Probiotics for preventing acute otitis media in children

Anna M. Scott, Justin Clark, Blair Julien, Farhana Islam, Kristian Roos, Keith Grimwood, Paul Little, Chris B. Del Mar

Research output: Contribution to journalReview articleResearchpeer-review

Abstract

Background

Acute otitis media (AOM), or acute middle ear infection, is one of the most frequently occurring childhood diseases, and the most common reason given for prescribing antibiotics in this age group. Guidelines often recommend antibiotics as first-line treatment for severe AOM. However, antibiotics also lead to antibiotic resistance, so preventing episodes of AOM is an urgent priority.

Objectives

To assess the effects of probiotics to prevent the occurrence and reduce the severity of acute otitis media in children.

Search methods

We searched CENTRAL, PubMed, Embase, and three other databases (October 2018), two trial registers (October 2018), and conducted a backwards and forwards citation analysis (August 2018). We did not apply any language, publication date, or publication status restrictions.

Selection criteria

Randomised controlled trials (RCTs) of children (aged up to 18 years), comparing probiotics with placebo, usual care, or no probiotic.

Data collection and analysis

Two review authors independently assessed the eligibility of trials for inclusion and risk of bias of the included trials, and extracted data using pre-piloted data extraction forms. We analysed dichotomous data as either risk ratio (RR) or odds ratios (OR) and continuous data as mean differences (MD).

Main results

We included 17 RCTs involving 3488 children, of which 16 RCTs were included in the meta-analyses. Of the 16 RCTs that reported the mean age of children, mean age overall was 2.4 years; in 4 RCTs the mean age of children participating in the trial was less than 1 year old; in 2 RCTs the mean age was between 1 and 2 years old; and in 10 RCTs the mean age was older than 2 years. Probiotic strains evaluated by the trials varied, with 11 of the included RCTs evaluating Lactobacillus-containing probiotics, and six RCTs evaluating Streptococcus-containing probiotics.

The proportion of children (i.e. the number of children in each group) experiencing one or more episodes of AOM during the treatment was lower for those taking probiotics (RR 0.77, 95% confidence interval (CI) 0.63 to 0.93; 16 trials; 2961 participants; number needed to treat for an additional beneficial outcome (NNTB) = 10; moderate-certainty evidence).

Post hoc subgroup analysis found that among children not prone to otitis media, a lower proportion of children receiving probiotics experienced AOM (RR 0.64, 95% CI 0.49 to 0.84; 11 trials; 2227 participants; NNTB = 9; moderate-certainty evidence). However, among children who were otitis prone, there was no difference between probiotic and comparator groups (RR 0.97, 95% CI 0.85 to 1.11; 5 trials; 734 participants; high-certainty evidence). The test for subgroup differences was significant (P = 0.007).

None of the included trials reported on the severity of AOM.

The proportion of children experiencing adverse events did not differ between the probiotic and comparator groups (OR 1.54, 95% CI 0.60 to 3.94; 4 trials; 395 participants; low-certainty evidence).

Probiotics decreased the proportion of children taking antibiotics for any infection (RR 0.66, 95% CI 0.51 to 0.86; 8 trials; 1768 participants; NNTB = 8; moderate-certainty evidence). Test for subgroup differences (use of antibiotic specifically for AOM, use of antibiotic for infections other than AOM) was not significant.

There was no difference in the mean number of school days lost (MD -0.95, 95% CI -2.47 to 0.57; 5 trials; 1280 participants; moderate-certainty evidence). There was no difference between groups in the level of compliance in taking the intervention (RR 1.02, 95% CI 0.99 to 1.05; 5 trials; 990 participants).

Probiotics decreased the proportion of children having other infections (RR 0.75, 95% CI 0.65 to 0.87; 11 trials; 3610 participants; NNTB = 12; moderate-certainty evidence). Test for subgroup differences (acute respiratory infections, gastrointestinal infections) was not significant.

Probiotic strains trialled and their dose, frequency, and duration of administration varied considerably across studies, which likely contributed to the substantial levels of heterogeneity. Sensitivity testing of funnel plots did not reveal publication bias.

Authors' conclusions

Probiotics may prevent AOM in children not prone to AOM, but the inconsistency of the subgroup analyses suggests caution in interpreting these results. Probiotics decreased the proportion of children taking antibiotics for any infection. The proportion of children experiencing adverse events did not differ between the probiotic and comparator groups. The optimal strain, duration, frequency, and timing of probiotic administration still needs to be established.

