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Objective@#To investigate the efficacy and safety of Posaconazole (Posa) in prophylaxis and salvage treatment of invasive fungal infections (IFI) during neutropenia in pediatric patients with leukemia.@*Methods@#A total of 18 pediatric patients (55 case-time) with leukemia in neutropenia stage receiving Posa treatment from December 2015 to August 2017 in Zhujiang Hospital of Southern Medical University, were analyzed retrospectively.Taking one induction chematherapy or one consolidation chemotherapy stage receiving Posa treatment was defined as 1 case-time.@*Results@#Out of 18 participants, 13 cases were patients with acute myeloid leukemia (AML) and 5 cases were patients with acute lymphocytic leukemia (ALL), including 36 males and 19 females.Median age of the participants was 7 years, ranged from 10 months to 14 years.Out of 55 case times, 45 of them were of primary prevention and the neutropenia periods ranged from 4 to 46 days, with the median of 15 days, and 93.33% of them were prevented from fungal infection.However, 3 of the 45 cases had sudden fungal infections and the Voriconazole was an effective treatment, and no one died.Six cases in this study experienced secondary prevention, and no patient experienced reinfection.The neutropenia terms of the 6 cases ranged from 10 to 17 days, with the median of 14 days.Four patients who suffered from Voriconazole and/or Carbophenol therapy failure received Posa as a rescue therapy and the response rate was 100%.None of patients had Posa intolerance due to severe adverse reaction and no Posa treatment-related grade Ⅱ toxic effects occurred.@*Conclusions@#Posa is an effective and safe therapy for pediatric patients with leukemia and IFI, and available for long-time usage.Serious adverse reaction is rare.
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Objective To investigate the efficacy and safety of Posaconazole (Posa) in prophylaxis and salvage treatment of invasive fungal infections (IFI) during neutropenia in pediatric patients with leukemia.Methods A total of 18 pediatric patients (55 case-time) with leukemia in neutropenia stage receiving Posa treatment from December 2015 to August 2017 in Zhujiang Hospital of Southern Medical University,were analyzed retrospectively.Taking one induction chematherapy or one consolidation chemotherapy stage receiving Posa treatment was defined as 1 case-time.Results Out of 18 participants,13 cases were patients with acute myeloid leukemia (AML) and 5 cases were patients with acute lymphocytic leukemia (ALL),including 36 males and 19 females.Median age of the participants was 7 years,ranged from 10 months to 14 years.Out of 55 case times,45 of them were of primary prevention and the neutropenia periods ranged from 4 to 46 days,with the median of 15 days,and 93.33％ of them were prevented from fungal infection.However,3 of the 45 cases had sudden fungal infections and the Voriconazole was an effective treatment,and no one died.Six cases in this study experienced secondary prevention,and no patient experienced reinfection.The neutropenia terms of the 6 cases ranged from 10 to 17 days,with the median of 14 days.Four patients who suffered from Voriconazole and/or Carbophenol therapy failure received Posa as a rescue therapy and the response rate was 100％.None of patients had Posa intolerance due to severe adverse reaction and no Posa treatment-related grade Ⅱ toxic effects occurred.Conclusions Posa is an effective and safe therapy for pediatric patients with leukemia and IFI,and available for long-time usage.Serious adverse reaction is rare.
