Edwardsiella tarda infections in humans: a systematic review of reported cases and clinical outcomes.

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This systematic review of 59 human cases found that Edwardsiella tarda infections, often linked to aquatic exposure in older adults, present with fever and abdominal pain but require timely antibiotic therapy for improved clinical outcomes.

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This systematic review analyzed 59 case reports of human *Edwardsiella tarda* infections published between 2000 and 2025, identifying a diverse range of clinical manifestations from gastroenteritis to severe extraintestinal diseases. The study found that seniors were the most affected demographic, with common presentations including bacteremia, meningitis, wound infections, and tuboovarian abscesses, often linked to seafood consumption or contact with aquatic animals. While the paper explicitly documents cases of tuboovarian abscesses as a complication of infection, it does not focus on gynecological pathology or endometriosis as primary subjects. Relevance to endometriosis: listed as one indication for GnRH antagonists, though the paper's main focus is uterine fibroids.

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Abstract

BackgroundEdwardsiella tarda, a rare human pathogen in the Enterobacteriaceae family, primarily inhabits aquatic environments and infects various animals. Human infections are uncommon but can lead to severe clinical outcomes. This systematic review aims to consolidate and analyze reported human cases of E. tarda infection.MethodsA comprehensive search was conducted across PubMed, Scopus, Embase, and Web of Science databases for studies published between January 2000 and October 2025.ResultsAfter applying exclusion criteria, 59 unique case reports were included. Cases spanned both genders, predominantly affecting older adults, with Japan reporting the highest number. A history of seafood consumption or contact with aquatic animals was common. Clinical presentations varied, though fever and abdominal pain were most frequent. Laboratory findings typically revealed elevated C-reactive protein and leukocytosis. Treatment regimens included antibiotics such as meropenem, ceftriaxone, ampicillin, metronidazole, and levofloxacin, the most frequently used.ConclusionsDespite its rarity, E. tarda can cause life-threatening infections. Awareness among clinicians regarding risk factors, diagnostic methods-particularly culture-based identification-and timely antibiotic therapy is crucial for improved outcomes.Clinical trial numberNot applicable.
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Methods

In this study, four scientific databases—Scopus, Embase, Web of Science, and PubMed—were searched from January 2000 to Oct 2025 to identify published articles on human cases of E. tarda infection. In addition, the references of relevant studies were manually checked, and the included articles were those relevant to the study. For search in the databases, the following keywords were used using appropriate AND, OR, or NOT boolean operators: “Edwardsiella”, “ Edwardsiella tarda ”, “ E. tarda ”, “human”, “patient”, “case”, “case report”, and “human subject”. The study was designed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines [ 12 ]. This study encompasses all published reports of human cases of E. tarda infection from January 2000 to October 2025. The analysis excludes articles that are categorized as reviews, letters to the editor, duplicate publications, conference papers, and those with incomplete full texts. Additionally, non-English publications and articles published outside the specified timeframe have also been omitted from this study. The subsequent data were collected and documented from selected studies, including the first author, year of publication, patients’ residence location, gender, age, history of seafood consumption or contact with marine animals, symptoms upon admission, diagnosis, clinical manifestations, underlying conditions, laboratory indices, imaging techniques, diagnosis methods, treatment modalities, and disease outcomes. Before data collection, the quality assessment of the articles was conducted by MR and MAS using the JBI Critical Appraisal Checklist for case reports [ 13 ]. Data was gathered by MR and MAS independently, and MR and YB reviewed the results to address any discrepancies.

