Lack of efficacy of a decongestant-antihistamine combination for otitis media with effusion ("secretory" otitis media) in children. Results of a double-blind, randomized trial

In a double-blind, randomized trial of 553 infants and children who had otitis media with effusion ("secretory" otitis media), we compared the efficacy of a four-week course of an oral decongestant-antihistamine combination (pseudoephedrine hydrochloride, 4 mg per kilogram of body weight per day, and chlorpheniramine maleate, 0.35 mg per kilogram per day) with that of placebo. Among patients with initially unilateral disease, resolution of middle-ear effusion occurred at four weeks in 38 per cent of those treated with placebo and 34 per cent of those treated with drug (P = 0.74). Among patients with initially bilateral disease the corresponding proportions were 19 and 21 per cent, respectively (P = 0.67). Side effects were reported more often among drug-treated than placebo-treated patients. Decongestant-antihistamine combinations do not appear to be indicated for the treatment of otitis media with effusion in infants and children.     

Multicenter, randomized, double-blind comparison of erythromycin estolate versus amoxicillin for the treatment of acute otitis media in children

Erythromycin is frequently prescribed in Germany for acute otitis media, but well-designed clinical trials under present epidemiological conditions are lacking. Therefore, a double-blind, randomized, multicenter trial was performed to compare the clinical efficacy and safety of erythromycin estolate versus amoxicillin in children with acute otitis media and to identify the risk factors associated with clinical failure. Investigators from 19 centers throughout Germany recruited 302 children with clinical, otoscopic, and tympanometric evidence of acute otitis media. In a double-blind fashion, patients were allocated randomly to a 10-day course of erythromycin estolate at 40 mg/kg/day in two divided doses or amoxicillin at 50 mg/kg/day in two divided doses. Clinical examinations, otoscopy, and tympanometry were performed at baseline, day 3–5, day 9–11, and at 5 weeks. Clinical outcome was assessed on day 9–11. Two-hundred eighty children were evaluable for efficacy (erythromycin group, 141; amoxicillin group, 139). Both groups were comparable with respect to demographic data and severity of disease at entry. Treatment was successful in 94% of the erythromycin-treated patients and in 96% of the amoxicillin-treated patients. Clinical outcome was statistically equivalent between groups within a range of 7 percentage points. Clinical recurrence was seen in eight erythromycin-treated children (5.7%) and in seven amoxicillin-treated children (5.0%) (P=0.81). Patients with bilateral disease at entry were at higher risk of unfavourable outcome, whereas age and presence/absence of otorrhea at entry were not associated with outcome. Treatment-related adverse events were recorded in eight (5.3%) of 151 erythromycin-treated patients and in 11 (7.3%) of 151 amoxicillin-treated patients. In this study in an outpatient setting in Germany, erythromycin estolate was as safe and effective as amoxicillin in the treatment of acute otitis media. Both drugs can be administered in a convenient twice-daily dosage schedule.     

Effects of amoxicillin treatment on the salivary microbiota in children with acute otitis media

Amoxicillin is a first-line antibiotic treatment for acute otitis media in children and one of the most commonly used antibiotics for human bacterial infections. We investigated changes in salivary bacterial communities among children treated with amoxicillin for acute otitis media (n = 18), using a culture-independent approach based on pyrosequencing of the V3 region of the bacterial 16S rRNA gene. The control group consisted of children with acute otitis media who were not given antibiotics (n = 15). One species-level phylotype assigned to the genus Streptococcus was identified across all (n = 99) saliva samples. Two additional species-level phylotypes from the genera Gemella and Granulicatella were shared by all (n = 45) samples of control subjects. Amoxicillin treatment resulted in reduced species richness and diversity, and a significant shift in the relative abundance of 35 taxa at different ranks from phylum to species-level phylotype. At the phylum level, prevalence of TM7 and Actinobacteria decreased at the end of treatment, whereas Proteobacteria had a higher relative abundance post-treatment. Multivariate analysis showed that samples from the same control subject taken over time intervals tended to cluster together. Among antibiotic-treated subjects, samples taken before and at the end of amoxicillin treatment formed two relatively well-separated clusters both of which greatly overlapped with samples taken about 3 weeks post-treatment. Our results point to a substantial but incomplete recovery of the salivary bacterial community from the antibiotic about 3 weeks after the end of treatment.     

