3个月龄以内婴儿败血症病原菌分布及抗菌药物耐药状况分析

Pathogen distribution and antibiotic resistance in infants with sepsis up to the age of 3 months

目的探讨月龄<3个月婴儿败血症的病原菌分布[排除凝固酶阴性葡萄球菌(CNS)]及其对抗菌药物耐药状况。方法选择2012年1月1日至2016年12月31日,广州医科大学附属广州市妇女儿童医疗中心收治的924例月龄<3个月的婴儿败血症患儿为研究对象。这924例患儿经血培养,共计分离出968株病原菌。回顾性分析924例月龄<3个月的婴儿败血症患儿的病原菌分布情况,早发型败血症(EOS)与晚发型败血症(LOS)患儿病原菌分布情况,以及常见革兰阴性杆菌、革兰阳性球菌对抗菌药物耐药情况。采用χ~2检验,对EOS和LOS患儿血培养分离出的大肠埃希菌、肺炎克雷伯菌、B族链球菌(GBS)、金黄色葡萄球菌、真菌所占比例进行比较。本研究遵循的程序符合广州医科大学附属广州市妇女儿童医疗中心医学伦理委员会制定的伦理学标准,并得到该委员会审查批准。结果 (1)本研究924例月龄<3个月的婴儿败血症患儿血培养共计分离出968株病原菌,其中革兰阴性杆菌为593株(61.3%,593/968),以大肠埃希菌(21.4%,207/968),肺炎克雷伯菌(19.6%,190/968)为主;革兰阳性球菌为318株(32.9%,318/968),以GBS(11.5%,111/968),金黄色葡萄球菌(7.7%,75/968),粪肠球菌(4.1%,40/968)为主;真菌为52株(5.4%,52/968);革兰阴性球菌为3株(0.3%,3/968);革兰阳性杆菌为2株(0.2%,2/968)。(2)197例EOS患儿血培养共计分离出226株病原菌,常见病原菌前3位依次为大肠埃希菌(23.9%,54/226),GBS(17.7%,40/226)和肺炎克雷伯菌(15.9%,36/226)。727例LOS患儿血培养共计分离出742株病原菌,常见病原菌前3位依次为肺炎克雷伯菌(20.8%,154/742),大肠埃希菌(20.6%,153/742)和GBS(9.6%,71/742)。EOS患儿血培养分离出的GBS所占比例为17.7%(40/226),明显高于LOS患儿的9.6%(71/742),二者比较,差异有统计学意义(χ~2=11.280,P=0.001)。EOS患儿血培养分离出的金黄色葡萄球菌及真菌所占比例分别为4.0%(9/226)与2.7%(6/226),均分别低于LOS患儿的8.9%(66/742)与6.2%(46/742),并且差异亦均有统计学意义(χ~2=5.849,P=0.016;χ~2=4.282,P=0.039)。(3)593株革兰阴性杆菌中,大肠埃希菌和肺炎克雷伯菌对氨苄西林耐药率均为最高,分别为81.1%和99.4%;对哌拉西林/他唑巴坦、阿米卡星、厄他培南、亚胺培南、头孢吡肟耐药率较低,为0~17.2%。(4)318株革兰阳性球菌中,GBS、金黄色葡萄球菌、粪肠球菌、屎肠球菌对万古霉素、替加环素、利奈唑烷的敏感性较高,耐药率均为0;金黄色葡萄球菌对青霉素G耐药率高达92.9%。结论革兰阴性杆菌是月龄<3个月婴儿败血症患儿的主要病原菌,其次是革兰阳性球菌。临床经验性选择抗菌药物治疗月龄<3个月婴儿败血症患儿时,应高度注意病原菌耐药问题。

Objective To investigate the pathogen distribution with coagulase negative staphylococcus（CNS）excluded and antibiotic resistance of infants with sepsis during the first3 months after birth.Methods A retrospective analysis was conducted on 968 isolates from 924 infants within 3 months of age who were admitted to the Guangzhou Women and Children′s Medical Center,Guangzhou Medical University from January 1,2012 to December 31,2016.The following items were analyzed,including pathogen distribution of 968 isolates from 924 infants within 3 months of age and with blood culture-confirmed sepsis,pathogen distribution of early-onset sepsis（EOS）infants and late-onset sepsis（LOS）infant,and antibiotic resistance of common Gram-negative bacilli and Gram-positive cocci.Chi-square test was taken to compare the constituent ratio of Escherichia coli,Klebsiella pneumoniae,group Bstreptococci（GBS）,Staphylococcus aureus,and fungi isolated from blood culture-confirmed sepsis between EOS and LOS infants.The procedures followed in this study were in line with the ethical standards established by the Medical Ethics Committee of the Guangzhou Women and Children′s Medical Center,Guangzhou Medical University and were reviewed and approved by the committee.Results（1）Among 968 isolates from 924 infants within 3 months of age,Gram-negative bacilli were predominant（593 strains,61.3%,593/968）,followed by Grampositive cocci（318 strains,32.9%,318/968）,fungi（52 strains,5.4%,52/968）,Gram-negative cocci（3 strains,0.3%,3/968）and Gram-positive bacilli（2 strains,0.2%,2/968）.Escherichia coli（21.4%,207/968）and Klebsiella pneumoniae（19.6%,190/968）were the main pathogens of Gramnegative bacilli. And GBS（11.5%,111/968）, Staphylococcus aureus（7.7%,75/968）,Enterococcus faecalis（4.1%,40/968）were the main pathogens of Gram-positive cocci.（2）A total of226 isolates were isolated from 197 EOS infants,of which the predominant pathogens were Escherichia coli（23.9%,54/226）,GBS（17.7%,40/226）and Klebsiella pneumoniae（15.9%,36/226）.Besides,a total of 742 isolates were isolated from 727 LOS infants,of which the predominant pathogens were Klebsiella pneumoniae（20.8%,154/742）,Escherichia coli（20.6%,153/742）,and GBS（9.6%,71/742）.The proportion of GBS in 226 isolates from EOS infants was17.7%（40/226）,which was significantly higher than that of the LOS infants（9.6%,71/742）,and the difference was statistically significant（χ~2=11.28,P =0.001）,whereas the proportion of Staphylococcus aureus and fungi in EOS infants were 4.0%（9/226）and 2.7%（6/226）,respectively,which both were lower than those of LOS infants 8.9%（66/742）and 6.2%（46/742）,respectively,and both the differences were also statistically significant（χ~2=5.85,P=0.016;χ~2=4.28,P=0.039）.（3） Among 593 strains of Gram-negative bacilli,Escherichia coli and Klebsiella pneumoniae showed high resistance to ampicillin（81.1% and 99.4%）,while low resistance to piperacillin/tazobactam,amikacin,ertapenem,imipenem and cefepime with the rate of resistance ranged from 0 to 17.2%.（4） Among 318 strains of Gram-positive cocci,GBS,Staphylococcus aureus,Enterococcus faecalis and Enterococcus faecium were highly sensitive to vancomycin,tigecycline and linezolid and the rates of resistance all were 0.In addition,Staphylococcus aureus showed high resistance to penicillin,and the rate of resistance was 92.9%.Conclusions Gram-negative bacilli is the main pathogen among infants with sepsis up to the age of 3 months,followed by Gram-positive cocci.Selection of anti-bacterial agents for the treatment of infants with sepsis up to the age of3 months should be highly aware of drug resistance.