Publish Time: 2023-07-19 Origin: Site
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In June 2023, the team of Professors Lu Guoping and Chen Weiming from the Pediatric Hospital Affiliated to Fudan University will cooperate with Difei Medical in theFrontiers in Pediatrics (IF=3.418）magazine publishedA case report of mucormycosis after chemotherapy in a child with neuroblastoma，To explore the clinical value of mNGS in rapid and comprehensive screening of pathogens, and then guide the selection of treatment options in a timely manner.
/ Research Background /
Mucormycosis is the third most common invasive fungal disease after candidiasis and aspergillosis, and its incidence has increased rapidly in the past few decades, with an overall mortality rate as high as 90%.The most common pathogens causing mucormycosis are Rhizopus, Mucor and Rhizopus japonica.According to the site of infection, mucormycosis can be divided into rhinocerebral, pulmonary, gastrointestinal, skin, and disseminated types, among which rhinocerebral mucormycosis is the most common.Mucormycosis mainly occurs in immunocompromised hosts, such as those with diabetes, malignancy, burns, autoimmune disease, penetrating trauma, or receiving corticosteroids.Diagnostic methods for mucormycosis include histopathological, microbiological, and molecular testing, and treatment relies primarily on amphotericin B.
Neuroblastoma is the most common extracranial solid tumor in infants and children, accounting for 8%-10% of all childhood tumors.
Case presentation
Figure 1 Timeline of infection diagnosis and treatment in children
Local hospital diagnosis and treatment process
Male, 6 years old, was admitted to a local hospital on October 6, 2021 due to 'high fever (39℃), accompanied by nasal bleeding and a small amount of vomiting'.The child was admitted to the hospital in July 2019 due to ''poor appetite for six months, significant weight loss, and pain in the right leg for 20 days', and was subsequently diagnosed with neuroblastoma, accompanied by intracranial and multiple bone Metastatic tumor. Before this hospitalization, the child had completed 3 cycles of maintenance high-risk chemotherapy and radical retroperitoneal tumor resection under general anesthesia.
After admission, the blood routine was regularly improved, and the results showed that the levels of white blood cells, neutrophils, platelets, and hemoglobin were always low (Figure 1).The blood culture in the local hospital was negative, and the empirical treatment was based on bacterial infection: Piperacillin/tazobactam (45mg/kg, q8h), ceftizoxime (50 mg/kg, bid), cefoperazone sulbactam (50 mg/kg, q12h), meropenem (20mg/kg , q8h), vancomycin (10mg/kg, q6h), and metronidazole (7.5mg/kg, q8h).At the same time, the child also received supportive treatment, with platelet transfusion (1U) on the 3rd, 7th and 12th day of admission, hemoglobin (1.5U) infusion on the 8th and 11th day of admission, and daily infusion during the 2nd to 13th day of admission. Inject human granulocyte stimulating factor (150ug, qd).
During the whole process of antibacterial treatment, the child still had intermittent fever, nasal bleeding and oral pain, and the CRP level increased(103.5mg/L on the 10th day of admission, 181.0mg/L on the 13th day of admission).So it was decided to transfer to the Children's Hospital Affiliated to Fudan University.
Pediatric hospital diagnosis and treatment process
Admission diagnosis and treatment
On October 20, 2021, the child was transferred to the PICU of the Children's Hospital Affiliated to Fudan University. The high fever persisted, with a maximum of 39.2°C, accompanied by a small amount of bleeding in both eyes and progressive aggravation of nasal and facial gangrene.CT showed swelling of the scalp, lung lesions, and bone destruction (Figure 2); CRP was greater than 160 mg/L.After admission, meropenem (40 mg/kg, q8h), vancomycin (15 mg/kg, q6h), micafungin (2 mg/kg, qd) and piperacillin-tazobactam (112.5 mg/ kg, q8h) anti-infection, and transfusion of platelets (1U), hemoglobin (1U) and albumin (10g) to support treatment.The child's condition did not improve significantly, and the CRP remained above 160mg/L.
Figure 2 CT imaging results
further examination and treatment
On the day the child was transferred to the PICU, a blood sample was sent for mNGS pathogen detection, and at the same time, a sterile brush was used to collect facial gangrene skin debris for smear microscopy.On the second day after being transferred to the PICU, the child developed dyspnea and septic shock, and was given mechanical ventilation support and maintenance of vasoactive drugs.On the third day after being transferred to the PICU, mNGS results of the blood samples of the children reported 21,325 sequences of Rhizoma racemosus, and electron microscopy of skin debris smears also indicated Mucorales infection(image 3).Finally, the child was diagnosed as mucormycosis caused by Panjaponica racemosa, and amphotericin B (5 mg/kg, ivgtt) antifungal treatment was given immediately.
Figure 3 The results of mNGS detection of blood samples and the results of electron microscopy of skin debris smears, both of which support the infection of Transverseus racemosa
Outcome and Prognosis
Despite treatment with amphotericin B immediately after the diagnosis of T. racemosa infection, the child progressed progressively and eventually died of severe multiorgan failure.
Literature review
PubMed, Ovid MEDLINE, Embase, Wanfang and CNKI databases were searched, and 41 confirmed cases of A. racemosa infection were finally included in 25 literatures, and the clinical characteristics and epidemiological data were summarized (Table 1).
The most common sites of infection with T. racemosa were the skin (N=17) and the lungs (N=10).Most cases were immunocompromised patients with underlying risk factors such as cancer (9, 22.0%), diabetes (6, 14.6%), burns (6, 14.6%), and organ transplantation (5, 12.2%).Excluding 8 cases whose age at diagnosis was unknown, the median age was 46 years (range, 4-84 years), of which 6 cases were younger than 10 years old.Five of the six pediatric cases were treated with liposomal amphotericin B (LAMB), and three of them were cured.Of all treated cases, 32 were treated with amphotericin B, resulting in a successful cure rate of 72% (23/10).An increase in the adoption of mNGS-based methods in pathogen detection was also observed.And the incidence of COVID-19 patients has been rising after 2020.
Table 1 Summary of the clinical and epidemiological characteristics of the cases infected with Panjaponica racemosa from 2010 to 2020
Summarize
1. This case is the first report of a case of mucormycosis in a child with neuroblastoma caused by the infection of Rhizoma racemosa.
2. The fatality rate of mucormycosis is high, and early diagnosis is also crucial while improving clinical cognition, especially in cases where broad-spectrum antibiotics are ineffective, etiological evidence should be sought more actively.
3. mNGS has achieved rapid and comprehensive pathogen screening, which has important clinical significance in guiding the selection of treatment options in a timely manner and resisting the rapid development of fatal infections.
references:
Shen H, Cai X, Liu J, Yan G, Ye Y, Dong R, Wu J, Li L, Shen Q, Ma Y, Ou Q, Shen M, Chen W and Lu G (2023) Case report: The clinical utility of metagenomic next-generation sequencing in mucormycosis diagnosis caused by fatal Lichtheimia ramosa infection in pediatric neuroblastoma. Front. Pediatr. 11:1130775. doi: 10.3389/fped.2023.1130775
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