Childhood antibiotic use linked with appendicitis risk
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Use of antibiotics during childhood had a dose-dependent relationship with increased risk for appendicitis, according to study results.
“Genetic and environmental factors as well as pathologic alterations of the microbiota in the appendix have been identified as potential risk factors,” Jacob Antonsen, of the digestive disease center at Bispebjerg Hospital in Denmark, and colleagues wrote. “Several studies have shown an altered composition of the microbiota in specimens of appendicitis, but it remains unclear whether the microbial changes are a trigger or a consequence of appendicitis.”
Researchers performed a cohort study from 1995 to 2014 comprising 1,385,707 children who received 7,406,397 antibiotic prescriptions. The primary outcome of the study was appendicitis requiring appendectomy according to previous use of antibiotics.
In the study cohort, there were 11,861 cases of appendicitis.
Children who received at least one course of antibiotics were at increased risk for developing appendicitis compared with children who were not exposed to antibiotics (adjusted RR = 1.72; 95% CI, 1.61-1.85). The risk ratio increased by 1.04 per course of antibiotics.
Children exposed to antibiotics in the first 6 months of life (RR = 1.46; 95% CI, 1.36-1.56) and children exposed to broad-spectrum antibiotics (RR = 1.33; 95% CI, 1.27-1.39) had a higher risk for appendicitis. However, the association disappeared after researchers adjusted for number of antibiotic courses.
“This nationwide cohort study shows a dose-response relationship between antibiotic exposure and the development of appendicitis in childhood and adolescence,” Antonsen and colleagues wrote. “Further research will need to clarify whether antibiotics are causally involved in development of appendicitis or if some children are more prone to acquiring bacterial infections, including appendicitis, and therefore have a high exposure to antibiotics.”
Perspective
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Jacob A. Kurowski, MD
While rates of appendicitis have remained the same or decreased over the past few decades, it remains the most common emergent surgery in pediatrics. Identifying modifiable risk factors for developing appendicitis is important. The authors of this study have shown an increased risk of developing appendicitis, not just with one or two courses, but especially as four, five and six courses of antibiotics are given, the risk ratio of appendicitis goes up quite a bit, up to a two-fold increase once you get to seven courses. There are quite a few patients in this study who received five to seven courses. It is a very robust cohort. I also appreciate the authors for presenting biologic and sociologic theories about the increased risk, whether it is the change in the appendiceal microbiome after antibiotics or that seeking care for infections in and of itself may increase the likelihood of seeking care for abdominal pain resulting in increased diagnosis of appendicitis.
Overall, the study lends credence to the idea of microbial stewardship. We need to improve stewardship in our emergency departments, in our front-line workers and our primary care doctors who might prescribe antibiotics to kids. If someone has a clear-cut case of bacterial infection, then antibiotics should be used. However, there are many times where we see less than ideal judgment, and antibiotics are given for a red ear or when there is a fever. There can be a lot of pressure on the provider to prescribe something because the child has been brought into the doctor’s office. Parents are well intentioned and want their kids to get better, but much of this is a viral infection that will run its course in childhood. This study is more evidence that overuse of antibiotics can have unintended consequences.
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