Probiotics for preventing acute otitis media in children.

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.

Paradigm shift in Sweden from tonsillectomy to tonsillotomy for children with upper airway obstructive symptoms due to tonsillar hypertrophy.

Tonsillotomy (TT) is now used more often than tonsillectomy (TE) for tonsil obstructive symptoms in Sweden. Both TE and TT give high patient satisfaction although TT results in fewer postoperative bleedings and shorter time when analgesics are needed. The objective of this study is to analyze the current prevalence of different tonsil surgery procedures, the rates of early and late bleeding and other complications. Data from the National Tonsil Surgery Register in Sweden were analyzed. Patients 1-15 years operated for symptoms due to tonsil hypertrophy were included. Surgical procedure, technique and bleedings during hospital stay were registered. Thirty days after surgery, unplanned contacts due to bleeding, infection or pain were reported as were symptom relief after 6 months. 24,083 patients were registered. Of the 10,826 children 1-15 years operated for obstructive symptoms, 64 % were TT or TT+A, and 34 % TE, TE+A. 69 % answered the 30-day questionnaire and 50 % the 6 months. Bleeding in hospital occurred in 1.38 %, late bleedings in 2.06 %: 3.7 % after TE+A, 0.8 % after TT+A. Differences in readmissions due to bleeding, number of days using analgesics, health care contacts due to pain and nosocomial infections were significant between TT and TE, but not differences with regard to symptom relief after 6 months.

Upper Respiratory Microbiota in Relation to Ear and Nose Health Among Australian Aboriginal and Torres Strait Islander Children.

BACKGROUND: We explored the nasal microbiota in Indigenous Australian children in relation to ear and nasal health. METHODS: In total, 103 Indigenous Australian children aged 2-7 years (mean 4.7 years) were recruited from 2 Queensland communities. Children's ears, nose, and throats were examined and upper respiratory tract (URT) swabs collected. Clinical histories were obtained from parents/medical records. URT microbiota were characterized using culturomics with Matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) identification. Real-time PCR was used to quantify otopathogen (Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis) loads and detect respiratory viruses. Data were analyzed using beta diversity measures, regression modeling, and a correlation network analysis. RESULTS: Children with historical/current otitis media (OM) or URT infection (URTI) had higher nasal otopathogen detection and loads and rhinovirus detection compared with healthy children (all P < .04). Children with purulent rhinorrhea had higher nasal otopathogen detection and loads and rhinovirus detection (P < .04) compared with healthy children. High otopathogen loads were correlated in children with historical/current OM or URTI, whereas Corynebacterium pseudodiphtheriticum and Dolosigranulum pigrum were correlated in healthy children. CONCLUSIONS: Corynebacterium pseudodiphtheriticum and D. pigrum are associated with URT and ear health. The importance of the main otopathogens in URT disease/OM was confirmed, and their role relates to co-colonization and high otopathogens loads.

Inflammatory Mediator Profiles in Secretory Otitis Media in Relationship to Viable Bacterial Pathogens and Bacterial and Viral Nucleic Acids.

Secretory otitis media (SOM) is characterized by persistence of fluid in the middle ear, often following an episode of acute otitis media. Our hypothesis is that failure to eliminate bacterial or viral pathogens may result in persistent low-grade inflammation. In this study, we analyzed inflammatory mediators in middle ear fluids from 67 children with SOM. This was combined with determinations of viable bacteria by culture along with detection of bacterial and viral genetic material by real-time polymerase chain reaction (PCR). The inflammatory mediators found at the highest concentrations (>30 ng/mL) were stem cell growth factor-ß (median 110 ng/mL), CXCL1, IL-16, IL-8, migration inhibitory factor, CXCL10, and CXCL9. Among bacterial pathogens, Moraxella catarrhalis and Haemophilus influenzae dominated, regardless of detection methods, while rhinovirus dominated among viral pathogens. Middle ear fluid levels of interleukin (IL)-1α, IL-17, IL-1ß, fibroblast growth factor basic, and tumor necrosis factor correlated strongly with presence of bacteria detected either by culture or PCR, while IL-1RA, IL-3, IL-6, IL-8, CCL3, CCL4, and granulocyte-colony stimulating factor correlated significantly with real-time PCR values. CXCL10, CXCL9, CCL2, and TRAIL correlated significantly with viral nucleic acid levels. To conclude, persistence of viral and bacterial pathogens may fuel persistent inflammation in SOM. Bacteria caused a broad inflammatory response, while viruses chiefly elicited the interferon-induced chemokines CXCL9 and CXCL10.

High Cytokine Levels in Tonsillitis Secretions Regardless of Presence of Beta-Hemolytic Streptococci.

