Antibiotic-associated diarrhea

Antibiotics, mainly the broad-spectrum varieties, not only eliminate bad bacteria (pathogens) that cause infections, but also a significant quantity of the good bacteria found in our intestines.

By reducing the amount of bacteria that help digestion, antibiotic treatments may occasionally cause diarrhea 1, 2, a symptom that may seem trivial to some, but for others could be inconvenient enough to lead them to stop their antibiotic course. In such a case, the infection is no longer treated, which could lead to complications.

The intestinal flora is diversified and rich in bacteria.

The diversity and quantity of intestinal bacteria are significantly reduced, which enables pathogenic bacteria to populate the intestinal lining.

23 800 000

prescriptions for antibiotics are written each year in Canada3

4 800 000

Up to 20% of patients will experience symptoms of antibiotic-associated diarrhea4


With 2 capsules of Bio-K+ 50 Billion
reduction of 65% in cases of antibiotic-associated diarrhea5

Risk level
of various antibiotics6, 7

Probiotic capsules
50 billion

Bio-K+ 50 Billion is renowned as an effective product to help reduce the risk of antibiotic-associated diarrhea.
(NPN 80015104)

Contains 15 capsules.

Clostridium difficile infections

Clostridium difficile (C. difficile) is a strictly anaerobic Gram+ bacillus bacteria that requires no oxygen and is highly sporulant. Linked to illness for the first time in 1978, C. difficile has been identified as a causal agent of pseudomembranous colitis (colon inflammation), which destroys the intestinal lining and is potentially fatal8, 9.

The main symptoms of a Clostridium difficile infection are10, 11 :

  • Diarrhea (up to 10-15 per day)
  • Fever
  • Loss of appetite
  • Nausea
  • Abdominal pain
  • Myalgia

It appears that an imbalance within the intestinal flora is the main cause of infection. Antibiotics, especially of the broad spectrum variety, eliminate a significant part of the intestinal flora’s microbial diversity, and C. difficile, qualified as an opportunistic bacteria, takes advantage of this situation to multiply and release A (enterotoxin) and B (cytoxin) toxins. These two toxins are responsible for the damage to the mucous lining, the induction of inflammatory cells and the onset of diarrhea10, 11.

C. difficile is normally spread through fecal-oral contact, meaning oral contamination by bacteria from fecal matter, either directly by hand contact, or indirectly through various food or water sources. Hospitals are one of the most common sites for C. difficile contamination10, 11.

Important fact :

Despite the preventative measures used in hospital settings, the C. difficile bacteria remains one of the most prevalent causes of nosocomial infections, with over 700,000 cases reported in the United States every year12.

Data on Clostridium difficile 4, 13, 14 :


of healthy adults and

20% à 40%

of recently hospitalized patients

are C. difficile carriers


of C. difficile infections

are community-acquired


of patients undergoing antibiotic therapy

suffer from diarrhea


of these patients develop a

C. difficile-related disease

Here are the main risk factors
leading to C. difficile infections15

Taking antibiotics


(65 years old)4


With 2 capsules of Bio-K+ C. Difficile
reduction of 95% in cases of Clostridium difficile-associated diarrhea5

See how  Probiotics help to reduce the risk of Clostridium Difficile bacteria associated Diarrhea in hospitalized patients.

Scientific studies

Studies on and antibiotic and clostridium difficile-associated diarrhea

Gao, X.W., M. Mubasher, C. Zhang, C. Reifer, K. Zhang. 2010. Dose-response Efficacy of a Probiotic Formula in Reducing Antibiotic-associated Diarrhea and Clostridium difficile-associated Diarrhea Incidence: A Double-blind, Randomized, Placebo-Controlled Study. American Journal of Gastroenterology, 105(7):1636-1641.


Dose-response effect of the prophylaxis use of a unique probiotic formula combining Lactobacillus acidophilus CL1285®, Lactobacillus casei LBC80R® and Lactobacillus rhamnosus CLR2® on antibiotic-associated diarrhea (AAD) Clostridium difficile-associated diarrhea (CDAD) in adult patients.

Results :

  • 65% reduction of AAD cases with 2 capsules of Bio-K+® 50 Billion
  • 56% reduction of the length of AAD with 2 capsules of Bio-K+® 50 Billion
  • 95% reduction of CDAD cases with 2 capsules of Bio-K+® 

Taking Bio-K+® 50 Billion capsules is effective in reducing the incidence and length of AAD and CDAD. Moreover, no serious side effect has been reported.

Maziade, P.J., A. Andriessen, P. Pereira, B. Currie, E.J.C. Goldstein. 2013. Impact of adding prophylactic probiotics to a bundle of standard preventative measures for Clostridium difficile infections: enhanced and sustained decrease in the incidence and severity at a community hospital. Current Medical Research and Opinion, 29(10): 1341-1347.