Results

Through a comprehensive literature search, 2270 records were identified. After removing 744 duplicate entries, 1526 unique studies remained. Following title and abstract screening, 1361 studies were excluded based on predefined criteria, leaving 165 articles for further evaluation. Subsequently, an additional 93 articles were excluded with specific reasons, and 72 studies proceeded to full-text review. Ultimately, 13 more studies were removed, resulting in the inclusion of 59 unique case reports in this systematic review (Fig. 1 ). All case reports selected for this study were low risk and their quality had been approved using the JBI Critical Appraisal Checklist for case reports. Fig. 1 The flowchart of the study selection The flowchart of the study selection The demographic characteristics of the included cases are summarized in Table 1 . Among the 59 reported cases, 33 patients (55.9%) were male, and 26 patients (40.1%) were female. The cases spanned a wide age range, with the majority being seniors (≥65 years; 25 patients). Additionally, the distribution across other age groups included infants (0–2 years; 4 cases), children (3–14 years; 4 cases), young adults (15–24 years; 7 cases), and adults (25–64 years; 19 cases) (Fig. 2 ). Table 1 The characteristics of the included studies-part 1 Study code * First author Year Country Gender Age (year) History of consuming/contacting sea animals Symptoms (at admission) Diagnosed as Clinical manifestation (at hospital) Reference S1 An 2023 USA F 20 Raw seafood Abdominal pain and distention, decreased oral intake, and hematochezia Spontaneous bacterial peritonitis and disseminated infection caused by E. tarda Ascites, persistent pulmonary vascular congestion, hematoma [ 14 ] S2 Anno 2018 Japan M 76 N/A Headache Chronic subdural hematoma, infected subdural hematoma by E. tarda Bilateral chronic subdural hematoma, worsening headache, loss of appetite, nausea, abdominal pain [ 15 ] S3 Batron 2019 Canada M 8 Contaminated fish (probably) Frequent loose stools and bleeding per rectum Crohn’s disease (initially), C. difficile colitis (later), E. tarda infection beside others (finally) Abdominal pain daily, loose, bloody bowel movements daily, weight loss, nausea, intermittent nonbilious vomiting, loose bloody stools, and poor appetite, Fever, Tachycardia, mild diffuse tenderness [ 16 ] S4 Bui 2021 USA F 72 Raw seafood Low-grade fever, abdominal cramping Suspected to rheumatoid artritis, proved to be subacute interstitial nephritis in association with E. tarda gastroenteritis Hypertention, edema, pain, hematuria [ 17 ] S5 Crosby 2013 USA M 57 Bited by catfish Fever, swollen hands, pain and numbness in hands Upper Extremity Myonecrosis caused by E. Tarda Fever, red and swollen hand, pain with passive motions, hand musculature was necrotic and foul smelling [ 18 ] S6 Ding 2022 China M 64 N/A Right upper abdominal pain for 3 days with chills and fever Bile duct stones, acute cholecystitis, septic shock, obstructive jaundice, hepatitis, bronchiectasis with infection (initially), E. tarda infection beside others (finally) Abdominal pain, nausea, vomiting, chills, fever, yellow eyes, yellow urine, mucous membranes all over the body [ 19 ] S7 Ebisawa 2018 Japan F 65 N/A Fatigue and diarrhea Mycotic aneurysm (initially), E. tarda infection beside others (finally) Diarrhea, General fatigue, Fever [ 20 ] S8 Frumberg 2016 USA M 23 N/A Worsening pain in hips Osteomyelitis, Periprosthetic infection caused by E.tarda Pain and limitation an body movement [ 21 ] S9 Fukuda 2023 Japan F 20 N/A Abdominal pain and frequent diarrhea Pancolitis-type ulcerative colitis, E. tarda infection Stabbing abdominal pain, severe bloody stool, diarrhea [ 22 ] S10 Fukunaga 2024 Japan F 48 No history Fever, nausea, and general fatigue Rapid dilatation of mycotic aneurysm of dissecting aorta caused by E. tarda Bacterieamia, increase in the aortic diameter, inflamation [ 23 ] S11 Gilani 2022 Iran F 4 Consumption of salmon over the last month but whithout any gastrointestinal issues. Contacting with a common goldfish which was kept in a tank in residence, several times Fever, frequency, and dysuria for a week, headache UTI, E. tarda infection Frequency and dysuria, Headache [ 24 ] S12 Golub-1 2010 USA F 42 N/A Abdominal pain and fever Bilateral salpingitis, left tuboovarian abscess, E. tarda infection Abdominal pain and fever [ 25 ] S13 Golub-2 2010 USA M 70 N/A Shortness of breath Pulmonary embolism, E. tarda infection Shortness of breath,coughing, sweats, chills, and fever [ 25 ] S14 Hara 2023 Japan F 65 No history of keeping fish Fever and abdominal pain for 2 days, tenderness in the right upper abdomen Acute cholecystitis, E. tarda infection N/A [ 26 ] S15 Hasegawa 2024 Japan M 82 N/A Abdominal pain Cholangitis and bacteraemia due to E. tarda and A. caviae Abdominal pain and fever [ 27 ] S16 Hashavya 2011 Israel F 3 weeks N/A Grunting and lethargy, progressing to respiratory failure Neonatal sepsis following maternal amnionitis by E. tarda Runting and lethargy, progressing to respiratory failure [ 28 ] S17 Hayashi 2020 Japan M 87 N/A Diarrhea, abdominal pain Peritonitis and gastroenteritis caused by E. tarda Redness and thickening of the cecal wall and purulent ascites without intestinal contents [ 29 ] S18 Healey 2021 USA F 59 Consumed raw oysters Generalized lower abdominal pain Sepsis with shock related to colitis, right lower lobe pneumonia, UTI, E. tarda infection Acute kidney injury, pancytopenia, respiratory deterioration, sepsis [ 30 ] S19 Ikematsu 2022 Japan M 72 Raw fish Cough, purulent sputum and anorexia Pleural empyema with gas formation caused by mixed infection of E. tarda with S. constellatus Periodontal lesions, coarse crepitations and reduced breath sounds, pleural effusion with foci of gas [ 31 ] S20 Jahromi 2020 USA M 58 Catfish injury Left hand swelling/pain and malaise for 36 hours Soft tissue infection suspected to Group-A Streptococcus, MRSA, V. vulnificus , Klebsiella, Clostridium, and E. coli . Limb infection and necrosis caused by E. tarda. Hand swelling increased moderately, and digit flexion and extension were limited [ 32 ] S21 John 2012 India M 18 N/A Lower gastrointestinal bleeding, loose stools, abdominal pain, fever Cushing’s syndrome, E. tarda infection Central obesity, proximal myopathy and striae typical of Cushing’s syndrome. High grade fever, tachycardia and hypotension suggestive of worsening sepsis [ 33 ] S22 Kadam 2011 India M Neonate N/A Refusal to feed and irregular breathing pattern E. tarda septicemia Refusal to feed and irregular breathing pattern [ 34 ] S23 Kawai 2011 Japan M 17 Contact with lizards, reptiles and fish Pain in his right lower leg, and had, high fever Bacterial and fungal osteomyelitis. Osteomyelitis caused by E. tarda Swollen right lower leg, inflammation [ 35 ] S24 Kimura 2023 Japan M 78 Raw seafood Hypotention, bradypenea, jaundice Massive empyema and cholangitis caused by E. tarda Septic shock, disseminated intravascular coagulation [ 36 ] S25 Koike 2021 Japan F 28 N/A Fever, tenderness only in the mid-upper abdomen Gastrointestinal infection, E. tarda infection Fever, liver dysfunction [ 37 ] S26 Litton 2016 USA F 68 Has a deep puncture wound in his hand with a used fish hook about two weeks prior to presentation Fatigue and body aches, a sacral decubitus ulcer Endocarditis, E. tarda infection Fever, atrial fibrillation was poorly rate controlled [ 38 ] S27 Makinoa 2018 Japan M 62 He often cooked fish himself using an electric heater while consuming alcohol Headache and rapidly progressing altered consciousness that led to coma over several hours. Could not follow verbal commands, and exhibited neck stiffness Meningoencephalitis due to E. tarda infection Fever, declined blood pressure, general tonic seizures, bilateral mydriasis with no light reflex, and an abnormal eye position without oculocephalic reflex. His consciousness deteriorated to deep coma. [ 39 ] S28 Manchanda 2006 India M 27 Bathed in village pound Fever, chills and rigors since 15 days and complaints of pain in right hypochondrium Liver abscess caused E. tarda Vomiting, loss of appetite, immobility due to right abdominal pain, liver abscess [ 40 ] S29 Matsukawa 2024 Japan F 76 Despite regularly eating raw fish, she had not eaten undercooked seafood or been in aquatic environments in the week leading up to her illness Fatigue and difficulty moving, tenderness in her left lower back UTI, pyelonephritis. Iliopsoas abscess, acute cholangitis, bile duct stone, E. tarda infection Fever, muscle weakness [ 41 ] S30 Mikamo 2003 Japan F 33 N/A High fever, lower abdominal pain, and an increasing amount of malodorous vaginal discharge Puerperal intrauterine infection caused by E. tarda Abdominal pain and fever [ 42 ] S31 Mizunoe 2006 Japan M 57 Raw seafood Fever, right chest pain, and exertional dyspnea Bacteremia