Probiotics and Infections and infections … · What About Safety? • The evidence support that...
Transcript of Probiotics and Infections and infections … · What About Safety? • The evidence support that...
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Probiotics and InfectionsPerspectives for pediatric conditions
Hans Hoekstra, M.D., Ph.D.Hieronimus Bosch Teaching Hospital‘s-Hertogenbosch, The Netherlands
Marrakech, SOMIPEV, April 7th 2018
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PROBIOTICS
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What are probiotics?
“Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.”
FAO/WHO 2002 Guidelines for the Evaluation of Probiotics in Food. ftp://ftp.fao.org/es/esn/food/wgreport2.pdf (accessed 26/1/2018)
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Saccharomyces
Mechanisms of effects are strain specific
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Disturbing observations on probiotics concerning
• Quantities of viable cells in samples tested, with pill-to-pilland lot-to-lot variations• Mislabeling of incorporated strains• Contamination with potentially pathogenic genera• Decreased shelf lives as stated on package• Probiotic matrices• Transfer of antibiotic resistance
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Probiotic yeast versus probiotic bacteria
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Map of the antibiotic susceptibility of probiotic strains (I)
Neut C et al. Med Mal Infect 2017; 47:477-83.
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Map of the antibiotic susceptibility of probiotic strains (II)
Neut C et al. Med Mal Infect 2017; 47:477-83.
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What About Safety?
• The evidence support that probiotics are generally safe for most populations
• There are reported cases of fungaemia in patients using Sb and bacteremia in patients taking LGG or L. casei
• Few cases of sepsis associated with Sb, LGG and B. subtilis have been reported
• Most cases occurred in an IC setting in the presence of a CVL; experts recommend the use of scrupulous hand hygiene when manipulating a CVL after handling probiotic preparations
• Sb is contraindicated in patients with a CVL, critically ill or immunocompromised patients
Doron S, Snydman DR. Risk and Safety of Probiotics. Clinical Infectious Diseases: 2015;60(Suppl 2):S129-S134. doi:10.1093/cid/civ085.
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Severe Infections are Declining in Many Countries, …
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But Antibiotics are the Most Commonly used Drugs in Western Countries
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Global Consumption of Antibiotics
TP Van Boeckel, Lancet Infect Dis.2014 742–750,
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Global Consumption of Antibiotics
TP Van Boeckel, Lancet Infect Dis.2014 742–750
Medical use of antibiotics increased 36% globally in a decade
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Use of antibiotics age in low resource settings
First antibiotic useage <2 years
Rogawski ET et al. Bull World Health Organ 2017;95:49-61
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Antibiotic prescription (age groups; 1000 individuals)
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Consequences of Antibiotic (Mis)use
• Antibiotic resistance
• Adverse drug events
• Drug side effects
• Antibiotic associated diarrhea (AAD)
• Clostridium difficile infection
• Disruption to microbiome (dysbiosis)
Ohl CA, Luther VP. J. Hosp. Med. 2011;6:S4
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After antibiotic exposure
Tight Junctions Disruption
Short ChainFatty Acids
Normal HGMDisruption HGM due to
antibiotic exposureDisturbed HGM and infection
(e.g., C difficile)
Luminal Osmosis
Inflammation
Antibiotic
AADBouhnik Y. Gut Microflora Digestive Physiology And Pathology. Paris; 2009:181-197.
Disruption Microbiome
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EUBIOSIS => “Normal" and "balanced" intestinal microbiota fulfills all the conditions for us to benefit from its health effects (metabolism, immunity, trophicity, barrier effect)
DYSBIOSIS => Intestinal dysbiosis can be defined as an unfavorable dysbalance of the intestinal microbiota.
vs
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The course of life of a microbiota
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Aim of the study
• Assess on healthy volunteers the effects on the gut microbiota of:
Ø Amoxicillin – Clavulanate (AC)
Ø Saccharomyces boulardii CNCM I-745 (Sb)
Ø AC in combination with Sb
• Assess the effects on gastro-intestinal symptoms, and especially antibiotic-associated
diarrhea (AAD)
Prospective randomized controlled study on the effects of Saccharomyces boulardii CNCM I-745 and
amoxicillin-clavulanate or the combination on the gut microbiota of healthy volunteers
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Biplot of Redundancy Analysis
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Urge to restrain unnecessary antibiotic prescription
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Recommendations for the use of probiotics in pediatric gastroenterology are now available
for most continents
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Considerations for clinician with probiotic strains in antibiotic-associated diarrhea (AAD) and
C. difficile-associated diarrhea (CDAD)
Physicians should evaluate the risk factors by:• Class of antibiotics (AAD reduction up to 60%) • Duration of antibiotic treatment• Need for hospitalization• Age• Co-morbidities• Previous episodes of AAD or CDAD
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Europe USA Latin America World APAC
(Cameron et al. 2017)c
Acute
gastroenteritis
T L. rhamnosus GG,
S. boulardii,
L reuteri
L. rhamnosus GG,
S. boulardii
L. rhamnosus GG,
S. boulardii,
L. reuteri
S. boulardii,
L. rhamnosus GG,
Indian Dahi
S. boulardii,
L. rhamnosus GG,
L reuteri
AAD P L. rhamnosus GG,
S. boulardii
L. rhamnosus GG,
S. boulardii
L. rhamnosus GG,
S. boulardii
S. boulardii;
L. rhamnosus GG,
B. lactis Bb12 + S.
thermophilus,
L. rhamnosus strains
E/N, Oxy and Pen
L rhamnosus GG
S.boulardii,
CDAD P S. boulardii S. boulardii
Recommendations for use of probiotics in childhood intestinal diseases by geographic region
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One size may not fit all
• Countries, climate, culture, politics• Conditions and diseases, indications• Socioeconomic status• Nutrition, diet• Microbiomes, pathogens• Antibiotic exposure• Vaccination
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• Antibiotic use in children could lead to long term disruption of the
microbiome with unknown, and possibly harmful, health effects
• Safe medical therapies (probiotics) are available for AGE/AAD/CDAD
• Positive evidence with probiotic drugs in these conditions mainly comes
from L. rhamnosus GG and S. boulardii CNCM I-745 strains
• Many other probiotics strains cannot be recommended because of
insufficient data or insufficient data on quality
• We need more good RCTs
Take home messages
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Thank you!