Abstract: OBJECTIVE To investigate the effects of respiratory Candida colonization on bacterial ventilator-associated pneumonia (VAP) and serine-threonine protease/nuclear factor-κB (Akt/NF-κB) signaling pathways in children. METHODS A total of 120 children undergoing mechanical ventilation in Shengjing Hospital Affiliated to China Medical University between Oct. 2018 and Nov. 2021 were selected, of which 65 cases with childhood bacterial VAP were included in VAP group (39 cases of respiratory Candida colonization) and 55 cases without VAP were included in control group (19 cases of respiratory Candida colonization). Logistic regression was used to analyze the risk factors of bacterial VAP in children, and the expression levels of Akt mRNA and NF-κB mRNA in peripheral blood of the study subjects were detected, and their relationship with the occurrence of VAP and respiratory Candida colonization in the respiratory tract was analyzed. RESULTS A total of 107 strains of pathogenic bacteria were isolated from 65 children with bacterial VAP, of which 97 strains of Gram-negative bacteria accounted for 90.65%, and 10 strains of Gram-positive bacteria accounted for 9.35%. Duration of mechanical ventilation, reintubation, impaired consciousness, and respiratory Candida colonization were influencing factors of bacterial VAP in children (P<0.05). Among the 65 children with bacterial VAP, there was no significant difference in the 28d mortality rate between the colonization group and non-colonization group (P=0.645). The expression of peripheral blood Akt mRNA and NF-κB mRNA in children with bacterial VAP were higher than those in control group (P<0.05). The area under the ROC curve (AUC) of Akt mRNA combined with NF-κB mRNA for evaluating the occurrence of bacterial VAP in children was 0.881, greater than that of the two indicators alone (0.797 and 0.790, respectively) (P<0.05). There was no significant difference in the peripheral blood Akt mRNA and NF-κB mRNA between children with or without respiratory Candida colonization in the VAP group and control group. CONCLUSION Candida colonization in respiratory tract increased the risk of bacterial VAP in children undergoing mechanical ventilation, and peripheral blood p-Akt mRNA and NF-κB mRNA showed high expression after VAP occurred. The activation of Akt/NF-κB signaling pathways mediated the occurrence and development of VAP, However, there was no significant relationship between respiratory Candida colonization and the activation of Akt/NF-κB signaling pathways.