caused by enteric bacteria, including K. pneumoniae . Empyema caused by E. tarda Ascites, pripheral edemain both legs, slightly anemic [ 43 ] S32 Miyajima 2018 Japan F 80 N/A Fever of 5 days duration Cholangitis associated with Lemmel syndrome, E. tarda infection Low grade fever, icteric sclerae [ 44 ] S33 Miyazawa 2017 Japan F 34 No history Membrane rupture Maternal peripartum septic shock caused by intrauterine infection with E. tarda Foul-smelling amniotic fluid, fever, fetal bradycardia [ 45 ] S34 Mowbray 2002 USA M 6 days The father worked on a boat Lethargy, decreased feeding, and emesis Maternal colonization and neonatal sepsis caused by E. tarda Lethargy, decreased feeding, and emesis [ 46 ] S35 Nishida 2016 Japan M 78 Raw seafood High fever, shaking chill Retrograde cholangitis, E. tarda infection High fever, chill [ 47 ] S36 Ota-1 2011 Japan F 70 She had eaten raw fish or shrimp once or twice a day Fever Autoimmune hemolytic anemia, liver abscess, E. tarda infection Chills and fever [ 48 ] S37 Ota-2 2020 Japan M 74 N/A Abdominal pain, appetite loss and vomiting Gastric submucosal abscess, E. tarda infection N/A [ 49 ] S38 Pham 2021 USA M 85 N/A Fever, hypotension, abdominal pain Suspected to E. coli and E. faecium . Perihepatic abscess caused by E. tarda Abdominal pain, cholecystitis [ 50 ] S39 Sarathi 2023 India M 71 Prick by a raw fishbone over the left thumb 4 days back N/A Cellulitis leading to sepsis, E. tarda infection Pain, swelling of the right hand, fever, erythema, tenderness, local rise of temperature [ 51 ] S40 Spencer 2008 USA M 8 He had pet gold fish Dehyderation, fever, neutropenia C. difficile toxin, rotavirus antigen, and ova and parasites enteric pathogens. Gastroenteritis caused by E. tarda Weight loss, abdominal cramping, watery blood-streaked stools, fever [ 52 ] S41 Suzuki 2018 Japan F 65 She had frequently eaten sashimi (sliced raw fish) and grilled eel, including within a few days prior to admission Fever, lumbago, and right groin pain. UTI, psoas abscess, vertebral osteomyelitis, E. tarda infection Abdominal pain [ 53 ] S42 Sydorchuk 2021 Ukraine M 22 Seafood Cramping abdominal pain, nausea, fever, fluid feces up to 5 times per day, general weakness Food bacterial poisoning, E. tarda infection The abdomen is soft, rumbling, and painful along the intestine, mostly in the right iliac section. Stool is liquid without pathological admixture, badly smelling [ 54 ] S43 Taguchi 2014 Japan M 77 N/A Abdominal pain and high-grade fever Infected hepatic cyst due to E. tarda Fever, abdominal pain and hepatic cyst [ 55 ] S44 Takeuchi 2009 Japan F 3 day N/A Fever Bacterial meningitis, Brain abscesses, E. tarda infection Vomiting, low oxygen saturation [ 56 ] S45 Tamada 2009 Japan F 69 N/A Fatigue, generalized edema, and severe anemia Urosepsis caused by E. tarda Dysuria, hypotention, fatigue [ 57 ] S46 Tonosaki 2021 Japan F 93 N/A Difficulty with mobility Acute cholecystitis, sepsis, disseminated intravascular coagulation, E. tarda infection Chest pain and difficulty with mobility [ 58 ] S47 Tsuchiya 2023 Japan M 77 N/A Back pain Thoracic spondylitis, E. tarda infection Paralysis in the lower extremities, respiratory insufficiency [ 59 ] S48 Tsuji 2008 Japan M 12 Raw fish and shrimps Abdominal pain, watery diarrhea, and vomiting Acute gastroenteritis caused by E. tarda Abdominal pain and developed watery diarrhea [ 60 ] S49 Wang 2024 China F 60 She is seafood saleswoman Pain, redness, and swelling localized to the palm of the right hand Cellulitis caused by E.tarda Fever, redness, swelling, ulcers, blisters, or black spots [ 61 ] S50 Yamamuro 2019 Japan F 64 N/A Anorexia and green diarrhea for a month Necrotizing fasciitis following E. tarda septicemia with gastroenteritis Unconsciousness, hypotention, tachycardia, septic shock [ 62 ] S51 Yamanoi 2018 Japan F 24 N/A Pregnancy (first admission), Abnormal vaginal bleeding (second admission), severe diarrhea, gastric discomfort, and a high fever (third admission) Placental abruption, E. tarda infection Fever, gastric discomfort [ 63 ] S52 Yousuf 2006 Malaysia M 27 N/A Fever, chills, abdominal pain Multiple liver abscesses, E. tarda infection Generalised body weakness, fever, four to five loose stools/day alternating with constipation, dehydration, abdominal diffuse tenderness, decreased air entry [ 64 ] S53 Zokumasu 2025 Japan M 83 N/A Impaired mobility Necrotizing Fasciitis Caused by E. tarda Severe pain in his right lower limb, erythema of right inguinal region to the lower extremity, skin necrosis [ 65 ] S54 Masuda 2025 Japan F 76 N/A Generalized fatigue, anorexia, gradual abdominal pain, reddish mass in the right upper abdomen Cholecystocutaneous Fistula Associated with E. tarda Worsening abdominal pain, reddish mass in the right upper abdomen [ 66 ] S55 Sangitha 2025 India M 63 N/A Fever, jaundice and right upper quadrant abdominal pain for 2 weeks Hepatobiliary Disease associated with E. tarda Pale, icteric and fever [ 67 ] S56 Zhou 2025 China F 32 Undercooked fish porridge Abdominal pain, vomiting, and diarrhea Septic shock; Acute gastroenteritis; infection-induced multi-organ dysfunction syndrome Watery stool, abdominal pain, vomiting, diarrhea, jaundice, shortness of breath [ 68 ] S57 Mao 2025 Vietnam M 56 Superficial wound during the butchering of fishes Mild fever, and the wound became swollen, painful, and pus was discharging Wound co-infection by E. tarda and Proteus vulgaris Wound on the dorsum of the foot, with swelling, erythema, tenderness, and purulent discharge. [ 69 ] S58 Fakih 2015 USA M 63 Contact with catfish Myalgias, nausea, vomiting, fever, confusion Septic shock due to E.tarda bacteriema febrile, hupotensive, acute renal failure [ 70 ] S59 Zhu 2019 China M 65 N/A fever, exhaustion, poor appetite, and right upper abdominal distending pain Brucellosis; liver abscess due to E. tarda Fever, anorexia, tenderness [ 71 ] - Studies are identified by uniqe codes that are similar to those used in Table 2 Abbreviations: A. caviae : Aeromonas caviae , ALP: alkaline phosphatase, ALT: alanine aminotransferase, AST: aspartate aminotransferase, C. difficile : Clostridium difficile , CRP: C-reactive protein, CSF: cerebrospinal fluid, CT: computed tomography, E. faecium: Enterococcus faecium , ESR: erythrocyte sedimentation rate, E. tarda : Edwardsiella tarda , GGT: gamma-glutamyl transferase, HPF: high-powered field, K. pneumoniae : Klebsiella pneumoniae , LDH: lactate dehydrogenase, MALDI-TOF MS: matrix-assisted laser desorption ionization–time of flight mass spectrometry, MRSA: methicillin-resistant Staphylococcus aureus , NGS: Next-generation sequencing, RBC: red blood cell, S. constellatus : Streptococcus constellatus , TEVAR: Thoracic endovascular aortic repair, UTI: Urinary tract infection, V. vulnificus : Vibrio vulnificus , WBC: white blood cell Fig. 2 The pie chart of age categories of cases with E. tarda infection. The most of E. tarda cases were seniors or adults The characteristics of the included studies-part 1 Suspected to rheumatoid artritis, proved to be subacute interstitial nephritis in association with E. tarda gastroenteritis Periodontal lesions, coarse crepitations and reduced breath sounds, pleural effusion with foci of gas Soft tissue infection suspected to Group-A Streptococcus, MRSA, V. vulnificus , Klebsiella, Clostridium, and E. coli . Limb infection and necrosis caused by E. tarda. Acute gastroenteritis caused by E. tarda Fever, jaundice and right upper quadrant abdominal pain for 2 weeks Mild fever, and the wound became swollen, painful, and pus was discharging Wound co-infection by E. tarda and Proteus vulgaris - Studies are identified by uniqe codes that are similar to those used in Table 2 Abbreviations: A. caviae : Aeromonas caviae , ALP: alkaline phosphatase, ALT: alanine aminotransferase, AST: aspartate aminotransferase, C. difficile : Clostridium difficile , CRP: C-reactive protein, CSF: cerebrospinal fluid, CT: computed tomography, E. faecium: Enterococcus faecium , ESR: erythrocyte sedimentation rate, E. tarda : Edwardsiella tarda , GGT: gamma-glutamyl transferase, HPF: high-powered field, K. pneumoniae : Klebsiella pneumoniae , LDH: lactate dehydrogenase, MALDI-TOF MS: matrix-assisted laser desorption ionization–time of flight mass spectrometry, MRSA: methicillin-resistant Staphylococcus aureus , NGS: Next-generation sequencing, RBC: red blood cell, S. constellatus : Streptococcus constellatus , TEVAR: Thoracic endovascular aortic repair, UTI: Urinary tract infection, V. vulnificus : Vibrio vulnificus , WBC: white blood cell The pie chart of age categories of cases with E. tarda infection. The most of E. tarda cases were seniors or adults Among the 59 reviewed studies, 31 (52.5%) were from Japan, suggesting a higher prevalence or reporting rate of E. tarda infections in Japan than in other countries. Additional reported cases were