Original languageEnglish
Article numberCD012941
Number of pages89
JournalCochrane Database of Systematic Reviews
Volume2019
Issue number6
DOIs
Publication statusPublished - 18 Jun 2019

Fingerprint

Probiotics
Otitis Media
Odds Ratio
Confidence Intervals
Anti-Bacterial Agents
Infection
Publications
Otitis
Numbers Needed To Treat
Publication Bias
Lactobacillus
Middle Ear
Microbial Drug Resistance
Streptococcus
PubMed
Respiratory Tract Infections

Cite this

Scott, Anna M. ; Clark, Justin ; Julien, Blair ; Islam, Farhana ; Roos, Kristian ; Grimwood, Keith ; Little, Paul ; Del Mar, Chris B. / Probiotics for preventing acute otitis media in children. In: Cochrane Database of Systematic Reviews. 2019 ; Vol. 2019, No. 6.
@article{79f0e11cf51949e9b278c9c7267cd5ba,
title = "Probiotics for preventing acute otitis media in children",
abstract = "BackgroundAcute otitis media (AOM), or acute middle ear infection, is one of the most frequently occurring childhood diseases, and the most common reason given for prescribing antibiotics in this age group. Guidelines often recommend antibiotics as first-line treatment for severe AOM. However, antibiotics also lead to antibiotic resistance, so preventing episodes of AOM is an urgent priority.ObjectivesTo assess the effects of probiotics to prevent the occurrence and reduce the severity of acute otitis media in children.Search methodsWe searched CENTRAL, PubMed, Embase, and three other databases (October 2018), two trial registers (October 2018), and conducted a backwards and forwards citation analysis (August 2018). We did not apply any language, publication date, or publication status restrictions.Selection criteriaRandomised controlled trials (RCTs) of children (aged up to 18 years), comparing probiotics with placebo, usual care, or no probiotic.Data collection and analysisTwo review authors independently assessed the eligibility of trials for inclusion and risk of bias of the included trials, and extracted data using pre-piloted data extraction forms. We analysed dichotomous data as either risk ratio (RR) or odds ratios (OR) and continuous data as mean differences (MD).Main resultsWe included 17 RCTs involving 3488 children, of which 16 RCTs were included in the meta-analyses. Of the 16 RCTs that reported the mean age of children, mean age overall was 2.4 years; in 4 RCTs the mean age of children participating in the trial was less than 1 year old; in 2 RCTs the mean age was between 1 and 2 years old; and in 10 RCTs the mean age was older than 2 years. Probiotic strains evaluated by the trials varied, with 11 of the included RCTs evaluating Lactobacillus-containing probiotics, and six RCTs evaluating Streptococcus-containing probiotics.The proportion of children (i.e. the number of children in each group) experiencing one or more episodes of AOM during the treatment was lower for those taking probiotics (RR 0.77, 95{\%} confidence interval (CI) 0.63 to 0.93; 16 trials; 2961 participants; number needed to treat for an additional beneficial outcome (NNTB) = 10; moderate-certainty evidence).Post hoc subgroup analysis found that among children not prone to otitis media, a lower proportion of children receiving probiotics experienced AOM (RR 0.64, 95{\%} CI 0.49 to 0.84; 11 trials; 2227 participants; NNTB = 9; moderate-certainty evidence). However, among children who were otitis prone, there was no difference between probiotic and comparator groups (RR 0.97, 95{\%} CI 0.85 to 1.11; 5 trials; 734 participants; high-certainty evidence). The test for subgroup differences was significant (P = 0.007).None of the included trials reported on the severity of AOM.The proportion of children experiencing adverse events did not differ between the probiotic and comparator groups (OR 1.54, 95{\%} CI 0.60 to 3.94; 4 trials; 395 participants; low-certainty evidence).Probiotics decreased the proportion of children taking antibiotics for any infection (RR 0.66, 95{\%} CI 0.51 to 0.86; 8 trials; 1768 participants; NNTB = 8; moderate-certainty evidence). Test for subgroup differences (use of antibiotic specifically for AOM, use of antibiotic for infections other than AOM) was not significant.There was no difference in the mean number of school days lost (MD -0.95, 95{\%} CI -2.47 to 0.57; 5 trials; 1280 participants; moderate-certainty evidence). There was no difference between groups in the level of compliance in taking the intervention (RR 1.02, 95{\%} CI 0.99 to 1.05; 5 trials; 990 participants).Probiotics decreased the proportion of children having other infections (RR 0.75, 95{\%} CI 0.65 to 0.87; 11 trials; 3610 participants; NNTB = 12; moderate-certainty evidence). Test for subgroup differences (acute respiratory infections, gastrointestinal infections) was not significant.Probiotic strains trialled and their dose, frequency, and duration of administration varied considerably across studies, which likely contributed to the substantial levels of heterogeneity. Sensitivity testing of funnel plots did not reveal publication bias.Authors' conclusionsProbiotics may prevent AOM in children not prone to AOM, but the inconsistency of the subgroup analyses suggests caution in interpreting these results. Probiotics decreased the proportion of children taking antibiotics for any infection. The proportion of children experiencing adverse events did not differ between the probiotic and comparator groups. The optimal strain, duration, frequency, and timing of probiotic administration still needs to be established.",
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Probiotics for preventing acute otitis media in children. / Scott, Anna M.; Clark, Justin; Julien, Blair; Islam, Farhana; Roos, Kristian; Grimwood, Keith; Little, Paul; Del Mar, Chris B.

