Xylitol chewing gum in prevention of acute otitis media: double blind randomised trial.

OBJECTIVE: To examine whether xylitol, which reduces the growth of Streptococcus pneumoniae, might have clinical importance in the prevention of acute otitis media. DESIGN: A double blind randomised trial with xylitol administered in chewing gum. SETTING: Eleven day care nurseries in the city of Oulu. Most of the children had had problems with recurrent acute otitis media. SUBJECTS: 306 day care children: 149 children in the sucrose group (76 boys; mean (SD) age 4.9 (1.5) years) and 157 in the xylitol group (80 boys; 5.0 (1.4) years). INTERVENTION: Either xylitol (8.4 g a day) or sucrose (control) chewing gum for two months. MAIN OUTCOME MEASURES: The occurrence of acute otitis media and antimicrobial treatment received during the intervention and nasopharyngeal carriage of S pneumoniae. RESULTS: During the two month monitoring period at least one event of acute otitis media was experienced by 31/149 (20.8%) children who received sucrose compared with 19/157 (12.1%) of those receiving chewing gum containing xylitol (difference 8.7%; 95% confidence interval 0.4% to 17.0%; P = 0.04). Significantly fewer antimicrobials were prescribed among those receiving xylitol: 29/157 (18.5%) children had at least one period of treatment versus 43/149 (28.9%) (difference 10.4%; 0.9% to 19.9%; P = 0.032). The carriage rate of S pneumoniae varied from 17.4% to 28.2% with no difference between the groups. Two children in the xylitol group experienced diarrhoea, but no other adverse effects were noted among the xylitol users. CONCLUSION: Xylitol seems to have a preventive effect against acute otitis media.     

Are antibiotics indicated as initial treatment for children with acute otitis media? A meta-analysis.

OBJECTIVE: To determine the effect of antibiotic treatment for acute otitis media in children. DESIGN: Systematic search of the medical literature to identify studies that used antibiotics in randomised controlled trials to treat acute otitis media. Studies were examined blind, and the results of those of satisfactory quality of methodology were pooled. SUBJECTS: Six studies of children aged 7 months to 15 years. MAIN OUTCOME MEASURES: Pain, deafness, and other symptoms related to acute otitis media or antibiotic treatment. RESULTS: 60% of placebo treated children were pain free within 24 hours of presentation, and antibiotics did not influence this. However, at 2-7 days after presentation, by which time only 14% of children in control groups still had pain, early use of antibiotics reduced the risk of pain by 41% (95% confidence interval 14% to 60%). Antibiotics reduced contralateral acute otitis media by 43% (9% to 64%). They seemed to have no influence on subsequent attacks of otitis media or deafness at one month, although there was a trend for improvement of deafness at three months. Antibiotics were associated with a near doubling of the risk of vomiting, diarrhoea, or rashes (odds ratio 1.97 (1.19 to 3.25)). CONCLUSIONS: Early use of antibiotics provides only modest benefit for acute otitis media: to prevent one child from experiencing pain by 2-7 days after presentation, 17 children must be treated with antibiotics early.     

Effect of recolonisation with "interfering" alpha streptococci on recurrences of acute and secretory otitis media in children: randomised placebo controlled trial

ObjectiveTo study the effect of recolonisation with α streptococci with the ability to inhibit the growth of otopathogens (“interfering” activity) on the recurrence of acute otitis media in susceptible children and the effect on the frequency of secretory otitis media.DesignDouble blind, randomised, placebo controlled study.SettingEar, nose, and throat clinic with three doctors.Participants130 children prone to otitis media aged between 6 months and 6 years, 108 of whom were eligible and followed for 3 months.InterventionsChildren with no recurrences during the last month received phenoxymethylpenicillin (n=22), and those with a recurrence within 1 month received amoxicillin clavulanic acid (n=86), both twice daily for 10 days. These were followed by a streptococcal or placebo solution sprayed into the nose for a further 10 days. At day 60 the same spray was started for another 10 days.ResultsAt 3 months 22 children (42%) given the streptococcal spray were healthy and had a normal tympanic membrane compared with 12 (22%) of those given placebo. This difference was shown separately for recurrences of both acute otitis media and secretory otitis media.ConclusionsSelected bacteria with the ability to inhibit the growth of common otopathogens can be used to protect against recurrent acute otitis media and secretory otitis media in children.     