from the United States (13 studies), India (5 studies), China (4 studies), and Canada, Iran, Israel, Malaysia, Ukraine, and Vietnam, each contributing one study (Table 1 ). We analyzed all published case reports from January 2000 to October 2025. The earliest documented case was reported in 2002, and subsequent reports appeared sporadically over the years. The number of reported cases remained relatively low, with only a slight increase in recent years. Notably, the highest number of cases in a single year was six, observed in 2018, 2021, and 2023. In most other years, reports were limited to one to four cases. This pattern suggests that E. tarda infections remain relatively rare, with no clear trend indicating a significant increase or decrease in incidence over time (Fig. 3 ). Fig. 3 The number of published studies of cases with E. tarda infection. The numbers of studies per year are shown as bars The number of published studies of cases with E. tarda infection. The numbers of studies per year are shown as bars A history of seafood consumption or recent contact with marine animals was only documented in 30 of the included studies. Among these, 10 cases (33.3%) reported recent seafood consumption, while 4 cases (13.3%) had a history of regular seafood consumption. Additionally, 5 cases (16.7%) involved injuries or bites from marine animals or sea-related tools, and another 5 cases (16.7%) were suspected to have had either contact with or consumption of marine animals. Furthermore, 3 cases (10.0%) had regular contact with marine animals due to their occupation or pet ownership, whereas 3 cases (10.0%) had no prior history of seafood consumption or contact with marine animals (Fig. 4 ). Fig. 4 The pie chart of the history of E. tarda cases about seafood consumption or contact with marine animals. Most cases reported recent seafood consumption, or a history of regular seafood consumption The pie chart of the history of E. tarda cases about seafood consumption or contact with marine animals. Most cases reported recent seafood consumption, or a history of regular seafood consumption Patients presented with a range of symptoms at the time of admission, with fever (reported in 27 cases) and abdominal pain (reported in 26 cases) being the most common. Similarly, during hospitalization, fever remained the most frequently observed clinical manifestation (26 cases), followed by abdominal pain (22 cases) (Table 1 ). A list of symptoms is provided in Table 2 . Table 2 The characteristics of the included studies-Part 2 Study code * Risk factor (background) Laboratory indeces Imaging and histopathology Diagnosis method Antibiotics Other treatments Outcome S1 Hemophagocytic lymphohistiocytosis, macrophage activation syndrome, idiopathic thrombocytopenic purpura, systemic juvenile idiopathic arthritis, chronic lung disease, pulmonary hypertension, adrenal insufficiency, portal hypertension, and congestive hepatopathy, taking immunosuppresor medicines Elevated levels of hepatic function parameters (ALT, ASP, ALP, total bilirubin, elevated levels of total protein, albumin and serum CRP 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, a CT of abdomen and pelvis with and without contrast showed near complete resolution of the left upper quadrant hematoma Blood culture, MALDI-TOF MS, NGS AMP N/A The patient was discharged after clearance of blood cultures and resolution of fever S2 Common bile duct stones Leukocytosis and elevated levels of serum CRP Bilateral chronic sub dural hematoma (CT) Culture CRO, MTZ Surgery, burr hole drainage The patient cured and was discharged with no residual neurological deficit S3 N/A Leukocytosis, Neutrophilia, Thrombocytosis. CRP was mildly elevated No intra abdominal abscesses (Ultrasound imaging), Chronic active gastritis and colitis (Endoscopy and Histopathology) Stool culture, blood culture VAN and MTZ (for C. difficile ), AMP, AMX Steroid therapy (Mesalamine, Prednisone, Azathioprine), Infliximab Improvement status, discharged on a tapering regimen of prednisone S4 Hypertension, hyperlipidemia, coronary artery disease, hypo thyroidism, and liver cysts High creatinine. Urinalysis showed 3+ protein, three RBCs per high powered field Two hepatic cysts (CT), A minimal change-like lesion with approximately 90% visceral epithelial cell foot process effacement with villous formation(histopathology) Culture CIP, the patient only took a few doses of adjunctive MTZ and DOX N/A She was cured and her edema resolved S5 Pulmonary hypertension, hepatitis C, and cirrhosis Leukocytosis and elevated level of serum creatinine Inflammation and necrosis (histopathology) Culture started with DRP, VAN, LEV then altered to CRO Surgery (fasciectomy), amputation Discharged and wound healed S6 Hepatitis Increase in WBCs, a rise in CRP, and an elevation in the percentage of neutrophils N/A Blood culture IMP, CPZ-S Choledochotomy stone drainage, T-tube drainage, cholecystectomy, blood transfusion Improvement status, Discharged without infection S7 Cirrhosis, hepatocellular carcinoma, chronic heart failure, pulmonary hypertension, diabetes mellitus, aneurysm Elevated WBCs and CRP A ruptured aneurysm of the descending aorta (chest CT) Blood culture, MicroS- can WalkAway and Matrix Assisted Laser Desorption/MALDI-TOF MS AMP-S (initially), VAN, MPM, AMP, GEN, AMX, AMX/CLV TEVAR She transfered to other hospitals, re-admitted, treated with antibiotics and other heart disease related treatments. Finally, after some years there has been no recurrence of symptoms after the second stent insertion. S8 Sickle beta thalassemia, infected artificial graft N/A Radiographs showed bilateral Ficat-Arlet stage IV osteonecrosis Culture FEP, VAN, CIP Physical therapy, aspirin, mechanical thrombo-prophylaxis He was discharged to acute rehabilitation, then home. At 30 months, he reported no activity restrictions and excellent satisfaction S9 N/A Only mild anemia and elevated CRP Edema and thickening of the entire colon wall, without perforation or abscess (CT), No severe finding (endoscopic examinations) A glutamate dehydrogenase assay and toxigenic culture (for C. difficile ), Stool culture (positive for E. tarda ), Blood culture (negative for E. tarda ) VAN and MTZ (for C. difficile ), CMZ Corticosteroids therapy (mesalazine, azathioprine), Vedolizumab or Ustekinumab Fever subsided, and abdominal pain and clinical manifestation of ulcerative colitis improved after corticosteroid administration. As of the day of discharge, corticosteroids were being administered. Steroid-free clinical remission was maintained for four months after hospital discharge. S10 Marfan’s syndrome, mycotic aneurysm of chronic aortic dissection Leukocytosis, CRP level was elevated A 53.6-mm mycotic aneurysm of the dissecting aorta (CT) Blood culture CRO Surgery The patient discharged without infection recurrence at the 5-month follow-up S11 None Urinalysis: 3–4 RBCs, many WBCs, and many bacteria per high-power field, as well as 1+ protein and positive nitritite No abnormalities (MRI) Urine culture (positive for E. tarda ), Blood culture (negative for E. tarda ), Chemical tests CRO, NFT N/A On the second day of hospitalization, due to the elimination of fever and improvement in the patient’s symptoms, the patient was discharged with the instruction to take NFT S12 Chlamydia infection and pelvic inflammatory disease N/A A left tuboovarian abscess (CT) Culture Initially CLDM, GEN, and DOX switched to CIP and MTZ Surgery The patient was discharged on AMX/CLV and DOX S13 Hypertension, hyperlipidemia, coronary artery disease and bypass graft surgery, glomerulonephritis leukocytosis, mild anemia, and mild thrombocytopenia. Ceatinine as well as total bilirubin were elevated No abnormality (X-ray) Culture AZM changed to CRO and MTZ, finally MOX N/A The patient was discharged on MOX S14 Asthma, depression, and irritable bowel syndrome Leukocytosis, and high levels of CRP Gallbladder distention, wall thickening, and inflammation of perigallbladder fat (CT). No evidence of gallbladder or common bile duct stones (Magnetic resonance cholangiopancreatography), An enlarged gallbladder (Laparoscopy), Intense neutrophilic infiltration of all layers of the gallbladder epithelium and necrosis in some layers (Histopathology) Blood and bile juice cultures CMZ N/A Following her discharge, she continued to take amoxicillin/clavulanate until postoperative day 15, experiencing no complications S15 Cholangitis, and a bile duct stent, atrial fibrillation, chronic heart failure, hypertension, chronic kidney disease, and hyperuricemia Elevated hepatic enzymes Dilated intrahepatic bile ducts (CT) Culture TZP, LEV, changed to AMX/CLV N/A He was discharged on Day 11 with no infection recurrence for 3 years follow-up. S16 N/A Leukocytosis and mild thrombocytopenia. Marked interstitial infiltrates (Chest X-ray) Culture, sequencing