The use of Probiotics in the prevention of

Antibiotic-Associated Diarrhea

Evidence Based MedicineEvidence Based Medicine

Lindsey Bowman Lindsey Bowman

QUESTION

P - Children or adults receiving antibiotic - Children or adults receiving antibiotic treatment for any reason.treatment for any reason.

I I - Co-treating with a probiotic - Co-treating with a probiotic

CC - Solely treating with antibiotic therapy - Solely treating with antibiotic therapy

OO - Prevention of antibiotic associated - Prevention of antibiotic associated diarrhea, three or more loose stools per diarrhea, three or more loose stools per day for at least two consecutive days day for at least two consecutive days within 12 days of starting the within 12 days of starting the antibiotics.antibiotics.

PurposePurpose

To determine if co-treating a patient To determine if co-treating a patient with probiotics while on antibiotic with probiotics while on antibiotic therapy decreases the incidence of therapy decreases the incidence of antibiotic-associated diarrhea.antibiotic-associated diarrhea.

Why?Why?

#1 It’s a commonly asked question in the #1 It’s a commonly asked question in the office.office.

#2 If the solution to preventing antibiotic-#2 If the solution to preventing antibiotic-associated diarrhea is as simple as co-associated diarrhea is as simple as co-treating with a probiotic, then why isn’t treating with a probiotic, then why isn’t it required when prescribing antibiotics?it required when prescribing antibiotics?

#3 AAD occurs in up to 30% of the #3 AAD occurs in up to 30% of the population treated with antibiotics population treated with antibiotics (Szajewska, 2005). (Szajewska, 2005).

BackgroundBackground

- There are no current guidelines - There are no current guidelines delineating a specific protocol for the delineating a specific protocol for the prevention of AAD. prevention of AAD.

- Preventive measures include - Preventive measures include prescribing antibiotics only when prescribing antibiotics only when necessary, therefore preventing the necessary, therefore preventing the number of possible cases. number of possible cases.

What is AAD?What is AAD?

Antibiotic-Associated Diarrhea is Antibiotic-Associated Diarrhea is three or more loose stools per three or more loose stools per day for at least two consecutive day for at least two consecutive days within 12 days of starting days within 12 days of starting the antibiotics.the antibiotics.

Why does AAD occur?Why does AAD occur?

~ 25% of cases are attributed to ~ 25% of cases are attributed to bacterial overgrowth bacterial overgrowth

~ 80% of cases are due to a “non-~ 80% of cases are due to a “non-specific cause” specific cause”

(Hawrelak, 2005)(Hawrelak, 2005)

Bacterial Overgrowth

Destruction of specific types of bacteria Destruction of specific types of bacteria in the colon due to the original antibiotic in the colon due to the original antibiotic treatment. treatment.

This allows for other naturally occurring This allows for other naturally occurring bacteria, most commonly bacteria, most commonly Clostridium Clostridium difficiledifficile to grow unchecked. to grow unchecked.

Causing a bacterial infection causing Causing a bacterial infection causing diarrhea.diarrhea.

““Non-specific causes”Non-specific causes” The antibiotic causes death of the natural

intestinal bacterial flora.

This changes the mechanism in which organic This changes the mechanism in which organic compounds are broken down.compounds are broken down.

Resulting in changes in the osmotic pressure Resulting in changes in the osmotic pressure within the lumen of the colon drawing fluid into within the lumen of the colon drawing fluid into the colon the colon

Excess fluid changes the consistency and transit Excess fluid changes the consistency and transit time of stool, producing diarrheatime of stool, producing diarrhea

What is the theory driving What is the theory driving the use of probiotics?the use of probiotics?

Probiotics Probiotics maintain the maintain the bacterial balance bacterial balance of the colonic of the colonic flora. In turn flora. In turn inhibiting diarrhea inhibiting diarrhea related to related to bacterialbacterial as well as well as as non-specificnon-specific causes.causes.

What are Probiotics?What are Probiotics?

Life-viable, non-pathogen microbial Life-viable, non-pathogen microbial organisms with 3 main properties:organisms with 3 main properties:

anti-inflammatoryanti-inflammatory

anti-viralanti-viral

anti-bacterialanti-bacterial

(Meier, 2005) (Meier, 2005)

StudiesStudies

StudStudyy

ProbiotiProbioticc

% of% of

PROBIOTICPROBIOTIC

pts withpts with

diarrheadiarrhea

% of % of PLACEBOPLACEBO

pts withpts with

diarrheadiarrhea

Risk Risk

ReductiReductionon

StudStudy y

typetype

HickHickson son et. et. al. al.

LactobaLactobacilluscillus

12%12% 34%34% 21.6%21.6% RandoRandomized mized double double blind blind

placebo placebo controllcontroll

eded

SzajSzajewskewska et a et al. al.

SaccharSaccharomyces omyces boulardiboulardi

ii

6.7% 6.7% 17.2%17.2% 10.5%10.5% Meta-Meta-analyanaly

sissis

0%

5%

10%

15%

20%

25%

30%

35%

Hickson et. al. Szajewska et. al

ProbioticPlacebo

Studies

% o

f patie

nts w

ith A

AD

% of Patients in both Control and Placebo groups that experienced AAD

StudiesStudies Probiotic Probiotic used used

Total # Total # of studies of studies included included in review in review

# of # of studies studies showing showing

a a significasignifica

nt nt decreasedecrease in AAD. in AAD.

