Document 70330

Probiotics in alleviating
infections in children
Prof. Hania Szajewska
The Medical University of Warsaw
Department of Paediatrics
Hierarchy of evidence
For questions about the effectiveness of an intervention
V
A
L
I
D
I
T
Y
Systematic
review
or meta-analysis
of RCTs
Randomised controlled
trial (RCT)
Obserwational studies
(case-control, cohort)
Observational studies
(case report, case series)
Experimental studies
B
I
A
S
Randomised controlled trial (RCT)
Eligible
patients
Randomisation
Treatment
Control
Outcome
Outcome
Systematic review
RCT N0 1
Analysis
RCT N0 2
Analysis
RCT N0 3
Analysis
RCT N0 4
Analysis
RCT N0 5
Analysis
RCT N0 6
Analysis
Meta-analysis
RCT N0 1
RCT N0 2
RCT N0 3
RCT N0 4
RCT N0 5
RCT N0 6
Statistical
techniques
Pooled
results
of all RCTs
Meta-analysis
• Why to perform a meta-analysis?
– To increase power
– To improve precision
Egger, Smith, Altman (ed.).
Systematic review in health care. Meta-analysis in context. BMJ Books 2000.
Acute gastroenteritis
Acute gastroenteritis
• ORS
– Despite the proven efficacy of oral rehydration, it
remains underused
• Why?
– ORS dose not reduce frequency of bowel
movements, fluid loss, duration of illness
• Consequence
– Interest in safe, effective, and inexpensive
agents as an additional treatment
ESPGHAN/ESPID Guidelines JPGN 2008;46:619-21
Rationale for the use of probiotics
O'Toole PW, Cooney JC. Interdiscip Perspect Infect Dis. 2008;2008:175285.
Acute gastroenteritis
Duration of diarrhoea
Metaanalysis
Szajewska et al.
Probiotic
Various
RCT (n)
8 (773)
WMD (95% CI)
-20 h (-26 to –14)
Various
7 (675)
-17 h (-29 to –7)
Various
18 (1917)
-19 h (-26 to –14)
Various
12 (970)
-30 h (-42 to –19)
J Pediatr Gastr Nutr 2001
Van Niel et al.
Pediatrics 2002
Huang et al.
Dig Dis Sci 2002
Allen et al.
Cochrane Review 2004
Reduced duration of diarrhoea
‘All animals are equal,
just some animals are
more equal than
others’
George Orwell
Is a meta-analytical approach
appropriate to assess the efficacy
of probiotics?
Lactobacillus GG
Up-date 2009 (12 RCTs, n=2611)
Duration of diarrhoea
11 RCTs, n=2483, WMD -1 day (-1.6 to -0.4)
Update: Szajewska et al. Aliment Pharmacol Therap 2007;25:257-64
Lactobacillus GG
Duration of RV diarrhoea
3 RCTs, n=201, WMD -2.1 day (-3.5 to -0.46
Szajewska et al. Aliment Pharmacol Therap 2007;25:257-64
Saccharomyces boulardii
Update 2009 (9 RCTs, n=1117)
Duration of diarrhoea
7 RCTs, n=944, WMD -1.1 d (-1.6 to -0.5)
Szajewska et al. Aliment Pharmacol Ther 2009 (in press)
Would you recommend probiotics to
treat acute gastroenteritis
in your patients?
Guidelines
ESPGHAN/ESPID 2008
• A. Guarino
• F. Albano
• S. Ashkenazi
• D. Gendrel
• H. Hoekstra
• R. Shamir
• H. Szajewska
NICE 2009
• R. Khanna
• M. Lakhanpaul
• S. Burman-Roy
• S. Murphy
ESPGHAN/ESPID Guidelines
• Probiotics may be an effective adjunct to the
management of AGE
• Because there is no evidence of efficacy for many
preparations, we suggest the use of probiotic
strains with proven efficacy and in appropriate
doses
Examples
• Lactobacillus GG
• Saccharomyces boulardii
ESPGHAN/ESPID Guidelines JPGN 2008;46:619-21
NICE guidelines
• Many studies
• High-quality SR suggesting a beneficial effect
– Shortening the duration of diarrhoea, reducing the stool frequency
– Studies varied in quality, in the specific probiotics studied, in the
treatment regimens used
• Despite some evidence of possible clinical effect, no
recommendation for the use of probiotics at this time
• Important field for further research
National Institute for Health and Clinical Excellence 2009
Nosocomial diarrhoea
Prevention of nosocomial diarrhoea
What is known on this topic?
