新生儿流感嗜血杆菌感染前瞻性多中心流行病学调查与病例对照研究

Multicenter prospective epidemiological studies and case-control study on Haemophilus influenza infection in hospitalized neonates

目的了解新生儿流感嗜血杆菌（Haemophilus influenza，Hi）感染发生情况、流行菌株生物学分型和菌株耐药背景以及Hi新生儿肺炎临床基本特征。方法采用多中心前瞻性流行病学断面研究方法，对中国川西地区4家医院0—28d入院初步诊断为新生儿感染性肺炎患儿痰液进行细菌培养，对Hi流行菌株进行生物学分型、PCR鉴定和药敏试验；以出院诊断为新生儿感染性肺炎的Hi分离阳性者为病例组，按1：1提取同期住院新生儿肺炎Hi分离阴性者为对照组进行病例对照研究。结果2014年11月至2015年10月参加调查的4家医院入院诊断为新生儿感染性肺炎患儿757例，痰培养送检率95．51％（723／757），痰培养病原菌总阳性率15．63％（113／723）；Hi阳性率1．94％（14／723），占新生儿呼吸道分离病原菌的12．39％（14／113）。全部14株Hi经PCR鉴定均为不可分型Hi；生物学分型I型57．1％（8／14）、Ⅲ型14．3％（2／14）、Ⅳ型28．6％％（4／14）；分离的14株流行菌株β-内酰胺酶阳性率35．7％（5／14），β-内酰胺酶阴性氨苄西林耐药7．1％（1／14），β-内酰胺酶阳性氨苄西林耐药35．7％（5／14），头孢呋辛耐药和中介率均为14．2％（2／14），头孢克洛耐药率35．7％（5／14），氧氟沙星耐药率21．4％（3／14），未发现阿莫西林克拉维酸和头孢噻肟耐药菌株。对10例出院诊断为新生儿肺炎的Hi阳性病例进行1：1配对分析，结果显示病例组与对照组在一般情况、临床主要症状、肺部体征、X线胸片表现以及白细胞分类和C-反应蛋白水平等方面差异均无统计学意义（P〉0．05）。结论川西地区新生儿Hi感染流行菌株全部为不可分型，生物学分型为I型、Ⅲ型和Ⅳ型；新生儿未分型Hi肺炎临床表现与其感染性肺炎并无明显差异。

Objective To explore the status of infection, biotype and resistant background of epidemic strains of Haemophilus influenza （Hi） in neonates, and the clinical features of neonatal pneumonia caused by Hi. Methods The multicenter prospective epidemiological cross-sectional design was used; four hospitals in west Sichuan China were chosen as research field, sputum bacterial culture was done and biological typing,PCR identification and drug sensitivity test of Hi epidemic strains were carried out among 0 to 28 days hospitalized neonates with infectious pneumonia in four hospitals located in west Sichuan China. The cases with discharge diagnosis of neonatal infectious pneumonia with Hi positive separation were assumed as case group, and the same number of cases with Hi negative separation were assumed as control group according to 1： 1 extraction at the same time. Results Totally 757 cases with admitting diagnosis of neonatal infectious pneumonia in four hospitals were investigated in west Sichuan from November 2014 to October 2015, and the rate of sputum culture was 95.51% （723/757）. The total pathogenic bacteria positive rate of sputum culture was 15.63% （113/723 ）, and Hi positive rate was 1.94% （ 14/723 ）, Hi accounting for 12. 39% （ 14/ 113） of the pathogenic bacteria in respiratory system. All the Hi strains （ 100% ） were non-typeable Haemophilus influenzae（NTHi） indentified by PCR. The main biotypes of 14 Hi strains were type Ⅰwith 57. 1% （8/14） ,type llI with 14. 3% （2/14） and type IV with 28.6% （4/14）. The total of 35.7% （5/14） bacterial strains of β-1actamase distributed in four hospitals ,7.1% （1/14） bacterial strains of β-1actamase-nonproduc- ing-ampicillin-resistant, and 35.7% （5/14） bacterial strains of β-1actamase-positive-ampicillin-resistant were found in four hospitals. The rate of resistance and mediation to cefuroxime were 14. 2% （2/14） respectively, the resistance rate to cefaclor was 35.7% （5/14）, and 21.4% （3/14） to ofloxacin. None of the 14 strains was resistant to amoxicillin clavulanic acid and cefotaxime. The 1：1 matching analysis had been done for 10 cases with discharge diagnosis of neonatal pneumonia caused by Hi. There were no statistical differences in general conditions, main symptoms, lung signs, X-ray appearance, classification of leukocyte and C-reactive protein levels between case group and control group （ P 〉 0. 05 ）. Conclusion All the Hi isolated from sputum were NTHi among 0 to 28 days inpatients with neonatal pneumonia and the main biotype were type Ⅰ , type Ⅲ and type Ⅳ in west Sichuan China. There were no significant differences in the clinical manifestations of neonatal pneumonia with NTHi infection and other infectious pneumonia.