凝固酶阴性葡萄球菌致新生儿败血症病原学及青霉素联合万古霉素治疗效果分析

Etiology of neonatal sepsis caused by coagulase-negative Staphylococci and therapeutic effect of penicillin combined with vancomycin

目的探讨凝固酶阴性葡萄球菌(CNS)致新生儿败血症的病原菌分布和耐药性,以及青霉素联合万古霉素治疗CNS致新生儿败血症的疗效。方法选择2019年1月至2020年12月南阳市中心医院收治的CNS致新生儿败血症185例为研究对象,根据治疗方法将患儿分为观察组(n=94)和对照组(n=91)。对照组患儿给予注射用青霉素钠静脉滴注,每次50000 U·kg^(-1),出生7 d内每12 h 1次,出生第7天后每8 h 1次。观察组在对照组基础上给予万古霉素治疗,第1天给予15 mg·kg^(-1)万古霉素静脉滴注,滴注时间﹥1 h,每日1次;第2天开始给予10 mg·kg^(-1)万古霉素静脉滴注,滴注时间﹥1 h,每日1次。2组患儿均治疗14 d。采用全自动细菌鉴定及药物敏感分析系统进行菌种鉴定和药物敏感性分析,按照《抗菌药物临床研究指导原则》评定临床疗效,应用流式细胞仪检测全血自然杀伤(NK)细胞活性,应用全自动血液细胞分析仪进行白细胞(WBC)计数,应用全自动生物化学分析系统检测血清免疫球蛋白(Ig)G、IgM水平,采用酶联免疫吸附法检测血清肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6、IL-8、C反应蛋白(CRP)水平。结果185例CNS致新生儿败血症患儿的病原菌前3位分别为表皮葡萄球菌、溶血葡萄球菌、人葡萄球菌,占比分别为40.54%(75/185)、28.11%(52/185)、14.05%(26/185)。表皮葡萄球菌对青霉素、氨苄西林、苯唑西林的耐药性分别为100.00%、97.33%、92.00%,对替考拉宁、万古霉素的敏感性均达100.00%;溶血葡萄球菌对青霉素、氨苄西林、苯唑西林、头孢曲松、红霉素的耐药性分别为100.00%、100.00%、96.15%、94.23%、92.31%,对替考拉宁、万古霉素的敏感性均达100.00%;人葡萄球菌对青霉素、氨苄西林的耐药性分别为100.00%、92.31%,对替考拉宁、万古霉素的敏感性均达100.00%。治疗后,观察组患儿的临床疗效优于对照组(Z=30.179,P<0.05)。观察组和对照组患儿的治疗总有效率分别为98.94%(93/94)、89.01%(81/91),观察组患儿的治疗总有效率显著高于对照组(χ^(2)=8.145,P<0.05)。观察组和对照组患儿的不良反应发生率分别为19.15%(18/94)、18.68%(17/91),2组患儿的不良反应发生率比较差异无统计学意义(χ^(2)=0.007,P>0.05)。2组患儿治疗前血清IgG、IgM水平和NK细胞活性比较差异无统计学意义(P>0.05);2组患儿治疗后血清IgG水平和NK细胞活性显著高于治疗前,血清IgM水平显著低于治疗前(P<0.05);观察组患儿治疗后血清IgG水平和NK细胞活性显著高于对照组,血清IgM水平显著低于对照组(P<0.05)。治疗前,2组患儿血清TNF-α、IL-6、IL-8、CRP水平及WBC计数比较差异均无统计学意义(P>0.05);2组患儿治疗后血清TNF-α、IL-6、IL-8、CRP水平及WBC计数显著低于治疗前(P<0.05);治疗后,观察组患儿血清TNF-α、IL-6、IL-8、CRP水平显著低于对照组(P<0.05);治疗后,2组患儿WBC计数比较差异无统计学意义(P>0.05)。结论CNS致新生儿败血症的病原菌以表皮葡萄球菌、溶血葡萄球菌、人葡萄球菌为主,3种CNS中均未检测出对万古霉素耐药菌株;万古霉素联合广谱青霉素治疗可显著提高CNS致新生儿败血症患儿免疫功能,降低炎症反应,提高临床疗效。

