Question: Please clarify the use of probiotics with
concomitant antibiotic therapy. I see this combination in practice and
am unclear whether it has clinical benefit for preventing
Response from Darrell Hulisz, PharmD
Associate Professor, Case Western Reserve University School
of Medicine; Clinical Specialist in Family Medicine, University
Hospitals, Case Medical Center, Cleveland, Ohio
Probiotics are live microorganisms which when administered in
controlled amounts may confer health benefits to patients by improving
microbial balance, primarily in the gastrointestinal (GI) tract.
Probiotics may contain a single isolate or a mixture of isolates, such
as Lactobacillus, Bifidobacterium, or Saccharomyces
species. These preparations are regulated as dietary supplements or
foods and are available as tablets, capsules, powders, or in fermented
foods such as yogurt.
Probiotics have been studied in a variety of GI conditions, such as
infectious diarrhea, irritable bowel syndrome, inflammatory bowel
disease, antibiotic-associated diarrhea, and Clostridium difficile infection.
This review focuses on the use of probiotics with concurrent antibiotic
treatment for the prevention of antibiotic-associated diarrhea. The
reader is referred elsewhere for information regarding probiotics for
the treatment of C difficile.
Probiotic formulations are similar to the beneficial microorganisms
found in the human gut.
However, the beneficial effects of probiotics in
some cases tend to be strain specific (eg, Lactobacillus species strain GG); thus, not all the positive results of one preparation can be generalized to other preparations.
It is well known that antibiotic therapy can disrupt the homeostatic
balance in the gut flora, causing an overgrowth of pathogenic microbes
relative to beneficial flora. This allows pathogenic bacteria to
colonize the gut and gain access to the GI mucosa, precipitating
diarrhea and predisposing patients to fluid and electrolyte
disturbances. Probiotics with specific strains of beneficial bacteria
and yeast aim to restore that balance.
The most commonly used probiotic microbes include Saccharomyces species (yeast) and lactic acid bacteria, specifically Lactobacillus and Bifidobacterium species. These bacteria liberate acid in the gut and lower luminal pH, which suppresses the growth of pathogenic flora.
Probiotics also decrease colonization of pathogenic organisms in the
gut by secreting hydrogen peroxide and organic acids that are locally
toxic to pathogenic bacteria and may competitively block microbial
adhesion to the gut epithelium.
Certain probiotic strains may have immunomodulating effects such as
increasing cytokine activity and stimulating lymphocyte and macrophage
phagocytosis in the intestine.
Numerous controlled studies investigating the use of probiotics to
prevent antibiotic-associated diarrhea have been included in several
meta-analyses.A meta-analysis by Cremonini and colleagues
examined 7 homogenous, placebo-controlled trials (n = 881) of probiotic
efficacy in preventing antibiotic-associated diarrhea. Results showed a
combined relative risk (RR) of 0.3966 (95% confidence interval [CI],
0.27-0.57) favoring a beneficial effect of probiotics (Saccharomyces boulardii and Lactobacillus species) for reducing the risk for antibiotic-induced diarrhea.
In 2002, D'Souza and coworkers
conducted a meta-analysis of 9 studies in which study groups received
probiotics with antibiotics and control groups received placebo with
antibiotics. The odds ratio in favor of probiotics for preventing
diarrhea associated with antibiotics was 0.39 (95% CI, 0.25-0.62; P < .001) for S boulardii (yeast) and 0.34 (95% CI, 0.19-0.61; P < .01) for Lactobacillus species. The combined odds ratio was 0.37 (95% CI, 0.26-0.53; P < .001) in support of probiotic treatment over placebo.
A subsequent 2005 meta-analysisevaluated the effectiveness of S boulardii
in preventing antibiotic-associated diarrhea in children and adults.
Only 5 randomized controlled trials (n = 1076) met criteria for review.
Treatment with S boulardii compared with placebo reduced the
risk for antibiotic-associated diarrhea from 17.2% to 6.7% (RR, 0.43;
95% CI, 0.23-0.78). The number needed to treat to prevent 1 case of
antibiotic-associated diarrhea was 10 (95% CI, 7-16).
The probiotic dosage and combinations that have shown efficacy for antibiotic-associated diarrhea are as follows
S boulardii 4 × 109 to 2 × 1010 colony forming units (CFU) daily for 1-4 weeks;
Lactobacillusrhamnosus strain GG 6 × 109 to 4 × 1010 CFU daily for 1-2 weeks;
L acidophilus and L bulgaricus 2 × 109 CFU daily for 5-10 days;
L acidophilus and Bifidobacterium longum 5 × 109 CFU daily for 7 days; and
L acidophilus and B lactis 1 × 1011 CFU daily for 21 days.
The adverse effects of probiotics are minimal and generally confined
to the GI tract. These include flatulence, constipation, and bloating.
Rare cases of probiotic-related bacteremia and fungemia have been reported.
Because probiotics contain live microorganisms, patients who are
immunocompromised, have severe underlying comorbidities, are critically
ill, or have short bowel syndrome may be more susceptible to probiotic
sepsis and should not receive them
Preparations containing Lactobacillus speciespreparations are contraindicated in patients with a hypersensitivity to lactose or milk.
Products containing S boulardii are contraindicated in patients with a yeast allergy.
Some probiotic formulations appear to be safe
and modestly effective for preventing antibiotic-associated diarrhea.
However, many unanswered questions remain regarding the use of
probiotics for this indication. There are no evidence-based guidelines
or consensus statements regarding probiotics for this use. However, the
American Academy of Pediatricsissued a Clinical Report on the use of probiotics and prebiotics in
children in 2010 that discussed a wide variety of conditions for which
these agents have been used, including antibiotic-associated diarrhea.
Additionally, the optimal dose, duration, and mode of delivery for
probiotics has not been fully elucidated.
Although various probiotics are marketed, only those formulations
evaluated in controlled clinical trials should be recommended. Patient
selection criteria would at a minimum include immunocompetent patients
with a history of antibiotic-associated diarrhea. Further studies should
delineate which patients benefit most from probiotics.