AMP, GEN then cheanged to CRO Mechanical ventilation and phenytoin treatment The patient was discharged at the age of 12 days in a good general condition S17 Child-Pugh A cirrhosis, hepatitis C Leukocytosis, Neutrophilia, high CRP levels thrombocytopenia, elevated prothrombin time, elevated hepatic functions parameters Circumferential thickening of the cecum (CT) Peritoneal fluid culture N/A Surgery Fully recovered S18 Advanced lung cancer, pulmonary hypertension, liver cirrhosis, hepatitis C, and alcoholism Low WBCs; low platelet count, high Creatinine. Urinalysis was positive for infection and was notable for the following: +1 protein, +1 blood, +4 urobilinogen, 2.5 hyaline casts per high power field, 51 to 100 WBCs with clumps Wall thickening throughout the right colon and inflammation extending along the colon and surrounding the terminal ileum and appendix (CT). Portal venous congestion, cirrhosis of the liver, pulmonary right lower lobe infiltrate, but no splenomegaly (CT) Blood culture FEP, MTZ, LEV Granix (tbo-filgrastim), albuterol/ipratropium nebulization, and radiation (for her cancer), mechanical ventilation (for her respiratory failure), vitamin C sepsis protocol The patient died, despite receiving aggressive treatment S19 Gastric cancer, gastrectomy Leukocytosis with neutrophilia, high CRP concentration, high procalcitonin and low serum albumin concentration Suspended air bubbles within the pleural effusion with septations in the left lower lung lobe (CT) Culture MPM, AMP-S Therapeutic thoracentesis Fully recovered S20 Alcohol abuse and hepatitis C N/A No abnormality (X-ray) Blood culture Broad spectrum antibiotics Surgery Expired 5 days after presentation S21 N/A He had serum potassium of 1.7 mmol/L. High cortisol and adrenocorticotropic hormone level (showing Cushing’s syndrome) Multiple discrete colonic ulcers, without active bleeding (lower gastrointestinal (LGI) endoscopy), normal (upper gastrointestinal (UGI) endoscopy). Amoebic trophozoites in large numbers (biopsy). No pituitary tumour (MRI). Enlarged adrenal glands bilaterally, but no ectopic source of ACTH production (CT). Blood culture and culture of the pus aspirated from the liver CRO, MTZ Diloxanide furoate, dexamethasone (for Cushing’s syndrome) After recovering from sepsis, he underwent a bilateral adrenalectomy to treat Cushing’s syndrome and achieved a complete recovery. S22 N/A Normal Hemoglobin, leukocytopenia, elevated levels of CRP N/A Blood culture CZX, AMK Vitamin K and fresh frozen plasma Expired S23 X-linked chronic granulomatous disease, liver abscess Leukocytosis, high ESR and CRP, elevated Serum (1 -3)-beta glucan A heterogeneous high-intensity area in the right tibia and significant high signal intensity in the surrounding soft tissue (MRI) Blood culture, urine culture CFZ N/A The patient was discharged after a total of 10 weeks of intravenous antibiotic therapy S24 Liver cirrhosis, primary biliary cholangitis, a history of curative treatment of chronic myelogenous leukemia Leukocytosis, High CRP levels, High procalcitonin A massive empyema in the right lung before treatment (CT and chest radiography) Culture N/A Infusion therapy,anticoagulation, and high doses of noradrenaline, dobutamine, and vasopressin Died from liver failure S25 Ovarian endometriotic cysts and endometriosis, taking low-dose norethisterone and ethinyl estradiol after ovary-sparing surgery High WBCs, CRP. High AST, GGT, LDH, and bilirubin No specific clinical findings (CT and endoscopic ultrasonography). Mitral regurgitation (echocardiography). Asymptomatic infarction (MRI). Mitral valve vegetation with inflammation of subvalvular tissues (Histopathology) Blood culture CMZ, changed to AMP-S and GEN after detecting E. tarda Surgical therapy She clinically improved and was discharged on day 67 S26 Prior mechanical prosthetic aortic valve implantation and mitral valve annuloplasty Normal WBC count, elevated procalcitonin An echodensity on the mechanical aortic valve, concerning for vegetation (echocardiography) Blood culture, 111In-labeled WBC scan VAN, TZP, CIP. Shifted to CRO and LEV (for E. tarda ) Non-surgical heart related therapy He was discharged after 21 days in the hospital and is on indefinite levofloxacin therapy. At the 6-month follow-up, he remains on this regimen without complications and has returned to his active lifestyle S27 Severe Alcohol abuse, pneumonia, macrocytic anemia Leukocytosis, thrombocytopenia, High CRP, high AST and ALT, elevated levels of creatinine. Reduction in the CSF cell count A small hematoma with perifocal edema at the trigone of the left lateral ventricle (CT) Blood and CSF cultures MPM Dexamethasone, dopamine, fosphenytoin sodium hydrate Died from cardiopulmonary arrest despite resuscitation on the third hospitalization day S28 N/A Leukocytosis with neutrophilia, ESR was raised. Liver function tests were also normal with elevated ALP An inhomogenous space-occupying lesion in postero superior quadrant of right lobe (ultrasound) Culture,SDS-PAGE CHL N/A The patient was discharged on Day 4 and fully recovered by 15 day of follow-up S29 Right femoral neck fracture and cervical spondylosis. Right bipolar hip arthroplasty for a right femoral neck Increased WBCs, CRP, total bilirubin, ALP, LDH, GGT, blood urea nitrogen, creatinine, and lactate. Decreased platelet count. Urine qualitative test: positive for WBCs, occult blood, and protein. iliopsoas abscess, a common bile duct calculus and multiple urinary calculi (CT). Blood and urine cultures MPM, then AMP and finally AMX (for E.tarda ) Acetaminophen, a left ureteral stent was placed The patient made good progress but experienced muscle weakness during her hospital stay. She was transferred to a rehabilitation facility on day 48 after adjusting socially. S30 Hepatitis C Leukocytosis, High CRP, and High ESR A small amount of fluid in the cul-de-sac, and there were no abnormal findings in the uterus or ovaries (ultrasonography) Culture CEF, ISP N/A The patient was discharged on Day 5 after the start of the antimicrobial chemotherapy. S31 Hepatic cancer, hepatectomy, malignant lymphoma Hemoglobin concentration was low, and his WBC count was elevated. There were elevations of CRP, total bilirubin, direct bilirubin, and serum creatinine. The albumin level was low A right pleural effusion (chest X-ray) Culture PAPM/BP Thoracic drainage Fully recovered S32 Hepatocellular carcinoma, gallbladder cancer, diabetes mellitus, mild interstitial pulmonary fibrosis, aspirin consumption High CRP and elevated blood glucose levels, elevated hepatic enzymes Dilation of intrahepatic bile duct (CT) Culture CFZ Endoscopic biliary drainage Fully recovered S33 Pregnancy Leukocytosis, High CRP, elevated activated partial thromboplastin, elevated prothrombin, low fibrinogen A hematoma in the abdominal wall and uterine wound (ultrasonography) Culture Firstly betalactams then altered to BPM N/A Inflammatory response was gradually decreased, and the patient was discharged on day 26 S34 Hypotonic and moderately jaundiced Thrombocytopenia, high CRP level, elevated total bilirubin level N/A Culture, rep-PCR AMP, GEN Intravenous fluid infusion He was developmentally normal at 11 months of age and the cause of unilateral hearing loss remained undetermined. S35 Pancreatoduodenectomy, advanced gasteric cancer Elevated hepatic enzymes N/A Blood culture CMZ N/A He was discharged without any complications S36 Cholecystectomy for gallbladder stone 10 years prior to this admission and allergic shock with iodine contrast material Remarkable anemia No diseases were appeared except for early gastric cancer (CT, endoscopy, ultrasonography and echo cardiography) Pus culture CFPH, then MPM (for E. taeda ) Prednisolone She was discharged after endoscopic submucosal dissection for early gastric cancer S37 Hypertension, chronic alcohol consumption, former smoker Leukocytosis and elevated CRP. Serum bilirubin, AST, ALT, LDH, ALP, and GGT were elevated Choledocholithiasis in the common bile duct, a gastric wall abscess and an intra-abdominal abscess (CT), A large mass was noted at the greater curvature of the stomach (endoscopic examination). Connection between the intraabdominal abscess and gastric mubmucosal abscess (Fistulography). Blood and abscess cultures CPZ Telmisartan, amlodipine besilate, amlodipine besilate, celecoxib, tramadol hydrochloride, acetaminophen, etizolam. Percutaneous drainage, Bile stone removing The patient was discharged without any complications S38 Chronic kidney disease receiving hemodialysis, hypertension, coronary artery disease, myelodys plastic syndrome, and chronic cholecystitis Leukocytosis with neutrophilia, high serum creatinine elevated direct bilirubin, and decreased platelet Acute cholecystitis (CT) Culture CRO, MTZ then after blood culture VAN was administered N/A Fully recovered S39 B cell lymphoma High WBCs with