In: Cochrane Database of Systematic Reviews, Vol. 2019, No. 6, CD012941, 18.06.2019.

Research output: Contribution to journalReview articleResearchpeer-review

TY - JOUR

T1 - Probiotics for preventing acute otitis media in children

AU - Scott, Anna M.

AU - Clark, Justin

AU - Julien, Blair

AU - Islam, Farhana

AU - Roos, Kristian

AU - Grimwood, Keith

AU - Little, Paul

AU - Del Mar, Chris B.

PY - 2019/6/18

Y1 - 2019/6/18

N2 - BackgroundAcute otitis media (AOM), or acute middle ear infection, is one of the most frequently occurring childhood diseases, and the most common reason given for prescribing antibiotics in this age group. Guidelines often recommend antibiotics as first-line treatment for severe AOM. However, antibiotics also lead to antibiotic resistance, so preventing episodes of AOM is an urgent priority.ObjectivesTo assess the effects of probiotics to prevent the occurrence and reduce the severity of acute otitis media in children.Search methodsWe searched CENTRAL, PubMed, Embase, and three other databases (October 2018), two trial registers (October 2018), and conducted a backwards and forwards citation analysis (August 2018). We did not apply any language, publication date, or publication status restrictions.Selection criteriaRandomised controlled trials (RCTs) of children (aged up to 18 years), comparing probiotics with placebo, usual care, or no probiotic.Data collection and analysisTwo review authors independently assessed the eligibility of trials for inclusion and risk of bias of the included trials, and extracted data using pre-piloted data extraction forms. We analysed dichotomous data as either risk ratio (RR) or odds ratios (OR) and continuous data as mean differences (MD).Main resultsWe included 17 RCTs involving 3488 children, of which 16 RCTs were included in the meta-analyses. Of the 16 RCTs that reported the mean age of children, mean age overall was 2.4 years; in 4 RCTs the mean age of children participating in the trial was less than 1 year old; in 2 RCTs the mean age was between 1 and 2 years old; and in 10 RCTs the mean age was older than 2 years. Probiotic strains evaluated by the trials varied, with 11 of the included RCTs evaluating Lactobacillus-containing probiotics, and six RCTs evaluating Streptococcus-containing probiotics.The proportion of children (i.e. the number of children in each group) experiencing one or more episodes of AOM during the treatment was lower for those taking probiotics (RR 0.77, 95% confidence interval (CI) 0.63 to 0.93; 16 trials; 2961 participants; number needed to treat for an additional beneficial outcome (NNTB) = 10; moderate-certainty evidence).Post hoc subgroup analysis found that among children not prone to otitis media, a lower proportion of children receiving probiotics experienced AOM (RR 0.64, 95% CI 0.49 to 0.84; 11 trials; 2227 participants; NNTB = 9; moderate-certainty evidence). However, among children who were otitis prone, there was no difference between probiotic and comparator groups (RR 0.97, 95% CI 0.85 to 1.11; 5 trials; 734 participants; high-certainty evidence). The test for subgroup differences was significant (P = 0.007).None of the included trials reported on the severity of AOM.The proportion of children experiencing adverse events did not differ between the probiotic and comparator groups (OR 1.54, 95% CI 0.60 to 3.94; 4 trials; 395 participants; low-certainty evidence).Probiotics decreased the proportion of children taking antibiotics for any infection (RR 0.66, 95% CI 0.51 to 0.86; 8 trials; 1768 participants; NNTB = 8; moderate-certainty evidence). Test for subgroup differences (use of antibiotic specifically for AOM, use of antibiotic for infections other than AOM) was not significant.There was no difference in the mean number of school days lost (MD -0.95, 95% CI -2.47 to 0.57; 5 trials; 1280 participants; moderate-certainty evidence). There was no difference between groups in the level of compliance in taking the intervention (RR 1.02, 95% CI 0.99 to 1.05; 5 trials; 990 participants).Probiotics decreased the proportion of children having other infections (RR 0.75, 95% CI 0.65 to 0.87; 11 trials; 3610 participants; NNTB = 12; moderate-certainty evidence). Test for subgroup differences (acute respiratory infections, gastrointestinal infections) was not significant.Probiotic strains trialled and their dose, frequency, and duration of administration varied considerably across studies, which likely contributed to the substantial levels of heterogeneity. Sensitivity testing of funnel plots did not reveal publication bias.Authors' conclusionsProbiotics may prevent AOM in children not prone to AOM, but the inconsistency of the subgroup analyses suggests caution in interpreting these results. Probiotics decreased the proportion of children taking antibiotics for any infection. The proportion of children experiencing adverse events did not differ between the probiotic and comparator groups. The optimal strain, duration, frequency, and timing of probiotic administration still needs to be established.

