儿童耐甲氧西林金黄色葡萄球菌感染临床特征及药物敏感性多中心研究

A multicentric study on clinical characteristics and antibiotic sensitivity in children with methicillin-resistant Staphylococcus aureus infection

目的了解儿童耐甲氧西林金黄色葡萄球菌(MRSA)感染的临床特征以及分离菌株的药物敏感情况。方法回顾性病例研究。收集2018年中国儿童细菌耐药监测协作组(ISPED)11家医院住院的452例MRSA感染患儿的临床资料及分离菌株药物敏感性。分析患儿一般情况、高危因素、抗菌药物治疗、预后,不同年龄组和不同感染型别的临床疾病、实验室检查结果差别,不同感染型别抗菌药物敏感性差异。采用t检验、Wilcoxon秩和检验或χ2检验进行组间比较。结果452例患儿中男264例、女188例,年龄为2日龄~17岁,其中≤1岁233例(51.5%)、>1~3岁79例(17.5%)、>3~5岁29例(6.4%)、>5~10岁65例(14.4%)、>10岁组46例(10.2%)。发病月份较多的为12月份(55例,12.2%)、2月份(47例,10.4%)、11月份(46例,10.2%)、1月份(45例,10.0%)、3月份(40例,8.8%)。社区获得性MRSA 335例(74.1%),医院获得性MRSA 117例(25.9%)。174例(38.5%)患儿存在基础疾病或长期激素及免疫抑制剂使用史。209例(46.2%)患儿本次住院接受医疗侵入置管。182例(40.3%)患儿入院前3个月有β内酰胺类、糖肽类、大环内酯类、碳青霉烯类、噁唑酮类、磺胺类等抗菌药物使用史。临床疾病以肺炎最常见(203例),然后依次为皮肤软组织感染(133例)、脓毒血症(92例)、深部组织脓肿(42例)、骨髓炎(40例)、化脓性关节炎(26例)、化脓性脑膜炎(10例)等。≤1岁组患儿肺炎的比例高于>1~3岁组、>3~5岁组、>5~10岁组、>10岁组[57.5%(134/233)比30.4%(24/79)、31.0%(9/29)、38.5%(25/65)、23.9%(11/46),χ2=17.374、7.293、7.410、17.373,P均<0.01]。社区获得性MRSA感染所致皮肤软组织感染比例高于医院获得性MRSA[33.4%(112/335)比17.9%(21/117),χ2=10.010,P=0.002],而所致肺炎比例则低[42.1%(141/335)比53.0%(62/117),χ2=4.166,P=0.041]。≤1岁组入院后首次外周血白细胞计数(WBC)高于>1岁患儿[(15±8)×109/L比(13±7)×109/L,t=2.697,P=0.007],而≤1岁组C反应蛋白低于>1~3岁组、>5~10岁组和>10岁组[8.00(0.04~194.00)比17.00(0.50~316.00)、15.20(0.23~312.00)、21.79(0.13~219.00)mg/L,Z=3.207、2.044、2.513,P均<0.05],降钙素原在各年龄组间比较差异无统计学意义(P均>0.05)。经治疗,治愈131例,好转278例,未愈21例,死亡12例,放弃10例。452株MRSA菌株对万古霉素和利奈唑胺均100.0%敏感,对青霉素100.0%耐药,红霉素耐药率为85.0%(375/441)、克林霉素为67.7%(294/434)、复方磺胺类为5.9%(23/391)、左氧氟沙星为4.5%(19/423)、庆大霉素为3.2%(14/438)、利福平为1.8%(8/440)、米诺环素为1.1%(1/91)。社区获得性MRSA及医院获得性MRSA两组间抗菌药物耐药率差异均无统计学意义(P均>0.05)。结论儿童MRSA感染主要见于3岁以下婴幼儿,好发季节为冬春季节,并以社区获得为主。临床疾病以肺炎、皮肤软组织感染、脓毒血症较多见。未发现对万古霉素、利奈唑胺耐药的MRSA菌株。MRSA对复方磺胺类、左氧氟沙星、庆大霉素、利福平、米诺环素普遍敏感,对红霉素、克林霉素耐药率高。临床医生需根据患儿临床特征及药敏情况,积极有效抗感染治疗,改善MRSA感染患儿临床预后。

