多黏菌素B治疗儿童重症耐碳青霉烯革兰阴性杆菌感染用药分析

doi:10.12372/jcp.2023.22e1184

摘要/Abstract

摘要：

目的评价多黏菌素B治疗儿童耐碳青霉烯类革兰阴性杆菌（CRGNB）感染的疗效和安全性。方法回顾性分析2020年7月—2021年12月儿科重症监护病房收治确诊或高度怀疑CRGNB感染并使用多黏菌素B抗感染患儿的临床资料。结果纳入20例CRGNB患儿，男11例、女9例，中位年龄为3.4（0.6~8.9）岁，12例治愈，1例死亡。基础疾病以血液肿瘤系统疾病最多（30.0%）。感染标本检出主要为深部痰液或肺泡灌洗液（75.0%），其次为血液（10.0%）。耐碳青霉烯肺炎克雷伯菌为最常分离的微生物（35.0%，7/20），其次为耐碳青霉烯铜绿假单胞菌（30%，6/20）；另有4例为多种CRGNB混合感染。所有患儿均采用多黏菌素B联合用药方式，以美罗培南为主（9例，45.0%），20例患儿均未观察到毒副反应。存在下呼吸道感染的15例患儿中，与单纯多黏菌素B静脉注射用药相比，增加局部雾化用药患儿的治愈率更高（P=0.002）。结论多黏菌素B治疗儿童CRGNB感染的疗效和安全性值得肯定，但目前亟需更多、更大规模的临床研究做进一步探索和评估。

关键词: 多重耐药, 耐碳青霉烯革兰阴性杆菌, 多黏菌素B, 儿科重症监护病房

Abstract:

Objective To evaluate the efficacy and safety of polymyxin B in the treatment of carbapenem-resistant Gram-negative bacteria (CRGNB) infection in children. Methods From July 2020 to December 2021, 32 cases of carbapenem-resistant Gram-negative bacteria infection in PICU with using polymyxin B were retrospectively analysed. Results 20 patients enrolled in the retrospective cohort, 11 males and 9 females, with a median age of 3.4 (0.6-8.9) years; 12 were cured and 1 died. The underlying diseases were most frequently haemato-oncological system diseases (30.0%). Infection specimens from 20 patients were mainly detected in sputum or bronchoalveolar lavage fluid (75%), followed by blood (10%). Carbapenem-resistant Klebsiella pneumoniae was the most frequently isolated organism (35.0%, 7/20), followed by carbapenem-resistant Pseudomonas aeruginosa with 30% (6/20). Another 4 cases were mixed infection of multiple carbapenem-resistant Gram-negative bacilli.. All children were treated with a polymyxin B combination, with meropenem as the mainstay (9 cases, 45.0%), and no adverse reactions were observed in 20 cases. Of the 15 children with lower respiratory tract infections, a higher cure rate was observed in children with the addition of topical nebulisation compared to the intravenous administration of polymyxin B alone (P=0.002).Conclusion The efficacy and safety of polymyxin B in the treatment of severe carbapenem-resistant Gram-negative bacterial infection in children is worthy of affirmation. However, more and large-scale clinical studies are urgently needed for further exploration and evaluation..

Key words: multi-drug resistance, carbapenem-resistant Gram-negative bacterial, polymyxin B, pediatric intensive care unit

林良康, 刘忠强, 乔莉娜, 李德渊, 张海洋. 多黏菌素B治疗儿童重症耐碳青霉烯革兰阴性杆菌感染用药分析[J]. 临床儿科杂志, 2023, 41(8): 578-583.

LIN Liangkang, LIU Zhongqiang, QIAO Lina, LI Deyuan, ZHANG Haiyang. Drug analysis of polymyxin B in the treatment of severe carbapenem-resistant Gram-negative bacteria infection in children[J]. Journal of Clinical Pediatrics, 2023, 41(8): 578-583.

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项目	数值
年龄[M(P₂₅~P₇₅)]/岁	3.4（0.6~8.9）
体重[M(P₂₅~P₇₅)]/kg	12.5（6.6~35.0）
男性[n(%)]	11（55.0）
基础疾病[n(%)]
中枢神经系统	1（5.0）
呼吸系统	2（10.0）
血液肿瘤系统	6（30.0）
肾脏/泌尿系统	1（5.0）
消化系统	3（15.0）
皮肤	1（5.0）
外伤	2（10.0)
其他	4（20.0）
感染标本来源[n(%)]
深部痰液/肺泡灌洗液	15（75.0）
血液	2（10.0）
皮肤表面分泌物	1（5.0）
脑脊液	1（5.0）
尿液	1（5.0）
静脉注射多黏菌素B持续时间[M(P₂₅~P₇₅)]/d	14.0（14.0~19.8）
静脉注射多黏菌素B剂量 ($\bar{x} \pm s$)/mg·kg^-1，q12h
负荷剂量	2.4±0.5
维持剂量	1.6±0.3
联合用药选择[n(%)]
美罗培南	9（45.0）
替加环素	4（20.0）
左氧氟沙星	3（15.0）
头孢哌酮舒巴坦	3（15.0）
哌拉西林他唑巴坦	1（5.0）
小儿危重病例评分($\bar{x} \pm s$)	62.0±1.5
不良反应[n(%)]
肾毒性	0（0）
神经毒性	0（0）
色素沉着	0（0）
结局[n(%)]
治愈	12（60.0）
有效	3（15.0）
放弃	4（20.0）
无效	1（5.0）

微生物	数值[n(%)]
单一菌株
CREC	1（5.0）
CRPA	6（30.0）
CRKP	7（35.0）
CRAB	1（5.0）
多重菌株
CRKP+CRAB	1（5.0）
CRPA+CRAB	1（5.0）
CRPA+CRKP+CRAB	2（10.0）
不明病原体经验用药	1（5.0）

药物	MIC/mg·L^-1	药敏	数值[n(%)]
多黏菌素B
	2	敏感	2（10.0）
	1	敏感	5（25.0）
	≤0.5	敏感	13（65.0）
替加环素
	>8	耐药	6（30.0）
	2	敏感	4（20.0）
	1	敏感	4（20.0）
	≤0.5	敏感	6（30.0）
碳青霉烯类
	<8	敏感	0（0）
	8~16	耐药	3（15.0）
	≥16	耐药	17（85.0）

项目	单纯静脉注射组(n=6)	静脉联合雾化组(n=9)	统计量	P
治疗时间[M(P₂₅~P₇₅)]/d	14.0（14.0~15.5）	16.0（14.0~21.0）	Z=0.94	0.349
不良反应[n(%)]	0（0）	0（0）	-	-
结局[n(%)]			-	0.002¹⁾
治愈	1（16.7）	9（100）
有效	3（50.0）	0（0）
放弃	1（16.7）	0（0）
无效	1（16.7）	0（0）