儿童流感病毒合并革兰阳性菌感染的临床特征及危险因素分析

Analysis of clinical characteristics and risk factors of influenza virus complicated with gram-positive bacterial infection in children

目的探讨儿童流感病毒合并革兰阳性菌感染的临床特征及危险因素。方法回顾分析2013年1月至2019年12月中国医科大学深圳市儿童医院住院的流感病毒合并革兰阳性菌感染患儿(观察组)的临床资料。抽取同期住院的110例无合并感染的流感病毒感染患儿作为对照组。分析两组患儿的临床资料,采用Logistic回归分析流感病毒合并革兰阳性菌感染的危险因素。结果观察组患儿108例,男68例,女40例,年龄(2.6±1.8)岁,5岁以下儿童100例(92.6%)。发病月份分布:1~3月61例,4~6月15例,7~9月13例,10~12月19例。甲型流感病毒感染73例,乙型流感病毒感染35例;合并肺炎链球菌感染94例(87.0%),A群链球菌感染11例,金黄色葡萄球菌感染8例。15例(13.9%)患儿有基础疾病。所有患儿均未接种肺炎球菌疫苗,2例1年内接种过流感疫苗。对照组患儿110例,男57例,女53例,年龄(5.0±2.4)岁。甲型流感病毒感染80例,乙型流感病毒感染30例。4例存在基础疾病。6例接种了13价肺炎球菌结合疫苗,12例1年内接种过流感疫苗。与对照组比较,观察组患儿年龄小[(2.6±1.8)岁比(5.0±2.4)岁,t=-7.935,P<0.001],多有基础疾病[13.9%(15/108)比3.6%(4/110),χ^(2)=7.200,P=0.007],接种流感疫苗比例少[1.9%(2/108)比10.9%(12/110),χ^(2)=7.439,P=0.006],住院时间长[6(5,7)d比4(3,5)d,Z=-7.278,P<0.001],首次使用神经氨酸酶抑制剂(neuraminidase inhibitors,NAI)时间多在病程48 h后[75.9%(82/108)比14.5%(16/110),χ^(2)=82.971,P<0.001]。观察组97份肺炎链球菌培养阳性标本,痰液/肺泡灌洗液89份,血液5份,脑脊液3份。所有肺炎链球菌对红霉素及克林霉素均耐药;非脑膜炎肺炎链球菌对头孢曲松、头孢噻肟、青霉素耐药率分别为7.7%、5.5%、1.1%;对万古霉素、利奈唑胺和左氧氟沙星均敏感。所有观察组患儿均予NAI及抗生素治疗,37例行纤维支气管镜肺泡灌洗,27例入重症监护病房接受治疗,10例无创持续气道正压通气,17例气管插管机械通气;6例死亡。Logistic回归分析显示有基础疾病、未接种流感和(或)肺炎球菌疫苗、首次NAI使用时间>48 h是流感病毒合并革兰阳性菌感染的危险因素。结论流感病毒合并革兰阳性菌感染可加重患儿病情甚至死亡;早期识别合并革兰阳性菌感染,及时予NAI及抗生素治疗,积极控制并发症有助于提高治愈率。流感季节加强流感疫苗及肺炎球菌疫苗接种有助于减少感染。

Objective To explore the clinical characteristics and risk factors of influenza virus complicated with gram-positive bacterial infection in children.Methods The clinical data of children with influenza virus complicated with gram-positive bacterial infection hospitalized at Shenzhen Children′s Hospital affiliated to China Medical University from January 2013 to December 2019(observation group)were retrospectively studied.During the same period,110 hospitalized children with influenza virus infection without co-infection were selected as the control group.The clinical data of the children in two groups were analyzed.Logistic regression analysis was used to analyze the risk factors of influenza virus complicated with gram-positive bacterial infection.Results There were 108 children in the observation group,including 68 boys and 40 girls,with the age of(2.6±1.8)years,and 100(92.6%)children under 5 years old.Incidence month distribution:61 cases from January to March,15 cases from April to June,13 cases from July to September,and 19 cases from October to December.In the observation group,73 cases were infected with influenza A virus,35 cases were infected with influenza B virus,94(87.0%)cases were complicated with Streptococcus pneumoniae infection,11 cases with Group A Streptococcus infection and 8 cases with Staphylococcus aureus infection.And 15(13.9%)cases had underlying diseases.None of the patients in the observation group received pneumococcal conjugate vaccine,and two cases received influenza vaccine within one year.There were 110 children in the control group,including 57 boys and 53 girls,with the age of(5.0±2.4)years old.There were 80 cases of influenza A virus infection and 30 cases of influenza B virus infection.Four cases had underlying diseases,six cases received 13-valent pneumococcal conjugate vaccine and 12 cases received influenza vaccine within one year.Compared with the control group,the children in the observation group were younger[(2.6±1.8)years vs.(5.0±2.4)years,χ^(2)=-7.935,P<0.001],had more underlying diseases[13.9%(15/108)vs.3.6%(4/110),χ^(2)=7.200,P=0.007],less proportion of influenza vaccine[1.9%(2/108)vs.10.9%(12/110),χ^(2)=7.439,P=0.006],the hospitalization time was longer[6(5,7)d vs.4(3,5)d,Z=-7.278,P<0.001],and mone cases of first use of neuraminidase inhibitors(NAI)for more than 48 hours[75.9%(82/108)vs.14.5%(16/110),χ^(2)=82.971,P<0.001].In the observation group,there were 97 culture-positive specimens of Streptococcus pneumoniae,including 89 of sputum/bronchoalveolar lavage fluid,five of blood culture and three of cerebrospinal fluid.All Streptococcus pneumoniae were resistant to erythromycin and clindamycin;the resistance rates of non-meningitis Streptococcus pneumoniae to ceftriaxone,cefotaxime and penicillin were 7.7%,5.5%and 1.1%,respectively,and all the strains were sensitive to vancomycin,linezolid and levofloxacin.All patients in the observation group were treated with NAI and antibiotics,37 cases were treated with bronchoalveolar lavage,27 cases were admitted to pediatric intensive care unit,10 cases were treated by non-invasive continuous positive airway pressure ventilation,and 17 cases received mechanical ventilation;6 cases died.Logistic regression analysis showed that underlying diseases,unvaccinated with influenza and(or)pneumococcal vaccine,and the first use of NAI>48 hours were risk factors for influenza virus complicated with gram-positive bacterial infection.Conclusion Influenza virus complicated with gram-positive bacterial infection can aggravate the illness and even death of children.Early identification of gram-positive bacterial infection,timely treatment of NAI and antibiotics,and active control of complications could be helpful to improve the cure rate.Strengthening influenza and pneumococcal vaccine during flu season can help reduce infection.