Severe Vibrio vulnificus Sepsis without Typical Wound Exposure in a Patient with Chronic Liver Disease and Diabetes: A Case Report

Abstract

Background

Vibrio vulnificus, a Gram-negative bacillus, is frequently present in warm estuarine and coastal waters and is a notable pathogen responsible for seafood-related fatalities globally. Infection typically arises from ingesting contaminated seafood or exposure of skin wounds to tainted seawater, resulting in primary or secondary sepsis, as well as severe skin and soft tissue infections.

Case Presentation

Upon hospital admission, a 51-year-old man with chronic gastritis, long-term alcohol use, type 2 diabetes, thrombocytopenia, and active hepatitis B and C presented with acute right upper quadrant abdominal pain, high fever, and a history of consuming raw fish (sashimi) before symptom onset, suggesting a foodborne infection. Despite denial of recent seawater exposure or seafood handling, his condition rapidly deteriorated, resulting in septic shock, moderate acute respiratory distress syndrome, and necrotizing fasciitis of the left lower extremity within 72 hours. Laboratory findings revealed severe thrombocytopenia, hyperlactatemia, multiple organ dysfunction, and metabolic acidosis. Vibrio vulnificus was identified via peripheral blood metagenomic next-generation sequencing. Whole-exome sequencing incidentally detected a heterozygous missense variant in the DOCK2 gene (c.4511C>T, p. Thr1504Met), classified as a variant of uncertain significance. In silico analyses suggested a benign effect, leaving any potential link to disease severity undetermined without functional confirmation.

Conclusion

Severe V. vulnificus sepsis may develop through foodborne transmission, even in the absence of typical exposure to seawater or seafood handling. Disease severity in this patient was primarily influenced by chronic liver disease, alcohol abuse, and diabetes. Clinicians should watch for V. vulnificus infection in patients with these risk factors who present with septic shock or rapidly progressive soft tissue infections, regardless of exposure history.

Introduction

Vibrio vulnificus, a Gram-negative bacillus commonly found in warm estuaries and coastal waters, is a significant pathogen responsible for numerous seafood-related fatalities globally.¹ Infections typically result from consuming contaminated seafood, leading to primary sepsis, or from exposing skin wounds to contaminated seawater, causing severe wound infections and potentially secondary sepsis.² Moreover, transmission can occur through injuries caused by contaminated tools during seafood handling or by insect bites.^3,4 A case of severe V. vulnificus sepsis is presented in a patient who denied typical seawater or wound exposure but reported consuming raw fish before symptom onset. Whole-exome sequencing identified a rare heterozygous variant of uncertain significance in the DOCK2 gene.

Case Presentation

A 51-year-old male presented with acute right upper quadrant abdominal pain and sudden onset fever (peak temperature 38.5°C), without nausea, vomiting, or jaundice. His medical history included chronic gastritis, long-term alcohol consumption, and past surgery for adrenal pheochromocytoma in 2016, requiring ongoing antihypertensive therapy. Newly diagnosed type 2 diabetes mellitus and thrombocytopenia were noted during pre-admission assessment. The patient denied recent seawater exposure or skin trauma from seafood handling but reported consuming raw fish (sashimi) several days before admission. Upon admission, vital signs showed a temperature of 36.7°C, heart rate of 92 bpm, respiratory rate of 20 breaths/min, and blood pressure of 82/53 mmHg. The patient was conscious but lethargic. Cardiopulmonary examination yielded no significant findings. Abdominal examination revealed tenderness in the right upper quadrant with a positive Murphy’s sign, consistent with prior abdominal CT findings of gallstones and acute cholecystitis. The left lower extremity initially appeared normal. The patient rapidly developed septic shock necessitating fluid resuscitation and norepinephrine administration, along with high-flow nasal cannula oxygen therapy for hypoxemia. Within a day, moderate acute respiratory distress syndrome (ARDS) developed. By the third day, purplish-red hemorrhagic bullae appeared on the anterior aspect of the left tibia and dorsum of the foot, accompanied by rapidly spreading surrounding erythema and edema, consistent with necrotizing fasciitis. Gastrointestinal bleeding subsequently developed, manifesting as melena.

