Risk of Hemolytic Uremic Syndrome Related to Treatment of Escherichia coli O157 Infection with Different Antimicrobial Classes.

Rajal K Mody,Paula Clogher,Katie Wymore,John Dunn,Sarah Lathrop,Melissa Tobin-D’Angelo,Kirk Smith,Beletshachew Shiferaw,Nicole Comstock,Sharon Hurd,Amanda Palmer,Patricia M Griffin,Magdalena Kendall Scott,Kari Burzlaff,Robert M Hoekstra

doi:10.3390/microorganisms9091997

Abstract

Treatment of Shiga toxin-producing Escherichia coli O157 (O157) diarrhea with antimicrobials might alter the risk of hemolytic uremic syndrome (HUS). However, full characterization of which antimicrobials might affect risk is lacking, particularly among adults. To inform clinical management, we conducted a case-control study of residents of the FoodNet surveillance areas with O157 diarrhea during a 4-year period to assess antimicrobial class-specific associations with HUS among persons with O157 diarrhea. We collected data from medical records and patient interviews. We measured associations between treatment with agents in specific antimicrobial classes during the first week of diarrhea and development of HUS, adjusting for age and illness severity. We enrolled 1308 patients; 102 (7.8%) developed confirmed HUS. Antimicrobial treatment varied by age: <5 years (12.6%), 5–14 (11.5%), 15–39 (45.4%), ≥40 (53.4%). Persons treated with a β-lactam had higher odds of developing HUS (OR 2.80, CI 1.14–6.89). None of the few persons treated with a macrolide developed HUS, but the protective association was not statistically significant. Exposure to “any antimicrobial” was not associated with increased odds of HUS. Our findings confirm the risk of β-lactams among children with O157 diarrhea and extends it to adults. We observed a high frequency of inappropriate antimicrobial treatment among adults. Our data suggest that antimicrobial classes differ in the magnitude of risk for persons with O157 diarrhea.

Highlights

IntroductionAntimicrobials differ by class in their ability to induce these mechanisms [6,7,8,9,10,11,12]
We have reported on a very large, population-based, observational study designed to assess the association between treatment of O157 diarrhea with agents in specific antimicrobial classes and the development of hemolytic uremic syndrome (HUS) among patients of all ages
Our findings strongly suggest that the magnitude of risk varies by antimicrobial class

Summary

Introduction

Antimicrobials differ by class in their ability to induce these mechanisms [6,7,8,9,10,11,12] Definitive proof of this risk has been elusive. Randomized controlled trials have been considered too dangerous and difficult because events leading to HUS have often started by the time a diagnosis is made. This leaves data from observational studies, which are hampered by the fact that sicker patients are probably both more likely to receive antimicrobials and to develop HUS. Variation in antimicrobial classes, dosing, and timing limits the ability of observational studies to accurately assess risk

Methods

Results

Conclusion