SAN FRANCISCO – Treatment of Shiga toxin–producing Escherichia coli 0157 infection with beta-lactams is associated with increased risk for postdiarrheal hemolytic uremic syndrome in both children and adults, according to findings from a population-based study.
Beta-lactam antibiotics are particularly troublesome in this setting, the findings suggest.
Among 1,308 patients with the infection, known as STEC 0157 – the leading cause of postdiarrheal hemolytic uremic syndrome (HUS) in the United States – 137 had HUS, and 44 had partial HUS, Dr. Melissa Tobin-D’Angelo reported at an annual scientific meeting on infectious diseases.
Up to 15% of patients with STEC 0157 diarrhea develop HUS, which comprises microangiopathic hemolytic anemia, acute azotemia, and thrombocytopenia, said Dr. Tobin-D’Angelo of the Georgia Department of Public Health, Atlanta.
Generally in this observational study, antibiotic treatment was used more commonly and HUS occurred less frequently with increasing age quartile. Among those under age 5 years, 12% received antibiotics and 22% had HUS; among those aged 5-14 years, 11% received antibiotics and 11% had HUS; among those aged 15-39 years, 45% received antibiotics and 5% had HUS; and among those aged 40 years or older, 52% received antibiotics and 4% had HUS.
Adults aged 40 and older were more likely than were those in all other age groups to receive beta-lactam antibiotics (8% vs. 4%) or metronidazole (31% vs. 11%), while children under age 15 years were more likely than were others to receive sulfonamides (5% vs. 1%), Dr. Tobin-D’Angelo reported at the conference, the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
No overall association was seen between antibiotic treatment and HUS, but among children aged 5-14 years, treatment with any antibiotic and treatment with metronidazole were significantly associated with HUS (odds ratios, 2.6 and 4.0, respectively). Also, among all subjects, beta-lactam antibiotics and sulfonamides were associated with at least partial HUS (odds ratios, 2.9 and 2.2, respectively), she noted.
Study subjects were patients with STEC 0157 identified through active, population-based surveillance in 10 states during 2006-2010. Patients or caregivers were interviewed, and data were extracted from medical records. Only antibiotic exposures during the first 7 days of illness or before HUS onset were included in the analysis.
"Controversy remains regarding antibiotic treatment of STEC 0157 and its possible association with an increased risk of HUS; antibiotics increase Shiga toxin production and release in vitro, but this varies by antibiotic class and dose, and it has varied by study," Dr. Tobin-D’Angelo said. Although observational studies have suggested that antibiotics increase the risk for HUS, those studies included only children and were limited by difficulties in controlling for the confounding effects of illness severity, she added.
The only randomized controlled trial was limited to trimethoprim-sulfamethoxazole, she noted.
The findings of the current study suggest that adults are considerably more likely than are children to receive antibiotics for the treatment of STEC 0157 diarrhea, and – as with prior findings in children – suggest that treatment with beta-lactams is associated with increased HUS risk in both children and adults, she said.
"We recommend that beta-lactams should not be prescribed to any patient of any age with known STEC 0157 infection and that clinicians should consider the risk of HUS when prescribing beta-lactams to any patients with diarrhea that could be caused by STEC 0157," she said. It is also prudent to avoid the use of other antibiotics for the treatment of STEC 0157 diarrhea because of evidence of increased HUS risk from other studies, and because of the lack of data demonstrating any therapeutic benefit, she added.
The conference was the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. Dr. Tobin-D’Angelo reported having no disclosures.