IgG Responses to Pneumococcal and Haemophilus Influenzae Protein Antigens Are Not Impaired in Children with a History of Recurrent Acute Otitis Media

Background

Vaccines including conserved antigens from Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi) have the potential to reduce the burden of acute otitis media. Little is known about the antibody response to such antigens in young children with recurrent acute otitis media, however, it has been suggested antibody production may be impaired in these children.

Methods

We measured serum IgG levels against 4 pneumococcal (PspA1, PspA 2, CbpA and Ply) and 3 NTHi (P4, P6 and PD) proteins in a cross-sectional study of 172 children under 3 years of age with a history of recurrent acute otitis media (median 7 episodes, requiring ventilation tube insertion) and 63 healthy age-matched controls, using a newly developed multiplex bead assay.

Results

Children with a history of recurrent acute otitis media had significantly higher geometric mean serum IgG levels against NTHi proteins P4, P6 and PD compared with healthy controls, whereas there was no difference in antibody levels against pneumococcal protein antigens. In both children with and without a history of acute otitis media, antibody levels increased with age and were significantly higher in children colonised with S. pneumoniae or NTHi compared with children that were not colonised.

Conclusions

Proteins from S. pneumoniae and NTHi induce serum IgG in children with a history of acute otitis media. The mechanisms in which proteins induce immunity and potential protection requires further investigation but the dogma of impaired antibody responses in children with recurrent acute otitis media should be reconsidered.     

Parent-Reported Otorrhea in Children with Tympanostomy Tubes: Incidence and Predictors

Purpose

Although common in children with tympanostomy tubes, the current incidence of tympanostomy tube otorrhea (TTO) is uncertain. TTO is generally a sign of otitis media, when middle ear fluid drains through the tube. Predictors for otitis media are therefore suggested to have predictive value for the occurrence of TTO.

Objective

To determine the incidence of TTO and its predictors.

Methods

We performed a cohort study, using a parental web-based questionnaire to retrospectively collect data on TTO episodes and its potential predictors from children younger than 10 years of age with tympanostomy tubes.

Results

Of the 1,184 children included in analyses (total duration of time since tube placement was 768 person years with a mean of 7.8 months per child), 616 children (52%) experienced one or more episodes of TTO. 137 children (12%) had TTO within the calendar month of tube placement. 597 (50%) children had one or more acute TTO episodes (duration <4 weeks) and 46 children (4%) one or more chronic TTO episodes (duration ≥4 weeks). 146 children (12%) experienced recurrent TTO episodes. Accounting for time since tube placement, 67% of children developed one or more TTO episodes in the year following tube placement. Young age, recurrent acute otitis media being the indication for tube placement, a recent history of recurrent upper respiratory tract infections and the presence of older siblings were independently associated with the future occurrence of TTO, and can therefore be seen as predictors for TTO.

Conclusions

Our survey confirms that otorrhea is a common sequela in children with tympanostomy tubes, which occurrence can be predicted by age, medical history and presence of older siblings.     

Study of middle ear disease using tympanometry in general practice.

Tympanometry was used to provide evidence of middle ear effusions in a prospective study of middle ear disease in 264 children aged 3 months to 6 years in general practice. Adequate measurements on both ears were obtained in 220 children, of whom 68 (31%) had evidence of middle ear effusion in one ear (29 children) or both ears (39 children) at entry to the study. In 28 (42%) of the 68 children persistence of the tympanometric findings was recorded for at least three months. Children of European descent were more likely to have evidence of middle ear effusion at the initial examination compared with African and West Indian children, as were those children whose siblings had a positive history of otitis media compared with those whose siblings had no such history. Children under 3 years were more likely to have evidence of an effusion than older children. Middle ear effusion as shown by tympanometry was not associated with a previous history of otitis media in the child but was associated with recent symptoms of respiratory infection or otalgia. A previous consultation for otitis media was, however, strongly associated with a greater likelihood of a consultation for otitis media during the follow up period. Comparing evidence of effusion by tympanometry with that by pneumatic otoscopy showed that using the appearance of the eardrum alone the sensitivity of otoscopy was 55%; the addition of mobility improved the sensitivity to 76% with little reduction in specificity. Further studies on populations using tympanometry are needed to determine the natural history, aetiology, and indications for referring children with middle ear effusion.     

Trial of three-day and ten-day courses of amoxycillin in otitis media.