Detection rates of bacteria in chronic otitis media with effusion in children

This study was performed to investigate polymerase chain reaction-based detection of bacterial DNA in middle ear fluid and assess the correlation between the PCR-positive rate with several factors associated with middle ear effusion. The purpose was to gain a further understanding of bacterial infection as a major cause of otitis media with effusion. Of the 278 specimens of middle ear fluid, 39 (14%) tested positive by ordinary culture. The overall detection rate of bacterial DNA using the PCR method was 36.7% for middle ear effusion, and bacterial DNA detection rates of Hemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis in the middle ear effusion were 29.1%, 4.7% and 10.8%, respectively. The bacterial DNA detection rate was higher in ears with a history of acute otitis media than those without the history. High detection rates were observed in patients younger than 48 months who have had a higher tendency to present with acute otitis media. We concluded that PCR is a more sensitive method for the detection of bacteria in middle ear effusion than ordinary culture, and acute otitis media is a major contributor to the pathogenesis of otitis media with effusion.     

Inositol supplementation in premature infants with respiratory distress syndrome.

BACKGROUND. Inositol influences cellular function and organ maturation. Feeding premature infants inositol-rich breast milk increases their serum inositol concentrations. Whether inositol supplementation benefits infants receiving fluids for parenteral nutrition, which are inositol-free, is not known. METHODS. We carried out a placebo-controlled, randomized, double-blind trial to determine the effects of administering inositol (80 mg per kilogram of body weight per day) during the first five days of life to 221 infants with respiratory distress syndrome who were receiving parenteral nutrition (gestational age, 24 to 32 weeks; birth weight, less than 2000 g). All the infants were treated with mechanical ventilation and some with surfactant as well. The primary end point was survival at 28 days without bronchopulmonary dysplasia. RESULTS. The 114 patients given inositol had significantly lower mean requirements for inspiratory oxygen (P less than 0.01) and mean airway pressure (P less than 0.05) from the 12th through the 144th hour of life than did the 107 infants given placebo. Eighty-one infants given inositol and 51 given placebo survived without bronchopulmonary dysplasia (71 vs. 55 percent; P = 0.005). In the 65 infants given surfactant, however, inositol had no effect on the degree of respiratory failure. Thirteen infants given inositol and 21 given placebo had retinopathy of prematurity (13 vs. 26 percent; P = 0.022); none of the infants given inositol had stage 4 disease, whereas 7 of those given placebo did (0 vs. 9 percent; P = 0.012). Among the infants given placebo, those who had poor outcomes (death, bronchopulmonary dysplasia, or stage 4 retinopathy of prematurity) had lower serum inositol concentrations during days 2 through 7 than those who had good outcomes (P less than 0.01). CONCLUSIONS. The administration of inositol to premature infants with respiratory distress syndrome who are receiving parenteral nutrition during the first week of life is associated with increased survival without bronchopulmonary dysplasia and with a decreased incidence of retinopathy of prematurity.     

Antibody Levels After Regular Childhood Vaccinations in the Immunological Screening of Children with Recurrent Otitis Media

Recurrent otitis media may be related to defects in specific antibody production, as suggested previously. This might be reflected in lower antibody responses to vaccinations administered in the context of the national childhood vaccination program in children suffering from recurrent otitis media. In a cross-sectional study we determined the levels of antidiphtheria, antitetanus, anti- Haemophilus influenzae type b (anti-Hib) and antimeasles antibodies in sera of 163 children with two or more episodes of acute otitis media per year and in 143 children with repeated periods of persistent otitis media with effusion each lasting at least 3 months. The control group consisted of 521 age-matched healthy children, who were free of recurrent respiratory tract infections. Children with recurrent acute otitis media, including highly otitis-prone children, showed higher antidiphtheria and antitetanus antibody titers compared to controls. No differences were observed in anti-Hib and antimeasles antibody levels between children with recurrent acute otitis media and controls, nor did any of the antibody levels in children with persistent otitis media with effusion differ from those in controls. Therefore, the results of our study do not point toward a generalized immunological hyporesponsiveness in children with recurrent acute otitis media and persistent otitis media with effusion. Determination of antibody responses to regular vaccines is not indicative for otitis-proneness.     