Cohort study of 31,832 hospitalized patients receiving antibiotic treatment to assess the effect of Bio-K+® probiotic combined with standard prevention methods (SPM) versus SPM only on Clostridium difficile infections (CDI).

Phase 1 (number of patients = 1,580): measure the impact of standard prevention methods.
Phase 2 50 to 60 milliards UFC per day of the Bio-K+® probiotic formula administered to all patients receiving antibiotic treatment. 
Phase 3 Same intervention as in phase 2, but in a new hospital (move). Phases 2 and 3 included 4,968 patients. 
Phase 4 25,284 patients followed the same protocol as in phases 2 and 3, with results compared to other similar hospitals in Québec. 

Results :

  • At the end of phase 3, C. difficile infections, following antibiotic treatment, had dropped from 18 cases per 1,000 admissions to less than 5.
  • Reductions in CDI cases (73%, p<0.001) and severe cases of CDI (76.4% p<0.001) have been noted. 
  • The recurrence of CDI was reduced by 39% (p<0.001). 
  • Over the subsequent six weeks, the average CDI rate was 2.71 cases per 10,000 patients/day at Pierre-Le Gardeur Hospital, compared to 8.50 cases per 10,000 patients/day in similar hospitals in Québec, Canada.  

Sampalis, J., F. Psaradellis, and E. Rampakakis. 2010. Efficacy of a probiotic formula in the reduction of antibiotic-associated diarrhea- a placebo controlled, double-blind randomized, multicenter study. Archives of Medical Science, 6(1):56-64.


A multi-center, randomized, double-blind and placebo-controlled trial to assess the effects of Bio-K+® on antibiotic-associated diarrhea (AAD) in hospitalized adult patients on a 3- to 14-day prescription of antibiotics. Patients were studied throughout their treatment and for 21 days following their last dose of antibiotics. 

½ bottle on the first 2 days, then 1 bottle per day throughout the antibiotic treatment + 5 days after final dose

Results :

  • 37.3% decrease in cases of patients with AAD for over a day (P=0.037)
  • 51.5% decrease in the average length of AAD cases (P=0.045)
Taking Bio-K+® Fermented Milk (50 Billion) is effective in preventing and reducing the severity of antibiotic-associated diarrhea in hospitalized patients taking antibiotics.

Beausoleil, M., N. Fortier, S. Guénette, A. L'Écuyer, M. Savoie, M. Franco, J. Lachaîne, K. Weiss. 2007. Effect of a fermented milk combining Lactobacillus acidophilus CL1285 and Lactobacillus casei in the prevention of antibiotic-associated diarrhea: A randomized, double-blind, placebo-controlled trial. Canadian Journal of Gastroenterology, 21(11):732-736.


A randomized, double-blind and placebo-controlled trial on 89 adult patients to assess the effect of a fermented milk combining Lactobacillus acidophilus CL1285®, Lactobacillus casei LBC80R® and Lactobacillus rhamnosus CLR2® in the prevention of antibiotic-associated diarrhea. 

Results :

  • 55% reduction in AAD cases (P=0.05)
  • 85% reduction in CDAD cases (P=0.06)
Taking Bio-K+® Fermented Milk (50 Billion) is effective in reducing AAD and is a strong factor in reducing CDAD in hospitalized patients taking antibiotics.

Study on the financial impact of using  in a hospital setting to prevent antibiotic-associated diarrhea and Clostridium difficile infections

Fansi, A.A.K., J.R. Guertin, J. LeLorier. 2012. Savings from the use of a probiotic formula in the prophylaxis of antibiotic-associated diarrhea. Journal of Medical Economics, 15(1):53-60.


Summary: Pharmaco-economic analysis comparing the use of 2 doses of Bio-K+® formula (50 Billion and 100 Billion) to a placebo. This analysis was based on published data adapted to the North American context.

Results :

  • Average savings of $1,968 per patient with a 50 Billion* dose
  • Average savings of $2,661 per patient with a 100 Billion* dose

*When used for an average of 13 days by all patients at risk of developing antibiotic- and Clostridium difficile-associated diarrhea.

Using the Bio-K+® probiotic formula (2 50 Billion capsules) in 1,000 hospitalized patients undergoing antibiotic treatment generated average savings of $2,661,218 compared to the standard procedures used.

Study demonstrating the importance of enteric coating in encapsulated probiotic products

Millette, M., A. Nguyen, K.M. Amine and M. Lacroix. 2013. Gastrointestinal survival of bacteria in commercial probiotic products. International Journal of Probiotics & Prebiotics, 8(4): 149-156.


