海口市儿童肺炎患者呼吸道标本流感嗜血杆菌的耐药性与分子流行病学特征

Drug resistance and molecular epidemiology of Haemophilus influenzae isolated from respiratory tract specimens of children with pneumonia in Haikou City

摘要:

目的 调查海口市肺炎患儿分离的流感嗜血杆菌临床分布、耐药状况及克隆传播情况，为预防和治疗儿童流感嗜血杆菌性肺炎提供理论依据。 方法 收集2021年海口市妇幼保健院5 342例住院肺炎患儿临床资料，分析患儿呼吸道标本流感嗜血杆菌阳性情况，检测菌株耐药性，并采用多位点序列分型（MLST）分析其同源性。 结果 5 342例肺炎患儿共分离352株流感嗜血杆菌，检出率为6.59%；男患儿检出率为7.10%，女患儿检出率为5.82%；年龄 < 30 d检出率为0.30%，30 d~为8.45%，2岁~为11.62%，4岁~为12.88%，≥ 6岁为2.56%，各年龄段检出率比较差异有统计学意义（P < 0.05）；春季检出率为14.04%，夏季为4.48%，秋季为4.62%，冬季为4.40%，各季节检出率比较差异有统计学意义（P < 0.001）。流感嗜血杆菌β-内酰胺酶阳性率为42.60%（141/331），对复方磺胺甲唑、氨苄西林、头孢呋辛的耐药率分别为76.43%、69.19%、51.36%，对阿奇霉素、阿莫西林/克拉维酸、头孢他啶和头孢曲松的耐药率 < 30%，对美罗培南和左氧氟沙星的耐药率 < 1%。51株流感嗜血杆菌经MLST测序分成15个ST型；其中ST107包含11株（21.57%），主要分布在4个月~1岁患儿（9株）和3岁患儿（2株）。 结论 海口市肺炎患儿分离的流感嗜血杆菌具有遗传多样性，且发生社区克隆传播，以2~3岁幼儿感染多见。春季是感染高发季节，ST107是春季流行优势克隆型。经验治疗时须谨慎使用复方磺胺甲唑、氨苄西林和头孢呋辛，阿莫西林/克拉维酸耐药率和β-内酰胺酶阴性菌株对氨苄西林耐药率升高，临床应引起重视。

Abstract:

Objective To investigate the clinical distribution, drug resistance and clonal transmission of Haemophilus influenzae (H. influenzae) isolated from children with pneumonia in Haikou City, and provide a theoretical basis for the prevention and treatment of H. influenzae pneumonia in children. Methods Clinical data of 5 342 hospitalized children with pneumonia in Haikou Hospital of the Maternal and Child Health in 2021 were collected. Positive rate of H. influenzae from children's respiratory tract specimens was calculated, and drug resistance and homology of multilocus sequence typing (MLST) of strains were analyzed. Results 352 H. influenzae strains were isolated from 5 342 children with pneumonia, with an isolation rate of 6.59%. Isolation rates of H. influenzae of male and female children were 7.10% and 5.82% respectively; isolation rates of H. influenzae of children at the age of < 30 days, 30 days-, 2 years-, 4 years-, and ≥ 6 years were 0.30%, 8.45%, 11.62%, 12.88% and 2.56% respectively, with a statistically significant difference among all age groups(P < 0.05). Isolation rates in spring, summer, autumn, and winter were 14.04%, 4.48%, 4.62%, and 4.40% respectively, seasonal difference was statistically significant (P < 0.001). Positive rate of H. influenzae β-lactamase was 42.60% (141/331). Resistance rates of H. influenzae to compound sulfamethoxazole, ampicillin, and cefuroxime were 76.43%, 69.19%, and 51.36% respectively, to azithromycin, amoxicillin/clavulanic acid, ceftazidime, and ceftriaxone were all < 30%, to meropenem and levofloxacin were < 1%. 51 H. influenzae strains were divided into 15 ST types by MLST sequencing, including 11 strains (21.57%) of ST107, which mainly distributed among children aged 4 months-1 year (9 strains) and 3 years (2 strains). Conclusion H. influenzae isolated from children with pneumonia in Haikou City is genetically diverse and transmitted through community cloning. Most children with pneumonia were aged 2-3 years old. Spring is the peak season of high infection incidence. ST107 is dominant in spring. Empiric treatment with compound sulfamethoxazole, ampicillin and cefuroxime should be cautious. Resistance to amoxicillin/clavulanic acid and resistance of β-lactamase negative strains to ampicillin increased, which should be paid attention in clinic.