Spontaneous bacterial peritonitis due to Edwardsiella tarda in an immuno-compromised dialysis patient: A case report and review of literature

Abstract

BACKGROUND

Edwardsiella tarda (E. tarda) belongs to the family Enterobacteriaceae and is generally seen to cause infections mainly in fish, but is also capable of infecting humans. Extraintestinal infections occur in patients with certain risk factors, including immunocompromised status. We recently diagnosed a case of spontaneous bacterial peritonitis (SBP) due to E. tarda in an immuno-compromised dialysis patient.

CASE SUMMARY

Patient was a 55-year-old male, with a history of diabetic nephropathy being treated with hemodialysis three times a week. He was referred to our hospital due to an increased volume of ascites, and blood examination revealed increased inflammatory reaction. At our emergency department, he developed fever, disturbance of consciousness, abdominal distension, and abdomen-wide pain. In addition, a dialysis shunt was confirmed in his right forearm, and the shunt site showed no signs of inflammation. No wounds were confirmed on or in his body. A blood examination revealed increased values of white blood cells, C-reactive protein, and creatinine. Plain chest and abdominal computed tomography scanning revealed increased ascites volume. Abdominal paracentesis was performed and a Gram stain revealed Gram-negative bacillus. These findings prompted diagnosis of SBP. The patient was admitted and treated with cefmetazole, causing fever resolution and symptom improvements. Later, E. tarda was identified in ascites culture. The patient improved with decreased inflammatory response and was discharged on the 12^th day of hospitalization. The antibiotic was terminated after 14 days of treatment. SBP in this case may have developed from chronic renal failure and diabetes mellitus.

CONCLUSION

We report the first known case of SBP due to E. tarda in an immuno-compromised dialysis patient.

Key Words: Spontaneous bacterial peritonitis; Edwardsiella tarda; Immunocompromised status; Hemodialysis; Treatment; Case report

Core Tip: Edwardsiella tarda (E. tarda) belongs to the family Enterobacteriaceae and causes infections mainly in fish but is also capable of causing both localized and systemic infections in humans. Extraintestinal infections occur in patients with certain risk factors, including immuno-compromised status, and chronic kidney diseases or diabetes mellitus. In the immuno-compromised or patients with significant underlying disease who have extraintestinal disease, prognosis is related to the extent of infection and the ability for source control. We present the first known case of spontaneous bacterial peritonitis due to E. tarda in an immuno-compromised dialysis patient.

INTRODUCTION

The genus Edwardsiella includes five pathogenic species: Edwardsiella anguillarum, Edwardsiella hoshinae, Edwardsiella ictalurid, Edwardsiella piscicida, and Edwardsiella tarda (E. tarda)[1]. Of these, the most isolated species is E. tarda, which is additionally the predominant species known to cause human disease[2]. It is a motile, facultative anaerobic Gram-negative rod-shaped, oxidase-negative, and catalase-positive Enterobacteriaceae, commonly found in marine environments such as lakes and ponds, rivers, wells, liquid sewage, and fresh and brackish water sources, as well as in reptilian stool, including from fish, lizards, snakes, and alligators[2-9]. This bacterium has also been cultured from animals that live in the ocean, though it has yet to be directly isolated from seawater[6].

Infections caused by this species occur primarily in fish, but have also been observed to affect reptiles, birds, or humans[1]. This important facultative intracellular pathogen can infect many different hosts, from fish to humans, but infections in humans are rarely seen[7,10,11]. In humans, the infections it causes can be both localized and systemic[2]. Incidence rates are at their highest in humid and subtropical climates, and may well be related to cultural elements such as consumption of raw foods and other dietary habits[2]. Other potential bacterial seeding events include exposure to fresh or brackish water environments, whether due to recreation or occupation[2]. Inoculation in humans often occurs either through penetration of the skin, or gastrointestinally due to the consumption of contaminated water or raw or undercooked seafood[2,3,6,10]. As a result, E. tarda infections most commonly manifest as self-limited gastroenteritis[4,5,8,12-17]. Incidence frequency may be increasing due to warming sea water temperatures, as well as greater human consumption of uncooked seafood[6]. In addition, serious skin and soft tissue infections have resulted from injuries occurring in freshwater lakes, such as foot lacerations or puncture wounds caused by catfish spines[2]. On the other hand, infection incidence rates do not vary seasonally[18].