Acute pharyngotonsillitis denotes tonsillar inflammation caused by bacteria or viruses. Here, we investigated if beta-hemolytic streptococci (ß-HS) tonsillitis would differ in inflammatory mediator response from tonsillitis of other causes. Tonsillar secretions were obtained from 36 acute pharyngotonsillitis patients and 16 controls. Bacteria were cultured quantitatively and 18 different viruses were quantified by real-time polymerase chain reaction. Cytokine and prostaglandin E2 (PGE2) levels were determined by enzyme-linked immunosorbent assays. Almost half of the patients' tonsillar secretions yielded high counts of ß-HS, and most samples contained viruses, irrespective of whether ß-HS were present or not. The Epstein-Barr virus (EBV) was the most common virus (patients 62% and controls 13%). Compared to controls, patients' secretions had higher levels of interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF), and PGE2, while few samples contained IL-12, IL-10, or interferon-gamma (IFN-γ). The presence of ß-HS in tonsillitis secretions could not be distinguished by any of the measured mediators, while the presence of EBV DNA tended to be associated with enhanced levels of IL-1ß and IL-8. The results suggest a common inflammatory response in acute pharyngotonsillitis, regardless of causative agent. The suggested correlation between intense inflammation and the presence of EBV DNA in tonsillitis secretions may be due to reactivation of the virus and/or the EBV-containing B cells.

Tonsil surgery efficiently relieves symptoms: analysis of 54 696 patients in the National Tonsil Surgery Register in Sweden.

CONCLUSION: Patients operated with tonsillar surgery report a high degree of symptom relief 6 months after surgery. OBJECTIVE: The purpose of this study was to analyze symptom relief 6 months after tonsil surgery in relation to age, indication, surgical procedure, primary bleeding and unplanned postoperative visits. The National Tonsil Surgery Register in Sweden offers data from 54,696 patients registered during 1997-2008. METHODS: This was a prospective assessment by questionnaire. Data were collected using three questionnaires, two completed by professionals and one 6 months postoperatively by the parents/patients. RESULTS: Among 54,696 patients, the most common surgical indications were obstruction (49.7%), followed by recurrent tonsillitis (35.2%). Symptom relief 6 months after surgery was high in all indication groups (>92%), and highest for patients operated on the indication peritonsillitis (>98%). The indications obstruction, recurrent tonsillitis or chronic tonsillitis reported a high degree (>96%) of symptom relief. Of the patients who underwent tonsillectomy with adenoidectomy, 97.5% were symptom-free compared to 96% of patients who had tonsillectomy alone and 96.1% who underwent tonsillotomy (p < 0.0001). In all, 13.9% of patients required an unplanned visit to the clinic postoperatively. Only 148 of 54,696 patients reported worsening of symptoms after surgery.

Bacterial interference in upper respiratory tract infections: a systematic review.

BACKGROUND: Published definitions of bacterial interference (BI) differ, some focusing on changes in the normal flora and others on changes in subsequent infection. A need for consensus was identified at a roundtable discussion of BI in upper respiratory tract infections (URTI). We conducted a systematic review of the available data to justify a consensus definition of BI specific to URTI as "a dynamic, antagonistic interaction between at least 2 organisms that affects the life cycle of each, changes the microenvironment, and alters the organisms' colonization, invasiveness, and ability to affect the health of the host." METHODS: Continued communication among the faculty postroundtable was used to identify and refine the search criteria to (1) in vitro and in vivo studies assessing bacterial URTI, (2) BI evaluated by response to treatment of URTI with antimicrobial agents, and (3) bacterial function in relation to interactions between normal (nonpathogenic) and pathological flora. The criteria were applied to systematic searches of MEDLINE (1950 onward), EMBASE (1974 onward), and the Cochrane Library (2007). RESULTS: Twenty-nine studies met the inclusion criteria, most focused on children with recurrent infections. Qualitative analysis supports the consensus definition. Interfering organisms affected the life cycle of test pathogens and inhibited their colonization, invasiveness, and health outcomes. Data were insufficient for statistical analysis. CONCLUSION: Interactions between interfering organisms and potential pathogens isolated from the same host can alter response to infection and treatment. More studies are needed, particularly in adults, to understand the role of interfering organisms, the influence of antibiotics, and the potential for recolonization posttreatment.

Reduced risk of primary postoperative hemorrhage after tonsil surgery in Sweden: results from the National Tonsil Surgery Register in Sweden covering more than 10 years and 54,696 operations.

