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

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.

Do asymptomatic STEC-long-term carriers need to be isolated or decolonized? New evidence from a community case study and concepts in favor of an individualized strategy

“…This approach appeared safe, since no HUS-related clinical or laboratory deterioration occurred. In contrast to these findings in asymptomatic long-term carriers, antibiotics are generally discouraged during STEC-related acute bloody diarrhea (12)(13)(14). In vitro, Stx production is boosted by sub-inhibitory concentrations of specific antibiotics.…”

“…This is plausible, as both antibiotics, targeting DNA-synthesis, induce the bacterial SOS stress response to DNA damage, which is linked to an increase in phage production and toxin release (24)(25)(26). Additionally, a retrospective analysis from the US FoodNet surveillance recently reported an augmented risk of HUS among children and adults with O157 diarrhea treated with β-lactams (14). For other strains, data were conflicting and hardly comparable due to different antibiotics at variable doses and variable susceptibility profiles.…”

“…However, the application of antibiotics to clinically asymptomatic persons always needs appropriate justification. Moreover, antibiotic therapy is commonly discouraged in STEC-disease (12)(13)(14), since some reports have raised concerns about an inherent potential of some antibiotics to enhance Stx release and thus HUS development mainly in STEC O157.…”

Overview of Side-Effects of Antibacterial Fluoroquinolones: New Drugs versus Old Drugs, a Step Forward in the Safety Profile?

“…In clinical studies, FQs therapy leads to beneficial results, although unfavorable results were reported in in vitro studies. Recently, Mody et al [ 392 ] suggested that the assessed antimicrobial classes for treating O157 diarrhea should be avoided, especially β-lactams, which increased the odds of the hemolytic-uremic syndrome. Targeted classes of antibiotics were β-lactams, FQs, nitroimidazoles (metronidazole), macrolides, and sulfonamides (sulfamethoxazole-trimethoprim).…”

“…Additionally, the increased number of fluorine atoms could be responsible, but it is still an unfounded hypothesis [ 100 ]. In patients with Escherichia coli -associated diarrhea treated with antibiotics associated with the hemolytic-uremic syndrome, production and the release of toxic seems to be the primary mechanism [ 392 ].…”