A comprehensive model for the aetiology of otitis media with effusion

Otitis media with effusion is highly prevalent among young children. Adverse effects of this disorder are mainly restricted to the group of children with a history of recurrent or persistent otitis media with effusion. Early identification, assessment and intervention might prevent these adverse effects. Up to now it is not possible to distinguish these children from those with transient otitis media with effusion. This article presents a comprehensive model for the aetiology of otitis media with effusion. Eustachian tube functioning and the immunological response to environmental pathogens are the two core elements. This model can be used to formulate specific hypotheses about the interaction of several factors that may lead to the early identification of children who are likely to develop persistent or recurrent otitis media with effusion.     

Experimental otitis media after nasal inoculation of Streptococcus pneumoniae and influenza A virus in chinchillas.

Otitis media developed in 67% of chinchillas inoculated intranasally with type 7 Streptococcus pneumoniae and influenza A virus. Only 4% of chinchillas inoculated with influenza alone and 21% of chinchillas inoculated with S. pneumoniae alone developed otitis media. Among the chinchillas that developed otitis media after inoculation with both pneumococcus and influenza, 73% of the affected ears contained effusion, and 27% of the affected ears showed tympanic membrane inflammation without middle ear effusion obtained on paracentesis. Although a majority of the ears with effusion yielded S. pneumoniae on culture, one-third of the effusions were sterile for aerobic bacteria. This model resembles conditions accompanying otitis media in humans and suggests that respiratory viral infection contributes significantly to the pathogenesis of acute otitis media.     

A controlled trial of antimicrobial prophylaxis for Lyme disease after deer-tick bites.

BACKGROUND. Borrelia burgdorferi, which causes Lyme disease, is transmitted by deer ticks (lxodes dammini) in the northeastern and midwestern United States. Although deer-tick bites are common in areas in which the disease is endemic, there is uncertainty about how to manage the care of persons who are bitten. METHODS. To assess the risk of infection with B. burgdorferi and the efficacy of prophylactic antimicrobial treatment after a deer-tick bite, we conducted a double-blind, placebo-controlled trial in an area of southeastern Connecticut in which Lyme disease is endemic. Children and adults who had been bitten by deer ticks were randomly assigned to receive either amoxicillin or placebo for 10 days. Subjects were followed for one year for clinical manifestations of Lyme disease. Serum samples obtained at enrollment and six weeks and three months later were tested for antibodies against B. burgdorferi. RESULTS. Of the 387 subjects, 205 (53 percent) were assigned to receive amoxicillin and 182 (47 percent) to receive placebo. Of 344 deer ticks submitted and analyzed by the polymerase chain reaction, 15 percent were infected with B. burgdorferi. Erythema migrans developed in two subjects, both of whom had received placebo. There were no asymptomatic seroconversions and no late manifestations of Lyme disease. The risk of infection with B. burgdorferi in the placebo-treated subjects was 1.2 percent (95 percent confidence interval, 0.1 to 4.1 percent), which was not significantly different (P = 0.22) from the risk in the amoxicillin-treated subjects (0 percent; 95 percent confidence interval, 0 to 1.5 percent). CONCLUSIONS. Even in an area in which Lyme disease is endemic, the risk of infection with B. burgdorferi after a recognized deer-tick bite is so low that prophylactic antimicrobial treatment is not routinely indicated.     