Extraintestinal infections have been reported, including cholecystitis, liver abscesses, other intra-abdominal abscesses, genitourinary infections, infections of the central nervous system, sepsis, bacteremia, and necrotizing fasciitis[2,3,16,18]. In Japan-based studies, hepatobiliary infection, including cholangitis, liver abscess, and cholecystitis, were found to be the most common clinical manifestations[18]. Extraintestinal infection risk factors include age of > 65 years; immunocompromised status; and subacute and chronic diseases including hepatobiliary diseases, malignancy, and diabetes mellitus, as well as iron overload states such as sickle cell disease[2,3,5,10,19]. On the other hand, this is a significant pathogen in near-drowning cases, even for healthy individuals[19]. There have additionally been reports of severe extraintestinal infections, including bacteremia, wound infections, necrotizing fasciitis, hepatobiliary infections such as liver abscess and cholecystitis, peritonitis, meningitis, osteomyelitis, salpingitis, endocarditis, urinary tract infection, tubo-ovarian abscess, gastric submucosal abscess, psoas abscess, epidural abscess, brain abscess, and empyema[3,7]. Lethal infections, including severe and/or disseminated infections, have only rarely been documented, but have directly resulted in fatal infections via the bloodstream in patients who have particular risk factors[5,6,14,16]. On the other hand, the literature also describes cases of hemangioma-related abscess, iliopsoas abscess following acute pyelonephritis, neonatal sepsis, spontaneous bacterial peritonitis (SBP), and infectious endocarditis on a native valve, in a young, non-immuno-compromised host[2,3,20-22]. In addition, peripartum infections are also rare, with very few cases of fatal neonatal infections reported to date[23]. Peripartum infection is rare but life-threatening, for both the neonate and the mother[23].

Here, we report the first known case of SBP caused by E. tarda in an immuno-compromised dialysis patient. In this case, we suspect that mild gastroenteritis, or skin or soft tissue infection including the shunt site, may have led to SBP.

CASE PRESENTATION

Chief complaints

A 55-year-old Japanese male was referred to our hospital with a complaint of a fever of 37 °C and abdominal bloating.

History of present illness

Two weeks prior, the patient developed a fever of 37 °C and abdominal bloating. The fever persisted, and the abdominal bloating gradually worsened. His dialysis doctor had informed him of an increased volume of ascites two weeks ago, and a blood examination revealed increased inflammatory reaction. Based on this, he was referred to our hospital for further investigation and treatment. In the past week, he had consumed no raw or undercooked seafood, nor had any recreational exposure to fresh- or brackish-water environments.

History of past illness

The patient’s medical history included aortic and mitral valve replacement, percutaneous coronary intervention, lacunar infarction, chronic obstructive pulmonary disease, and hemodialysis three times a week due to diabetic nephropathy. He was prescribed aspirin, vonoprazan fumarate, warfarin potassium, and budesonide/glycopyrrolate/formoterol fumarate by the dialysis clinic.

Personal and family history

The patient was a regular smoker who smoked 20 cigarettes per day, with a 35-year history of smoking, and he drank on social occasions. He had worked in the construction industry, and resigned from his job when he was 50 years old. He had not undergone any regular medical check-ups in the past five years, ever since his retirement. He had no allergies. He had received five doses of the novel coronavirus (COVID-19) vaccine. He was single and lived alone. He did not require any assistance with everyday activities. Additionally, the patient had no family history of hereditary diseases or malignant diseases.

Physical examination

The patient was 172 cm tall and weighed 70 kg (body mass index: 23.7). At the outpatient department, his vital signs were abnormal: His blood pressure was 90/60 mmHg, his heart rate was 105 regular beats/minute, his body temperature was 37.4 °C, his oxygen saturation was 94% under ambient air, his respiratory rate was 18/minute, and his Glasgow Coma scale score was 14 points (E4V4M6). A physical examination revealed that he had developed abdominal distension, and pain throughout the abdomen. In addition, a dialysis shunt was confirmed in his right forearm, and the shunt site showed no signs of inflammation. No wounds were confirmed on or in his body.