Severe thrombocytopenia, markedly elevated lactate, acute kidney injury, hepatic dysfunction, and metabolic acidosis with hypoxemia were observed upon admission through laboratory investigations. Inflammatory markers were found to be increased, and virological screening confirmed active hepatitis B and C infections. Immunoglobulin profiling revealed elevated IgG levels, along with decreased C3 and C4 complement levels (Table 1). On the third day, chest CT scans revealed bilateral pulmonary infiltrates mainly in the lower lobes, indicative of pneumonia and acute lung injury. Lower extremity Doppler ultrasound showed subcutaneous soft tissue edema without abscess formation, and deep vein thrombosis was ruled out. On day 11, magnetic resonance imaging (MRI) of the left lower extremity demonstrated intramuscular hyperintensity consistent with persistent soft tissue edema (Figure 1). Deep vein thrombosis was ruled out by Doppler ultrasound. Metagenomic next-generation sequencing (mNGS) of peripheral blood confirmed Vibrio vulnificus as the etiological agent. Repeat mNGS analysis of the wound swab on day 14 once again detected V. vulnificus, Candida albicans, and Staphylococcus haemolyticus (Table 2).

Table 1.

Laboratory Data

Groups	Variables	Value
Complete blood count	WBC (×109/L)	7.24
	Neutrophil (%)	87
	Lymphocyte (%)	10.6
	RBC (×1012/L)	3.87
	Hb (g/L)	141
	PLT (×109/L)	41
Blood chemistry panel	Glucose (mmol/L)	14.82
	Creatinine (μmol/L)	255.2
	Urea (mmol/L)	15.83
	Total bilirubin (μmol/L)	53.9
	Direct bilirubin (μmol/L)	24.2
	ALT (U/L)	21.1
	AST (U/L)	166
	Albumin (g/L)	33.4
	Globulin (g/L)	49.4
	Total Protein (g/L)	82.8
	HbA1c (%)	8.39
	LDH (U/L)	251
	Lactate (mmol/L)	18.17
	CRP (mg/L)	144.19
	PCT (ng/mL)	>92.980
Coagulation panel	PT (s)	19.6
	INR	1.63
	PTA (%)	48
	APTT (sec)	56
	TT (sec)	25
	D-dimer (ng/mL FEU)	1104
Arterial blood gas	pH	7.32
	PaCO2 (mmHg)	30
	PaO2 (mmHg)	65
	HCO3− (mmol/L)	18
Virological screening	HBsAg (IU/mL)	28.22
	HBcAb (IU/mL)	>10.00
	HBeAb (IU/mL)	>3.00
	Anti-HCV (s/co)	94.72
Immunoglobulin panel	IgG (g/L)	33.1
	IgA (g/L)	6.04
	IgM (g/L)	5.2
	C3 (g/L)	0.51
	C4 (g/L)	0.066

Figure 1.

Imaging findings on Day 3 and Day 11. Chest CT scan images in lung (A) and mediastinal (B) windows demonstrating bilateral lower lobe pulmonary opacities (red arrows). Sagittal MRI of the left lower extremity (C and D) reveals intramuscular hyperintensity (red arrows) consistent with soft tissue edema.

Table 2.

mNGS Results

Days	Sample	Pathogens	Classified	Type	Sequence Numbers
D3	Peripheral blood	Bacteria	G−	Vibrio vulnificus	8100
		Fungi	-	-	-
		Virus	RNA	Hepatitis C virus	27494
		Bacteria	G+	Staphylococcus haemolyticus	122
D14	Wound swab	Bacteria	G−	Vibrio vulnificus	4
		Fungi	-	Candida albicans	176

The rapid development of septic shock, ARDS, and necrotizing fasciitis within 72 hours, despite the lack of immunosuppression or typical exposure history, prompted whole-exome sequencing following informed consent. Analysis identified a heterozygous missense variant in the DOCK2 gene (c.4511C>T, p. Thr1504Met; East Asian allele frequency: 0.0109%), categorized as a variant of uncertain significance (VUS) according to ACMG guidelines. In silico analysis (Table 3) produced conflicting predictions: SIFT, MutationTaster2, and BayesGenomics tools (BGIP1/2) all predicted the variant to be a polymorphism, while Condel and REVEL (score 0.051) yielded neutral or inconclusive outcomes. Subsequent Sanger sequencing confirmed the presence of this variant in the patient (Figure 2).

