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Specific Antibiotics Increase the Risk of Flare-Ups in Patients with Inflammatory Bowel Disease: Results from a
Bobby Lo1,2, Luc Biederman3, Gerhard Rogler3
1Gastro Unit, Medical Section, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark.
Introduction:
Inflammatory bowel disease [IBD] patients have a relapsing-remitting disease course, and amongst environmental factors that aggravate the disease course, common drugs aside from non-steroidal anti-inflammatory drugs have not been studied in detail. While the microbiome is considered to play a significant role on the disease course, the impact of antibiotics is poorly understood. This study investigated the potential impact of different classes of antibiotics on the course of disease in IBD using the Danish National Patient Registry.
Methods:
Danish IBD patients were studied using two nested case-control cohorts exploring associations between antibiotic types and IBD flare-ups, defined as IBD-related hospitalizations and/or high-dose systemic steroid exposure. Multivariate logistic regression and eXtreme Gradient Boosted decision tree [GBDT] machine learning methods evaluated antibiotic risks.
Results:
Two cohorts with 15 636 and 5178 patients were analysed for risk of hospitalization and course of steroids, respectively. The risk of a flare-up was significantly increased with antecedent exposure to quinolones (ATC:J01M; odds ratio [OR]: 3.04-3.82), antimycotics [ATC:J02A; OR: 1.50-2.30], agents against amoebiasis and protozoal infections [ATC:P01A; OR: 1.95-3.18], intestinal anti-infectives [ATC:A07A; OR: 2.09-2.32], and beta-lactam antibiotics [ATC:J01C; OR: 1.36]. The GBDT models achieved an area under the curve of 0.71-0.85 for predicting flare-ups, with the same above-mentioned antibiotics being in the ten most important variables.
Conclusion:
We found distinctive antibiotics to be significantly associated with an increased risk of IBD flare-ups. Our findings are corroborated by our GBDT machine learning models. Healthcare providers should be aware of the deleterious potential of specific antibiotic groups in patients with IBD only using these agents in a restrictive manner or preferentially consider alternative antibiotic groups.
Insights
Certain antibiotics significantly increase the risk of flare-ups in inflammatory bowel disease (IBD) patients. Healthcare providers should use these specific antibiotic classes cautiously in IBD management.
Area of Science:
- Gastroenterology
- Pharmacology
- Microbiome Research
Background:
- Inflammatory bowel disease (IBD) is characterized by a relapsing-remitting course.
- Environmental factors influencing IBD exacerbations are not fully understood, particularly the role of common medications beyond NSAIDs.
- The impact of antibiotic use on IBD disease activity remains poorly elucidated.
Purpose of the Study:
- To investigate the association between different classes of antibiotics and the risk of disease flare-ups in patients with IBD.
- To identify specific antibiotic types that may exacerbate IBD activity.
Main Methods:
- A nested case-control study design was employed using the Danish National Patient Registry.
- Two cohorts analyzed IBD flare-ups, defined by IBD-related hospitalizations or high-dose systemic steroid use.
- Multivariate logistic regression and Gradient Boosted Decision Tree (GBDT) machine learning models were utilized to assess antibiotic risks.
Main Results:
- Analysis of 15,636 patients revealed increased flare-up risk associated with quinolones, antimycotics, anti-protozoal agents, intestinal anti-infectives, and beta-lactam antibiotics.
- Odds ratios for increased flare-up risk ranged from 1.36 to 3.82 depending on the antibiotic class.
- GBDT models demonstrated strong predictive performance (AUC 0.71-0.85) and identified these antibiotic classes among the most significant variables.
Conclusions:
- Specific antibiotic classes are significantly linked to an elevated risk of IBD flare-ups.
- Findings were validated by machine learning models, highlighting the potential adverse effects of certain antibiotics in IBD patients.
- Clinicians should exercise caution when prescribing these antibiotics to IBD patients, considering alternatives or restrictive use.
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