polymorphic predominance No abnormality in hand and fingers dut to fish contact (radiography) Blood culture, biochemical tests MPM (for E.tarda ), LZD (deescalated after E. tarda detection) Rituximab, cyclophosphamide, doxorubicin, vincristine, and oral prednisolone chemotherapy Prophylactic acyclovir, cotrimoxazole Cellulitis was resolved and the complete blood count showed normal parameters. MEM was stopped and the patient was discharged with the advice of oral faropenem S40 Renal transplantation High Serum creatinine. Leukocytosis with neutrophilia. A urine analysis was unremarkable. Stools were hemoccult positive. N/A Stool culture AMX, CEF Azathioprine, intravenous hydration The patient was discharged from hospital to complete high-dose AMX (three-day course) S41 Gastrectomy, cholecystectomy, splenectomy, and chemotherapy for gastric cancer. Diarrhea, alcoholic abuse Leukocytosis with neutrophilia, high urea nitrogen, high creatinine, high albumin, and elevated levels of CRP Bilateral renal enlargement with perinephric stranding and bilateral psoas abscess (CT). Vertebral osteomyelitis (MRI). ileocecal diverticulitis (CT) Blood culture CRO, changed to CMZ for E. tarda, finally changed to MPM Surgical drainage and discectomy Her symptoms gradually improved. She was discharged after 12 weeks of antimicrobial therapy S42 N/A Increased neutrophils N/A Feces culture NFX, NOR A Trisolum solution, Rheosorbilact, Rehidron, Enterosgel, Spasmalgon The patient’s condition was satisfactory after Day 2, bowel movements were normalized, abdominal pain disappeared S43 Diabetes mellitus and chronic myelogenous leukemia Elevated WBCs, CRP. Low hemoglobin A known cyst in the external lobe (CT) Culture N/A External percutaneous transhepatic cholangeal drainage, stent The patient was discharged 16 days after drainage of the infected hepatic cyst S44 N/A High CRP levels Brain abscesses (CT), multiple abscesses (MRI) Pus culture CTX, AMP, MEM External derinage Fully recovered S45 End-stage endometrial cancer, hysterectomy, bilateral salpingo-oophorectomy, and systematic lymphadenectomy, adjuvant radiotherapy, chemotherapy Leukocytosis, anemia, AST 72 U/l, ALT 154 U/l, blood urea nitrogen 58.6 mg/dl, creatinine 1.71 mg/dl N/A Urine and blood culture CZOP N/A Expired on 8th day S46 Resection of left breast cancer, total hysterectomy for uterine fibroids, and shingles Increased WBCs and CRP, decreased platelet count, increased lactate level and abnormalities in the coagulation/fibrinolysis system Multiple gallbladder stones and mild hyperplasia (CT) Blood culture CPZ-S, changed to PZFX and then changed to TZP. TZP was continued, AMK was initiated, and CLDM and LEV was also used. N/A As the fever remained, antibiotic administration was continued until day 29, and the patient was discharged on day 35 to resume rehabilitation S47 Diabetes, prostate cancer, and pancreatic cancer with hepatic metastasis Hyperleukocytosis and high CRP Endplate erosion at the T1/2 disk (CT), bone edema in the T1-2 vertebrae and fluid accumulation in the T1/2 disk (MRI). Pulmonary embolism, pneumonia, and ileus (CT) Blood, urine, and abscess cultures TZP was changed to CFZ for E. tarda, then changed to MEM and then LEV Posterior instrumented fusion at C7–T3 His condition stabilized, leading to ICU discharge, but he still had lower limb paralysis. Six months later, he could walk short distances, and CT showed bony fusion. S48 N/A N/A N/A Stool culture AMP Intravenous fluid infusion His symptoms had improved and he was discharged S49 N/A Leukocytosis with neutrophilia, High CRP level L, and elevated interleukin-6 level N/A Culture, NGS IMP, AMK Topical mucopolysaccharide polysulfate cream, underwent infrared radiation therapy The patient was discharged on Day 12 S50 N/A Pancytopenia, high CRP, hepatic disorder, renal dysfunction, hypoglycemia, and coagulation disorder An edematous change in the small intestine wall indicated enteritis (CT) Blood culture, biochemical tests, 16s rRNA PCR MPM, VAN, CIP Surgery The patient was cured and discharged on day 57 S51 N/A Severe anemia with a hemoglobin level of 3.9 g/dl. Slight elevation of the WBC count and CRP (third admission) Hematoma (abdominal ultrasound examination, CT), a cyst (CT) Pus culture TZP, AMP-S, MPM Emergency cesarean section, blood transfusion, laparoscopic surgery, drainage procedure Fully recovered S52 None Leukocytosis with neutrophilia. Blood urea was raised. Liver function tests were remarkable. Raised right hemi-diaphragm with basal consolidation (chest X-ray). Multiple hypoechoic lesions in the liver (ultrasonography). Multiple lesions in hepatic lobes (CT) Blood culture CAZ, MTZ. Changed to AMP and finally AMX/CLV and MTZ for E. tarda Drainage of liver abscesses, exploratory laparotomy The patient died of septic shock. S53 Chronic heart failure secondary to atrial fibrillation Leukocytosis, thrombocytopenia, elevated C-reactive protein, and increased serum lactate N/A Culture MPM, VAN Norepinephrine and vasopressin, Tracheostomy, renal replacement therapy Expired S54 Follicular Lymphoma C-reactive protein elevated, high blood urea nitrogen, high creatinine, elevated prothrombin time-international normalized, Multiple intra-abdominal tumors involving the subdiaphragmatic space, para-aorta, intrapelvic space, adrenal glands, and inguinal areas (CT) Abscess culture N/A Rituximab, cyclophosphamide, doxorubicin, and prednisolone Expired four days after admission S55 Diabetes mellitus, pulmonary tuberculos, extrahepatic portal vein obstruction Anemia, total WBC count was normal, elevated levels of hepatic function parameters N/A Blood culture MPM N/A Discharged after 10 days S56 Abortion, systemic lupus erythematosus and rheumatoid arthritis Leukocytosis with neutrophilia, High CRP elevated level of interleukin-6, high procalcitonin Edematous change in the small intestine (CT) Blood and urine culture: etagenomics next-generation sequencing MPM N/A Discharged S57 Diabetes mellitus, a history of pulmonary tuberculosis Elevated white blood cell count with neutrophil predominance; C-reactive protein was elevated N/A Pus culture, real-time PCR VAN, CFX changed to CAZ, GEN Excision of all necrotic tissues Complete wound healing was achieved after 2 weeks S58 N/A N/A Diffuse hypoperfusion of solid bowel organs with concern for necrosis (CT) Blood culture Broad-spectrum antibiotics Intubated and resuscitated with fluids Expired S59 Alcohol abuse, brucellosis Elevated white blood cell count with neutrophil predominance, elevated platelets, C-reactive protein was elevated Hypoechoic lesion of the hepatic left lobe (ultrasonography) NGS CRO N/A Discharged on the 18th day - Studies are identified by unique codes that are similar to those used in Table 1 Abbreviation of antibiotics: AMK: amikacin, AMP: ampicillin, AMP-S: ampicillin-sulbactam, AMX: amoxicillin, AMX/CLV: amoxicillin/clavulanic acid, AZM: azithromycin, BPM: biapenem, CAZ: ceftazidime, CEF: cefepime, CFPH: cefcapene pivoxil hydrochrolide hydrate, CFZ: cefazolin, CHL: chloramphenicol, CIP: ciprofloxacin, CLDM: clindamycin, CMZ: cefmetazole, CPZ: cefoperazone, CPZ-S: cefoperazone-sulbactam, CRO: ceftriaxone, CTX: cefotaxime, CZOP: cefozopran, CZX: ceftizoxime, DOX: doxycycline, DRP: doripenem, FEP: cefepime, GEN: gentamicin, IMP: imipenem, ISP: isepamicin, LEV: levofloxacin, LZD: linezolid, MOX: moxifloxacin, MPM: meropenem, MTZ: metronidazole, NFT: nitrofurantoin, NFX: nifuroxazide, NOR: norfloxacin, PAPM/BP: panipenem/betamipron, PZFX: pazufloxacin, TZP: piperacillin/tazobactam, VAN: vancomycin, CFX: cefoxitin, CAZ: ceftazidime The characteristics of the included studies-Part 2 Physical therapy, aspirin, mechanical thrombo-prophylaxis Advanced lung cancer, pulmonary hypertension, liver cirrhosis, hepatitis C, and alcoholism The patient died, despite receiving aggressive treatment Prior mechanical prosthetic aortic valve implantation and mitral valve annuloplasty Leukocytosis with neutrophilia, ESR was raised. Liver function tests were also normal with elevated ALP Hemoglobin concentration was low, and his WBC count was elevated. There were elevations of CRP, total bilirubin, direct bilirubin, and serum creatinine. The albumin level was low Chronic kidney disease receiving hemodialysis, hypertension, coronary artery disease, myelodys plastic syndrome, and chronic cholecystitis Leukocytosis with neutrophilia, high serum creatinine elevated direct bilirubin, and decreased platelet Increased WBCs and CRP, decreased platelet count, increased lactate level and abnormalities in the coagulation/fibrinolysis system Emergency cesarean section, blood transfusion, laparoscopic surgery, drainage procedure Norepinephrine and vasopressin, Tracheostomy, renal replacement therapy Rituximab, cyclophosphamide, doxorubicin, and prednisolone Abortion, systemic lupus erythematosus and rheumatoid arthritis