Hostname: page-component-586b7cd67f-t7czq Total loading time: 0 Render date: 2024-11-27T14:49:24.329Z Has data issue: false hasContentIssue false

Metronidazole overexposure in children and its association with new-onset Crohn’s disease (IBD)

Published online by Cambridge University Press:  14 February 2024

Mudassir Nisar
Affiliation:
Department of Medicine, Services Institute of Medical Sciences, Lahore, Punjab, Pakistan
Hamza Ashraf
Affiliation:
Department of Medicine, Allama Iqbal Medical College, Lahore, Punjab, Pakistan
Haider Ashfaq*
Affiliation:
Department of Medicine, Allama Iqbal Medical College, Lahore, Punjab, Pakistan
*
Corresponding author: Haider Ashfaq; Email: [email protected]

Abstract

Type
Concise Communication
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.
Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of The Society for Healthcare Epidemiology of America

Metronidazole is an antibiotic and an antiprotozoal medication, and it is administered independently or in conjunction with other antibiotics to treat infections affecting different body parts, including the reproductive system, gastrointestinal tract, nervous system, and more, with some major observed symptoms of diarrhea and vaginal or urethral discharge. Its primary mode of action is to inhibit bacterial growth. The direct link between its mechanism of action and its association with new-onset Crohn’s disease (CD) is an area of active research. It might result from the complex interplay of genetic and environmental factors and the gut microbiome. In a cross-sectional study conducted in Pakistan, it was found that metronidazole ranked as the second most frequently self-administered antibiotic, with a utilization rate of 35.20%. Reference Aslam, Zin and Jamshed1 This highlights the extensive over-the-counter use of this antibiotic for the treatment of various infections and is primarily attributed to a lack of proper diagnosis and reliance on self-prescription instead of seeking guidance from healthcare professionals and laboratories.

According to a meta-analysis, the use of antibiotics in children, specifically metronidazole, was associated with an increased risk of inflammatory bowel disease (IBD), particularly CD (OR: 5.01; 95% CI: 1.65–15.25). Reference Ungaro, Bernstein and Gearry2 This risk was more pronounced when the antibiotic was taken during the 24 months preceding the index date. The correlation between CD and the use of antibiotics was more pronounced in boys than in girls (P = .01). Reference Virta, Auvinen, Helenius, Huovinen and Kolho3 Also, in a case–control analysis aimed at investigating the potential link between antibiotic usage 2–5 years prior to diagnosis and the development of IBD, it was observed that a somewhat stronger association was present, especially in cases of CD with ≥1 and ≥2 instances of antibiotic dispensation. Reference Shaw, Blanchard and Bernstein4 Another nation-wide study in Denmark from 1995 to 2018 showed that exposure to oral antibiotics within the initial 5 years of life was linked to an elevated risk of developing pediatric inflammatory bowel disease (PIBD) (hazard ratio [HR] = 1.33 with a 95% confidence interval [CI] of 1.2–1.5, P < .0001). Additionally, the risk was heightened when patients had received four or more antibiotic prescriptions as opposed to having no antibiotics (HR = 1.33 with a 95% CI of 1.2–1.5, P < .0001). Reference Jawad, Jansson, Wewer and Malham5 These figures and associations clearly depict that there is an increased risk of CD in infants and young children who are overexposed to antibiotics, specifically metronidazole, which is the most commonly used medication for diarrhea and dysentery.

Based on these investigations, it can be clearly concluded that new-onset CD due to overexposure to metronidazole in children is a critical aspect of pediatric healthcare. Hence, it is important for both medical practitioners and the general public to be aware of the potential harmful side effects of metronidazole usage, especially in children. Healthcare professionals should play a vital role in educating patients, offering counseling, and ensuring the correct use of this pharmaceutical. The absence of strict laws regulating the over-the-counter availability of antibiotics and the limited availability of health insurance further compound this issue. Self-medication and poor diagnostic approach among general public are the major underlying causes. Therefore, it is necessary for the public to be aware of the harmful aspects of self-medication, and they should be aware of the dangers of metronidazole overuse. Lastly, it is advisable to establish legislation for the management of antimicrobial prescriptions. Reference Aslam, Zin and Jamshed1

Acknowledgments

None to declare.

Author contribution

Conceptualization: Mudassir Nisar; Data curation: Mudassir Nisar; Writing – original draft: Hamza Ashraf, Haider Ashfaq; Writing – review and editing: Hamza Ashraf, Haider Ashfaq, Mudassir Nisar.

Financial support

This research is funded by Cambridge Open Equity Initiative (COEI) through its agreement with Allama Iqbal Medical College, Lahore, Pakistan.

Competing interests

None to declare.

Footnotes

This paper has not been previously published and is not currently under consideration by another journal.

References

Aslam, A, Zin, CS, Jamshed, S, et al. Self-Medication with antibiotics: prevalence, practices and related factors among the Pakistani public. Antibiot (Basel) 2022;11:795.CrossRefGoogle ScholarPubMed
Ungaro, R, Bernstein, CN, Gearry, R, et al. Antibiotics associated with increased risk of new-onset Crohn’s disease but not ulcerative colitis: a meta-analysis. Am J Gastroenterology 2014;109:17281738.CrossRefGoogle Scholar
Virta, L, Auvinen, A, Helenius, H, Huovinen, P, Kolho, K-L. Association of repeated exposure to antibiotics with the development of pediatric crohn’s disease—a nationwide, register-based finnish case-control study. Am J Epidemiol 2012; 175: 775784.CrossRefGoogle ScholarPubMed
Shaw, SY, Blanchard, JF, Bernstein, CN. Association between the use of antibiotics and new diagnoses of crohn’s disease and ulcerative colitis. Am J Gastroenterology 2011;106:21332142.CrossRefGoogle ScholarPubMed
Jawad, AB, Jansson, S, Wewer, V, Malham, M. Early life oral antibiotics are associated with pediatric-onset inflammatory bowel disease-a nationwide study. J Pediatr Gastroenterology Nutr 2023;77:366372.CrossRefGoogle ScholarPubMed