In vitro demonstration of the gastrointestinal survival of the main probiotic products currently available. Bio-K+® capsules’ resistance to acidity, digestive enzymes and bile salts was compared to that of several commercial encapsulated probiotics. Said resistance was assessed in an in vitro simulator using a two-step process that included gastric digestion, at a pH of 1.5 for 120 minutes (2 hours), and intestinal digestion for 180 minutes (3 hours).

Results :

  • Probiotic products without an enteric coating did not survive passage through the simulated gastrointestinal tract; bacterial degradation was evident.
Bacteria contained in Bio-K+® capsules (with enteric coating) feature excellent survivability through the gastrointestinal system, as these do not dissolve in the stomach, but rather in the intestines, which is the main action site for probiotic bacteria.

Studies demonstrating the potential of in reducing cancerous cells

Baldwin, C., M. Millette, M.T. Ruiz, F.M. Luquet, D. Oth, M. Lacroix. 2010. Probiotic L. acidophilus and L. casei mix sensitize tumoral cells to 5-fluorouracil-induced apoptosis. Nutrition and Cancer, 62:371-378.


Summary: In vitro study demonstrating the effect of combining Bio-K+® strains in the presence of 5-fluorouracil (5-FU, chemotherapeutic medication) on induced apoptosis of colon tumour cells (LS513). LS513 cells were treated for 48 hours using increasing concentrations of lactic bacteria, found in Bio-K+® products, in the presence of 100 μg/ml of 5-FU.

Results :

  • 50% increase of 5-FU’s effectiveness with a concentration of 100 billion Bio-K+® probiotics.
These results appear to demonstrate that the probiotic strains contained in Bio-K+® products might have the capacity to make 5-FU treatments more effective and less toxic in patients with colon cancer.


Karska-Wysocki, B., M. Bazo and W. Smoragiewicz. 2010. Antibacterial activity of Lactobacillus acidophilus and Lactobacillus casei against methicillin-resistant Staphylococcus aureus (MRSA). Microbiological Research, 165(8):674-86.

Millette, M., F.M. Luquet, M.T. Ruiz, M. Lacroix. 2008. Characterization of probiotic properties of Lactobacillus strains. Dairy Science and Technology, 88: 695-708.

Millette, M., F.M. Luquet, M. Lacroix. 2007. In vitro control of selected pathogens by a Lactobacillus acidophilus and L. casei-fermented milk. Letters in Applied Microbiology, 44:314-319.

References :

Hogenauer et al. 1998.
Mechanisms and management of antibiotic-associated diarrhea. Clin Infect Dis. 27:702-710.
CPS, CPNA 2008
Individual Monographs.
Programme intégré canadien de surveillance de la résistance aux antimicrobiens
Rapport de l’utilisation des antimicrobiens chez les humains. 2011. Site du gouvernement du Canada.
Hookman and Barkin. 2009
Clostridium difficile associated infection, diarrhea and colitis. World J Gastroenterol. 15 (13): 1554-1580.
Gao et al. 2010.
Dose-response Efficacy of a Probiotic Formula in Reducing Antibiotic-associated Diarrhea and Clostridium difficile-associated Diarrhea Incidence: A Double-blind, Randomized, Placebo-Controlled Study. American Journal of Gastroenterology, 105(7):1636-1641.
eCPS, CPNA 2015.
Individual Monographs.
Barlett 2002.
N Engl J Med. 346: 334-339
Bartlett et al. 1978.
Role of Clostridium difficile in antibiotic-associated pseudomembranous colitis. Gastroentrol. 75:778-782.
Larson et al. 1978.
Clostridium difficile and the aetiology of pseudomembranous colitis. Lancet. 311:1063-1066.
Aslam et al. 2005.
Treatment of Clostridium difficile-associated disease: old therapies and new strategies. Lancet Inf Dis. 5:549-57.
Bartlett. 2006.
Narrative review: the new epidemic of Clostridium difficile-associated enteric disease. Ann Intern Med. 145:758-64.
IMS Clinical Plus database 2011,
extrapolated to 2013 using 2% growth y-o-y
Lee and Cohen. 2013.
Community-Acquired Clostridium difficile Infection: An Emerging Problem. Curr Emerg Hosp Med Rep. 1 (3): 149-153.
McFerland. 2008.
Renewed Interest in a Difficult Disease: Clostridium difficile Infections- Epidemiology. Curr Opin Gastroenterol. 25 (1): 24-35.
Turck et al 2003.
Incidence and risk factors of oral antibiotic-associated diarrhea in an outpatient pediatric population. J Pediatr Gastroenterol Nutr. Jul;37(1):22-6

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