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      Reduction of group A beta-hemolytic streptococcus pharyngo-tonsillar infections associated with use of the oral probiotic Streptococcus salivarius K12: a retrospective observational study

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          Abstract

          Recurrent pharyngo-tonsillar infections caused by group A beta-hemolytic streptococci (GABHS) occur frequently in young children, and the treatment of these infections contributes substantially to the total current requirement for antibiotic prescribing. Our study goal was to assess through a retrospective observational analysis whether the administration of the oral probiotic, Streptococcus salivarius K12 (SsK12), could reduce the occurrence of GABHS pharyngo-tonsillar infections in children who had a recent history of recurrent episodes of these infections. Twelve primary care pediatricians identified, through their databases, a total of 130 children who had experienced recurrent GABHS pharyngo-tonsillar infections over a period of at least 6–12 months prior to their inclusion in the study. Of these children, 76 then undertook a 90-day program requiring once-a-day dosing with a commercially available (Bactoblis) lozenge containing SsK12. No probiotic supplement was given to the remaining 54 (control) children. Each subject was monitored for the occurrence of GABHS pharyngo-tonsillitis and also for acute otitis media, bronchitis, sinusitis, and bronchopneumonia for at least 12 months following their entry to the study. Even 9 months after the use of SsK12 had been stopped, the probability of new GABHS infections was significantly lower ( P>0.001) when compared to the period before dosing commenced. When compared to the untreated children, those taking SsK12 appear to have had significantly fewer GABHS infections both during the 90-day period of prophylaxis and during the following 9 months ( P<0.001). These observations are supportive of the use of probiotic SsK12 for the control of recurrent GABHS pharyngo-tonsillar infections in children, and as an associated benefit, the use of this probiotic could lead to reduced antibiotic consumption. Follow-up controlled prospective studies should now be initiated in order to further establish the efficacy of this newly emerging prophylactic strategy.

          Most cited references14

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          Empirical validation of guidelines for the management of pharyngitis in children and adults.

          Recent guidelines for management of pharyngitis vary in their recommendations concerning empirical antibiotic treatment and the need for laboratory confirmation of group A streptococcus (GAS). To assess the impact of guideline recommendations and alternative approaches on identification and treatment of GAS pharyngitis in children and adults. Throat cultures and rapid antigen tests were performed on 787 children and adults aged 3 to 69 years with acute sore throat attending a family medicine clinic in Calgary, Alberta, from September 1999 to August 2002. Recommendations from 2 guidelines (those of the Infectious Diseases Society of America and of the American College of Physicians-American Society of Internal Medicine/American Academy of Family Physicians/US Centers for Disease Control and Prevention) were compared with rapid testing alone, a clinical prediction rule (ie, the modified Centor score), and a criterion standard of treatment for positive throat culture results only. Sensitivity and specificity of each strategy for identifying GAS pharyngitis, total antibiotics recommended, and unnecessary antibiotic prescriptions. In children, sensitivity for streptococcal infection ranged from 85.8% (133/155; 95% confidence interval [CI], 79.3%-90.0%) for rapid testing to 100% for culturing all. In adults, sensitivity ranged from 76.7% (56/73; 95% CI, 65.4%-85.8%) for rapid testing without culture confirmation of negative results to 100% for culturing all. In children, specificity ranged from 90.3% (270/299; 95% CI, 86.4%-93.4%) for use of modified Centor score and throat culture to 100% for culturing all. In adults, specificity ranged from 43.8% (114/260; 95% CI, 37.7%-50.1%) for empirical treatment based on a modified Centor score of 3 or 4 to 100% for culturing all. Total antibiotic prescriptions were lowest with rapid testing (24.7% [194/787]; 95% CI, 21.7%-27.8%) and highest with empirical treatment of high-risk adults (45.7% [360/787]; 95% CI, 42.2%-49.3%), due to a high rate of unnecessary prescriptions in adults (43.8% [146/333]; 95% CI, 38.4%-49.4%). Guideline recommendations for the selective use of throat cultures but antibiotic treatment based only on positive rapid test or throat culture results can reduce unnecessary use of antibiotics for treatment of pharyngitis. However, empirical treatment of adults having a Centor score of 3 or 4 is associated with a high rate of unnecessary antibiotic use. In children, strategies incorporating throat culture or throat culture confirmation of negative rapid antigen test results are highly sensitive and specific. Throat culture of all adults or those selected on the basis of a clinical prediction rule had the highest sensitivity and specificity.
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            Safety assessment of the oral cavity probiotic Streptococcus salivarius K12.

            Streptococcus salivarius is a prominent member of the oral microbiota and has excellent potential for use as a probiotic targeting the oral cavity. In this report we document safety data relating to S. salivarius K12, including assessment of its antibiogram, metabolic profiles, and virulence determinants, and we examine the microbial composition of saliva following the dosing of subjects with K12.
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              Distribution and persistence of probiotic Streptococcus salivarius K12 in the human oral cavity as determined by real-time quantitative polymerase chain reaction.

              The bacteriocin producer Streptococcus salivarius K12 is used as a probiotic targeting the oral cavity, so our study aimed to assess whether its dispersal and persistence could be monitored using real-time quantitative polymerase chain reaction. To this end, we designed polymerase chain reaction primers and a hybridization probe specifically targeting salA, which encodes for the prepropeptide of salivaricin A. Using a single individual as our subject, we administered four lozenges of K12 Throat Guard per day over 3 days, then measured salA gene levels for 16 different oral sites at six different intervals over 35 days. Four samples each from gingival sulci and from teeth all remained negative. In contrast, in saliva and at all mucosal membranes K12 was detected, but with varying amounts and time profiles. Relatively high salA gene copy numbers, calibrated on the basis of colony-forming units, were seen on the tongue (maximum 4.6 x 10(4)/swab at day 4), in stimulated saliva (2.4 x 10(4)/ml, day 4) and on buccal membranes (1.3 x 10(4)/swab, day 8). K12 was present on both sides of the pharynx but asymmetrically in both quantity and duration. In conclusion, we have developed a real-time quantitative-polymerase chain reaction for counting S. salivarius K12 at various sites in the oral cavity. In the individual studied, K12 could be detected at the mucosal membranes for as long as 3 weeks, but with steadily decreasing numbers after day 8. Thus, K12 may have the potential to control oral bacterial infections only when the uptake is repeated frequently.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2016
                19 January 2016
                : 12
                : 87-92
                Affiliations
                [1 ]Primary Care Department, Local Health Unit (ASL), Piacenza, Italy
                [2 ]Department of Health Science (DISSAL), University of Genoa, Genoa, Italy
                Author notes
                Correspondence: Giuseppe Gregori, Primary Care Department, Local Health Unit (ASL), Via Conciliazione 45/A, 29121 Piacenza, Italy, Email g.greg@ 123456agonet.it
                Article
                tcrm-12-087
                10.2147/TCRM.S96134
                4725641
                26855579
                ed5d6c7f-7a7d-4839-93d9-bc766e66ed96
                © 2016 Gregori et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
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                Original Research

                Medicine
                recurrent pharyngo-tonsillar infections,group a beta-hemolytic streptococcus,streptococcus salivarius k12

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