Aeromonas sobria Induced Sepsis Complicated with Necrotizing Fasciitis in a Child with Acute Lymphoblastic Leukemia

: Aeromonas species are gram negative and able to induce systemic diseases (i.e., gastroin-testinal, respiratory, and cardiovascular, diseases, in addition to infection of brain and soft tissues). In this study, we describe the development of necrotizing fasciitis in a young immunocompromised girl, with a low response to drug treatment and who died after some months.


Introduction
Aeromonas species are gram negative, non-sporulating facultative anaerobic bacilli that produce β-lactamases [1], able to colonize both humans and animals [2]. Aeromonas is ubiquitous in water, including chlorinated drinking water, where flagella facilitate biofilm formation [3]. The virulence of Aeromonas is multifactorial, due to cytotoxic, cytolytic, hemolytic, and enterotoxin proteins [4,5]. In human infections, the most common clinical isolates are Aeromonas hydrophila, Aeromonas caviae, and Aeromonas veronii biovar sobria [6], that induce systemic diseases (i.e., gastrointestinal, respiratory, and cardiovascular diseases, in addition to infection of brain and soft tissues) [7][8][9]. Aeromonas infections can develop in healthy and trauma patients, but immunocompromised hosts with hematological malignancies or solid tumors are considered to be at greatest risk [10].
In this study, we describe the development of necrotizing fasciitis in a young immunocompromised girl.

Case Presentation Section
We report a 6-year-old Caucasian girl with acute lymphoid leukemia that developed a necrotizing fasciitis related to Aeromonas veronii biovar sobria infection.
Therefore, platelets were transfused, acetaminophen (10 mL/day os) was administered, and a blood sample was taken for microbiological evaluation.
On 02 August, a new clinical evaluation revealed the presence of fever (38.6 • C) and severe pain (VAS 10), edema, and skin rash of the right upper limb. Laboratory testing revealed a decrease in liver function and plasma proteins, and an increase in procalcitonin levels ( Table 2). Microbiology diagnosed a sepsis caused by Aeromonas veronii biovar resistant to ampicillin (minimal inhibitory concentration (MIC) > 32), but sensitive to ciprofloxacin (MIC < 0.06), ceftriaxone (MIC < 0.25), cefuroxime (MIC < 1), trimethoprim/sulphametoxazole (MIC < 20), and ceftazidime (MIC < 0.12). An antimicrobial, antiviral, and antimycotic empirical treatment plus acetaminophen (10 mL os) and ketorolac (10 mg i.m.) was started without clinical benefit. On 03 August, a clinical impairment was observed, and a swab of the skin rash was sent for a new microbiology evaluation. Abdominal ultrasound was normal, whereas the echo-color Doppler of the right upper limb showed a diffuse edema of skin soft tissues without signs of thrombosis with normal function of the venous tract. Blood chemical testing confirmed the low levels of red cells with a decrease in liver function (Table 2). Blood gas analysis documented a severe respiratory failure (PO2 33 mmHg; PCO2 32 mmHg) therefore the patient was transferred to the intensive care unit (ICU).
In the ICU, the right upper limb appeared marbled with edema and severe pain (VAS 10). Dexamethasone was discontinued and a treatment with furosemide, piperacillin + tazobactam, acyclovir, clindamycin, and oxygen was started.
On 04 August, clinical evaluation documented that the patient was in comatose status and an infection sustained by Klebsiella species was detected (Table 3). On 06 August, the fasciotomy of the right limb revealed the presence of a black fluid where microbiology testing detected the presence of Aeromonas veronii biovar sobria (resistant to ampicillin, MIC > 32, but sensitive to ceftazidime MIC < 0.12, cefuroxime MIC < 1, ceftriaxone MIC < 0.25, and ciprofloxacin MIC < 0.06). On physical examination, her lower limb was warm in the presence of erythema. After 12 h, the swelling of her leg and the progression of skin lesions (circumferential erythema developed in bullae formations) increased until the development of a compartment syndrome, which rapidly required a surgical treatment with fasciotomy and negative pressure wound therapy (Figure 1). testing detected the presence of Aeromonas veronii biovar sobria (resistant to ampicillin, MIC > 32, but sensitive to ceftazidime MIC < 0.12, cefuroxime MIC < 1, ceftriaxone MIC < 0.25, and ciprofloxacin MIC < 0.06). On physical examination, her lower limb was warm in the presence of erythema. After 12 h, the swelling of her leg and the progression of skin lesions (circumferential erythema developed in bullae formations) increased until the development of a compartment syndrome, which rapidly required a surgical treatment with fasciotomy and negative pressure wound therapy (Figure 1).       (Table 4); therefore, tigecycline (30 mg/12 h) was added to the therapy, but after 7 days, due to both the progression of leukemia and the presence of a severe antimicrobial resistance infection (Table 4), the child died.  On 22 August, microbiological evaluation of urine sample documented an infection sustained by the Acinetobacter Bahmani complex (Table 4); therefore, tigecycline (30 mg/12 h) was added to the therapy, but after 7 days, due to both the progression of leukemia and the presence of a severe antimicrobial resistance infection (Table 4), the child died.

Discussion
In this paper, we report an uncommon case of Aeromonas sobria sepsis with necrotizing fasciitis in an immunocompromised child. In a previous manuscript, Zhang et al. [11] evalu-Reports 2021, 4, 9 6 of 7 ated 15 patients globally (median age 49.5 years; range: 27-80 years) and documented that, in patients with acute myeloid leukemia or acute lymphoblastic leukemia and Aeromonas sobria infection, the most common manifestation was the lower limb infection (66.7%). In this study, the authors reported that even if an empirical antibiotic treatment is started, the mortality is high. In our case presentation, we describe the development of sepsis and lower limb infection in a young child (6 years) with acute lymphoblastic leukemia. The patient developed a first-time sepsis and then lower limb infection despite starting empirical antimicrobial treatment. This effect could be related to the co-administration of corticosteroid and chemotherapy. To date, no definitive data have been published regarding the correlation between glucocorticoid treatment and systemic infection. However, Fardet et al. [12], based on analysis of a primary care database, documented that glucocorticoid use can induce the development of respiratory infections, even if they were not able to evaluate the role of chemotherapy or biological drugs in these infections. In our study, chemotherapy probably increased the risk of septicemia by Aeromonas sobria with the development of lower limb infection. Radiological chest and ultrasound excluded the presence of other systemic diseases, and swabs excluded the presence of infection in other sites and, after a few days, fasciculitis induced a systemic impairment with severe respiratory failure and immune depression. Systemic antimicrobial therapy did not reduce the infection. Both fasciotomy and amputation of the lower limb improved the symptoms, but after a few days, the clinical condition worsened. Microbiology detected a multi-resistant Aeromonas in tissues and, despite antimicrobial treatment being started, the patient died.

Conclusions
In conclusion, this study suggests that the risk of lower limb infection in the presence of Aeromonas infection must be carefully evaluated, in order to quickly start an appropriate antimicrobial treatment.