Risk Factors Of Invasive Fungal Infection In Hematological Malignancies Patients And Its Relationship To Intestinal Microecology

1Objective1.1To investigate the incidence and risk factors of invasive fungal infections in immunocompromised patients, and furthermore provide some advices for prevention and treatment to invasive fungal infections.1.2Observe the dynamic changes of intestinal microflora before and after fungal infection.Reveal the variation characteristics of intestinal bacteria group in patients with invasive fungal infection and its relationship with fungal translocation.1.3Simulating the comdition of invasive fungal infection in clinical patients to establish an animal model of invasive fungal infection. Provide experimental materials for the mechanism of intestinal microecology, immunity, metabolic characteristics and prevention for the invasive fungal infections of further research.2Meathods2.1A retrospective cohort study was performed to identify the risk factors of invasive fungal infection in495patients with hematopoietic malignancies, who were admitted to our hospital in the period between January to December2013, by chi square test and multivariate logistic regression analysis. 2.2During the period between March2013to May2014,we collected33copies of blood and stool of patients in blood ward,which include the first time to be hospitalized,the stage of infected with fungal and recovery stage of fungal infection. Analysis the changes of haemocytes, serum protein and intestinal microecology.2.3Animal model studies:to establish a mouse model of invasive fungal infection by giving three-combined antibiotics for a week, the tail vein injecting of5-FU at a time, and intragastric giving Candida albicans.3Results3.116.4%(81/495) of total patients were infected by funguses. Among which, the incidence of invasive fungal infections in patients with acute leukemia, chronic leukemia, myelodysplastic syndrome, lymphoma and multiple myeloma patients were31.1%(66/212),0%(0/19),31.2%(5/16),4.8%(10/207) and0.0%(0/41) respectively. The risk factors for invasive fungal infections in patients with hematopoietic malignancies were as follows:1. The patients whose lowest WBC count in peripheral blood was lower or equal to1.0E+9/L;2. The patients suffered from neutropenia longer than7days;3.The patients were treated by glucocorticoid;4.The patients were treated with more than three categories of antibiotics. The protective factor was prophylactic use of antifungal drugs. OR values of above factors were15.830,41.667,3.745,8.264and39.085respectively as well as P values of above factors were0,0.011,0.035,0.007and0.000respectively.3.2When infected with fungal, patients with blood disease have a lower neutrophil than that of the non infection period. In the infected stage,the bacteria is reduced while the fungi is increased,and the total number and types of intestinal microflora are significantly lower than recovery period.3.3One week after the model established, the SCID mouse has no death, while the ICR mouse has a33.3%mortality. The organs Candida albicans cultivation of the ICR mouse is:14/18in the lung,13/18in the liver and16/18in the kidney. The intestinal Candida albicans cultivation of the ICR mouse is:small intestine has a lowest average value of1.3E+4CFU/segment, caecum and ileum respectively has a value of1.1E+5CFU/section and1.2E+5CFU/section. The third days of using antibiotics, bacteria appears obviously less, while yeast-like colonies is increased. The anatomical phenomenon of candida albican infected mice is:hemorrhagic colonic, flatulented jejunum, larger and darker gallbladder and so on.4Conclusions4.1There is a high incidence of fungal infection in the immunocompromised people.The key measures to reduce incidence of invasive fungal infections in Immunocompromised patients were using antibiotics and glucocorticoid appropriately, using antifungal drugs and colony stimulating factor in time, and rebuilding the microbial ecology in patients.4.2In fungal infection period, peripheral white blood cell counts, peripheral neutropenia counts and serum total protein is deceased,meanwhile the intestinal flora is significantly imbalanced. It suggested that low immunity and imbalance of intestinal microecology are the two important causes of invasive fungal infection.4.3This study established a stabile and low mortality invasive fungal infection model of the ICR mouse. This model is suitable for the study of endogenous fungal infection associated with intestinal microecology, immunity, metabolic characteristics and its prevention.