
儿童急性淋巴细胞白血病诱导缓解期感染的病原菌及耐药情况分析
陈再生, 郑灵, 陈以乔, 杨景辉, 李健
中国当代儿科杂志 ›› 2017, Vol. 19 ›› Issue (2) : 176-181.
儿童急性淋巴细胞白血病诱导缓解期感染的病原菌及耐药情况分析
Pathogens of infections in the induction period of childhood acute lymphoblastic leukemia and drug resistance of isolated strains
目的 探讨儿童急性淋巴细胞白血病诱导缓解期感染的发生情况,以及病原菌特点及耐药情况,为诱导缓解期感染的预防和治疗提供依据。方法 回顾性分析130例初发儿童急性淋巴细胞白血病的临床资料,对诱导缓解期的感染情况、致病菌菌株及耐药菌谱进行分析。结果 临床感染和/或微生物感染发生率为76.2%,最常见的感染部位是肺部 (46.2%)。严重感染占52.3%,包括60例肺部感染和/或21例败血症。130例患儿中共检出病原菌50株,其中细菌29株、真菌21株,28.5%的患儿至少有1种微生物感染。细菌29株中G-菌19株 (65.5%)、G+菌10株 (34.5%)。最常见的G-菌为肺炎克雷伯菌、大肠埃希菌、铜绿假单胞菌,对亚胺培南100%敏感。最常见的G+菌为绿色链球菌,对万古霉素100%敏感。真菌占16.2%,以白色假丝酵母菌最常见。与非严重感染患儿相比,严重感染患儿粒细胞缺乏出现更早、持续时间更长,发热事件的比例和CRP更高,住院天数也更长,差异具有统计学意义 (P < 0.05)。结论 肺部感染是儿童急性淋巴细胞白血病诱导缓解期常见的感染;G-菌是最主要的病原菌。使用碳青霉烯类抗生素并适时联合万古霉素或抗真菌药能有效控制严重感染。
Objective To investigate the infections occurring in the induction period of childhood acute lymphoblastic leukemia (ALL), the pathogens of the infections, and drug resistance of isolated strains. Methods A retrospective analysis was performed for the clinical data of 130 children with newly-diagnosed childhood ALL. Infections occurring during the induction chemotherapy, pathogenic strains, and drug-resistance spectrum were analyzed. Results The incidence rate of clinical infection and/or microbial infection reached 76.2%. The lungs were the most common infection site (46.2%). The children with severe infection accounted for 52.3%, among whom 60 had pulmonary infection and/or 21 had sepsis. A total of 50 pathogenic strains were detected, which consisted of 29 bacterial strains and 21 fungal strains. Of all the children, 28.5% experienced infections caused by at least one microbe. Among the 29 bacterial strains, there were 19 (65.5%) Gram-negative bacteria and 10 (34.5%) Gram-positive bacteria. The most common Gram-negative bacteria were Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa, which were 100% sensitive to imipenem. The most common Gram-positive bacterium was Streptococcus viridans, which was 100% sensitive to vancomycin. The infections caused by fungi accounted for 16.2%, with Candida albicans as the most common fungus. Compared with those with non-severe infections, the children with severe infections had a significantly shorter time to the occurrence of agranulocytosis, a significantly longer duration of agranulocytosis,significantly higher incidence of fever and C-reactive protein (CRP) level, and a significantly longer length of hospital stay (P < 0.05). Conclusions Pulmonary infections are common in the induction period of childhood ALL. Gramnegative bacteria are the most common pathogenic bacteria. Severe infections can be controlled by carbapenems combined with vancomycin and antifungal agents.
Acute lymphoblastic leukemia / Induction period / Infection / Child
[1] Fisher BT,Sammons JS,Li Y,et al.Variation in risk of hospital-onset clostridium difficile infection across beta-lactam antibiotics in children with new-onset acute lymphoblastic leukemia[J].J Pediatric Infect Dis Soc,2014,3(4):329-335.
[2] Badiei Z,Khalesi M,Alami MH,et al.Risk factors associated with life-threatening infections in children with febrile neutropenia:a data mining approach[J].J Pediatr Hematol Oncol,2011,33(1):e9-e12.
[3] 中华医学会儿科学分会血液学组,《中华儿科杂志》编辑委员会.儿童急性淋巴细胞白血病诊疗建议(第四次修订)[J].中华儿科杂志,2014,52(9):645-644.
[4] Metkar SS,Froelich CJ.Human neutrophils lack granzyme A,granzyme B,and perforin[J].Blood,2004,104(3):905-906.
[5] Khurana M,Lee B,Feusner JH.Fever at diagnosis of pediatric acute lymphoblastic leukemia:are antibiotics really necessary[J].J Pediatr Hematol Oncol,2015,37(7):498-501.
[6] O'Connor D,Bate J,Wade R,et al.Infection-related mortality in children with acute lymphoblastic leukemia:an analysis of infectious deaths on UKALL2003[J].Blood,2014,124(7):1056-1061.
[7] Ma X,Urayama K,Chang J,et al.Infection and pediatric acute lymphoblastic leukemia[J].Blood Cells Mol Dis,2009,42(2):117-120.
[8] Li SD,Chen YB,Li ZG,et al.Infections during induction therapy of protocol CCLG-2008 in childhood acute lymphoblastic leukemia:a single-center experience with 256 cases in China[J].Chin Med J (Engl),2015,128(4):472-476.
[9] Afzal S,Ethier MC,Dupuis LL,et al.Risk factors for infectionrelated outcomes during induction therapy for childhood acute lymphoblastic leukemia[J].Pediatr Infect Dis J,2009,28(12):1064-1068.
[10] Ammann RA,Bodmer N,Hirt A,et al.Predicting adverse events in children with fever and chemotherapy-induced neutropenia:the prospective multicenter SPOG 2003 FN Study[J].J Clin Oncol,2010,28(12):2008-2014.
[11] 陈晓娟,邹尧,杨文钰,等.CCLG-ALL2008方案治疗儿童急性淋巴细胞白血病复发患儿的特征分析[J].中国当代儿科杂志,2015,17(4):321-326.
[12] Hatzistilianou M,Rekliti A,Athanassiadou F,et al.Procalcitonin as an early marker of bacterial infection in neutropenic febrile children with acute lymphoblastic leukemia[J].Inflamm Res,2010,59(5):339-347.
[13] Christ-Crain M,Jaccard-Stolz D,Bingisser R,et al.Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections:cluster-randomised,singleblinded intervention trial[J].Lancet,2004,363(9409):600-607.
[14] 史柳红,杨燕文,钱娟,等.血液系统恶性肿瘤合并脓毒症患儿的临床特点及死亡因素分析[J].临床儿科杂志,2012,30(1):10-14.
[15] Bothra M,Seth R,Kapil A,et al.Evaluation of predictors of adverse outcome in febrile neutropenic episodes in pediatric oncology patients[J].Indian J Pediatr,2013,80(4):297-302.
[16] Pokala HR,Leonard D,Cox J,et al.Association of hospital construction with the development of healthcare associated environmental mold infections (HAEMI) in pediatric patients with leukemia[J].Pediatr Blood Cancer,2014,61(2):276-280.
[17] 金玲,张永红.粒细胞减少伴发热患者的抗感染治疗[J].临床药物治疗杂志,2011,9(1):12-15.
[18] 白燕,金润铭,张志泉,等.恶性血液病患儿肺部真菌感染的诊疗体会[J].中国小儿血液与肿瘤杂志,2007,12(05):220-222.
国家和福建省临床重点专科建设项目资助。