sugar iron-alkaline/acid with H2S and arginine dihydrolase was negative—provisionally identified to be Edwardsiella spp. and further identified to be E. tarda by VITEK 2 compact system. Antimicrobial susceptibility test was performed on Muller Hinton agar by disc diffusion method using Amikacin (30 µg), Gentamicin (10 µg), Trimethoprim/Sulfamethoxazole (25µg), Ampicillin (10µg), Chloramphenicol (30µg), Ciprofloxacin (5µg), Cefotaxime (30 µg), Meropenem (10µg) and polymyxin (300 µg) for identification purpose and interpreted according to Clinical and Laboratory Standards Institute (CLSI, 2021). ATCC Escherichia coli 25922 was used as the control strain. The isolate was susceptible to all the agents tested except ampicillin, cefotaxime, and polymyxin. The same organism with a similar antibiogram was isolated from the aspirate of cellulitis as well. By the time antibiogram was available, the patient had already received the upgraded antibiotic intravenous (IV) meropenem for 48 hours, hence allowed to continue; however, linezolid was deescalated. On day 5, cellulitis was resolved and the complete blood count showed normal parameters. IV meropenem was stopped and the patient was discharged on day 6 with the advice of oral faropenem (200 mg) 1T BD for 10 days. This case of sepsis could be successfully treated by prompt initiation of meropenem.

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Fig. 1

Small nonlactose fermenting translucent colonies of E. tarda on MacConkey agar.

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Discussion

We did the literature search over the past 10 years (2013-2022) by the search engines PubMed using Medical Subjects Headings (MeSH) terms “E. tarda,” “bacteremia,” “catfish injury,” and “underlying malignancy.” Only monomicrobial infections due to E. tarda were included in the review. All articles published in English were included in this analysis. We reviewed 519 kinds of literature on the subject (E. tarda) over the past 10 years (2013–2022) out of which 25 were found relevant and included in the review. Clinical details of all published kinds of literature are compiled in ►Table 1.^[2,4-26] As per the review, E. tarda was found to be the cause of various infections such as sepsis, cholangitis, endocarditis, deep abscess, myonecrosis, osteomyelitis, and pelvic inflammatory disease. Out of these, nine were isolated solely from blood, seven from pus/ tissue fluids along with blood, five solely from pus/tissue/fluids, and three from stool. All reports are from abroad, especially from Japan. Out of all, 12 had a history of either consumption/bite of catfish, and five were positive for Hepatitis C. All were adults/elderly except for one case of zero-day neonatal sepsis. There was one report of soft-tissue infection and sepsis following a catfish bite and one case of deep leg abscess following trauma by the barb of freshwater fish from the United States and one report of bacteremia during chemotherapy for acute lymphoblastic leukemia from Japan (►Table 1).^[2,4-26] So, to the best of our knowledge, the present case is a rare report of E. tarda sepsis following fishbone injury cellulitis in an individual with underlying hematological malignancy.

The genus Edwardsiella, although belongs to the family Enterobacterales, strongly differs in habitats, pathogenic, biochemical, and physiological properties and is weakly related to other members of the family with a genetically distinct taxon. Further, unlike other members, Edwardsiella species are susceptible to commonly used antibiotics including penicillin that is very unusual for Enterobacterales. E. tarda is a normal gut flora of fish and humans, can cause opportunistic infections, especially in immunocompromised patients, and infection may range from mild gastroenteritis to fatal sepsis.^[27]

E. tarda has two genomic strains—ATCC23685 strain commonly found in normal human gut flora, while EIB 202 is a virulent strain that causes disease in freshwater/ marine fish.^[28]E. tarda produces several virulence factors as shown by different studies such as—invasive to HEp-2 cell monolayers, hemolysin, and siderophore production. They have a high affinity for red blood cells due to specific fimbriae and thus have hemagglutination properties.^[29] Few studies show that it releases dermato toxins that damage the skin and a high propensity for causing cellulitis. Further, flagellar genes of E. tarda—fliC12, fliA, and flhDC—are essential for the length and number of flagellar filaments to facilitate their swimming and swarming ability.^[30] Our patient was a known case of diffuse large B cell lymphoma and received the fifth cycle of chemotherapy (R-CHOP). In addition, he had a history of prick by a raw fishbone over his left thumb leading to cellulitis that may have allowed the bacteria to enter the bloodstream more easily. The underlying comorbidity of malignancy and chemotherapy might have facilitated for rapid development of systemic infection (sepsis) following a fishbone injury cellulitis. Thus, clinicians should be aware of the pathogenic potential of this bacteria. As per literature, the majority of E. tarda infections have been reported from abroad involving soft tissue and sepsis and had multiple comorbidities with high potential for mortality. To the best of our knowledge, there was only one report of sepsis with multiple liver abscesses associated with Cushing's syndrome because of recreational aquatic exposure from Vellore, India.^[31] Thus, early identification and initiation of intravenous broad-spectrum antibiotic treatment are key to saving the patient from fatal systemic illness.