Antibiotic Awareness Week

What is the problem?

Almost a hundred years after the discovery of penicillin, the first antibiotic, the world is still facing challenges similar to those of the pre-antibiotic era. While we readily agree that as a great lifesaver antibiotics are one of the major discoveries of the last century, we also recognise that their misuse has led to increasing rates of antibiotic resistance and represents a growing threat to modern society ^1,2. Despite multiple public awareness campaigns, antibiotics continue to be used for common colds and viral infections, and they are often freely bought in pharmacies allowing the end user to continue misusing them. With the resultant increase in antibiotic resistance, we are again facing the dangers of pre-antibiotic times as simple bacterial infections can be fatal. And on top of that, resistance is far from the only negative consequence of antibiotic use. We now know that antibiotics have both short and long term effects on our health.

Short term effects

Common short term effects of antibiotic use include nausea, vomiting, and antibiotic-associated diarrhoea (AAD) ³. Many of these can be attributed to changes in the composition of our gut microbiota. This is because antibiotics, especially broad-spectrum ones, affect not only the targeted bacterial pathogens but also the indigenous microbiota, disturbing the microbial communities. This dysbiosis often leads to the most common short-term effects of antibiotic use, namely AAD.

AAD can occur in 5-39% of patients, depending on the antibiotic route of administration, the type of antibiotics, and the host factors ^4,5. AAD is diagnosed when diarrhoea occurs after antibiotic treatments, with no other apparent cause ⁶. Although usually mild, around 20% of AAD cases are caused by an overgrowth of Clostridium difficile resulting in Clostridium difficile-associated diarrhoea (CDAD), which can lead to the more severe and life-threatening pseudomembranous colitis ^4,5. Furthermore, in vulnerable target groups (children, elderly, or those with chronic diseases), antibiotic use is often linked to a vicious circle of reinfections: new antibiotic prescription, new AAD episodes,  and additional microbial disbalance, all resulting in poor quality of life. Diarrhoea in institutionalized people also increases the workload for care staff, placing an additional financial burden on the healthcare system. In addition, C. difficile infection (CDI) is a particularly alarming growing problem in healthcare facilities, as C. difficile spores are very difficult to clear and infection increases not only care costs but also mortality.

Long term effects

There is also growing evidence that antibiotics induce long term changes in the microbiota, especially when used early in life. The most common effects of antibiotics on the gut microbiota are decreases in bacterial diversity, in bacterial richness, and in the colonization of beneficial Bifidobacterium species ^7,8. Antibiotic use is linked to increased abundance of Enterobacteriaceae, which lead to a pro-inflammatory state ^7,8. These changes in the gut microbiota profoundly affect the immune system and host metabolism and can last from weeks or months up to even 2 years after cessation of the antibiotics. More importantly, antibiotic treatment early in life leads to changes in the gut microbiota and is linked to a higher risk of later developing obesity, diabetes, inflammatory bowel disease, asthma and allergies ^9–11.

Is there a role for probiotics?

Probiotics have proven effective in prevention and treatment of AAD and CDAD based on a number of  clinical trials and meta-analyses. In the last 2 years, probiotics have also been approved for the treatment and prevention of AAD and CDAD by the World Gastroenterology Organization (WGO) and the American Gastroenterology Association (AGA). The WGO guidelines indicate strong support for using probiotics in the prevention of AAD in children and adults who receive antibiotic therapy ¹². The AGA guidelines recommend certain probiotic formulations for the prevention of C. difficile infection in children and adults taking antibiotics ¹³.

Together with the Maastricht University Medical Centre (MUMC+) in the Netherlands, Winclove Probiotics has developed the multispecies premium probiotic formulation Ecologic® AAD, which was specifically developed to reduce antibiotic-associated side effects.

The formulation Ecologic^® AAD has been tested in clinical trials and shown to:

• Significantly reduce AAD in adults ¹⁴,
• Significantly expedite restoration of the intestinal microbiota after antibiotic intake ¹⁵,
• Cause clinical resolution of (recurrent) CDI,
• Significantly reduce AAD in nursing home residents ¹⁶.

If you would like to know more about Ecologic® AAD, don’t hesitate to contact us. We’d be happy to discuss the science and the market information behind Ecologic® AAD with you.

References:
1.               Jernberg, C., Löfmark, S., Edlund, C. & Jansson, J. K. Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology 156, 3216–3223 (2010).
2.               Langdon, A., Crook, N. & Dantas, G. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. Genome Medicine 8, (2016).
3.               Agamennone, V., Krul, C. A. M., Rijkers, G. & Kort, R. A practical guide for probiotics applied to the case of antibiotic-associated diarrhea in the Netherlands. Pharmaceutisch Weekblad 154, 17–24 (2019).
4.               Wilkins, T. D. & Lyerly, D. M. Clostridium difficile Testing: after 20 Years, Still Challenging. J Clin Microbiol 41, 531–534 (2003).
5.               Czepiel, J. et al. Clostridium difficile infection: review. Eur J Clin Microbiol Infect Dis 38, 1211–1221 (2019).
6.               Zimmermann, P. & Curtis, N. The effect of antibiotics on the composition of the intestinal microbiota – a systematic review. Journal of Infection 79, 471–489 (2019).
7.               Yassour, M. et al. Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability. Sci. Transl. Med. 8, (2016).
8.               Bokulich, N. A. et al. Antibiotics, birth mode, and diet shape microbiome maturation during early life. Science Translational Medicine 8, 343ra82-343ra82 (2016).
9.               Azad, M. B., Bridgman, S. L., Becker, A. B. & Kozyrskyj, A. L. Infant antibiotic exposure and the development of childhood overweight and central adiposity. Int J Obes 38, 1290–1298 (2014).
10.             Mueller, N. T. et al. Prenatal exposure to antibiotics, cesarean section and risk of childhood obesity. International Journal of Obesity 39, 665–670 (2015).
11.             Arrieta, M.-C. et al. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci. Transl. Med. 7, (2015).
12.             World Gastroenterology Organisation. World Gastroenterology Organisation Global Guidelines Probiotics and prebiotics. (2017).
13.             Su, G. L. et al. AGA Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders. Gastroenterology 159, 697–705 (2020).
14.             Koning, C. J. M. et al. The effect of a multispecies probiotic on the intestinal microbiota and bowel movements in healthy volunteers taking the antibiotic amoxycillin. American Journal of Gastroenterology 103, 178–189 (2007).
15.             Koning, C. J. M. et al. The effect of a multispecies probiotic on the composition of the faecal microbiota and bowel habits in chronic obstructive pulmonary disease patients treated with antibiotics. British Journal of Nutrition 103, 1452–1460 (2010).
16.             van Wietmarschen, H. A., Busch, M., van Oostveen, A., Pot, G. & Jong, M. C. Probiotics use for antibiotic-associated diarrhea: a pragmatic participatory evaluation in nursing homes. BMC Gastroenterol 20, 151 (2020).