# of # of studies studies showing showing

no no significasignifica

nt nt decreasedecrease in AAD in AAD

Study Study typetype

Hawrelak Hawrelak et. al. et. al.

LactobacilLactobacilluslus 66 44 22 Meta-Meta-

analysianalysiss

Johnston Johnston et. al. et. al.

LactobacilLactobacilli spp., li spp.,

BifidobactBifidobacterium erium spp., spp.,

StreptococStreptococcus spp., cus spp.,

as well asas well as SaccharoSaccharo

myces myces boulardiiboulardii

1010 99 11 Meta-Meta-analysianalysi

ss

Studies

0

1

2

3

4

5

6

7

8

9

Hawrelak et. al. Johnston et. al.

# of studies showinga decrease in AAD

# of studies showingNO decrease in AAD

# of Studies

Meta-Analysis

Number of studies within each Meta-Analysis that showed or

failed to show a significant decrease in AAD with Probiotic use

TrendTrend

Three out of the four studies Three out of the four studies concluded that there was a concluded that there was a significant decrease in AAD with significant decrease in AAD with probiotic use.probiotic use.

The fourth study concluded that The fourth study concluded that further research was necessary to further research was necessary to determine the role of probiotics in determine the role of probiotics in AAD.AAD.

ProblemsProblems

LACK of HOMGENICITYLACK of HOMGENICITY

AgeAge Type of antibiotic usedType of antibiotic used Strain of probiotic usedStrain of probiotic used Length of antibiotic and probiotic Length of antibiotic and probiotic

treatmenttreatment

Ages included in each Ages included in each studystudy

StudyStudy AgeAge

Hickson et. al. Hickson et. al. >50 years >50 years

Szajewska et al. Szajewska et al. 0 to >90 years 0 to >90 years

Hawrelak et. al. Hawrelak et. al. 2 weeks to 93 years 2 weeks to 93 years

Johnston et. al. Johnston et. al. 0-18 years 0-18 years

Why not?Why not?

If there is an obvious trend toward a If there is an obvious trend toward a decrease in AAD with probiotic use decrease in AAD with probiotic use and these studies have been done in and these studies have been done in patients of all ages why not treat?patients of all ages why not treat?

None of the studies reported any None of the studies reported any adverse side effects.adverse side effects.

RisksRisks

Immunocompermised patients can Immunocompermised patients can become become septicseptic due to the introduction due to the introduction of probiotics.of probiotics.

There have been no reported cases of There have been no reported cases of sepsis in a “otherwise healthy sepsis in a “otherwise healthy individual”individual”

(Boyle, 2006). (Boyle, 2006).

ConclusionConclusion

Similar to all other clinical decisions, this Similar to all other clinical decisions, this is a matter of weighing the potential pros is a matter of weighing the potential pros and cons.and cons.

While there is a obvious trend in the While there is a obvious trend in the research before guidelines can be made research before guidelines can be made ffurther studies need to be done analyzing urther studies need to be done analyzing specific strains of probiotics, patient specific strains of probiotics, patient population, as well as antibiotic types and population, as well as antibiotic types and length of treatment. length of treatment.

References Hickson, M., D'Souza, A.L., Muthu, N., Rogers, T.R., Want, Hickson, M., D'Souza, A.L., Muthu, N., Rogers, T.R., Want,

S., & Chakravarthi, R. (2007). Use ofS., & Chakravarthi, R. (2007). Use of probiotic Lactobacillus probiotic Lactobacillus preparation to prevent diarrhoea associated with preparation to prevent diarrhoea associated with antibiotics: randomized double blind placebo controlled antibiotics: randomized double blind placebo controlled trial. trial. BMJ,BMJ, 335335, 80., 80.

Szajewska, H., & Mrukowicz, J. (2005). Meta-analysis: non-Szajewska, H., & Mrukowicz, J. (2005). Meta-analysis: non-pathogenic yeast Saccharomyces boulardii in the pathogenic yeast Saccharomyces boulardii in the prevention of antibiotic-associtaed diarrhoea. prevention of antibiotic-associtaed diarrhoea. Aliment Aliment Pharmacology & TheraputicsPharmacology & Theraputics, , 22, 365-372.22, 365-372.

Boyle, R.J., Robins-Browne, R.M., & Tang, M.L. (2006). Boyle, R.J., Robins-Browne, R.M., & Tang, M.L. (2006). Probiotic use in clinical practice: what are the risks?. The Probiotic use in clinical practice: what are the risks?. The American Journal of Clinical Nutrition, 83, 1256-1264.American Journal of Clinical Nutrition, 83, 1256-1264.

Meier, Remy F. (2005).Probiotics: A New Treatment for Meier, Remy F. (2005).Probiotics: A New Treatment for Antibiotic-Associated Diarrhea?. Digestion. 72, 49-50.Antibiotic-Associated Diarrhea?. Digestion. 72, 49-50.