AB - BackgroundAcute otitis media (AOM), or acute middle ear infection, is one of the most frequently occurring childhood diseases, and the most common reason given for prescribing antibiotics in this age group. Guidelines often recommend antibiotics as first-line treatment for severe AOM. However, antibiotics also lead to antibiotic resistance, so preventing episodes of AOM is an urgent priority.ObjectivesTo assess the effects of probiotics to prevent the occurrence and reduce the severity of acute otitis media in children.Search methodsWe searched CENTRAL, PubMed, Embase, and three other databases (October 2018), two trial registers (October 2018), and conducted a backwards and forwards citation analysis (August 2018). We did not apply any language, publication date, or publication status restrictions.Selection criteriaRandomised controlled trials (RCTs) of children (aged up to 18 years), comparing probiotics with placebo, usual care, or no probiotic.Data collection and analysisTwo review authors independently assessed the eligibility of trials for inclusion and risk of bias of the included trials, and extracted data using pre-piloted data extraction forms. We analysed dichotomous data as either risk ratio (RR) or odds ratios (OR) and continuous data as mean differences (MD).Main resultsWe included 17 RCTs involving 3488 children, of which 16 RCTs were included in the meta-analyses. Of the 16 RCTs that reported the mean age of children, mean age overall was 2.4 years; in 4 RCTs the mean age of children participating in the trial was less than 1 year old; in 2 RCTs the mean age was between 1 and 2 years old; and in 10 RCTs the mean age was older than 2 years. Probiotic strains evaluated by the trials varied, with 11 of the included RCTs evaluating Lactobacillus-containing probiotics, and six RCTs evaluating Streptococcus-containing probiotics.The proportion of children (i.e. the number of children in each group) experiencing one or more episodes of AOM during the treatment was lower for those taking probiotics (RR 0.77, 95% confidence interval (CI) 0.63 to 0.93; 16 trials; 2961 participants; number needed to treat for an additional beneficial outcome (NNTB) = 10; moderate-certainty evidence).Post hoc subgroup analysis found that among children not prone to otitis media, a lower proportion of children receiving probiotics experienced AOM (RR 0.64, 95% CI 0.49 to 0.84; 11 trials; 2227 participants; NNTB = 9; moderate-certainty evidence). However, among children who were otitis prone, there was no difference between probiotic and comparator groups (RR 0.97, 95% CI 0.85 to 1.11; 5 trials; 734 participants; high-certainty evidence). The test for subgroup differences was significant (P = 0.007).None of the included trials reported on the severity of AOM.The proportion of children experiencing adverse events did not differ between the probiotic and comparator groups (OR 1.54, 95% CI 0.60 to 3.94; 4 trials; 395 participants; low-certainty evidence).Probiotics decreased the proportion of children taking antibiotics for any infection (RR 0.66, 95% CI 0.51 to 0.86; 8 trials; 1768 participants; NNTB = 8; moderate-certainty evidence). Test for subgroup differences (use of antibiotic specifically for AOM, use of antibiotic for infections other than AOM) was not significant.There was no difference in the mean number of school days lost (MD -0.95, 95% CI -2.47 to 0.57; 5 trials; 1280 participants; moderate-certainty evidence). There was no difference between groups in the level of compliance in taking the intervention (RR 1.02, 95% CI 0.99 to 1.05; 5 trials; 990 participants).Probiotics decreased the proportion of children having other infections (RR 0.75, 95% CI 0.65 to 0.87; 11 trials; 3610 participants; NNTB = 12; moderate-certainty evidence). Test for subgroup differences (acute respiratory infections, gastrointestinal infections) was not significant.Probiotic strains trialled and their dose, frequency, and duration of administration varied considerably across studies, which likely contributed to the substantial levels of heterogeneity. Sensitivity testing of funnel plots did not reveal publication bias.Authors' conclusionsProbiotics may prevent AOM in children not prone to AOM, but the inconsistency of the subgroup analyses suggests caution in interpreting these results. Probiotics decreased the proportion of children taking antibiotics for any infection. The proportion of children experiencing adverse events did not differ between the probiotic and comparator groups. The optimal strain, duration, frequency, and timing of probiotic administration still needs to be established.

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U2 - 10.1002/14651858.CD012941.pub2

DO - 10.1002/14651858.CD012941.pub2

M3 - Review article

VL - 2019

JO - Cochrane database of systematic reviews (Online)

JF - Cochrane database of systematic reviews (Online)

SN - 1469-493X

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