A randomised double-blind controlled trial compared three-day and 10-day courses of amoxycillin (25 mg/kg daily) in children with otitis media. Seventeen doctors from five centres admitted 84 children between the ages of 2 and 10 years. Symptoms and signs were measured on admission to the trial, on day 3, and on day 15. Mother''s observations were recorded daily for 10 days. Audiograms were performed at four and 12 weeks after the end of the trial. The treatment groups showed little difference in the speed of resolution of symptoms and signs, the numbers of primary treatment failures, or the frequency of recurrent ear infections. There were no complications in either group. Most children with otitis media can probably be successfully and safely treated with no more than a three-day course of amoxycillin providing their progress is reviewed about the fifth or sixth day after treatment started. This policy could save over 1 million pounds annually in antibiotic costs.     

Acute otitis media: clinical course among children who received a short course of high dose antibiotic.

A prospective study was carried out in 274 children aged 3 to 10 years with acute otitis media. They were randomly allocated to one of two treatment regimens: (a) a seven day course of amoxycillin 125 mg three times a day, and (b) a two day course of amoxycillin 750 mg twice a day. They were followed up by symptom diaries and clinical examination. The findings in the 243 children who completed the trial showed that the short course of treatment was as effective as the seven day course in the speed of resolution of symptoms and signs, irrespective of previous history of otitis media or of episodes in which bulging of the eardrums was observed at presentation. A subgroup of 185 children was followed up for one year after entry to the trial. During this period no appreciable differences emerged between the two antibiotic regimens, either in recurrence rate of otitis media or in the frequency of hearing loss at one month and six months after entry to the study. Side effects of treatment were few, and those that could be attributed to antibiotic use occurred with equal frequency in the two treatment groups.     

Colonization and turnover of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in otitis-prone children

Recurrent otitis media are frequently intractable during childhood. It is unclear whether recurrent otitis media is caused by etiological bacteria colonization or by new infections. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were isolated from the nasopharynx of 7 otitisprone and 2 non-prone children with recurrent otitis media. Plural bacterial species and strains were found in all children while affected by otitis media. The same strain was repeatedly isolated from all otitisprone children even after administration of antibiotics but was not from the non-prone children. Antibiotic susceptibility did not differ significantly among the same repeatedly isolated strains. This pilot study suggests that the etiological bacteria tend to colonize and is hard to eliminate in otitis-prone children.     

Bactericidal antibody response against P6, protein D, and OMP26 of nontypeable Haemophilus influenzae after acute otitis media in otitis-prone children

The bactericidal antibody response to three nontypeable Haemophilus influenzae (NTHi) outer membrane proteins (D, P6, and OMP26) was studied in 24 otitis-prone children (aged 7-28?months) after an acute otitis media (AOM) caused by NTHi. The study was carried out to understand the contribution of antigen-specific bactericidal antibody responses in the class of children who are most vulnerable to recurrent otitis media infections. Levels of protein D (P?=?0.005) and P6 (P?=?0.026) but not OMP26 antibodies were higher in bactericidal sera compared with nonbactericidal sera. For five (24%) and 16 (76%) of 21 bactericidal sera tested, removal of anti-protein D and P6 antibody, respectively, resulted in a two- to fourfold drop in bactericidal antibody. Antibodies to OMP26 did not make any contribution to the overall bactericidal activity in any serum samples. Eleven of 21 sera (52%) had bactericidal activity against a heterologous NTHi (86-028 NP) strain but the titers were significantly lower (P?相似文献   

Characterization of Streptococcus pneumoniae isolated from children with otitis media

Streptococcus pneumoniae is the main causative agent of acute otitis media in children. Serotype-based vaccines have provided some protection against otitis media, but not as much as anticipated, demonstrating the need for alternative vaccine options. Pneumococcal otitis media isolates were obtained from children 5 years old or younger from hospitals around Mississippi in the prevaccine era (1999-2000). These isolates were compared by capsular typing, pneumococcal surface protein A (PspA) family typing, antibiotic susceptibility, and DNA fingerprinting. Our study shows that there is great genetic variability among pneumococcal clinical isolates of otitis media, except with regard to PspA. Therefore, efforts focused on the development of a PspA-based pneumococcal vaccine would be well placed.     

Acute otitis media: a new treatment strategy.