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Objective To investigate the risk factors for childhood acute leukemia complicated with streptococcus mitis bacteriaemia and to explore a better therapeutic regimen of antibiotics.Methods Seventy-eight cases of childhood acute leukemia complicated with bacteriaemia hospitalized in Zhujiang Hospital of Southern Medical University from January 2012 to December 2016 were collected,among them there were 8 cases (10.26％) caused by streptococcus mitis.The susceptible factors,clinical manifestations,drug susceptibility,treatments and outcomes of 8 cases of streptococcus mitis bacteriaemia were summarized and analyzed.Results All of 8 cases were attacked during the agranulocytosis phase lasting for more than 1 week after chemotherapy for acute leukemia.Four cases of them had been exposed to the third-generation cephalosporins for more than 7 days,and 5 cases exposed to proton pump inhibitor (PPI) for more than 10 days.The incidence of remittent fever,shiver,stomatitis and pneumonia was 100.0％ (8/8 cases),62.5％ (5/8 cases),62.5％ (5/8 cases) and 62.5％ (5/8 cases),respectively.And severe pneumonia occurred at a rate of 37.5％ (3/8 cases).The sensitivity to Linezolid,Vancomycin,Penicillin and Cefotaxime was 100.0％,100.0％,37.5％ and 25.0％,respectively.Five of the 7 cases treated with Meropenem had a fever 3 days later and then they took Linezolid as a replacement according to the drug sensitivity.One case was treated with Cefoperazone-Sulbactam.The duration time of fever,positive blood culture,agranulocytosis and course of antibiotics therapy was 1-19 d(10.4 d on average),4-22 d(13.4 d on average),10-30 d (21.6 d on average),9-26 d (18.3 d on average),respectively.Among 3 patients with severe pneumonia,1 patient received the respirator assisted ventilation for 1 week.Conclusions Streptococcus mitis is one of the major causes of severe infection among children with acute leukemia.Agranulocytosis after chemotherapy,stomatitis,exposure to PPI and antibiotics may be the risk factors for streptococcus mitis infection.Fever,stomatitis,respiratory and digestive symptoms are the common clinical manifestations.Streptococcus mitis is resistant to Penicillin and Cefotaxime,but sensitive to Linezolid,which can shorten the course of infection and improve the outcomes.Thus,Linezolid may serve as an optional therapy for streptococcemia mitis bacteriaemia.
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Objective To investigate the relationship between Methotrexate (MTX) and its cognitive dysfunction,and to explore the possible mechanism of neurotoxicity induced by MTX.Methods Thirty healthy male SD rats weighting 180-220 g were divided into 3 groups using random number table:control group,60 mg/kg MTX (MTX60) group and 100 mg/kg MTX (MTXt00) group,with 10 rats in each group.The rats in MTX60 group,MTX100 group received 60 mg/kg MTX and 100 mg/kg MTX,respectively.The rats in control group accepted the same volume of 9 g/L saline injection as MTX group.Spatial memory of rats was evaluated by using Morris water maze test at different time points after pretreatment with MTX.After the Morris water maze test,the hippocampus were harvested and the expressions of C/EBP homologous protein (CHOP),cysteinyl aspartate specific proteinase 12(caspase-12) and cleave cysteinyl aspartate specific proteinase 3 (cleaved caspase-3) were detected by using Western blot.Meanwhile,cell apoptosis and pathological change of hippocampal neurons were detected by terminal dexynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) assay and HE staining respectively.Results In the Morris water maze test,the time in platform quadrant of rats in MTX60 group and MTX100 group was shorter than that of rats in control group during probe training [(27.30 ±3.98) s and (21.63 ±4.22) s vs (33.30 ±6.31) s,F =13.94,P ＜0.05],and the time in target quadrant of MTX100 group was shorter than that of MTX60 group (P ＜ 0.05).Compared with the control group,there were degenerated neurons in hippocampus cornu ammonis 1 (CA1) area in MTX60 group and MTX100 group.The number of TUNEL-positive cells of the hippocampus CA1 area increased significantly in MTX60 group and MTX100 group rats [(4.72 ±0.12)％ and (9.12±0.12)％ vs (1.11 ±0.49)％,F=95.272,P ＜0.05],and the TUNEL-positive cells of rats in MTX100 group were more than those of MTX60 group (P ＜ 0.05).The expressions of CHOP,caspase-12 and cleaved caspase-3 also increased compared with the control group (CHOP:2.98 ±0.31 and 4.15 ±0.61 vs 0.38 ±0.12,F =232.74,P ＜ 0.05;caspase-12:0.33 ±0.04 and 0.43 ±0.06 vs 0.14 ±0.02,F =120.70,P ＜ 0.05;cleaved caspase-3:0.35 ± 0.04 and 0.44 ± 0.06 vs 0.05 ± 0.03,F =198.64,P ＜ 0.05),and the protein expression levels of rats in MTX100 group were higher than MTX60 group (all P ＜ 0.05).Conclusions MTX can induce cognitive impairment in rats,and endoplasmic reticulum stress mediated hippocampal neurons apoptosis may play an important role in the mechanism of MTX-induced cognitive impairment in rats.