Gillian A M Tarr1, Hanna N Oltean2, Amanda I Phipps3, Peter Rabinowitz4, Phillip I Tarr5. 1. Department of Epidemiology, University of Washington, Box 357236, Seattle, Washington, 98195, USA. Electronic address: gillian.tarr@ahs.ca. 2. Washington State Department of Health, 1610 NE 150th St., Shoreline, Washington, 98155, USA. Electronic address: Hanna.Oltean@doh.wa.gov. 3. Department of Epidemiology, University of Washington, Box 357236, Seattle, Washington, 98195, USA. Electronic address: aiphipps@uw.edu. 4. Department of Environmental and Occupational Health Sciences and Center for One Health Research, University of Washington, Box 357234, Seattle, Washington, 98195, USA. Electronic address: peterr7@uw.edu. 5. Department of Pediatrics, Washington University in St. Louis School of Medicine, One Children's Place, St. Louis, Missouri, 63110, USA. Electronic address: tarr@wustl.edu.
Abstract
BACKGROUND: The veracity of the association between antibiotic use and hemolytic uremic syndrome (HUS) caused by Escherichia coli O157:H7 has been a topic of debate. We postulated that criteria used to define HUS affect this association. METHODS: We reviewed 471 hospitalized E. coli O157:H7 cases reported in Washington State, 2005-2014, to determine HUS status by various case definitions and antibiotic treatment. We used age-adjusted logistic regression models to estimate the effect of treatment on HUS status according to four common, but heterogeneous, definitions: the Council of State and Territorial Epidemiologists (CSTE) definition, hematology-focused and age-focused definitions from the literature, and hospital diagnosis. RESULTS: Inter-annual variation in antibiotic use was high, but no meaningful change in antibiotic use was observed over this ten-year period. Thirteen percent of cases <18 years-old received antibiotics, compared to 54% of cases ≥18 years-old. The CSTE, hematology-focused, age-focused, and hospital diagnosis definitions identified 149, 57, 74, and 89 cases of HUS, respectively. The association between antibiotic treatment and HUS varied by definition: CSTE odds ratio (OR) 1.57 [95% confidence interval (CI) 0.98, 2.55]; hematology-focused OR 1.73 (95% CI 0.83, 3.54); age-focused OR 2.29 (95% CI 1.20, 4.39); and hospital diagnosis OR 1.94 (95% CI 1.01, 3.72). CONCLUSIONS: Each definition yielded an estimate of the association in the direction of increased risk of HUS with antibiotics. While the range of OR point estimates was relatively small, confidence intervals for two HUS definitions crossed the null and two did not, potentially altering the inference an investigator makes. Discrepant reports of the association between antibiotic use and HUS in the literature might be due in part to the choice of HUS definition, and a consistent definition of HUS should be adopted for research and public health purposes.
BACKGROUND: The veracity of the association between antibiotic use and hemolytic uremic syndrome (HUS) caused by Escherichia coli O157:H7 has been a topic of debate. We postulated that criteria used to define HUS affect this association. METHODS: We reviewed 471 hospitalized E. coli O157:H7 cases reported in Washington State, 2005-2014, to determine HUS status by various case definitions and antibiotic treatment. We used age-adjusted logistic regression models to estimate the effect of treatment on HUS status according to four common, but heterogeneous, definitions: the Council of State and Territorial Epidemiologists (CSTE) definition, hematology-focused and age-focused definitions from the literature, and hospital diagnosis. RESULTS: Inter-annual variation in antibiotic use was high, but no meaningful change in antibiotic use was observed over this ten-year period. Thirteen percent of cases <18 years-old received antibiotics, compared to 54% of cases ≥18 years-old. The CSTE, hematology-focused, age-focused, and hospital diagnosis definitions identified 149, 57, 74, and 89 cases of HUS, respectively. The association between antibiotic treatment and HUS varied by definition: CSTE odds ratio (OR) 1.57 [95% confidence interval (CI) 0.98, 2.55]; hematology-focused OR 1.73 (95% CI 0.83, 3.54); age-focused OR 2.29 (95% CI 1.20, 4.39); and hospital diagnosis OR 1.94 (95% CI 1.01, 3.72). CONCLUSIONS: Each definition yielded an estimate of the association in the direction of increased risk of HUS with antibiotics. While the range of OR point estimates was relatively small, confidence intervals for two HUS definitions crossed the null and two did not, potentially altering the inference an investigator makes. Discrepant reports of the association between antibiotic use and HUS in the literature might be due in part to the choice of HUS definition, and a consistent definition of HUS should be adopted for research and public health purposes.
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