Streptococcus salivarius Probiotics to Prevent Acute Otitis Media in Children
MD Suvi Sarlin, MD, PhD Ulla Koskela, MD, PhD Minna Honkila, MD Paula A Tähtinen, PhD Tytti Pokka, MSc Marjo Renko, PhD Terhi Tapiainen
JAMA Network Open, doi:10.1001/jamanetworkopen.2023.40608
IMPORTANCE New approaches for the prevention of acute otitis media (AOM), the most common reason for antibiotic use in children, are needed. OBJECTIVE To assess the efficacy of the Streptococcus salivarius K12 oral probiotics in the primary prevention of AOM. DESIGN, SETTING, AND PARTICIPANTS This double-blind, randomized placebo-controlled clinical trial was conducted from August 1, 2020, to May 31, 2021, at 50 day care centers in the Oulu region of Finland. A total of 827 children aged 1 to 6 years attending day care were included. The exclusion criteria consisted of ongoing antimicrobial prophylaxis or immunodeficiency. The follow-up time was 6 months and was completed on May 31, 2021. Data were analyzed from October 24, 2022, to September 16, 2023, based on intention to treat. INTERVENTION Eligible participants were randomly allocated to receive 1 daily dose of a S salivarius K12 product or placebo every evening for 6 months. A daily dose was defined as 1 sachet of soluble oral powder for children younger than 3 years or 1 chewable tablet for children 3 years or older containing 1 × 10 9 colony-forming units of S salivarius K12.
MAIN OUTCOMES AND MEASURES The primary outcome was the proportion of children with at least 1 episode of AOM requiring antimicrobial therapy within 6 months of randomization. All physician visits and purchases of antimicrobial drugs were retrieved from the electronic national medical record and prescription register. The primary outcome was met if the legal guardian had purchased an antimicrobial prescription for AOM.
RESULTS A total of 827 children with a mean (SD) age of 4.1 (1.6) years (433 boys [52.4%]) were randomized to S salivarius K12 oral products (n = 413) or placebo (n = 414). Thirty-four children (8.2%) in the S salivarius group and 24 children (5.8%) in the placebo group experienced at least 1 episode of AOM requiring antimicrobial therapy during the 6-month follow-up period (relative risk, 1.42 [95% CI, 0.86-2.34]; proportion difference, -2.44% [95% CI, -5.94% to 1.09%]; P = .17). Time to first AOM episode did not differ between the groups (174 [95% CI, 171-177] days in the S salivarius group vs 176 [95% CI, 173-179] days in the placebo group; P = .18).
CONCLUSIONS AND RELEVANCE In this randomized placebo-controlled clinical trial, the daily use of the S salivarius K12 products for 6 months did not reduce the occurrence of AOM. New approaches for primary prevention of AOM among children are needed.
Additional Contributions: We thank the staff at day care centers in the cities of Oulu, Kempele, Tyrnävä, Liminka, and Muhos, Finland. Aino Ruohola, MD, PhD, University of Turku, Turku, Finland, provided discussions and comments throughout the study and Leena Okkonen, RN, Oulu University Hospital Oulu, Oulu, Finland, helped in the project in her role as study nurse; they were not compensated financially for their contributions.