Laboratory examinations

A routine laboratory examination, taken upon arrival at the outpatient department, revealed increased values for white blood cells, proportion of neutrophil, lactic acid dehydrogenase, creatinine, C-reactive protein, activated partial thromboplastin time, prothrombin time (international normalized ratio), fibrinogen and fibrin degradation products, and thyroid-stimulating hormone, and deceased values for proportion of lymphocyte and eosinophil, hemoglobin, albumin, creatine kinase, amylase, and free triiodothyronine (Table 1). No urinalysis was performed, as the patient was completely unable to urinate. Negative test results were returned by a rapid antigen test to check for influenza, Quick Chaser Flu A, B (S type) (MIZUHO MEDY, Japan) as well as by an ID NOW™ COVID-19 assay (Abbott, United States), an isothermal nucleic acid amplification near-patient test that is marketed as providing a qualitative result (positive, negative, or invalid) in 15 minutes.

Table 1 Routine laboratory examination findings taken at the outpatient department.

Parameter (unit)	Measured value	Normal value
White blood cells (103/µL)	14.1	3.9-9.7
Neu (%)	92	37-72
Lym (%)	2	25-48
Mon (%)	5	2-12
Eos (%)	0	1-9
Bas (%)	1	0-2
Hemoglobin (g/dL)	10.2	13.4-17.1
Platelets (103/µL)	263	153-346
Aspartate transaminase (IU/L)	14	5-37
Alanine aminotransferase (IU/L)	6	6-43
Lactic acid dehydrogenase (U/L)	235	124-222
Alkaline phosphatase (U/L)	104	38-113
Gamma-glutamyl transpeptidase (IU/L)	29	0-75
Total bilirubin (mg/dL)	0.7	0.4-1.2
Total protein (g/dL)	6.7	6.5-8.5
Albumin (g/dL)	3.3	3.8-5.2
Creatine kinase (U/L)	18	57-240
Blood urea nitrogen (mg/dL)	19	9-21
Creatinine (mg/dL)	3.38	0.6-1
Amylase (IU/L)	24	43-124
Sodium (mEq/L)	135	135-145
Potassium (mEq/L)	4	3.5-5
Chloride (mEq/L)	102	96-107
Calcium (mg/dL)	9.5	8.5-10.2
Inorganic phosphorus (mg/dL)	2.7	2-4.5
C-reactive protein (mg/dL)	19.76	0-0.29
Plasma glucose (mg/dL)	82	65-109
Glycosylated hemoglobin A1c (NGSP) (%)	4.8	4.6-6.2
Activated partial thromboplastin time (seconds)	63.2	23-36
Prothrombin time (International normalized ratio)	2.04	0.85-1.15
Fibrinogen and fibrin degradation products (μg/mL)	41.9	0-10

NGSP: National glycohemoglobin standardization program.

Imaging examinations

Plain head and thoracoabdominal computed tomography scans revealed ascites and bilateral kidney atrophy (Figure 1A). The ascites had increased compared to the previous scan, taken 62 days earlier (Figure 1B). An electrocardiogram revealed left axis deviation and sinus tachycardia.

Figure 1 Plain computed tomography scan. A: At the outpatient department. Ascites and bilateral kidney atrophy are confirmed. The ascites had increased compared to 62 days prior; B: 62 days prior. Ascites and bilateral kidney atrophy are confirmed.

FINAL DIAGNOSIS

An abdominal paracentesis was performed, and pale blooded ascites was confirmed (Figure 2A). Examination of the ascites revealed a neutrophil count of 15.2 × 10³/µL, and the Gram stain revealed Gram-negative bacillus (Figure 2B). This was compatible with the exudate, and the ascites findings are shown in Table 2. These findings prompted a diagnosis of SBP.

Figure 2 Ascites findings taken by abdominal paracentesis at the outpatient department. A: Gross appearance. Pale bloody ascites is confirmed; B: Gram stain of ascites (1000 × magnification). Gram-negative bacilli were confirmed, and were later identified as Edwardsiella tarda.

