A Case Report and Literature Review of a Death Caused by Aeromonas daca Complicated with Septic Shock

Background: For decades, Aeromonas daca has often been mistaken for Aeromonas hydrophila by phenotypic identication systems and shows obvious characteristics of virulence. The clinical data of patients with A. daca reported in China and elsewhere in the past 5 years were retrospectively analyzed to improve clinicians' understanding of the disease. Methods: The diagnosis and treatment of a patient who died of diffuse alveolar hemorrhage caused by A. daca in our hospital were reported. The CNKI, Wanfang and VIP databases were searched with "Aeromonas daca" as the keyword, and the PubMed database was searched with "Aeromonas dhakensis" as the keyword; these searchers covered publications from the last 5 years. The data reported in the literature from China and elsewhere were analyzed retrospectively. Results: The patient, a 26-year-old male with no underlying disease, was admitted to our hospital for 3 days because of cough, expectoration and shortness of breath. According to blood and lavage uid cultures and next-generation sequencing (NGS), the patient was diagnosed with an A. daca infection. He soon deteriorated to a critical condition complicated with septic shock and died after active rescue treatment. A total of three relatively complete English-language studies were retrieved, yielding data on 3 patients in total. and the best


Background
Aeromonas was originally isolated from children with diarrhea in Dhaka, Bangladesh, and described in 2002. Over the past decade, increasing evidence has shown that Aeromonas species are widely distributed in the environment and can cause a variety of infections in humans and animals, especially in coastal areas; Aeromonas dauricus in particular has a special status [1]. For decades, Aeromonas daca has often been mistaken for Aeromonas hydrophila by phenotypic identi cation systems and shows obvious characteristics of virulence. This paper reports the diagnosis and treatment of a patient who died from an infection of A. daca complicated with septic shock. The clinical data of patients with A. daca reported in China and elsewhere in the past 5 years were retrospectively analyzed to improve clinicians' understanding of the disease.

Materials And Methods
This paper reports the diagnosis and treatment of a patient with A. daca infection at the First A liated Hospital of Chongqing Medical University in August 2020. The CNKI, Wanfang and VIP databases were searched with "Aeromonas Dakar" as the keyword, and the PubMed database was searched with "Aeromonas dhakensis" as the keyword; these searchers covered publications from the last 5 years. Three cases with relatively complete data reported in Chinese and foreign literature were analyzed retrospectively. Factors such as sex, age, basic diseases, diagnostic methods, complications and prognosis were analyzed.

Case data
A male, born 1993-10-02, was admitted to the hospital on 2020-08-09 complaining of "cough with fatigue for 3 + days and fever for 1 + days". Three days before admission, the patient caught a cold after swimming, accompanied by cough and fatigue, and did not show signi cant improvement after treatment with drugs purchased from the local clinic (cephalosporins). One day prior to admission, the patient developed a fever (maximum body temperature unknown) and showed symptoms including sputum expectoration, chest pain, wheezing, shortness of breath and blood in the sputum. Therefore, the patient was treated at the local People's Hospital. A CT scan of the chest showed edema and bleeding in the right upper lobe of the lung. The hospital recommended he be seen by a doctor in a higher-tier hospital. Therefore, the patient was admitted to our hospital and was treated to improve liver and kidney function given the following ndings: alanine aminotransferase 150 IU/L, aspartate transferase 84 IU/L, creatinine 197 IU/L, and uric acid 607 ml. No obvious electrolyte abnormalities were found. There were no obvious abnormalities in blood coagulation. In the routine blood test, the total number of leukocytes was 7.06 * 10 ^ 9/L, and the percentage of neutrophils. Blood gas analysis (no oxygen inhalation) indicated pH 7.32, P CO2 43 mmHg, P O2 37 mmHg, HCO 3 22.21 mmol/L, Lac 4.8 mmol/L, SO 2 65%, and PCT 99.57 ng/ml. A chest CT plain scan revealed 1. bilateral lung infection and 2. fatty liver (Fig. 1). The patient was admitted to our emergency department with "severe pneumonia". A physical examination on admission revealed a temperature of 37.5 °C, pulse 82 beats/min, respiratory rate 18 breaths/min, BP 129/81 mmHg, and SO 2 65%. The patient was awake, alert, and oriented but presented with cyanotic lips, clear breath sounds in both lungs, wet rales in the right lung, arrhythmia, and no pathological murmur in any of the valve auscultation areas. The patient also presented with abdominal weakness, no tenderness and rebound pain. There was no edema in either lower limb. After admission, the patient was treated with noninvasive mechanical ventilation, imipenem-cilastatin sodium 1 g Q8h combined with 600 mg Q12h as an anti-infective, reduced glutathione and polyene phosphatidylcholine to treat the liver, acetylcysteine and ambroxol to treat the expectoration symptoms, and maintenance of water and electrolyte balance and other symptomatic treatments. Despite the above treatment measures, the patient's wheezing symptoms were not obviously relieved, and the oxygen saturation progressively decreased. At approximately 03:30 in the morning, the nger oxygen saturation decreased to 70-80% (on noninvasive mechanical ventilation), and the blood pressure dropped to 75/45 mmHg. Considering the patient's severe pneumonia complicated with septic shock, endotracheal intubation was performed immediately after communicating with the patient's family members. Diffuse bleeding in the airway could be seen under electronic bronchoscopy, mainly in the right lung, and invasive mechanical ventilation was given.
After bronchoscopic balloon occlusion and drug hemostasis, the patient still had obvious bleeding in the airway, and the oxygen saturation could not be maintained normal, so he was scheduled to be treated with arti cial extracorporeal pulmonary circulation (ECMO). However, while the doctors were preparing to log onto the computer, the patient had a progressive decrease in blood pressure, and his oxygen saturation could not be measured. The patient nally died after emergency treatment.
We sought to further con rm the diagnosis after death, but autopsy was refused after communicating with the patient's family. After active discussion in the department, a percutaneous lung biopsy was performed to obtain lung tissue samples for pathological examination and next-generation sequencing (NGS). After obtaining ethical informed consent, a percutaneous lung biopsy was performed at the bedside, and 4 grayish brown sections of soft tissue with a diameter of approximately 2 cm were obtained. Postoperative histopathology showed acute and chronic in ammatory cell in ltration (Fig. 2), bronchoalveolar lavage culture indicated hydrophilic Aeromonas caviae, blood culture indicated hydrophilic A. caviae, and lung puncture followed by tissue NGS showed A. daca (Table 1).