References
Armitage, Berry, Matthews, JAMA Network Open | Pediatrics Effectiveness of S salivarius Probiotics to Prevent Acute Otitis Media in Children JAMA Network Open
Chonmaitree, Jennings, Golovko, Nasopharyngeal microbiota in infants and changes during viral upper respiratory tract infection and acute otitis media, PLoS One,
doi:10.1371/journal.pone.0180630Franch-Llasat, Bellaubí-Pallarés, Mo, Chamarro-Martí, García-Rodríguez et al., Pneumococcal meningitis secondary to otitis media in two patients with COVID-19 Omicron variant, Int J Emerg Med,
doi:10.1186/s12245-022-00448-yHatakka, Blomgren, Pohjavuori, Treatment of acute otitis media with probiotics in otitis-prone children-a double-blind, placebo-controlled randomised study, Clin Nutr,
doi:10.1016/j.clnu.2007.01.003Hullegie, Schilder, Marchisio, A strong decline in the incidence of childhood otitis media during the COVID-19 pandemic in the Netherlands, Front Cell Infect Microbiol,
doi:10.3389/fcimb.2021.768377Jokinen, Palmu, Kilpi, Acute otitis media replacement and recurrence in the Finnish Otitis Media Vaccine trial, Clin Infect Dis,
doi:10.1093/cid/cis799Kadambari, Goldacre, Morris, Goldacre, Pollard, Indirect effects of the COVID-19 pandemic on childhood infection in England: population based observational study, BMJ,
doi:10.1136/bmj-2021-067519Karppinen, Toivonen, Schuez-Havupalo, Effectiveness of the ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against all respiratory tract infections in children under two years of age, Vaccine,
doi:10.1016/j.vaccine.2019.04.026Kuitunen, Artama, Haapanen, Renko, Rhinovirus spread in children during the COVID-19 pandemic despite social restrictions-a nationwide register study in Finland, J Med Virol,
doi:10.1002/jmv.27180Kuitunen, Artama, Mäkelä, Backman, Heiskanen-Kosma et al., Effect of social distancing due to the COVID-19 pandemic on the incidence of viral respiratory tract infections in children in Finland during early 2020, Pediatr Infect Dis J,
doi:10.1097/INF.0000000000002845Kuitunen, Renko, Antibiotic prescriptions during the first 2 years of the COVID-19 pandemic in Finnish children, Acta Paediatr,
doi:10.1111/apa.16515Kumpu, Kekkonen, Kautiainen, Milk containing probiotic Lactobacillus rhamnosus GG and respiratory illness in children: a randomized, double-blind, placebo-controlled trial, Eur J Clin Nutr,
doi:10.1038/ejcn.2012.62Lévesque, Lamothe, Frenette, Coaggregation of Streptococcus salivarius with periodontopathogens: evidence for involvement of fimbriae in the interaction with Prevotella intermedia, Oral Microbiol Immunol,
doi:10.1034/j.1399-302X.2003.00085.xMarchisio, Santagati, Scillato, Streptococcus salivarius 24SMB administered by nasal spray for the prevention of acute otitis media in otitis-prone children, Eur J Clin Microbiol Infect Dis,
doi:10.1007/s10096-015-2491-xMarom, Schwarz, Gluck, Ginzburg, Tamir, Trends in pediatric acute otitis media burden during the first COVID-19 year, Otol Neurotol,
doi:10.1097/MAO.0000000000003581Pierro, Colombo, Giuliani, Effect of administration of Streptococcus salivarius K12 on the occurrence of streptococcal pharyngo-tonsillitis, scarlet fever and acute otitis media in 3 years old children, Eur Rev Med Pharmacol Sci
Pierro, Pasquale, Cicco, Oral use of Streptococcus salivarius K12 in children with secretory otitis media: preliminary results of a pilot, uncontrolled study, Int J Gen Med,
doi:10.2147/IJGM.S92488Power, Burton, Chilcott, Dawes, Tagg, Preliminary investigations of the colonisation of upper respiratory tract tissues of infants using a paediatric formulation of the oral probiotic Streptococcus salivarius K12, Eur J Clin Microbiol Infect Dis,
doi:10.1007/s10096-008-0569-4Roos, Håkansson, Holm, Effect of recolonisation with "interfering" alpha streptococci on recurrences of acute and secretory otitis media in children: randomised placebo controlled trial, BMJ,
doi:10.1136/bmj.322.7280.210Sarlin, Tejesvi, Turunen, Impact of Streptococcus salivarius K12 on nasopharyngeal and saliva microbiome: a randomized controlled trial, Pediatr Infect Dis J,
doi:10.1097/INF.0000000000003016Services, None
Tapiovaara, Lehtoranta, Swanljung, Lactobacillus rhamnosus GG in the middle ear after randomized, double-blind, placebo-controlled oral administration, Int J Pediatr Otorhinolaryngol,
doi:10.1016/j.ijporl.2014.07.011Vesikari, Forsten, Seppä, Effectiveness of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugated vaccine (PHiD-CV) against carriage and acute otitis media-a double-blind randomized clinical trial in Finland, J Pediatric Infect Dis Soc,
doi:10.1093/jpids/piw010Zupancic, Kriksic, Kovacevic, Kovacevic, Influence of oral probiotic Streptococcus salivarius K12 on ear and oral cavity health in humans: a systematic review, Probiotics Antimicrob Proteins,
doi:10.1007/s12602-017-9261-2