OBJECTIVES/HYPOTHESIS: To analyze the incidence of primary bleeding following tonsil surgery and to evaluate risk factors. STUDY DESIGN: Register study of the results from the National Tonsil Surgery Register in Sweden covering the period 1997 to 2008 and 54,696 operations. METHODS: Data were collected by means of three questionnaires, two filled in by professionals and one 6 months postoperatively by the patient/parent. RESULTS: A total of 719 patients experienced primary postoperative bleeding during the hospital stay (1.3%). A number of independent factors were correlated with decreased risk of post-tonsillectomy hemorrhage: younger age (P < .0001), female sex (P < .0001), type of surgery (tonsillotomy) (P = .0006), and surgery performed on a day-surgery basis (P < .0001). Indication for surgery and number of operations performed at the department did not correlate with postoperative bleeding risk. A significant decrease in primary postoperative hemorrhage rate from 2% to 0.96% was found during the study period. CONCLUSIONS: Primary hemorrhage following tonsil surgery is rare. During the study period, a significant decrease in primary bleeding rates occurred. The changes in practice with an increasing proportion of day-surgery cases and tonsillotomy have contributed to the reduced risk, but cannot completely explain the reduction.

Final pH affects the interference capacity of naturally occurring oral Lactobacillus strains against mutans streptococci.

OBJECTIVES: To establish the effects of three factors: previous caries experience; colonization of Streptococcus mutans; and final pH on autologous lactobacilli-mediated inhibition against a panel of mutans streptococci in young subjects with different caries experiences. DESIGN: The inhibition capacity was determined by the use of the agar overlay method and the final pH in culture medium was measured after 20 h. Using a logistic regression model, the risk of having an incomplete lactobacilli-mediated inhibition was calculated. RESULTS: All three factors significantly influenced the interference outcome in the order; final pH of the Lactobacillus strains, oral colonization of autologous S. mutans and caries experience. A high risk occurred at a lower pH and at a wider pH range for individuals with previous caries experience and autologous colonization of S. mutans compared with caries-free subjects who were not colonized. At a final pH of 4.0, this risk was approximately eight times higher than that of the latter group. Two mutans Streptococcus strains in the test panel demonstrated high individual predictive values of inhibition mediated by oral lactobacilli. CONCLUSIONS: Generation of a low pH either directly via organic acid production and/or production of bacteriocins or metabolites at a low pH may promote mutans Streptococcus growth inhibition, in vitro. Furthermore, a shift of pH range for the risk of incomplete inhibition of mutans streptococci suggests a less effective inhibition at a wider pH range for naturally occurring lactobacilli from individuals with earlier caries experience containing own S. mutans.

Lactobacillus-mediated interference of mutans streptococci in caries-free vs. caries-active subjects.

In order to assess whether naturally occurring oral lactobacilli have probiotic properties, lactobacilli were isolated from saliva and plaque from children and adolescents, with or without caries lesions. The interference capacities of these lactobacilli were investigated against a panel of 13 clinical isolates and reference strains of Streptococcus mutans and Streptococcus sobrinus, as well as against the subject's autologous mutans streptococci, using the agar-overlay technique. Lactobacillus-mediated inhibition differed significantly between the three subject groups (no caries, arrested caries, or active caries), demonstrating increased inhibition in subjects without present or previous caries experience compared to subjects with arrested caries or subjects presenting with frank lesions. Lactobacilli from subjects lacking S. mutans inhibited the growth of the test panel of mutans streptococci significantly better than lactobacilli from subjects who were colonized. Furthermore, subjects without caries experience harbored lactobacilli that more effectively repressed the growth of their autologous mutans streptococci. Twenty-three Lactobacillus spp. completely inhibited the growth of all mutans streptococci tested. Species with maximum interference capacity against mutans streptococci included Lactobacillus paracasei, Lactobacillus plantarum, and Lactobacillus rhamnosus. Naturally occurring oral lactobacilli significantly inhibited the growth of both test strains of mutans streptococci and the subject's autologous mutans streptococci in vitro, and this effect was more pronounced in caries-free subjects.

The Use of Probiotics in Head and Neck Infections.

Recurrent episodes of infections in the upper respiratory tract are very common. The pathogenesis behind these recurrences is still not well understood, but much attention has been paid to the adherence of the microorganisms to epithelial structures and to the protective function of the normal bacterial flora (bacterial interference). Thus, in vitro as well as in vivo studies have shown that both aerobic and anaerobic bacteria of the normal flora in the upper respiratory tract can hinder the growth of pathogens and the establishment of a renewed infection. Studies have shown that lack of interfering bacteria facilitates recurrence of these diseases. Recolonization with interfering alpha-streptococci has been performed successfully in acute streptococcal pharyngotonsillitis, as well as in acute otitis media. The number of recurrences has significantly been lowered in these diseases after recolonization with alpha-streptococci, which is the dominating normal bacteria in the upper respiratory tract. Several mechanisms have been proposed to be responsible for this interaction, such as competition of the adhering sites at the epithelial cells, production of hydrogen peroxide, competition for nutritients, and production of specific growth inhibiting factors such as bacteriocins. Other human components like lactoferrin are also important in the defense against microorganisms, and are important parts of the unspecific and specific immune system.