Elevated white blood cell count with neutrophil predominance; C-reactive protein was elevated Elevated white blood cell count with neutrophil predominance, elevated platelets, C-reactive protein was elevated - Studies are identified by unique codes that are similar to those used in Table 1 Abbreviation of antibiotics: AMK: amikacin, AMP: ampicillin, AMP-S: ampicillin-sulbactam, AMX: amoxicillin, AMX/CLV: amoxicillin/clavulanic acid, AZM: azithromycin, BPM: biapenem, CAZ: ceftazidime, CEF: cefepime, CFPH: cefcapene pivoxil hydrochrolide hydrate, CFZ: cefazolin, CHL: chloramphenicol, CIP: ciprofloxacin, CLDM: clindamycin, CMZ: cefmetazole, CPZ: cefoperazone, CPZ-S: cefoperazone-sulbactam, CRO: ceftriaxone, CTX: cefotaxime, CZOP: cefozopran, CZX: ceftizoxime, DOX: doxycycline, DRP: doripenem, FEP: cefepime, GEN: gentamicin, IMP: imipenem, ISP: isepamicin, LEV: levofloxacin, LZD: linezolid, MOX: moxifloxacin, MPM: meropenem, MTZ: metronidazole, NFT: nitrofurantoin, NFX: nifuroxazide, NOR: norfloxacin, PAPM/BP: panipenem/betamipron, PZFX: pazufloxacin, TZP: piperacillin/tazobactam, VAN: vancomycin, CFX: cefoxitin, CAZ: ceftazidime Given the diverse clinical presentations of E. tarda infection, patients were initially diagnosed with a range of conditions (Table 1 ). In some cases, the initial diagnosis remained valid, but the infectious agent was later identified as E. tarda rather than the originally suspected pathogen. In other instances, the initial diagnosis was revised entirely after further testing confirmed E. tarda as the primary cause of infection (Table 1 ). Among the 59 cases, 44 patients had documented underlying conditions, 13 did not provide information on comorbidities, and 2 explicitly reported having none. Detailed information on these underlying conditions is provided in Table 3 . Broadly, the comorbidities can be categorized as follows: cancer (17 records), cardiovascular diseases (12 records), liver-related conditions (9 records), respiratory disorders (9 records), hepatitis C (6 records), biliary tract issues—including cholangitis, cholecystitis, and bile duct stones (6 records), hematologic disorders (6 records), renal or urinary tract diseases (6 records), alcoholism (6 records), diabetes (6 records), disorders of the female reproductive system (4 records), and gastrointestinal conditions (4 records) (Fig. 5 ). Table 3 The number of reports of symptoms/clinical manifestations of the patients with E. tarda infection at admission and during hospital stay Symptoms (at admission) Report No. Symptoms (during hospital stay) Report No. Fever 27 Fever 26 Abdominal pain 26 Abdominal pain/tenderness 22 Skeletal/general pain 12 Nausea/vomiting/emesis 9 Diarrhea 9 Skeletal/general pain 9 Fatigue 7 Shortness of breath/respiratory failure 9 Shortness of breath/respiratory failure 5 Limb swelling/necrosis/inflamation 9 Chills 4 Diarrhea 7 Nausea/vomiting 5 Difficulty with mobility 6 Headache 3 Bacterieamia/sepsis 6 Limb swelling 4 Chills 4 Gastrointestinal bleeding 3 Lethargy/altered consciousness 4 Lethargy/altered consciousness 3 Ascites 3 Difficulty with mobility 3 Poor appetite 3 Poor Appetite 3 Tachycardia 3 Anorexia 3 Badly smelling 3 Hypotention 2 Fatigue 3 Anemia 2 Hypotention 4 Refusal to feed 2 Hematoma 2 Dysuria 1 Headache 2 Malaise 1 Loose bloody stools 2 Jaundice 1 Weight loss 2 A sacral decubitus ulcer 1 Neck stiffness 1 Rigors 1 Malodorous vaginal discharge 1 Membrane rupture 1 Dehyderation, 1 Generalized edema 1 Abnormal vaginal bleeding 1 Cough 1 Purulent sputum 1 Fig. 5 Underlying diseases in E. tarda -infected human cases. The numbers of reports for each underlying diseases in E. tarda cases are shown in bars The number of reports of symptoms/clinical manifestations of the patients with E. tarda infection at admission and during hospital stay Underlying diseases in E. tarda -infected human cases. The numbers of reports for each underlying diseases in E. tarda cases are shown in bars Various laboratory indices were evaluated in the patients, revealing a range of abnormalities as detailed in Table 3 . Notably, the most frequently observed alterations were elevated C-reactive protein (CRP) levels (33 cases) and leukocytosis (24 cases). These findings are further illustrated in Fig. 6 . Fig. 6 The laboratory indices measured in E. tarda cases. The numbers of reports for each laboratory indices in E. tarda cases are shown in bars The laboratory indices measured in E. tarda cases. The numbers of reports for each laboratory indices in E. tarda cases are shown in bars A variety of imaging techniques were employed in 48 patients, with computed tomography (CT) being the most frequently used modality (performed for 32 patients). In contrast, histopathological examination was carried out in only 5 cases. Because these diagnostic methods were applied for different clinical purposes, their findings were diverse and could not be systematically aggregated or analyzed in detail in our study. Nevertheless, all the results are documented in Table 3 . In all 59 studies included in the review, E. tarda was identified through culture methods. Blood culture was the most frequently utilized technique, reported in 29 studies, followed by abscess/pus culture (8 studies), stool culture (5 studies), and urine culture (5 studies). In addition, bile juice culture, cerebrospinal fluid (CSF) culture, and peritoneal fluid culture were reported in one study each. Other detection methods employed in some cases included polymerase chain reaction (PCR), next-generation sequencing (NGS), matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF MS), WBC scan, MicroScan WalkAway, and SDS-PAGE (Table 3 ). Several antibiotics were employed in the treatment of E. tarda infections. The most frequently reported antibiotics were meropenem (MPM) in 11 records, followed by ceftriaxone (CRO) in 10 records, ampicillin (AMP) in 8 records, metronidazole (MTZ) in 8 records, levofloxacin (LEV) in 7 records, and vancomycin (VAN) in 7 records. The complete list of antibiotics used is detailed in Table 3 and visually represented in Fig. 7 . It is important to note that many patients received combinations of different antibiotics, making it difficult to ascertain the efficacy of each agent individually. Additionally, only a few studies specifically reported which antibiotic was administered following the detection of E. tarda . Fig. 7 The most commonly used antibiotics to treat the E. tarda infections. The numbers of reports for each antibiotics are shown in bars. AMK: amikacin, AMP: ampicillin, AMP-S: ampicillin-sulbactam, AMX: amoxicillin, AMX/CLV: amoxicillin/clavulanic acid, AZM: azithromycin, BPM: biapenem, CAZ: ceftazidime, CEF: cefepime, CFPH: cefcapene pivoxil hydrochrolide hydrate, CFZ: cefazolin, CHL: chloramphenicol, CIP: ciprofloxacin, CLDM: clindamycin, CMZ: cefmetazole, CPZ: cefoperazone, CPZ-S: cefoperazone-sulbactam, CRO: ceftriaxone, CTX: cefotaxime, CZOP: cefozopran, CZX: ceftizoxime, DOX: doxycycline, DRP: doripenem, FEP: cefepime, GEN: gentamicin, IMP: imipenem, ISP: isepamicin, LEV: levofloxacin, LZD: linezolid, MOX: moxifloxacin, MPM: meropenem, MTZ: metronidazole, NFT: nitrofurantoin, NFX: nifuroxazide, NOR: norfloxacin, PAPM/BP: panipenem/betamipron, PZFX: pazufloxacin, TZP: piperacillin/tazobactam, VAN: vancomycin The most commonly used antibiotics to treat the E. tarda infections. The numbers of reports for each antibiotics are shown in bars. AMK: amikacin, AMP: ampicillin, AMP-S: ampicillin-sulbactam, AMX: amoxicillin, AMX/CLV: amoxicillin/clavulanic acid, AZM: azithromycin, BPM: biapenem, CAZ: ceftazidime, CEF: cefepime, CFPH: cefcapene pivoxil hydrochrolide hydrate, CFZ: cefazolin, CHL: chloramphenicol, CIP: ciprofloxacin, CLDM: clindamycin, CMZ: cefmetazole, CPZ: cefoperazone, CPZ-S: cefoperazone-sulbactam, CRO: ceftriaxone, CTX: cefotaxime, CZOP: cefozopran, CZX: ceftizoxime, DOX: doxycycline, DRP: doripenem, FEP: cefepime, GEN: gentamicin, IMP: imipenem, ISP: isepamicin, LEV: levofloxacin, LZD: linezolid, MOX: moxifloxacin, MPM: meropenem, MTZ: metronidazole, NFT: nitrofurantoin, NFX: nifuroxazide, NOR: norfloxacin, PAPM/BP: panipenem/betamipron, PZFX: pazufloxacin, TZP: piperacillin/tazobactam, VAN: vancomycin In addition to antibiotic therapy, several patients received supplementary treatments based on their overall clinical condition. While some of these interventions were not directly aimed at managing E. tarda infection, they were employed to improve the patients’ general status and final outcomes. For a clearer understanding of the comprehensive treatment strategies applied, these additional therapies are also briefly mentioned in Table 3 . Among the 59 cases included in our study, 49 patients recovered following treatment, while 10 patients died due to complications such as cardiopulmonary arrest, liver failure, and septic shock (Table 3 ).

