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Results of a systematic review ;


Timely use of probiotics reduces the risks of antibiotic-associated diarrhoea.

Antibiotics undoubtedly revolutionized modern medicine since their discovery. Life expectancy has risen from less than 60 years before widespread antibiotic use to about 80 years for developed countries nowadays [1]. Through their anti-bacterial function antibiotics have provided a way to change the outcome of otherwise potentially deadly infections. Yet the mechanisms that make antibiotics so incredibly useful can at the same time also harm our natural immune system and with this, our health. 

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The problem with antibiotics



Antibiotics kill the bacteria that cause infections, but are not selective for only these bacteria. Many bacteria in our bodies, especially in our guts, synthesize required metabolites and help us fight invading pathogens [2]. Disturbance in this intestinal microbiota can cause some opportunistic pathogens to overgrow and become harmful. One of the main risks associated with antibiotic use is the overgrowth of Clostridium difficile (C. difficile). Overgrowth of this bacterium can cause C. difficile infection (CDI) which gives rise to diarrhoea ranging from a mild form to life threatening [3]. 




It is important to start taking probiotics early during antibiotic treatment

Although previous studies have given convincing evidence that probiotics recover the disturbance of the microbiota and prevent the overgrowth of bacteria such as C. difficile, some contradictory statements have been made and no official guidelines for probiotic use in combination with antibiotics have been postulated. To help guide clinical practice, researchers at Cornell University Weill Cornell Medical College and University of Colorado have joined their efforts to systematically review all previous trials evaluating the use of probiotics and CDI [4]. Not only did they find an overwhelming decrease in CDI occurrence when antibiotic treatment was combined with probiotic treatment, results also clearly indicate the importance of starting probiotic treatment early in the antibiotic treatment. 



Evaluating the data


In their systematic review, the investigators searched a number of databases for studies that used randomized controlled trials to evaluate the use of probiotics and CDI in hospitalized adults taking antibiotics. All found studies were assessed on the risk of bias and on the overall quality of evidence. 19 studies, comprising of over 6000 patients in total, met the inclusion criteria and were used for further analysis. Among the 6000 patients, almost half were in a control group that received a placebo. Furthermore, distinctions were made in starting point of probiotic treatment with respect to antibiotic treatment and composition of strains in the probiotic supplement.  



Efficiency of probiotic treatment decreases with every day of delay in starting the probiotics 

Analysis of the data clearly demonstrated a lower incidence of CDI in patients simultaneously treated with pro- and antibiotics. Of the group treated with probiotics 1.6% developed CDI, whereas this was 3.9% for the control group not treated with probiotics (P< 0.001). Patients treated with probiotics had a relative risk of 0.42 to develop CDI as compared with their non-treated counterparts. Effectively, this means that on average one case of CDI can be prevented for every 43 patients treated with probiotics.

As a second finding, the study gives convincing evidence that probiotics are significantly more effective when given closer to the first antibiotic dose (P=0.02). Probiotics given within two days of the first antibiotic dose reduced the relative risk of developing CDI to 0.32 with a 95% confidence interval of 0.22-0.48, whereas administration after two days reduced the relative risk only to 0.70, with a 95% confidence interval of 0.40-1.23. It should be noted that in this case no significant risk reduction can be concluded.

Further analysis even indicated that efficiency of probiotic treatment decreased with every day of delay in starting the probiotics (P=0.04). Although no significant differences were found between studies using different individual probiotic formulations, it was found that most promising results came from studies using Lactobacillus species and multispecies probiotics containing Lactobacillus species.



The impact of probiotics



The findings of these results are of great importance both clinically and economically. Clinically it provides convincing evidence to update guidelines in favour of co-treatment of antibiotics with probiotics. Even giving indications for guidelines towards an early start of probiotic treatment and usage of multi-species formulations. Economically, this could lead to great savings as it is estimated that every CDI case costs about 7000 US$. With a capacity to prevent 100.000 cases annually, probiotics could save over 500 million dollar per year in the US alone. In the UK, it has been estimated that 340 £ (over 500 US$) could be saved per patient treated with probiotics.

The results confirm previous research on which Ecologic AAD is based [3] and show similar trends towards probiotic treatment associated with antibiotic risk reduction [5].



Read the scientific article 



1. Ventola C.L. The Antibiotic Resistance Crisis: Part 1: Causes and Threats. Pharmacy and Therapeutics. 2015;40(4):277-283.  

2. Blaser M. Antibiotic overuse: Stop the killing of beneficial bacteria Nature 476, 393–394   3.

Hell, M., Bernhofer, C., Stalzer, P., Kern, J. M., & Claassen, E. (2013). Probiotics in Clostridium difficile infection: reviewing the need for a multistrain probiotic. Beneficial Microbes, 4(1), 39-51.   4.

Shen N.T et al. Timely use of Probiotics in Hospitalized Adults Prevents Clostridium difficile Infection: a Systematic Review with Meta-Regression Analysis, Gastroenterology , Volume 0 , Issue 0  

5. Koning C.J.M et al. The effect of a Multispecies Probiotic on the Intestinal Microbiota and Bowel Movement in Healthy Volunteers Taking the Antibiotic Amoxycillin




probiotics and antibiotic-associated diarrhoea

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