Otitis media with effusion and hearing loss in children with Cornelia de Lange syndrome

The development of children who have syndromes with mental retardation and/or language delay can be worsened by sensorineural or conductive hearing loss (HL). Given the existing scarcity of data, we investigated the prevalence of otitis media with effusion and/or HL in 50 children with Cornelia de Lange syndrome (CdLS) aged 1-18 years, and its impact on the children's performance. The children underwent otological and audiological examinations in order to ascertain the relative frequencies of otitis media with effusion and/or hearing impairment; their demographic and clinical data were obtained by questionnaires and from information in their medical charts. Otitis media with effusion was diagnosed in 94%, and its prevalence was similar in all age groups; HL was detected in 40 children (80%). Conductive HL due to middle ear effusion was the main cause of hearing impairment alone (60%) or in combination with sensorineural deficit (20%). HL had a negative impact on performance regardless of the type. A history of routine audiological and/or otological assessments was reported by a minority of parents. Our findings indicate that otitis media with effusion and/or HL is an important feature of children with CdLS and may negatively affect their performance. Careful follow-up throughout childhood is necessary to detect and treat any hearing loss in children with CdLS in order to minimize its impact on performance.     

Withdrawal reaction after long-term therapeutic use of benzodiazepines

We conducted a double-blind, placebo-controlled trail in which 40 patients who had undergone long-term therapy with benzodiazepines were switched to placebo or to diazepam in a dose approximately equivalent to their usual dose of the benzodiazepine; the dose of diazepam was then tapered during an eight-week period. Patients were assessed clinically and psychologically and had weekly sessions of behavioral therapy. The subjects who received placebo had more symptoms, assessed their symptoms as more severe, and stopped taking the study drug at a higher rate than those receiving the tapering doses of diazepam. The subjects in the placebo group also had symptoms shortly after being switched to placebo, whereas those in the diazepam group had symptoms much later. Some withdrawal symptoms were distinct from those of anxiety (e.g., tinnitus, involuntary movement, and perceptual changes). Withdrawal symptoms occurred earlier in patients who had received short-acting benzodiazepines than in those who had received long-acting benzodiazepines. Symptoms gradually disappeared over a four-week period in both the placebo and the diazepam groups. Serial determination of plasma benzodiazepine concentrations was a useful way to assess compliance, treatment outcome, and relapse during withdrawal. We conclude that a clinically important, mild, but distinct withdrawal syndrome occurs after discontinuation of long-term therapeutic use of benzodiazepines.     

Morphological basis for impaired protective efficiency by the nasal mucosa in infants with and without recurrent acute otitis media: a light and electron microscopy study

The structure of the nasal mucosa in biopsy specimens from the inferior turbinate in 'normal healthy' infants (n = 27) was compared with that in age-matched infants (n = 59) with increased frequency of recurrent acute otitis media (RAOM). Light and transmission electron microscopic examination revealed that the healthy infants, i.e., the control subjects, had almost as extensive structural changes in their nasal mucosa as those with RAOM. Only 1 infant in each group was considered to have normal nasal mucosa from a morphological point of view. The high frequencies of structural abnormalities in the nasal mucosa in infants, healthy or with RAOM, is likely to be due to frequent infections causing damage so often and to such high extent that the repair processes became insufficient and thus did not restore the structure of the nasal mucosa. Mucosal lining defects may decrease the resistance to infections, resulting in frequent relapses further adding to the mucosal damage, i.e., a self-ongoing circle.     

Consequences of unremitting middle-ear disease in early life. Otologic, audiologic, and developmental findings in children with cleft palate