Discussion
Aeromonas is a gram-negative bacillus that is widely distributed in freshwater, estuarine and marine environments and can cause a variety of conditions in humans, such as diarrhea, hepatobiliary infections, skin and soft tissue infections and bacteremia, especially in patients with malignant tumors or cirrhosis [2]. A previous report showed that most human infections caused by Aeromonas were associated with three species: A. hydrophila, Aeromonas veronii and A. caviae [2]. A reclassi cation of the genus Aeromonas was proposed in 2013; A. darkii is a newly discovered species [3]. However, in commercial phenotypic tests in clinical laboratories, A. daca is often mistaken for A. hydrophila/caviae/aeruginosa. Recent in vitro studies have shown that the pathogenicity of A. daca is multifactorial, and increasing evidence shows that A. daca is more virulent than other Aeromonas species [4,5]. However, the importance of the clinical administration of treatments for A. hydrophila is misleading due to inaccurate species identi cation. With the introduction of molecular identi cation methods, the order of the three previously dominant species has changed dramatically. According to recent research data, A. daca is the second most common species, accounting for 25.7% of the identi ed strains [1]. In clinical studies, A. daca is an independent risk factor for 14-day sepsis-related death in patients with bacteremia caused by A. aeruginosa [6]. The 14-day infection-related mortality rate of patients with A. daca infection is 25%, and the 14-day infection-related mortality rate and the crude hospital mortality rate of all A. aeruginosa are 10.5% and 26.3%, respectively [7]. Possible pathogenic factors of some species of Aeromonas include toxins (cytotoxic toxins that cause cell morphological changes), proteases, hemolysins, lipases, adhesins, lectins, mbriae, enterotoxins, various enzymes and adventitia structures (such as the S layer and capsule). Other factors that may promote toxicity include VacB [8], enolase [9] and the presence of the type VI secretory system [10][11][12][13][14][15]. Therefore, theoretically, infection with Aeromonas may lead to complications such as septic shock, while the toxic reaction to infection with A. daca is more fatal. As reported by our unit, the patient was complicated with diffuse alveolar hemorrhage and septic shock. The disease developed rapidly, and the patient died after emergency treatment.
A. daca can produce three different types of β-lactamases, namely, class C cephalosporinase, class D penicillinase and "CPHA" type B metallo-β-lactamases (MBLs) [2]; that is, it has speci c enzymes for hydrolyzing carbapenem antibiotics and second-and third-generation cephalosporins. However, the production of carbapenem cannot be easily detected in traditional drug sensitivity tests unless a large number of inoculants or additional tests are used. It has been reported that when carbapenem antibiotics were used to treat Aeromonas aeruginosa, A. aeruginosa resistant to carbapenem antibiotics appeared [16]. For severe Candida daca infection, it is suggested that a large number of inoculations and/or additional drug sensitivity tests should be performed prior to carbapenem treatment. Therefore, third-generation cephalosporins and carbapenems should be used cautiously in the treatment of severe A. dacarum infection, and the best regimen is cefepime or uoroquinolones.

Conclusions
A. daca infection is lethal, and accurate taxonomy can improve our understanding of the epidemiological distribution and virulence potential of this human pathogen. At present, due to the virulence and potential antimicrobial resistance of A. daca, accurate identi cation is encouraged. The authors believe that molecular biological detection should be carried out for severe infections caused by Aeromonas species. Therefore, the improvement of the understanding of A. daca can help us to further guide clinical treatment, and early accurate diagnosis and treatment are key to improving the prognosis and reducing the mortality of patients with septic shock. Third-generation cephalosporins and carbapenems should be used cautiously in the treatment of severe A. daca infection, and the best regimen is cefepime or uoroquinolones.