Table 2 Ascites findings taken at the outpatient department.

Parameter (unit)	Measured value
Appearance	Pale blooded
Total protein (g/dL)	4.4
Albumin (g/dL)	2.3
Glucose (mg/dL)	46
Lactate dehydrogenase (U/L)	293
Cell count (103/µL)	16.9
Mononuclear cell (103/µL)	1.7
Neutrophilic cell (103/µL)	15.2

TREATMENT

The patient was admitted to our hospital, and treatment for SBP was initiated with cefmetazole. As a result, his fever resolved on the 4^th day of hospitalization, and his symptoms improved on the 6^th day of hospitalization. On the 6^th day of hospitalization, E. tarda was identified in ascites culture, prompting a change of antibiotic to cefalexin. Antimicrobial susceptibility testing is shown in Table 3. On the other hand, the cytology of the ascites was revealed to be class 2, ruling out malignant disease. The patient improved with a decreased inflammatory response and was discharged on the 12^th day of hospitalization. The antibiotic was terminated after 14 days of treatment.

Table 3 Results of antimicrobial susceptibility testing of ascites taken at the outpatient department.

Antibiotics	MIC	Sensitivity
Ampicillin	< 8	S
Ampicillin/sulbactam	< 8	S
Piperacillin	< 8	S
Piperacillin/tazobactam	< 16	S
Cefazolin	< 4	S
Cefaclor	< 8	S
Cefotiam	< 8	S
Cefmetazole	< 8	S
Flomoxef	< 8	S
Cefoperazone/sulbactam	< 16	S
Cefotaxime	< 1	S
Ceftazidime	< 4	S
Ceftriaxone	< 1	S
Cefepime	< 2	S
Cefcapene	< 0.25	S
Imipenem/cilastatin	< 1	S
Meropenem	< 1	S
Aztreonam	< 4	S
Gentamicin	< 2	S
Amikacin	< 4	S
Minocycline	< 2	S
Levofloxacin	< 0.5	S
Fosfomycin	< 4	S
Sulfamethoxazole-trimethoprim	< 2	S

MIC: Minimum inhibitory concentration; S: Susceptible.

OUTCOME AND FOLLOW-UP

The patient remains free of recurrence. The clinical course of the patient is shown in Figure 3.

Figure 3 Clinical course of the patient. E. tarda: Edwardsiella tarda; CT: Computed tomography; CMZ: Cefmetazole; CEX: Cefalexin; WBC: White blood cell; CRP: C-reactive protein.

DISCUSSION

We report the first known case of SBP caused by E. tarda in an immuno-compromised dialysis patient. This is new knowledge, and consequently there is value in reporting this event.

The patient had several risk factors for extraintestinal infections, such as chronic kidney disease and diabetes mellitus. The patient had diabetic nephropathy, and underwent routine dialysis. Due to the advanced stage of renal disease and the underlying diabetes, the patient was in an immuno-compromised state. The etiology remains unclear. However, we suspect that mild gastroenteritis or skin and soft tissue infection might lead to SBP, though the patient did not present symptoms of gastroenteritis nor skin or soft tissue infection. In this case, it is speculated that SBP may have developed due to the patient’s immuno-compromised status.

The virulence has been attributed to the production of virulence factors, which include catalases and contact-dependent hemolysins, the ability to invade epithelial cells, and resisting phagocytic killing[2]. More specifically, lipopolysaccharide (endotoxin) plays a crucial part in these bacteria’s pathogenesis[1]. In addition, desialylation by E. tarda sialidase is significant in regulating its invasiveness[24]. Pathogenic E. tarda strains exhibit greater sialidase activity and more N-acetylneuraminate lyase messenger ribonucleic acid level up-regulation than non-pathogenic strains do[24]. This bacterium can also survive and replicate within macrophages, as means of evading the host’s defenses[11]. Interactions between E. tarda and macrophages are crucial when it comes to determining edwardsiellasis outcomes[11]. Pathogen survival within macrophage cells likely necessitates fitness genes, which counteract a number of host-killing mechanisms[25]. The pathogen has been known to exit macrophages during infections[25]. The pathogen population that has exited from macrophages displays a reprogrammed transcriptional profile, with significant upregulation of type III secretion system (T3SS)/T6SS-related genes[25]. Furthermore, this macrophage-exiting population had both increased epithelial cell infectivity and an activation of resistance to complex host defenses, in turn promoting full in vivo virulence of E. tarda[25]. This pathogen is able to take advantage of macrophages as a niche to prime virulence, and to spread infection, which underscores the intramacrophage infection cycle’s importance for E. tarda pathogenesis[25]. Therefore, this is an important pathogenic bacterium able to replicate within macrophages, as a key part of pathogenesis[25].