Objective To investigate the pathogenic distribution and drug resistance in children with neonatal sepsis caused by coagulase-negative Staphylococci(CNS),and to analyze the efficacy of penicillin combined with vancomycin in the treatment of neonatal sepsis caused by CNS.Methods A total of 185 cases of neonatal sepsis caused by CNS admitted to Nanyang Central Hospital from January 2019 to December 2020 were selected as the research subjects,and the children were divided into the observation group(n=94)and the control group(n=91)according to the treatment method.The children in the control group were treated with penicillin intravenously,50000 U·kg^(-1) at each time,once every 12 hours within 7 days after birth and once every 8 hours after the 7^(th) day of birth;the children in the observation group was treated with vancomycin on the basis of the control group,15 mg·kg^(-1) vancomycin was given intravenously on the first day,the time of intravenous drip was more than 1 hour,once a day;from the second day,10 mg·kg^(-1) vancomycin was given intravenously,the time of intravenous drip was more than 1 hour,once a day.The children in the both groups were treated for 14 days.The strain identification and drug sensitivity was analyzed by using automatic bacterial identification and drug sensitivity analysis system,and the clinical efficacy was evaluated according to the guiding principles for clinical research of antibiotics,the activity of natural killer(NK)cells in whole blood was detected by flow cytometry,the number of white blood cell(WBC)was counted by automatic blood cell analyzer,and the levels of serum immunoglobulin(Ig)G and IgM were detected by automatic biochemical analysis system,and the levels of serum tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-8,C-reactive protein(CRP)were detected by enzyme-linked immunosorbent assay.Results The constituent ratio of the top three of pathogenic bacteria in 185 children with neonatal sepsis caused by CNS were Staphylococcus epidermidis,Staphylococcus haemolyticus and Staphylococcus hominis,which accounted for 40.54%(75/185),28.11%(52/185)and 14.05%(26/185),respectively.The resistance of Staphylococcus epidermidis to penicillin,ampicillin and oxacillin was 100.00%,97.33% and 92.00%,respectively;its sensitivity to teicoplanin and vancomycin was all of 100.00%.The resistance of Staphylococcus haemolyticus to penicillin,ampicillin,oxacillin,ceftriaxone and erythromycin was 100.00%,100.00%,96.15%,94.23% and 92.31%,respectively;its sensitivity to teicoplanin and vancomycin was all of 100.00%.The resistance of Staphylococcus hominis to penicillin and ampicillin was 100.00%and 92.31%,respectively;its sensitivity to teicoplanin and vancomycin was all of 100.00%.After treatment,the clinical effect of children in the observation group was better than that in the control group(Z=30.179,P<0.05).The total effective rate of children in the observation group and the control group was 98.94%(93/94)and 89.01%(81/91),respectively.The total effective rate of children in the observation group was significantly higher than that in the control group(χ^(2)=8.145,P<0.05).The incidence of adverse reactions of children in the observation group and the control group was 19.15%(18/94)and 18.68%(17/91).There was no significant difference in the incidence of adverse reactions of children between the two groups(χ^(2)=0.007,P>0.05).There was no significant difference in the levels of IgG,IgM in serum and NK cell activity of children between the two groups before treatment(P>0.05).The level of IgG in serum and NK cell activity of children after treatment in the two groups were significantly higher than those before treatment,and the level of IgM in serum was significantly lower than that before treatment(P<0.05).The level of IgG in serum and NK cell activity of children after treatment in the observation group were significantly higher than those in the control group,and the level of IgM in serum was significantly lower than that in the control group(P<0.05).There was no significant difference in the levels of TNF-α,IL-6,IL-8,CRP in serum and WBC count of children between the two groups before treatment(P>0.05).After treatment,the levels of TNF-α,IL-6,IL-8,CRP in serum and WBC count of children in the two groups were significantly lower than those before treatment(P<0.05).The levels of TNF-α,IL-6,IL-8,CRP in serum of children in the observation group were significantly lower than those in the control group(P<0.05).There was no significant difference in WBC count of children between the two groups(P>0.05).Conclusion Staphylococcus epidermidis,Staphylococcus haemolyticus and Staphylococcus hominis are the main pathogens of CNS induced neonatal sepsis.The three main CNS are not resistant to vancomycin.The vancomycin combined with penicillin can significantly improve immune function,reduce inflammatory reaction,and improve clinical effect of children with neonatal sepsis caused by CNS.