新生儿细菌性脑膜炎TLR2/9基因多态性及病原菌耐药性

TLR2/9 gene polymorphism and drug resistance of pathogenic bacteria in neonatal bacterial meningitis

目的探讨新生儿细菌性脑膜炎Toll样受体(TLR)2/9基因多态性及病原菌耐药性。方法回顾性选取海南西部中心医院2019年4月-2023年4月收治的61例细菌性脑膜炎新生儿的临床资料并设为研究组,对照组选取同期出生的61名健康新生儿的临床资料;统计新生儿细菌性脑膜炎病原菌及耐药性;采用限制性片段长度多态性聚合酶链反应(PCR-RFLP)检测两组患儿外周血中TLR2基因rs5743708位点和TLR9基因rs352140位点基因型分布。结果新生儿细菌性脑膜炎培养分离病原菌64株,其中革兰阴性菌38株,革兰阳性菌26株,以大肠埃希菌、肺炎克雷伯菌、无乳链球菌为主;大肠埃希菌对头孢曲松(76.19%)和头孢唑林(85.71%)耐药率较高,肺炎克雷伯菌对头孢唑林(100.00%)和头孢呋辛(100.00%)耐药率较高,而两者均对阿米卡星、美罗培南和亚胺培南较为敏感;无乳链球菌对克林霉素(100.00%)和红霉素(100.00%)耐药率较高,对头孢曲松、美罗培南和万古霉素较为敏感;研究组TLR2 rs5743708位点AA基因型频率、A等位基因频率分别为36.07%、47.54%高于对照组(P<0.05),G等位基因频率52.46%低于对照组(P<0.05);研究组TLR9基因rs352140位点TT基因型频率、T等位基因频率分别为40.98%、53.28%高于对照组(P<0.05),CC基因型频率、C等位基因频率分别为34.43%、46.72%低于对照组(P<0.05)。结论新生儿细菌性脑膜炎多为革兰阴性菌感染,检出病原菌以大肠埃希菌、肺炎克雷伯菌、无乳链球菌为主,不同病原菌对常用抗菌药耐药性不同;TLR2/9基因多态性可能参与新生儿细菌性脑膜炎病情进展。

OBJECTIVE To investigate the Toll-like receptor(TLR)2/9 gene polymorphism and pathogenic bacte-ria resistance in neonatal bacterial meningitis.METHODS The clinical data of 6l newborns with bacterial meningitis admitted to Hainan West Central Hospital from Apr.2019 to Apr.2023 were retrospectively selected and set up as the study group,and the clinical data of 61 healthy neonates born during the same period were selected as the control group.The pathogenic bacteria and drug resistance of neonatal bacterial meningitis were analyzed.The genotype distribution of the rs5743708 locus of the TLR2 gene and the rs352140 locus of the TLR9 gene in the peripheral blood of the two groups of children were detected by polymerase chain reaction(PCR-RFLP)with restriction fragment length polymorphism.RESULTS A total of the 64 strains of pathogenic bacteria were isolated from neonatal bacterial meningitis culture,including 38 strains of gram-negative bacteria and 26 strains of gram-positive bacteria,with Escherichia coli,Klebsiella pneumoniae and Streptococcus agalactis predominating.E.coli had a high rate of resistance to ceftriaxone(76.19%)and cefzolin(85.71%),and K.pneumoniae had a high rate of resistance to cefzolin(100.00%)and cefuroxime(100.00%),while both were more susceptible to amicacin,meropenem and imipenem.S.agalactis had a high rate of resistance to clindamycin(100.00%)and erythromycin(100.o0%),while was more susceptible to ceftriaxone,meropenem and vancomycin.The frequency of AA genotype and A allele at rs5743708 locus of the TLR2 genes in the study group were 36.07% and 47.54%,respectively,higher than those in the control group(P<0.05),while the frequency of G allele was 52.46%lower than that in the control group(P<0.05);The frequency of TT genotype and T allele at rs352140 locus of the TLR9 gene in the study group were 40.98%and 53.28%,respectively,higher than those in the control group(P<0.05),while the frequency of CC genotype and C allele frequency were 34.43%and 46.72%,respectively,lower than those in the control group(P<0.05).CONCLUSIONS Neonatal bacterial meningitis was mostly caused by gram-negative bacteria,and E.coli,K.pneumoniae and S.agalactis were the most detected pathogens,and the resistance of different pathogens to common antibiotics was different.TLR2/9 gene polymorphism may be involved in the progression of neonatal bacterial meningitis.