Probiotics in alleviating infections in children

Prof. Hania SzajewskaThe Medical University of Warsaw Department of Paediatrics

Systematic review

or meta-analysisof RCTs

Randomised controlled trial (RCT)

Obserwational studies(case-control, cohort)

Observational studies(case report, case series)

Experimental studies

Hierarchy of evidenceFor questions about the effectiveness of an intervention

VALIDITY

BIAS

Randomised controlled trial (RCT)

Eligible patients

Treatment

Randomisation

Control

Outcome Outcome

Systematic review

RCT N0 4

RCT N0 3

RCT N0 1

RCT N0 2

RCT N0 5

RCT N0 6

Analysis

Analysis

Analysis

Analysis

Analysis

Analysis

Meta-analysis

RCT N0 4

RCT N0 3

RCT N0 1

RCT N0 2

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 Probiotic RCT (n) WMD (95% CI) Szajewska et al. J Pediatr Gastr Nutr 2001

Various 8 (773) -20 h (-26 to –14)

Van Niel et al.Pediatrics 2002

Various 7 (675) -17 h (-29 to –7)

Huang et al.Dig Dis Sci 2002

Various 18 (1917) -19 h (-26 to –14)

Allen et al.Cochrane Review 2004

Various 12 (970) -30 h (-42 to –19)

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)

Update: Szajewska et al. Aliment Pharmacol Therap 2007;25:257-64

Duration of diarrhoea11 RCTs, n=2483, WMD -1 day (-1.6 to -0.4)

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 boulardiiUpdate 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

• 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

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

Lactobacillus GG RR (95% CI) NNT (95% CI)

Szajewska J Pediatr 2000

0.2 (0.06-0.6) 4 (2-10)

Mastretta JPGN 2002

0.8 (0.6-1.3) NS

B. bifidum+Str. therm RR (95% CI) NNT (95% CI)

Saavedra Lancet 1994

0.2 (0.06-0.8) 5 (3-20)

Chouraqui JPGN 2004

0.7 (0.4-1.3) NS

Prevention of nosocomial diarrhoeaWhat is known on this topic?

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 J Pediatr 2000 0.2 (0.06-0.6) 4 (2-10)

Mastretta JPGN 2002 0.8 (0.6-1.3) NS

Hojsak 2009 0.4 (0.25-0.7) 15 (9-34)

B. bifidum+Str. therm RR (95% CI) NNT (95% CI)Saavedra Lancet 1994 0.2 (0.06-0.8) 5 (3-20)

Chouraqui JPGN 2004 0.7 (0.4-1.3) NS

Would you recommend probiotics to prevent nosocomial infections

in your patients?

Respiratory tract infections

Type of studies

• RCTs

Types of participants

• Adults & children

Types of interventions

• Any probiotic

Type of comparisons

• Placebo or no treatment

Types of outcome measures

• Prevention of upper or lower RTI

Prevention of respiratory tract infections Systematic review

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

Comparesthe efficacy of

1-strain (L acidophilus NCFM) and

2-strain preparations(L acidophilus / B

animalis subs. lactis Bi-07)

Copyright ©2009 American Academy of PediatricsLeyer et al. Pediatrics 2009;124:e172-e179

Results

Leyer et al. Pediatrics 2009;124:e172-e179

Results

Leyer et al. Pediatrics 2009;124:e172-e179

NS

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?

• STEPS – Safety– Tolerability– Effectiveness– Price– Simpilicity

Probiotics for infections in childrenTo use or not to use?

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 BurwellDean of Harvard Medical School

from 1935 to 1949Pickering. BMJ 1956

Cracow, Poland

Thank you for your

attention