The incidence of acute otitis media and its response to treatment only with nose drops and analgesics (but without antibiotics or myringotomy) were assessed over three months by 45 doctors in and around Tilburg. In addition, over 17 months 60 general practitioners assessed the effects of this limited treatment in children aged 2 to 12 years and referred all those in whom the condition took an unsatisfactory course (either a severe course--illness continuing beyond three to four days with high temperature or pain, or both--or persistent discharge after 14 days) to an ear, nose, and throat specialist. Those referred because of appreciable illness continuing beyond three or four days were entered into a further study, comparing the effects of myringotomy alone, antibiotics alone, and myringotomy and antibiotics combined. Bacteriology was assessed in all children in whom the course of the condition was unsatisfactory. More than 90% of an estimated 4860 children seen over 17 months (estimation based on incidence of severe course in the three month study) recovered within a few days. The course of the condition was severe in only 126 (2.7%) patients; haemolytic streptococci group A were identified in 30 of these 126 patients but Haemophilus influenzae in only one. One hundred of these patients with a severe course entered the trial of treatment, which showed antimicrobial treatment either alone or in combination to be more effective than myringotomy alone. Whether combined treatment was more effective than antibiotics alone remained unconfirmed. Acute otitis media in children can be treated with nose drops and analgesics alone for the first three to four days. Patients in whom this regimen is not accompanied by satisfactory recovery can be recognised within a short time and treated by the general practitioner.     

Influence of Pneumococcal Conjugate Vaccine on Acute Otitis Media with Severe Middle Ear Inflammation: A Retrospective Multicenter Study

The Japanese guidelines for acute otitis media in children recommend classifying acute otitis media by age, manifestations and local findings, and also recommend myringotomy for moderate-grade cases with severe local findings, severe-grade cases, and treatment-resistant cases. The heptavalent pneumococcal conjugate vaccine was released in Japan in February 2010. In Hiroshima City, public funding allowing free inoculation with this vaccine was initiated from January 2011, and the number of vaccinated individuals has since increased dramatically. This study investigated changes in the number of myringotomies performed to treat acute otitis media during the 5-year period from January 2008 to December 2012 at two hospitals and five clinics in the Asa Area of Hiroshima City, Japan. A total of 3,165 myringotomies for acute otitis media were performed. The rate of procedures per child-year performed in <5-year-old children decreased by 29.1% in 2011 and by 25.2% in 2012 compared to the mean rate performed in the 3 years prior to the introduction of public funding. A total of 895 myringotomies were performed for 1-year-old infants. The rate of myringotomies per child-year performed for acute otitis media in 1-year-old infants decreased significantly in the 2 years after the introduction of public funding for heptavalent pneumococcal conjugate vaccine compared to all years before introduction (p<0.000001). Our results suggest a benefit of heptavalent pneumococcal conjugate vaccine for acute otitis media in reducing the financial burden of myringotomy. In addition, this vaccine may help prevent acute otitis media with severe middle ear inflammation in 1-year-old infants.     

Acute red ear in children: controlled trial of non-antibiotic treatment in general practice.

OBJECTIVE--To examine the efficacy and safety of conservative management of mild otitis media ("the acute red ear") in children. DESIGN--Double blind placebo controlled trial. SETTING--17 group general practices (48 general practitioners) in Southampton, Bristol, and Portsmouth. PATIENTS--232 children aged 3-10 years with acute earache and at least one abnormal eardrum (114 allocated to receive antibiotic, 118 placebo). INTERVENTIONS--Amoxycillin 125 mg three times a day for seven days or matching placebo; 100 ml paracetamol 120 mg/5 ml. MAIN OUTCOME MEASURES--Diary records of pain and crying, use of analgesic, eardrum signs, failure of treatment, tympanometry at one and three months, recurrence rate, and ear, nose, and throat referral rate over one year. RESULTS--Treatment failure was eight times more likely in the placebo than the antibiotic group (14.4% v 1.7%, odds ratio 8.21, 95% confidence interval 1.94 to 34.7). Children in the placebo group showed a significantly higher incidence of fever on the day after entry (20% v 8%, p less than 0.05), mean analgesic consumption (0.36 ml/h v 0.21 ml/h, difference 0.14, 95% confidence interval 0.07 to 0.23; p = 0.0022), mean duration of crying (1.44 days v 0.50 days, 0.94; 0.50 to 1.38; p less than 0.001), and mean absence from school (1.96 days v 0.52 days, 1.45; 0.46 to 2.42; p = 0.0132). Differences in recorded pain were not significant. The prevalence of middle ear effusion at one or three months, as defined by tympanometry, was not significantly different, nor was there any difference in recurrence rate or in ear, nose, and throat referral rate in the follow up year. No characteristics could be identified which predicted an adverse outcome. CONCLUSIONS--Use of antibiotic improves short term outcome substantially and therefore continues to be an appropriate management policy.     

