Prebiotics and probiotics failed to prevent AOM

Andi L. Shane, MD, MPH, MSc

In a prospective multicenter, randomized, double-blind placebo-controlled study performed between November 2007 and April 2009 in France, researchers concluded that daily consumption of a probiotic and prebiotic supplemented formula did not reduce the risk of acute otitis media (AOM), recurrent AOM, antibiotic utilization or upper respiratory infections over a 12 month period among 224 children aged 7 to 13 months at high risk for AOM.

The intent-to-treat analysis included 112 subjects in the intervention and placebo group and 101 subjects in each group with the per protocol analysis. One hundred and sixty six (84%) children completed the study, with noncompliance being the most common reason for drop out. Neither the intent-to-treat nor per protocol analyses revealed differences in the incidence of AOM, episodes of recurrent AOM, lower respiratory tract infections, frequency of antibiotic courses, nor nasopharyngeal flora composition of S. pneumoniae, H. influenzae, or M. catarrhalis.

The strengths of the study included intent to use an AOM scoring instrument that has been developed and validated by the researchers (Paradise algorithm), requested limitation of probiotic-containing products during the study period, comprehensive periodic assessments, collection of volume of study product consumed daily, the collection of nasopharyngeal specimens periodically, and inclusion of potential confounding factors as covariates in the modeling.

Study weaknesses included permissiveness of AOM episodes not assessed clinically with the Paradise algorithm and inclusion of AOM episodes assessed by a non-study investigator. Furthermore, a microbiological etiology of AOM was not obtained, potentially resulting in opportunities for diagnostic bias. Although the original intent was to utilize a standardized clinical scoring system for assessment of AOM, this was replaced by a more permissive standard of deferring to any provider’s clinical assessment.

The three probiotic organisms in the commercially available formula were Streptococcusthermophilus NCC 2496,S.salivarius DSM13084, and Lactobacillus rhamnosus LPR CGMCC 1.3274 and Raftilose/Raftiline were the prebiotics. The researchers did not specify how the formula was reconstituted and did not provide any information about volumes consumed, although requested that at least 300 mL to 630 mL be consumed by each subject daily. Based on potential differences in volumes of reconstituted study product consumed, it is possible that the dose of probiotics and prebiotics consumed may have varied widely. Additionally, “breast-feeding” was assessed at baseline but data regarding human milk consumption during the study period was not provided. Human milk is a source of prebiotics and regular ingestion of human milk may have provided subjects with an unmeasured source of prebiotics.

Finally, the study authors title their manuscript, “Probiotics and Prebiotics in Preventing Episodes of AOM…” It is important to note that they studied three probiotic organisms in combination with two prebiotic products in a powdered formula that was reconstituted and administered by caretakers of the subjects. Caution must be exercised in extrapolating the findings of this study to concluding that all probiotics and prebiotics are ineffective in preventing AOM in high risk children. As an example, if ampicillin, gentamicin and metronidazole failed to treat a series of children with intra-abdominal abscess, one would not conclude that antibiotics are ineffective in treating intra-abdominal abscesses, but rather this combination of ampicillin, gentamicin, and metronidazole was ineffective in treating a series of intra-abdominal abscesses.

The study results must be considered within the context of potential variability in doses of probiotic organisms and prebiotic ingested, the clinical interpretation that led to AOM diagnoses, and the challenges associated with compliance with daily administration of a study product.

This study was well designed and the authors should be commended for their efforts to study the applications of a combination probiotic-prebiotic infant formula to prevent AOM and upper respiratory conditions in at-risk children. Additional studies with other probiotic and prebiotic products may provide additional evidence to support or refute their applications.