Background

Edwardsiella tarda is a Gram-negative, motile, facultative anaerobic, rod-shaped bacterium classified within Enterobacteriaceae [ 1 ]. The genus Edwardsiella was first identified by Trabulsi et al. in 1962 [ 2 ]. These organisms have successively been named the “Bartholomew group” by King and Adler [ 3 ], the “Asakusa group” by Sakazaki [ 4 ], and “Edwardsiella” by Ewing et al. [ 5 ]. Cultures resembling “ E. tarda ” were first isolated in Israel in 1961 by Altmann et al. from two patients suffering from gastroenteritis. Dr. Edwards confirmed that this finding from the E. tarda infection group showed a weaker immune system than the other group. Since then, similar cultures have been sporadically isolated from patients, water tortoises, and various environmental sources in Israel [ 6 , 7 ]. Edwardsiella tarda is characterized by its production of hydrogen sulfide (H 2 S) and indole. It ferments glucose (with gas) and maltose, but notably does not ferment lactose, sucrose, mannitol, dulcitol, salicin, inositol, raffinose, rhamnose, or xylose. This organism also decarboxylates lysine and ornithine, and it does not utilize malonate, mucate, or citrate [ 7 ]. Edwardsiella tarda inhabits aquatic environments and among animals, particularly cold-blooded species and reptiles. It acts as a pathogen in various animals, including eels, catfish, and pet reptiles, and is considered a rare opportunistic pathogen in humans. This bacterium is isolated from feces, blood, cerebrospinal fluid, and wounds [ 1 , 8 – 10 ]. The health complications caused by E. tarda in humans include gastroenteritis and severe extraintestinal infections such as wound infections, meningitis, bacteremia, tuboovarian abscess, osteomyelitis, liver abscess, and infection of prosthetic organs [ 11 ]. E. tarda is isolated chiefly from stool and associated with gastroenteritis in humans. In fact, there is limited published data on human cases of E. tarda. In this present study, we aimed to analyze human cases of E. tarda and systematically review the diagnosis, symptoms, treatment, clinical manifestation, and associated diseases related to E. tarda.

Discussion

This systematic review underscores that although E. tarda infections are rare, they can lead to severe and life-threatening conditions, particularly in elderly patients and those with pre-existing comorbidities. The low incidence of these infections might contribute to a delay in recognition; however, their potential for causing critical complications necessitates that clinicians maintain a high index of suspicion when evaluating patients with compatible clinical features. Despite the limited number of case reports, the clinical outcomes observed, ranging from septic shock and liver failure to cardiopulmonary complications, highlight the importance of early and accurate diagnosis. Similar to our findings, in a study by Hirai et al., the complications caused by E. tarda were mostly liver abscess, end-stage cancer, and Cholecystitis [ 1 ]. Also, in another study by Kamiyama et al., who reviewed 26 patients with E. tarda from 2005 to 2016 in Japan, most clinical diagnoses were liver abscess, cholangitis, and cholecystitis. Most cases afflicted with E. tarda had a weaker immune system in comparison with healthy people [ 72 ]. The severity of the infection, particularly in vulnerable populations such as the elderly and immunocompromised individuals, further emphasizes the need for prompt intervention. The primary diagnostic tool used across all studies was bacterial culture, a method that is both accessible and straightforward. However, the success of this technique depends significantly on the clinician’s awareness of the potential for E. tarda infection. In practice, recognizing the constellation of symptoms that could suggest an E. tarda infection is crucial. Educating healthcare professionals on these clinical signs and on when to perform targeted testing can lead to more timely and accurate diagnoses. Our review indicates a predominance of case reports from Japan, followed by significant reports from the United States and sporadic cases from other regions. Similarly, in Hirai et al.‘s study, in which the cases affected with E. tarda from 1980 to 2015 were reviewed, most cases were reported from Japan [ 1 ]. One plausible explanation for the higher incidence in Japan is the common consumption of raw seafood, which is a recognized risk factor for E. tarda infection. Additionally, the higher detection rates in developed countries may reflect better diagnostic capabilities and increased clinical vigilance toward rare pathogens. These findings suggest that in regions with advanced healthcare infrastructure, rare infections are more likely to be identified and reported, whereas underdiagnosis might occur in settings with limited resources. Although many patients received combination therapy, making it difficult to attribute success to any single agent, the high rate of recovery emphasizes the effectiveness of prompt, appropriate antimicrobial intervention. Antibiotic regimens that included meropenem (MPM), ceftriaxone (CRO), ampicillin (AMP), metronidazole (MTZ), and levofloxacin (LEV) were most frequently reported. These agents belong to key antibiotic classes such as beta-lactams, nitroimidazoles, and fluoroquinolones. In a study by Fukuda et al. that reviewed all cases of inflammatory bowel disease in patients with E. tarda infection, LEV was the most commonly used antibiotic to treat E. tarda infection [ 22 ]. In another study by Tsuchiya et al. that reviewed the cases with the musculoskeletal system infection caused by E. tarda, LEV, VAN, MPM, cefazolin, and CRO were used mostly to treat the cases [ 59 ]. An additional important observation from our review is the heightened vulnerability of elderly patients and those with underlying conditions, including cancer, cardiovascular diseases, liver disorders, and diabetes. Similar findings were also reported in previous studies [ 59 , 72 ]. These individuals are more likely to experience a complicated disease course, which underscores the need for targeted screening and aggressive management strategies in these populations. In conducting our systematic review, we acknowledge several limitations that may influence the comprehensiveness and applicability of our findings. Firstly, we included only studies published in English. While this approach is common, it can lead to language bias, potentially omitting relevant data from non-English publications. Secondly, our study focused solely on peer-reviewed journal articles, excluding other sources such as books, conference proceedings, and dissertations. This decision may have led to the omission of pertinent information presented in these alternative formats. Thirdly, we restricted our search to studies published from January 2000 onward. While this timeframe was chosen to reflect more recent clinical practices and diagnostic techniques, it may have excluded earlier reports that could provide valuable insights into the historical presentation and management of E. tarda infections. Fourthly, by focusing on published case reports, our review may be subject to publication bias, as cases with unusual presentations or outcomes are more likely to be reported, potentially skewing the overall understanding of E. tarda infections. Lastly, the included case reports varied in the depth and detail of the information provided, which posed challenges for data extraction and synthesis. This heterogeneity may affect the reliability of aggregated findings and limit the ability to draw definitive conclusions.

Conclusions

In conclusion, while E. tarda remains an uncommon pathogen, its capacity to cause serious infections cannot be overlooked. Clinicians should be aware of the diagnostic value of culture-based methods and the importance of early intervention with effective antibiotic therapies. Furthermore, the geographic distribution of cases suggests that both dietary habits and the availability of advanced diagnostic resources may influence the reported incidence of E. tarda infections. Future research should aim to develop standardized diagnostic protocols and treatment guidelines to further improve patient outcomes and enhance our understanding of the epidemiology of this rare but dangerous pathogen.

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SciLite annotations

organisms 65
humans human enterobacteriaceae multicellular animals human human multicellular animals paracolobactrum anguillimortiferum o160848 paracolobactrum anguillimortiferum spirochete symbiont of mixotricha paradoxa enterobacteriaceae edwardsiella edwardsiella o160848 multicellular animals crocodylia multicellular animals nettastomatidae catfish crocodylia humans candidatus gribaldobacteria bacterium o160848 humans o160848 humans human o160848 human o160848 human edwardsiella paracolobactrum anguillimortiferum o160848 human human multicellular animals o160848 multicellular animals multicellular animals multicellular animals o160848 o160848 o160848 o160848 o160848 o160848 o160848 o160848 o160848 o160848 nitzschia sp. irtacc152 paracolobactrum anguillimortiferum tetraodon pardalis pseudomonas punctata strain u5/41 enterococcus k. pneumoniae bacteriophage pkp126 nctc 5050 +5 more
chemicals 47
meropenem ceftriaxone ampicillin metronidazole levofloxacin water hydrogen sulfide indole glucose maltose lactose sucrose mannitol salicin inositol raffinose rhamnose xylose lysine ornithine bopindolol malonate diethylcarbamazine citrate meropenem ceftriaxone ampicillin metronidazole levofloxacin vancomycin meropenem ceftriaxone ampicillin metronidazole levofloxacin beta-lactam benzimidazoles fluoroquinolone antibiotic cefazolin lactate methicillin amoxicillin clavulanic acid momordicoside s panipenem betamipron piperacillin tazobactam

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