Tip of the Iceberg: Understanding the Unintended Consequences of Antibiotics.

Preventing the development of antibiotic resistance is 1 of the primary goals of antimicrobial stewardship. The overuse of antibiotics directly contributes to the development of resistant pathogens, and the emergence of bacterial resistance is a public health threat associated with significant morbidity and mortality. However, bacterial resistance is not the only unintended consequence of antibiotic overuse. Alterations in the intestinal flora can result in an immune misbalance leading to immune dysregulation and inflammation. Because antibiotic exposure results in significant intestinal dysbiosis, the relationship between antibiotic use and the development of chronic diseases has been investigated, with some convincing evidence directly associating antibiotic exposure with obesity and inflammatory bowel disease. In this issue of Pediatrics, Horton et al evaluated the association between antibiotic exposure and a new diagnosis of juvenile idiopathic arthritis (JIA) in children aged 1 to 15 years. The authors performed a nested case–control study by using a UK population-representative medical records database. Each case of newly diagnosed JIA was compared with 10 ageand gender-matched control subjects. Antibiotic exposure was found to be associated with an increased risk of developing JIA, and the magnitude of the association increased with additional antibiotic courses. These findings remained significant after adjusting for confounders, including infection. In an effort to minimize the potential bias in which antibiotics would have been prescribed for symptoms associated with the early manifestations of JIA, the authors used the first joint symptom or referral to rheumatology as the index date of JIA onset. Secondary analysis revealed no difference among antibiotics with or without anaerobic activity. When the authors focused specifically on the diagnosis of upper respiratory tract infections (URIs), they found that antibiotic-treated URIs were more strongly associated with the development of JIA compared with untreated URIs. The authors concluded that antibiotics could potentially be a modifiable risk factor for JIA, and overprescribing of antibiotics may be unnecessarily placing some children at risk for the development of JIA.