Lactobacillus GG
RR (95% CI)
NNT (95% CI)
Szajewska
0.2 (0.06-0.6)
4 (2-10)
0.8 (0.6-1.3)
NS
B. bifidum+Str. therm
RR (95% CI)
NNT (95% CI)
Saavedra
0.2 (0.06-0.8)
5 (3-20)
0.7 (0.4-1.3)
NS
J Pediatr 2000
Mastretta
JPGN 2002
Lancet 1994
Chouraqui
JPGN 2004
What is new of this topic?
LGG in the prevention of nosocomial gastrointestinal
and respiratory tract infections
• Population
– N=742 hospitalized children
• Intervention
– LGG 109 CFU in 100 ml of a fermented milk product
• Comparison
– Placebo
• Outcome
– GI & RT infections
Hojsak I, Abdovic S, Szajewska H, Kolacek S. J Pediatr Gastroenterol Nutr 2009;48:E85.
LGG in the prevention of nosocomial
gastrointestinal and respiratory tract infections
• Conclusion
– LGG administration can be recommended as a
valid measure for decreasing the risk of
nosocomial gastrointestinal and respiratory tract
infections in paediatric facilities
Hojsak I, Abdovic S, Szajewska H, Kolacek S. J Pediatr Gastroenterol Nutr 2009;48:E85.
Summary of evidence
Lactobacillus GG
RR (95% CI)
NNT (95% CI)
Szajewska
0.2 (0.06-0.6)
4 (2-10)
0.8 (0.6-1.3)
NS
0.4 (0.25-0.7)
15 (9-34)
B. bifidum+Str. therm
RR (95% CI)
NNT (95% CI)
Saavedra
0.2 (0.06-0.8)
5 (3-20)
0.7 (0.4-1.3)
NS
Mastretta
Hojsak
J Pediatr 2000
JPGN 2002
2009
Lancet 1994
Chouraqui
JPGN 2004
Would you recommend probiotics
to prevent nosocomial infections
in your patients?
Respiratory tract infections
Prevention of respiratory tract infections
Systematic review
Type of
studies
Types of
participants
Types of
interventions
Type of
comparisons
Types of outcome
measures
• RCTs
• Adults & children
• Any probiotic
• Placebo or no treatment
• Prevention of upper or
lower RTI
Vouloumanou et al. Int J Antimicrob Agents 2009;34:197.e1-10.
What this review found
• Prevention
– 14 RCTs
• 4 RCTs – reduced incidence of RTIs
• 10 RCTs – no effect
• Severity of subsequent RTIs
– Reduction in 5 out of six trials that reported relevant
data
• Duration of RTI
– Reduction reported in 3 of nine trials
Vouloumanou et al. Int J Antimicrob Agents 2009;34:197.e1-10.
What is new on this topic?
Leyer et al. Pediatrics 2009;124:e172-e179
Compares
the efficacy of
1-strain (L acidophilus
NCFM) and
2-strain preparations
(L acidophilus / B
animalis subs. lactis
Bi-07)
Leyer et al. Pediatrics 2009;124:e172-e179
Copyright ©2009 American Academy of Pediatrics
Results
Leyer et al. Pediatrics 2009;124:e172-e179
Results
NS
Leyer et al. Pediatrics 2009;124:e172-e179
Conclusion
• Summary
– Daily dietary probiotic supplementation for 6
months was a safe effective way to reduce fever,
rhinorrhoea, and cough incidence and duration
and antibiotic prescription incidence, as well as
number of missed school days attributable to
illness, for children 3 to 5 y of age.
Would you recommend probiotics to
prevent respiratory tract infections
in healthy children 3-5 years of age?
Would you recommend L. acidophilus
NCFM (alone or in combination with
B. animalis Bi-07) to prevent
respiratory tract infections
in healthy children 3-5 years of age?
Probiotics for infections in children
To use or not to use?
• STEPS
– Safety
– Tolerability
– Effectiveness
– Price
– Simpilicity
Final comment…
'Half of what you are taught as medical
students will in ten years have been shown
to be wrong, and the trouble is, none of your
teachers knows which half…’
S Burwell
Dean of Harvard Medical School
from 1935 to 1949
Pickering. BMJ 1956
Thank you
for your
attention
Cracow, Poland
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