Introduction
Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease with unknown causes. Patients experience periods with active disease and symptoms such as diarrhoea, pain and weight loss. Little is known about environmental factors that trigger flare-ups, including the effects of commonly used medications. Recent studies suggest a link between microbial factors and IBD, making it important to investigate the impact of antibiotics on flare-ups.
Aims & Methods
We aimed to investigate whether certain antibiotics increase the risk of flares in patients with IBD. We utilized a previously described1 cohort of all patients with IBD in Denmark between 1974 and 2018. The cohort is based on the Danish Nationwide Patient Registry, which registers all healthcare related visits, treatments and procedure on an individual level. We utilized data between 1994 and 2018 and two distinct cohorts was created for the purpose of identifying flares. The first cohort was characterized by having an IBD-related hospital stay. The second cohort was characterized by experiencing a flare of IBD in need of systemic steroids. Patient were matched 1:5 using K-nearest neighbour. Antibiotics were grouped into the 3rd level of the Anatomical Therapeutic Chemical (ATC) classification system, with anthelmintics grouped into the 2nd level due to low numbers and all given within 60 days before the outcome. Logistic regression analysis was used to calculate odds ratios (ORs) with a 95% confidence interval (95% CI), with adjusting variables including year of remission/flare, sex, age at diagnosis, year of diagnosis, type of IBD, socioeconomic status2, use of 5-ASA, use of budesonide, use of immunosuppressants, and use of subtypes of biologics.
Results
There were in total 69,908 IBD patients in the original cohort. After applying the abovementioned algorithm, a total of 15,636 and 5,178 patients were included in the cohort for hospitalisation and steroid use, respectively.
Using a multivariate logistic regression model, both cohorts observed a significant increase in odds ratios for certain antibiotics in relation to hospitalization and steroid course. Specifically, for the need of a course of steroids, quinolones (OR 3.83 (95% CI: 2.73-5.35)), antimycotics (OR 2.30 (95% CI: 1.53-3.40)), agents against amoebiasis and protozoal (OR 2.06 (95% CI: 1.39-3.01)), betalactam antibiotics (OR 1.35 (95% CI: 1.10-1.66)), and intestinal anti-infectives (OR 2.12 (95% CI: 1.08-3.98)) were associated with an increased risk for a flare requiring steroids.
Regarding the need for an IBD-related hospitalization, agents against amoebiasis and protozoal (OR 3.48 (95% CI: 2.72-4.44)), quinolones (OR 3.10 (95% CI: 2.48-3.86)), intestinal anti-infectives (OR 2.42 (95% CI: 1.54-3.76)) and antimycotics (OR 1.58 (95% CI: 1.17-2.12)) were all found to be significantly associated.
Conclusion
This study provides evidence that certain types of antibiotics increase the risk of flare-ups in patients with IBD. Quinolones, antimycotics, agents against amoebiasis and protozoal, betalactam, and intestinal anti-infectives were all associated with increased odds ratios for hospitalization and a need for a course of steroids. These findings highlight the importance of carefully considering the use of antibiotics in IBD patients and the need for further research on the effects of different antibiotics on disease progression.
References
1 Lo B, Zhao M, Burisch J. Identifying patients with inflammatory bowel disease in the Danish National Patient Register. Dan Med J. 2023 Mar 27;70(4):A07220458. PMID: 36999818.
2 https://www.dst.dk/en/Statistik/dokumentation/nomenklaturer/socio
Disclosure
An unrestricted grant was received from the Aage og Johanne Louis-Hansens Fond to support this study.