Moraxella catarrhalis is only a weak activator of the mannose-binding lectin (MBL) pathway of complement activation

A hemolytic bystander assay was used to assess the functional serum mannose-binding lectin (MBL) activating capacity of five isolates of Moraxella catarrhalis obtained from children who suffered recurrent acute otitis media episodes. Results showed that this organism is only a poor activator of the lectin pathway of complement activation, with subsequent consequences for the etiology of otitis media by this organism.     

Dr. Mary Fanning: caring for AIDS patients at Toronto General.

Although amoxicillin has long been the preferred drug for treatment of acute otitis media, resistant strains of two relatively common causal organisms have emerged, prompting a search for other antibiotics. We performed a randomized double-blind trial comparing amoxicillin and trimethoprim-sulfamethoxazole in 221 children in whom acute otitis media was diagnosed in an outpatient setting. Diagnosis was on the basis of symptoms, otoscopic examination and acoustic reflectometry. No culture specimens were taken. A research nurse, using the same methods, evaluated patients in a follow-up home visit at around 14 days and measured compliance by examination of the medicine bottle. Equal proportions of children in the two groups were cured or improved (88% and 87%). Therapeutic efficacy was related to compliance in both groups, and there were few side effects in either group. This study had statistical power of 80% to detect a difference of 15%. We conclude that trimethoprim-sulfamethoxazole can be considered a first-line antibiotic in the treatment of acute otitis media.     

Twice-daily antibiotics in the treatment of acute otitis media: trimethoprim-sulfamethoxazole versus amoxicillin-clavulanate.

Twice-daily trimethoprim-sulfamethoxazole has been shown to be effective in the treatment of acute otitis media except that caused by group A beta-streptococci. Amoxicillin-clavulanate potassium is effective in vitro against all bacterial pathogens causing acute otitis media and has been reported to be effective when given twice daily for urinary tract infections, acute otitis media and respiratory tract infections. To determine whether the in-vitro efficacy of amoxicillin-clavulanate carries over clinically, we conducted a prospective randomized double-blind trial in 219 children presenting at a pediatric walk-in clinic. Diagnosis and follow-up assessments were made by means of examination of the tympanic membrane and acoustic otoscopy. Of the 219 children 202 (101 in either group) were assessed by a specially trained nurse at a follow-up visit 12 to 16 (mean 14) days after treatment was begun. Cure was defined as absence of symptoms and normal results of both visual inspection of the tympanic membrane and acoustic reflectometry; improvement was defined as absence of symptoms and either normal appearance of the tympanic membrane or normal results of acoustic reflectometry; treatment failure was defined as abnormal appearance of the tympanic membrane along with an acoustic reflectometry reading of 5 units or more. There were no differences in age (mean 60 months), sex or proportion of subjects with unilateral versus bilateral disease between the two groups. The combined rate of cure an improvement was significantly higher with trimethoprim-sulfamethoxazole (93%) than with amoxicillin-clavulanate (82%) (p = 0.03). The rate of compliance (more than 80% of the drug taken) did not differ significantly between the two groups. Gastrointestinal side effects were more common with amoxicillin-clavulanate (p less than 0.0001). Our results suggest that for acute otitis media twice-daily trimethoprim-sulfamethoxazole is more effective clinically and produces fewer side effects than twice-daily amoxicillin-clavulanate.     

Participation of mast cells in chronic otitis media

In the pathogenesis of chronic otitis media (COM), much attention is paid to the molecular mechanisms of local inflammatory reactions in which mast cells (MCs) may be involved due to their role not only in allergic but also inflammatory processes. The aim of this study was to assess the density of mast cells in chronic otitis media in relationship to different clinical courses of COM, bacterial infections and types of disease. The MCs expression was measured immunohistochemically in paraffin-embedded granulation tissue specimens taken during surgery, by staining with a monoclonal antibody against tryptase. The density of tryptase-positive mast cells was lower in tissue samples from the group with a good clinical course than in those from the group with poor healing and recurrence (p = 0.006). There were no differences between the groups of patients with granulomatous and cholesteatomatous chronic otitis media (p = 0.66) or between the groups of patients with and without bacterial infection (p = 0.30), although the density of mast cells was lower for those with Pseudomonas aeruginosa/Proteus sp./ /Staphylococcus MRSA infection. In conclusion, the expression of mast cells in chronic otitis media granulation tissue was found to differ depending on the clinical course of the disease, but not on bacterial infection or type of COM. This may suggest that mast cells contribute to the maintenance of the inflammatory process, but not to antibacterial defense in chronic otitis media.