儿童急性白血病合并缓症链球菌血症8例

Acute leukemia complicated with streptococcus mitis bacteriaemia in 8 children

目的探讨儿童急性白血病合并缓症链球菌血症的危险因素及抗生素选用方案。方法选取南方医科大学附属珠江医院2012年1月至2016年12月收治的儿童急性白血病合并菌血症病例78例，其中缓症链球菌血症8例（10.26%）。总结缓症链球菌血症发生的易感因素、临床表现、药敏试验结果、治疗方案及病情转归。结果8例患儿均发生于白血病化疗后1周以上粒细胞缺乏期，其中4例感染前有7 d以上第三代头孢菌素暴露史，5例有10 d以上质子泵抑制剂（PPI）用药史。弛张高热发生率为100.0%（8/8例），寒战、口腔溃疡和肺炎的发生率均为62.5%（5/8例）。重症肺炎发生率为37.5%（3/8例）。对万古霉素、利奈唑胺、青霉素和头孢噻肟的敏感率分别为100.0%、100.0%、37.5%和25.0%。7例应用美罗培南，其中5例在用药3 d后发热无改善，根据血培养药敏结果更换为利奈唑胺；1例患儿应用头孢哌酮/舒巴坦。8例患儿的体温恢复正常时间、血培养转阴时间、粒细胞缺乏持续时间和抗生素总疗程分别为1～19 d（平均10.4 d）、4～22 d（平均13.4 d）、10～30 d（平均21.6 d）、9～26 d（平均18.3 d）。3例重症肺炎患儿中，1例行呼吸机辅助通气1周。结论缓症链球菌是急性白血病患儿合并感染的主要病原体之一；化疗后粒细胞缺乏、口腔溃疡、PPI应用及抗生素暴露史为缓症链球菌感染的高危因素；发热、口腔溃疡及消化道、呼吸道症状为常见临床表现；青霉素及头孢菌素类药物耐药率高，利奈唑胺敏感且疗效确切，可缩短病程，改善预后，并作为经验用药。

Objective To investigate the risk factors for childhood acute leukemia complicated with streptococcus mitis bacteriaemia and to explore a better therapeutic regimen of antibiotics.Methods Seventy-eight cases of childhood acute leukemia complicated with bacteriaemia hospitalized in Zhujiang Hospital of Southern Medical University from January 2012 to December 2016 were collected, among them there were 8 cases （10.26%） caused by streptococcus mitis.The susceptible factors, clinical manifestations, drug susceptibility, treatments and outcomes of 8 cases of streptococcus mitis bacteriaemia were summarized and analyzed.Results All of 8 cases were attacked during the agranulocytosis phase lasting for more than 1 week after chemotherapy for acute leukemia.Four cases of them had been exposed to the third-generation cephalosporins for more than 7 days, and 5 cases exposed to proton pump inhibitor （PPI） for more than 10 days.The incidence of remittent fever, shiver, stomatitis and pneumonia was 100.0%（8/8 cases）, 62.5%（5/8 cases）, 62.5%（5/8 cases） and 62.5%（5/8 cases）, respectively.And severe pneumonia occurred at a rate of 37.5%（3/8 cases）. The sensitivity to Linezolid, Vancomycin, Penicillin and Cefotaxime was 100.0%, 100.0%, 37.5% and 25.0%, respectively.Five of the 7 cases treated with Meropenem had a fever 3 days later and then they took Linezolid as a replacement according to the drug sensitivity.One case was treated with Cefoperazone-Sulbactam.The duration time of fever, positive blood culture, agranulocytosis and course of antibiotics therapy was 1-19 d（10.4 d on average）, 4-22 d（13.4 d on average）, 10-30 d （21.6 d on average）, 9-26 d（18.3 d on average）, respectively.Among 3 patients with severe pneumonia, 1 patient received the respirator assisted ventilation for 1 week.Conclusions Streptococcus mitis is one of the major causes of severe infection among children with acute leukemia.Agranulocytosis after chemotherapy, stomatitis, exposure to PPI and antibiotics may be the risk factors for streptococcus mitis infection.Fever, stomatitis, respiratory and digestive symptoms are the common clinical manifestations.Streptococcus mitis is resistant to Penicillin and Cefotaxime, but sensitive to Linezolid, which can shorten the course of infection and improve the outcomes.Thus, Linezolid may serve as an optional therapy for streptococcemia mitis bacteriaemia.