OBJECTIVE: To investigate the clinical features, distribution of pathogenic bacteria, and drug resistance of bloodstream infection in children with acute leukemia. METHODS: Clinical data of 93 blood culture-positive children with acute leukemia from January 2015 to December 2019 in Department of Pediatrics, The Second Hospital of Anhui Medical University were analyzed retrospectively. RESULTS: In these 93 cases, 78 cases were in the period of neutrophil deficiency. There were 54 Gram-negative bacteria (G^-) (58.1%) found through blood culture, and the top 4 strains were Escherichia coli (15.1%), Klebsiella pneumoniae (13.9%), Pseudomonas aeruginosa (6.5%), and Enterobacter cloacae (6.5%). There were 39 Gram-positive bacteria (G⁺) (41.9%) detected, and the top 4 strains were Staphylococcus epidermidis (10.8%), Streptococcus pneumoniae (6.5%), Staphylococcus hemolyticus (5.4%), and Staphylococcus human (5.4%). Among 74 strains of pathogenic bacteria from acute lymphoblastic leukemia (ALL) children, there were 29 strains of G⁺ bacteria (39.2%) and 45 strains of G^- bacteria (60.8%). While in 19 strains from acute myeloblastic leukemia (AML) patients, G^- bacteria accounted for 47.4% and G⁺ bacteria accounted for 52.6%. In 15 ALL children without neutropenia, G⁺ bacteria made up the majority of the strains (66.7%). In the 93 strains of pathogenic bacteria, 13 (13.9%) strains were multidrug-resistant. Among them, extended-spectrum β-lactamases accounted for 42.9%, carbapenemase-resistant enzyme Klebsiella pneumoniae 15.4%, and carbapenemase-resistant enzyme Enterobacter cloacae strains 33.3%, which were detected from G^- bacteria. While, 13.3% of methicillin-resistant coagulase-negative Staphylococci accounted for 13.3% detected from G⁺ bacteria, but linezolid, vancomycin, teicoplanin Staphylococcus and Enterococcus resistant were not found. The average procalcitonin (PCT) value of G^- bacteria infection was (11.02±20.282) ng/ml, while in G⁺ infection it was (1.81±4.911) ng/ml, the difference was statistically significant (P<0.05). The mean value of C-reactive protein (CRP) in G^- infection was (76.33±69.946) mg/L, and that in G⁺ infection was (38.34±57.951) mg/L. The prognosis of active treatment was good, and only one case died of septic shock complicated with disseminated intravascular coagulation (DIC) and gastrointestinal bleeding caused by carbapenemase-resistant enzyme enterobacteriaceae. CONCLUSION G^- is the major bacteria in acute leukemia children with bloodstream infection, but the distribution of ALL and AML strains is different. G^- bacteria dominates in ALL, while G⁺ bacteria and G^- bacteria are equally distributed in AML. Non-agranulocytosis accompanied by bloodstream infections is dominant by G⁺ bacteria. The mean value of PCT and CRP are significantly higher in G^- bacteria infection than in G⁺ bacteria.
Acute Disease ; Anti-Bacterial Agents/therapeutic use* ; Bacteremia/microbiology* ; Bacteria ; Child ; Drug Resistance, Bacterial ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Microbial Sensitivity Tests ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Procalcitonin ; Retrospective Studies ; Sepsis/drug therapy*

Based on network pharmacology and in vivo experiment, this study explored the therapeutic effect of Tetrastigma hemsle-yanum(SYQ) on sepsis and the underlying mechanism. The common targets of SYQ and sepsis were screened out by network pharmacology, and the "SYQ-component-target-sepsis" network was constructed. The protein-protein interaction(PPI) network was established by STRING. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were performed based on DAVID to predict the anti-sepsis mechanism of SYQ. The prediction results of network pharmacology were verified by animal experiment. The network pharmacology results showed that the key anti-sepsis targets of SYQ were tumor necrosis factor(TNF), interleukin(IL)-6, IL-1β, IL-10, and cysteinyl asparate specific proteinase 3(caspase-3), which were mainly involved in Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor kappaB(NF-κB) signaling pathway. The results of animal experiment showed that SYQ can decrease the content of C-reactive protein(CRP), procalcitonin(PCT), lactate dehydrogenase(LDH), IL-6, TNF-α, and IL-1β, increase the content of IL-10, and down-regulate the protein levels of Bcl-2-associa-ted X(Bax)/B-cell lymphoma 2(Bcl2), cleaved caspase-3, TLR4, MyD88, and p-NF-κB p65/NF-κB p65. In summary, SYQ plays an anti-inflammatory role in the treatment of sepsis by acting on the key genes related to inflammation and apoptosis, such as TNF-α, IL-6, IL-lβ, IL-10, Bax, Bcl2, and cleaved caspase-3. The mechanism is the likelihood that it suppresses the TLR4/MyD88/NF-κB signaling pathway, which verifies relative prediction results of network pharmacology.
Animals ; Anti-Inflammatory Agents/therapeutic use* ; C-Reactive Protein ; Caspase 3/metabolism* ; Interleukin-10 ; Interleukin-6/metabolism* ; Lactate Dehydrogenases/metabolism* ; Myeloblastin/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; NF-kappa B/metabolism* ; Network Pharmacology ; Procalcitonin/therapeutic use* ; Sepsis/genetics* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; bcl-2-Associated X Protein/metabolism*