Table 3.

In silico Prediction of the DOCK2 c.4511C>T (P. Thr1504Met) Variant

SIFT	MutationTaster2	BGIP1/BGIP2	Condel	REVEL (score)	GERP++	PhyloP	Pathogenicity
Polymorphism	Polymorphism	Polymorphism	Neutral	0.051	Conserved	Not conserved	VUS

Figure 2.

DOCK2 Gene Sequencing Electropherogram. Sanger sequencing electropherogram showing the heterozygous missense variant c.4511C>T (p. Thr1504Met) in the DOCK2 gene. The red arrow indicates the variant position where C and T peaks overlap, confirming the heterozygous state.

Upon admission, the patient received empiric antimicrobial therapy with meropenem, later adjusted to meropenem, teicoplanin, and caspofungin. On Day 3, peripheral blood mNGS identified V. vulnificus, leading to a switch to cefoperazone-sulbactam plus levofloxacin on Day 8. Linezolid was added on Day 16. Cefoperazone-sulbactam was stopped on Day 22, while levofloxacin and linezolid were continued. Hemorrhagic bullae were punctured on Day 3. Plastic surgery consultation on Day 15 advised against amputation; instead, local debridement and daily dressing changes were initiated. Despite performing conventional blood cultures and wound cultures, V. vulnificus was not isolated. Treatment decisions relied on mNGS identification and established susceptibility profiles of V. vulnificus to third-generation cephalosporins, tetracyclines, and fluoroquinolones in the absence of isolate-specific antimicrobial susceptibility testing. Gastrointestinal bleeding occurred on Day 16 and Day 25, managed endoscopically with hemoclip placement. After 38 days in the hospital, the patient was discharged in stable condition for further rehabilitation at a lower-level facility.

Discussion

A patient in this case report developed fulminant septicemia from a Vibrio vulnificus infection. Despite no typical exposure to seawater or wounds, a history of consuming raw fish (sashimi) suggested a foodborne origin. The patient’s unusual symptoms and lack of typical exposure history complicated the initial diagnosis. Clinicians should consider an underlying gastrointestinal infection when initial symptoms resemble acute cholecystitis. This case highlights the diagnostic value of mNGS in critically ill patients with hidden infections. Because of the atypical presentation and negative conventional cultures, prompt suspicion of V. vulnificus would not have occurred without mNGS, which enabled rapid pathogen identification and facilitated timely, targeted antimicrobial therapy.

The severity of Vibrio vulnificus infection is influenced by the host’s immune status. Known risk factors include chronic liver disease, alcoholism, diabetes, and other immunodeficiencies.⁵ In Florida, individuals with liver disease faced an 80-fold increased risk of V. vulnificus infection and a 200-fold increased risk of death from consuming raw oysters.⁶ Recent US studies confirm liver disease or alcoholism as the primary mortality risk (odds ratio 6.5).⁷ Foodborne transmission, though fewer in cases, has a higher fatality rate (40% vs 12%). South Korea reports a low V. vulnificus infection incidence (0.18 per 100,000) but with significant economic impact and loss of healthy life years.⁸ Globally, viral hepatitis B and C affect 304 million people,⁹ potentially increasing severe V. vulnificus infections. Climate change, coastal population growth, and aging populations may increase severe V. vulnificus infections.¹⁰ The patient, with hepatitis B and C, alcohol use, and diabetes, fits the high-risk profile. Consuming raw fish (sashimi) aligns with the heightened mortality risk in foodborne cases.

Incidentally, a heterozygous missense variant in the DOCK2 gene (c.4511C>T, p. Thr1504Met) was detected through whole-exome sequencing. While biallelic DOCK2 loss-of-function leads to severe combined immunodeficiency,¹¹ the identified variant is labeled as a variant of uncertain significance. Various in silico tools consistently predicted neutral or benign effects for this variant (Table 3). Due to the lack of functional validation, a definitive causal relationship between this variant and the patient’s disease susceptibility or severity cannot be determined. Therefore, the fulminant clinical course is more likely attributable to the patient’s established host risk factors than to this incidental genetic discovery.

