Low Risk of Hemolytic Uremic Syndrome after Early Effective Antimicrobial Therapy for Shigella dysenteriae Type 1 Infection in Bangladesh

Abstract

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.