Bennish Michael L, Khan Wasif A, Begum Monira, Bridges Emily A, Ahmed Sabeena, Saha Debasish, Salam Mohammad A, Acheson David, Ryan Edward T
Africa Centre for Health and Population Studies, Mtubatuba, South Africa.
Clin Infect Dis. 2006 Feb 1;42(3):356-62. doi: 10.1086/499236. Epub 2005 Dec 21.
Hemolytic uremic syndrome (HUS) may complicate up to 15% of cases of Shiga toxin (Stx)-expressing enterohemorrhagic Escherichia coli (STEC) O157:H7 infections in children. Administration of antimicrobials has been reported to increase the risk of STEC-associated HUS by >10-fold, presumably by increasing the expression and release of Stx by dying STEC bacteria. Shigella dysenteriae type 1 also expresses Stx. However, the effect of antimicrobial therapy on Stx release and the risk of HUS in humans is unknown.
We measured serial stool Stx concentrations before and after administration of antimicrobials in 20 children infected with S. dysenteriae type 1 who had frank dysentery of <72 h duration. We also reviewed the results of 7 shigellosis drug trials performed in Bangladesh during 1988-2000 to estimate the risk of HUS. In these studies, antimicrobials were administered within 96 h after the onset of dysentery.
Stx levels decreased in stool samples obtained from 17 of 20 children after administration of antimicrobial agents; none of the 20 children developed HUS. Of 378 individuals infected with S. dysenteriae type 1 who were enrolled in drug trials (128 adult men [age, 18-60 years] and 250 children [age, 6 months to 15 years]), 351 (93%) received an antimicrobial agent to which the S. dysenteriae organism was susceptible <or=96 h after the onset of symptoms; HUS developed in 1 child. The risk of developing HUS was 0.0026 for all participants (95% confidence interval, <0.001 to 0.015) and was 0.004 for children (95% confidence interval, 0.001-0.022).
In persons infected with S. dysenteriae type 1, early administration of effective antibiotics is associated with decreased Stx concentrations in stool and a low risk of developing HUS.
溶血性尿毒综合征(HUS)可能使高达15%的儿童志贺毒素(Stx)表达性肠出血性大肠杆菌(STEC)O157:H7感染病例出现并发症。据报道,使用抗菌药物会使STEC相关HUS的风险增加10倍以上,推测是通过增加濒死STEC细菌的Stx表达和释放。痢疾志贺菌1型也表达Stx。然而,抗菌治疗对人类Stx释放及HUS风险的影响尚不清楚。
我们测量了20名感染痢疾志贺菌1型且患急性痢疾病程小于72小时的儿童在使用抗菌药物前后的系列粪便Stx浓度。我们还回顾了1988 - 2000年在孟加拉国进行的7项志贺菌病药物试验结果,以评估HUS风险。在这些研究中,抗菌药物在痢疾发作后96小时内给予。
20名儿童中有17名在使用抗菌药物后粪便样本中的Stx水平下降;这20名儿童均未发生HUS。在参与药物试验的378名感染痢疾志贺菌1型的个体(128名成年男性[年龄18 - 60岁]和250名儿童[年龄6个月至15岁])中,351名(93%)在症状发作后≤96小时接受了痢疾志贺菌对其敏感的抗菌药物治疗;1名儿童发生了HUS。所有参与者发生HUS的风险为0.0026(95%置信区间,<0.001至0.015),儿童为0.004(95%置信区间,0.001 - 0.022)。
在感染痢疾志贺菌1型的人群中,早期给予有效的抗生素与粪便中Stx浓度降低及发生HUS的低风险相关。