Acute respiratory tract infections (RTIs) of viral origin place a substantial burden on health care resources and society. Randomized controlled trials have shown positive effects of probiotics on clinical outcomes in these commonly occurring RTIs. Two meta-analyses published by the York Health Economics Consortium (YHEC) and Cochrane reported the efficacy of probiotics in reducing incidence and duration of RTIs, number of antibiotic courses, and days absent from work. The aim of this study was to assess the potential health-economic impact of probiotics on RTI-associated events and expenses in the US primary care setting. A state-transition microsimulation model reproduced a study population representative of the US national demographics for age and gender (1/1,000 sample). RTI incidence was based on the influenza-like illness outpatient consultation rate reported by the Centers for Disease Control and Prevention (CDC) FluView. Data on vaccination, on factors that negatively impact RTI outcomes, on resource utilization, and on productivity loss were obtained from US national databases. Analyses were performed for both meta-analyses independently. Outcomes included cost savings for the health care payer, related to a reduced number of RTI episodes, less outpatient consultations, and decreased medical prescriptions as well as cost savings from a broader societal perspective related to productivity loss. The analysis showed that generalized probiotic intake in the US population for 2017-2018 would have allowed cost savings for the health care payer of 4.6 million USD based on the YHEC scenario and 373 million USD for the Cochrane scenario, by averting 19 million and 54.5 million RTI sick days, respectively, compared to no probiotics. Antibiotic prescriptions decreased with 1.39-2.16 million courses, whereas absence from work decreased by 3.58-4.2 million days when applying the YHEC and Cochrane data, respectively. When productivity loss is included, total savings for society represented 784 million or 1.4 billion USD for the YHEC and Cochrane scenarios, respectively. Subgroup analyses demonstrated an incremental benefit of probiotics in at-risk groups, which might be of relevance for targeted interventions. Sensitivity analyses confirmed the robustness of the model outcomes. Our analysis demonstrated a positive impact of probiotics on the health care and economic burden of flu-like RTIs. Improved disease outcomes translated into considerable cost savings for both the payer and society.

[This corrects the article DOI: 10.3389/fphar.2019.00980.].

Probiotics are typically marketed as foods and dietary supplements, categories for products intended to maintain health in generally healthy populations and which, unlike drugs, cannot claim to treat or cure disease. This review addresses the existing evidence that probiotics are beneficial to healthy people. Our approach was to perform a descriptive review of efficacy evidence that probiotics can prevent urinary, vaginal, gastrointestinal, and respiratory infections, and improve risk factors associated with cardiovascular health or reduce antibiotic use. Other endpoints such as mental, dental, or immune health were not specifically addressed. We concluded that there is sufficient evidence of efficacy and safety for clinicians and consumers to consider using specific probiotics for some indications - such as the use of probiotics to support gut function during antibiotic use or to reduce the risk of respiratory tract infections - for certain people. However, we did not find a sufficiently high level of evidence to support unconditional, population-wide recommendations for other preventive endpoints we reviewed for healthy people. Although evidence for some indications is suggestive of the preventive benefits of probiotics, additional research is needed.

Background

Overall reduction of antibiotic use is a widely adopted public health goal. Given evidence that consuming probiotics reduce the incidence, duration and/or severity of certain types of common acute infections, we hypothesized that probiotics are associated with reduced antibiotic use. This systematic review of randomized controlled trials (RCTs) assessed the impact of probiotic supplementation (any strain, dose or duration), compared to placebo, on antibiotic utilization for common, acute infections in otherwise healthy people of all ages.

Methods

We searched 13 electronic databases including MEDLINE, Embase and CENTRAL from inception to 17th January 2017. Backward and forward citation searches were also conducted. Two reviewers independently selected studies for inclusion and extracted study data. We assessed risk of bias for individual studies using criteria adapted from the Centre for Reviews and Dissemination, and the quality of evidence for each outcome was assessed using the GRADE system. Studies that evaluated similar outcomes were pooled statistically in meta-analyses using a random-effects model.

Results

We screened 1533 citations, and of these, 17 RCTs met our predefined inclusion criteria. All 17 were conducted in infants and/or children with a primary aim of preventing acute respiratory tract infections, acute lower digestive tract infections or acute otitis media. Included studies used 13 probiotic formulations, all comprising single or combination Lactobacillus and Bifidobacterium delivered in a range of food or supplement products. Mean duration of probiotic supplementation ranged from 4 days to 9 months. Trial quality was variable. Meta-analysis demonstrated that infants and children who received probiotics to prevent acute illnesses had a lower risk of being prescribed antibiotics, relative to those who received placebo (Pooled Relative Risk = 0.71, 95% CI: 0.54-0.94). When restricted to five studies with a low risk of bias, the pooled relative risk was 0.46 (95% CI: 0.23-0.97). Significant statistical heterogeneity was present in effect size estimates, which appeared to be due to one trial which could partly be considered as an outlier.

Conclusions

Probiotics, provided to reduce the risk for common acute infections, may be associated with reduced antibiotic use in infants and children. Additional well-designed studies are needed to substantiate these findings in children and explore similar findings in other population groups.