The rapid development of this case is likely due to a dual mechanism. Firstly, infection with Vibrio vulnificus, a pathogen with multiple virulence factors, led to rapid host invasion and tissue damage. Secondly, the host’s traditional susceptibility factors, including chronic liver disease (active hepatitis B and C, prolonged alcohol use), and newly identified diabetes, notably weakened immune defenses. The synergistic interplay between a highly virulent pathogen and a host with well-established risk factors satisfactorily elucidates the observed severity.

The study is limited by several factors. Being a single-case report, it does not allow for definitive conclusions. Additionally, the DOCK2 variant identified is likely benign based on silico predictions. However, without functional validation, we cannot establish any causal relationship between this variant and disease susceptibility or severity. Future research should involve larger cohort studies to screen DOCK2 variants in patient populations with similar clinical phenotypes and to clarify the exact pathogenic mechanisms through in vitro functional experiments.

Conclusion

Vibrio vulnificus sepsis can occur through foodborne transmission, even without a typical history of contact with seawater or seafood. Chronic liver disease, diabetes, and alcoholism play a crucial role in determining the severity of the disease. Clinicians should strongly suspect Vibrio vulnificus infection in patients with these risk factors who present septic shock or rapidly progressive soft tissue infections, even without a typical contact history.

Funding Statement

This work was supported by the Department of Education of Guangdong Province [Grant 2025JD035].

Abbreviations

ACMG, American College of Medical Genetics and Genomics; ALT, Alanine aminotransferase; APTT, Activated partial thromboplastin time; ARDS, Acute respiratory distress syndrome; AST, Aspartate aminotransferase; BGIP1/BGIP2, BayesGenomics inference platform 1 and 2; C3, Complement component 3; C4, Complement component 4; Condel, CONsensus DELeteriousness score; CRP, C-reactive protein; CT, Computed tomography; DOCK2, Dedicator of cytokinesis 2; FEU, Fibrinogen equivalent units; G+, Gram-positive; G-, Gram-negative; GERP++, Genomic Evolutionary Rate Profiling (score); Hb, Hemoglobin; HbA1c, Glycated hemoglobin; HBeAb, Hepatitis B e antibody; HBsAg, Hepatitis B surface antigen; HBcAb, Hepatitis B core antibody; HCO₃⁻, Bicarbonate; HCV, Hepatitis C virus; INR, International normalized ratio; IU, International unit (in IU/mL); IgG, Immunoglobulin G; IgA, Immunoglobulin A; IgM, Immunoglobulin M; LDH, Lactate dehydrogenase; mNGS, Metagenomic next-generation sequencing; MRI, Magnetic resonance imaging; MutationTaster2, MutationTaster 2 (prediction tool); PaCO₂, Partial pressure of carbon dioxide; PaO₂, Partial pressure of oxygen; PCT, Procalcitonin; pH, Potential of hydrogen (acidity measure); PhyloP, Phylogenetic P-value (conservation score); PLT, Platelets; PT, Prothrombin time; PTA, Prothrombin activity; RBC, Red blood cells; REVEL, Rare Exome Variant Ensemble Learner (score); RNA, Ribonucleic acid; SIFT, Sorting Intolerant From Tolerant (prediction tool); TT, Thrombin time; VUS, Variant of uncertain significance; WBC, White blood cells.

Data Sharing Statement

All data associated with this paper are available, and data not presented in the manuscript can be accessed from the corresponding author, Zuopeng Zhang, upon reasonable request.

Ethical Approval and Patient Consent Statement

The case report was reviewed and approved by the Institutional Review Board of The First Affiliated Hospital of Guangzhou Medical University (approval number: ES 2026 K063 01). The research adhered to the principles of the Declaration of Helsinki concerning medical research with human subjects, and all procedures were conducted in accordance with ethical guidelines and standards of good clinical practice. Written informed consent for publication of the patient’s clinical details and clinical images was obtained from the patient.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

All the authors declare no relevant conflicts of interest in this article.