Gastroenteritis caused by E. tarda generally resolves without the need for antibiotics[2,26]. For treatment, it has been established that most strains are susceptible to common antibiotic therapeutic agents[2]. However, strains can demonstrate resistance to broad-spectrum antibiotics, leading to the need to make appropriate use of culture-based antibiotics[14]. Historically, E. tarda has shown greatest resistance to polymyxin B and colistin; in more recent research, it has been demonstrated to possess resistance to macrolides, lincosamides, streptogramins, glycopeptides, rifampin, and fusidic acid[2]. E. tarda can express beta-lactamase, but likely only at low levels; it has not been demonstrated to confer beta-lactam resistance[2]. Based on this knowledge, empiric treatment can start with antimicrobials that generally target organisms that are Gram-negative, and susceptibility to beta-lactams, cephalosporins, aminoglycosides, and oxyquinolones has been demonstrated through in vitro studies[2]. However, tetracycline combined with gentamycin is effective for eliminating bacteria resistant to both gentamycin and tetracycline[27]. Furthermore, when necessary, medical professionals should consider early surgical treatment of parenteral infections, and administer antibiotics in a timely manner[5]. Regarding prevention, a review of Japanese literature showed that the bacterium can cause invasive perinatal infections in both mothers and infants, and that fetal meningitis risk could bear some relation to raw fish being a commonly eaten food in Japan[28]. Therefore, there is a great need to make it common knowledge that pregnant women should avoid eating high-risk raw fish, such as freshwater fish[28]. On the other hand, there is currently no established standard treatment for SBP due to E. tarda; we must wait for further accumulation of evidence, and it is therefore necessary to discuss the length of the treatment period. More specifically, in our case, we should have continued the antibiotics treatment until confirming a negative reading in the ascites culture.

In new knowledge, the biocide triclosan (TCS) is commonly added to household and personal care items in order to stop microbial growth, and has come to be regarded as an emerging pollutant[29]. Its ubiquitous distribution may be a significant contributor to the development of antimicrobial resistance[29]. While reducing minimum inhibitory concentrations as a result of exposure withdrawal did not lead to a full restoration of bacterial susceptibility to the initial level, it has been shown in a study that reduced use of TCS could help to greatly reduce antimicrobial resistance and cross-resistance in pathogenic bacteria[29]. This may also lead to a candidate for treatment.

In immuno-compromised patients, or patients who have a significant underlying disease, who also suffer from extraintestinal disease, prognosis depends on infection extent and source control ability[2]. More specifically, overall 30-day bacteremia mortality was 12%, while overall 90-day mortality was 27%[18,30]. In addition, septicemia represents a severe complication, associated with mortality rates as high as 40% or 50%[2,5,26]. Therefore, much like in this case, when treating patients with underlying diseases, medical professionals should keep the characteristic clinical findings of this infection in mind[30].

This case report has several limitations. First, it reviews only a single case report. Therefore, the actual situation and nature of the disease may differ from the results of the literature review, as a result of reporting bias. Additional studies are needed in order to further evaluate the impact of clinical presentation, laboratory, bacteriology, imaging examinations, and treatment patterns, and the outcomes. Second, microbiological examinations do not have 100% sensitivity or specificity, meaning that we cannot fully rule out the possibility of the involvement of other organisms not identified through culturing.

CONCLUSION

In conclusion, we report the first known case of SBP caused by E. tarda in an immuno-compromised dialysis patient. This case suggests that clinicians should keep this pathogen in mind when encountering SBP in patients with an underlying disease. In addition, timely diagnosis and appropriate treatment are essential for the management of this disease.