Objective To investigate the clinical characteristics of pediatric methicillin-resistant Staphylococcus aureus(MRSA)infection and the antibiotic sensitivity of the isolates.Methods The clinical data of children with MRSA infection and antibiotic sensitivity of the isolates from 11 children′s hospitals in Infectious Diseases Surveillance of Paediatrics(ISPED)group of China between January 1,2018 and December 31,2018 were collected retrospectively.The children′s general condition,high-risk factors,antimicrobial therapy and prognosis,differences in clinical disease and laboratory test results between different age groups,and differences of antibiotic sensitivity between community-acquired(CA)-MRSA and hospital-acquired(HA)-MRSA were analyzed.The t test and Wilcoxon rank sum test were used for statistical analysis of the quantitative data and Chi-square test were used for comparison of rates.Results Among the 452 patients,264 were males and 188 were females,aged from 2 days to 17 years.There were 233 cases(51.5%)in the≤1 year old group,79 cases(17.5%)in the>1-3 years old group,29 cases(6.4%)in the>3-5 years old group,65 cases(14.4%)in the>5-10 years old group,and 46 cases(10.2%)in the>10 years old group.The main distributions of onset seasons were 55 cases(12.2%)in December,47 cases(10.4%)in February,46 cases(10.2%)in November,45 cases(10.0%)in January,40 cases(8.8%)in March.There were 335 cases(74.1%)CA-MRSA and 117(25.9%)cases HA-MRSA.Among all cases,174 cases(38.5%)had basic diseases or long-term use of hormone and immunosuppressive drugs.During the period of hospitalization,209 cases(46.2%)received medical interventions.There were 182 patients(40.3%)had used antibiotics(β-lactams,glycopeptides,macrolides,carbapenems,oxazolones,sulfonamides etc)3 months before admission.The most common clinical disease was pneumonia(203 cases),followed by skin soft-tissue infection(133 cases),sepsis(92 cases),deep tissue abscess(42 cases),osteomyelitis(40 cases),and septic arthritis(26 cases),suppurative meningitis(10 cases).The proportion of pneumonia in the≤1 year old group was higher than the>1-3 years old group,>3-5 years old group,>5-10 years old group,>10 years old group(57.5%(134/233)vs.30.4%(24/79),31.0%(9/29),38.5%(25/65),23.9%(11/46),χ2=17.374,7.293,7.410,17.373,all P<0.01)The proportion of skin and soft tissue infections caused by CA-MRSA infection was higher than HA-MRSA(33.4%(112/335)vs.17.9%(21/117),χ2=10.010,P=0.002),and the proportion of pneumonia caused by HA-MRSA infection was higher than CA-MRSA(53.0%(62/117)vs.42.1%(141/335),χ2=4.166,P=0.041).The first white blood cell count of the≤1 year old group was higher than that children>1 year old((15±8)×109/L vs.(13±7)×109/L,t=2.697,P=0.007),while the C-reactive protein of the≤1 year old group was lower than the 1-3 years old group,>5-10 years old group,>10 years old group(8.00(0.04-194.00)vs.17.00(0.50-316.00),15.20(0.23-312.00),21.79(0.13-219.00)mg/L,Z=3.207,2.044,2.513,all P<0.05),there were no significant differences in procalcitonin(PCT)between different age groups(all P>0.05).After the treatment,131 cases were cured,278 cases were improved,21 cases were not cured,12 cases died,and 10 cases were abandoned.The 452 MRSA isolates were all sensitive to vancomycin(100.0%),linezolid(100.0%),100.0%resistant to penicillin,highly resistant to erythromycin(85.0%,375/441),clindamycin(67.7%,294/434),less resistant to sulfonamides(5.9%,23/391),levofloxacin(4.5%,19/423),gentamicin(3.2%,14/438),rifampicin(1.8%,8/440),minocycline(1.1%,1/91).The antimicrobial resistance rates were not significantly different between the CA-MRSA and HA-MRSA groups(all P>0.05).Conclusions The infection of MRSA is mainly found in infants under 3 years old.The prevalent seasons are winter and spring,and MRSA is mainly acquired in the community.The main clinical diseases are pneumonia,skin soft-tissue infection and sepsis.No MRSA isolate is resistant to vancomycin,linezolid.MRSA isolates are generally sensitive to sulfonamides,levofloxacin,gentamicin,rifampicin,minocycline,and were highly resistant to erythromycin and clindamycin.To achieve better prognosis.clinicians should initiate anti-infective treatment for children with MRSA infection according to the clinical characteristics of patients and drug sensitivity of the isolates timely and effectively.