To learn whether chronic otitis media with effusion during early life has lasting otologic, audiologic, or developmental consequences, we evaluated 24 closely matched pairs of children with repaired palatal clefts whose treatment had been equivalent except with regard to persistent otitis media during early life. One group had undergone early (mean age, 3.0 months) myringotomy with placement of tympanostomy tubes, followed by assiduous monitoring and an aggressive treatment program to maintain ventilation in the middle ear. The other group had undergone initial myringotomy later (mean age, 30.8 months) or not at all (two subjects) and presumably had had continuous middle-ear effusion throughout most or all of the first few years of life. Eardrum scarring was equal in both groups. Hearing acuity and consonant articulation were impaired in both groups, but hearing acuity was less impaired (P = 0.05 to 0.10) and consonant articulation significantly less impaired (P = 0.03) in the group undergoing early myringotomy. Mean verbal, performance, and full-scale IQs and scores on psychosocial indexes were normal in both groups and did not differ significantly between the groups. These findings support the hypothesis that early, longstanding otitis media may result in impairment of hearing and of speech, but they do not support the hypothesis that cognitive, language, and psychosocial development are adversely affected.     

Increased IgM-Type Betalactoglobulin Antibodies in Children with Recurrent Otitis Media

Total concentrations of IgA, IgG, IgM and IgE, precipitating antibodies to cow milk, milk-specific IgE, as well as anti-milk antibodies and betalactoglobulin antibodies of the IgA, IgG and IgM classes determined by the ELISA method were studied and compared in children with recurrent otitis media, and children who had never had otitis. The children with recurrent otitis had a higher total IgE at 1 year of age and a higher total IgM at 3 years. The only difference in milk-specific antibodies was an increased titre of betalactoglobulin antibodies of IgM type in children with recurrent otitis. This new finding suggests that immunological mechanisms might play a part in recurrent otitis, which has been shown to be more common in bottle-fed than in breast-fed infants. So far, the role of betalactoglobulin antibodies in the pathogenesis of otitis media remains uncertain.     

Clinical manifestations of aural fullness

Purpose: Even though aural fullness is ubiquitous among patients presenting to otolaryngology clinics, the association between aural fullness and disease development has not yet been clearly determined. Materials and Methods: Our study was performed on outpatients from June 2006 to February 2010 whose major complaint was "ear fullness", "aural fullness", or "ear pressure". We assessed their demographic and clinical characteristics, including sex, associated diseases, symptoms, otoscopic findings, audiology test results, and final diagnoses. Results: Among 432 patients, 165 (38.2%) were males and 267 (61.8%) were females, with mean ages of 42±19 years and 47±17 years, respectively. Tinnitus, hearing disturbance, autophony (p<0.01) as well as nasal obstruction and sore throat (p<0.05) showed a statistically significant correlation with aural fullness. Among patients who complained of hearing fullness, tests and measures such as impedance audiometry, speech reception threshold, and pure tone audiometry generated statistically significant results (p<0.05). Ear fullness was most frequently diagnosed as Eustachian tube dysfunction (28.9%), followed by otitis media with effusion (13.4%) and chronic otitis media (7.2%). However, 13.4% of patients could not be definitively diagnosed. Conclusion: Among patients complaining of ear fullness, Eustachian tube dysfunction, otitis media with effusion, chronic otitis media were most commonly observed. Performance of otoscopy, nasal endoscopy, the Valsalva maneuver, and additional audiological tests is necessary to exclude other diseases.     

Urinary tract infections associated with otitis media in infants and children

One hundred six infants and children with otitis media were screened for the incidence of urinary tract infections (UTI) by urine culture. Seventeen patients (16%) who had UTI were compared with the 80 patients with sterile urine for differences in host factors and laboratory features. The mean age, WBC counts, and ESR values were similar. Patients with UTI-associated otitis media had a higher incidence of hematuria. Prevalence of high (greater than or equal to 103 degrees F) fever was higher among the boys with UTI. However, because of the lack of definite clinical and laboratory clues to determine the presence or absence of UTI, urine culture is the only test to uncover otitis media patients with concomitant UTI.     

