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急性髓系白血病患儿门诊抗菌药物预防的可行性、疗效及不良反应

Feasibility, efficacy, and adverse effects of outpatient antibacterial prophylaxis in children with acute myeloid leukemia.

作者信息

Inaba Hiroto, Gaur Aditya H, Cao Xueyuan, Flynn Patricia M, Pounds Stanley B, Avutu Viswatej, Marszal Lindsay N, Howard Scott C, Pui Ching-Hon, Ribeiro Raul C, Hayden Randall T, Rubnitz Jeffrey E

机构信息

Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.

出版信息

Cancer. 2014 Jul 1;120(13):1985-92. doi: 10.1002/cncr.28688. Epub 2014 Mar 26.

Abstract

BACKGROUND

Intensive chemotherapy for pediatric acute myeloid leukemia incurs the risk of infectious complications, but the benefits of antibiotic prophylaxis remain unclear.

METHODS

In the current study, among 103 children treated on the AML02 protocol between October 2002 and October 2008 at St. Jude Children's Research Hospital, the authors retrospectively assessed the effect of antibiotic prophylaxis on the frequency of febrile neutropenia, clinically or microbiologically confirmed infections (including bacteremia), and antibiotic resistance, as well as on the results of nasal and rectal surveillance cultures. Initially, patients received no prophylaxis or oral cephalosporin (group A). The protocol was then amended to administer intravenous cefepime alone or intravenous vancomycin plus either oral cephalosporin, oral ciprofloxacin, or intravenous cefepime (group B).

RESULTS

There were 334 infectious episodes. Patients in group A had a significantly greater frequency of documented infections and bacteremia (both P < .0001) (including gram-positive and gram-negative bacteremia; P = .0003 and .001, respectively) compared with patients in group B, especially viridans streptococcal bacteremia (P = .001). The incidence of febrile neutropenia without documented infection was not found to be different between the 2 groups. Five cases of bacteremia with vancomycin-resistant enterococci (VRE) occurred in group B (vs none in group A), without related mortality. Two of these cases were preceded by positive VRE rectal surveillance cultures.

CONCLUSIONS

Outpatient intravenous antibiotic prophylaxis is feasible in children with acute myeloid leukemia and reduces the frequency of documented infection but not of febrile neutropenia. Despite the emergence of VRE bacteremia, the benefits favor antibiotic prophylaxis. Creative approaches to shorten the duration of prophylaxis and thereby minimize resistance should be explored.

摘要

背景

小儿急性髓系白血病强化化疗会引发感染并发症风险,但抗生素预防的益处仍不明确。

方法

在本研究中,作者回顾性评估了2002年10月至2008年10月在圣裘德儿童研究医院按照AML02方案治疗的103例儿童中,抗生素预防对发热性中性粒细胞减少症的发生频率、临床或微生物学确诊感染(包括菌血症)、抗生素耐药性以及鼻和直肠监测培养结果的影响。最初,患者未接受预防措施或口服头孢菌素(A组)。之后方案修订为单独给予静脉注射头孢吡肟或静脉注射万古霉素加口服头孢菌素、口服环丙沙星或静脉注射头孢吡肟(B组)。

结果

共发生334次感染发作。与B组患者相比,A组患者记录在案的感染和菌血症发生频率显著更高(均P < 0.0001)(包括革兰氏阳性和革兰氏阴性菌血症;分别为P = 0.0003和0.001),尤其是草绿色链球菌菌血症(P = 0.001)。两组间未发现有记录感染的发热性中性粒细胞减少症发生率存在差异。B组发生了5例耐万古霉素肠球菌(VRE)菌血症(A组无),无相关死亡病例。其中2例之前直肠VRE监测培养呈阳性。

结论

门诊静脉注射抗生素预防对急性髓系白血病儿童可行,可降低记录在案的感染频率,但不能降低发热性中性粒细胞减少症的频率。尽管出现了VRE菌血症,但抗生素预防的益处更大。应探索创新方法以缩短预防持续时间,从而尽量减少耐药性。

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