Effect of early or delayed insertion of tympanostomy tubes for persistent otitis media on developmental outcomes at the age of three years

BACKGROUND: A main indication for the insertion of tympanostomy tubes in infants and young children is persistent otitis media with effusion, reflecting concern that this condition may cause lasting impairments of speech, language, cognitive, and psychosocial development. However, evidence of such relations is inconclusive, and evidence is lacking that the insertion of tympanostomy tubes prevents developmental impairment. METHODS: We enrolled 6350 healthy infants from 2 to 61 days of age and evaluated them regularly for middle-ear effusion. Before the age of three years 429 children with persistent effusion were randomly assigned to have tympanostomy tubes inserted either as soon as possible or up to nine months later if effusion persisted. In 402 of these children we assessed speech, language, cognition, and psychosocial development at the age of three years. RESULTS: By the age of three years, 169 children in the early-treatment group (82 percent) and 66 children in the late-treatment group (34 percent) had received tympanostomy tubes. There were no significant differences between the early-treatment group and the late-treatment group at the age of three years in the mean (+/-SD) scores on the Number of Different Words test, a measure of word diversity (124+/-32 and 126+/-30, respectively); the Percentage of Consonants Correct-Revised test, a measure of speech-sound production (85+/-7 vs. 86+/-7); the General Cognitive Index of McCarthy Scales of Children's Abilities (99+/-14 vs. 101+/-13); or on measures of receptive language, sentence length, grammatical complexity, parent-child stress, and behavior. CONCLUSIONS: In children younger than three years of age who have persistent otitis media, prompt insertion of tympanostomy tubes does not measurably improve developmental outcomes at the age of three years.     

High incidence of Haemophilus influenzae in nasopharyngeal secretions and middle ear effusions as detected by PCR.

PCR was used to detect Haemophilus influenzae in samples of nasopharyngeal secretion and middle ear effusion (MEE). Nasopharyngeal secretions were collected from 102 patients with otitis media with effusion and from 111 healthy subjects. Eighty samples of MEE were collected from patients with otitis media with effusion. A pair of primers was designed to amplify a DNA segment of the gene encoding P6 outer membrane protein of H. influenzae. The amplified PCR product was detected with an internal probe that hybridized specifically to the P6 DNA of H. influenzae. Samples of MEE and nasopharyngeal secretion were also examined by a conventional culture method. The incidence of P6 gene DNA in nasopharyngeal secretions detected by PCR was about two times higher than that of H. influenzae detected by the conventional culture. Culture-positive samples were all positive in the PCR test. In MEEs, the rate of detection of the P6 gene DNA target was about five times higher than that of H. influenzae detected by the culture method. All patients who had P6 gene DNA in MEEs were found to have the DNA in nasopharyngeal secretions. These findings suggest that the presence of H. influenzae in MEEs and in nasopharyngeal secretions is more common than previously reported.     

High incidence of Alloiococcus otitidis in children with otitis media, despite treatment with antibiotics

Acute otitis media (AOM) and otitis media with effusion (OME) are common diseases in childhood. Alloiococcus otitidis is a newly recognized species of gram-positive bacterium which was recently discovered as a pathogen associated with OME. Although some studies show that A. otitidis is frequently detected in children with OME, no study is available concerning the clinical efficiency of antibiotics against this organism. The prevalence of A. otitidis in 116 middle ear effusion specimens from 36 AOM and 52 OME patients was examined by culture and PCR. In addition, the prevalence of the bacterium was retrospectively investigated in relation to antibiotic use. A. otitidis was detected in 20 (50%) AOM and 47 (61%) OME specimens. The organism was the most frequent bacterium in AOM as well as in OME and was highly detected even in patients who had been treated with antibiotics, such as beta-lactams or erythromycin. The incidence of A. otitidis in our study was higher than that in Western countries, and our results suggest that drug-resistant strains of A. otitidis may be frequently spread in Japanese children. Our study suggests that antibiotics such as beta-lactams or erythromycin may not be sufficiently effective to eliminate this organism. Further investigation is expected to reveal the clinical role of the organism in otitis media.     

Biotypes of serologically nontypable Haemophilus influenzae isolated from the middle ears and nasopharynges of patients with otitis media with effusion.

A biotype analysis was performed on serologically nontypable Haemophilus influenzae isolates from the middle ear effusions and nasopharynges of 33 children with chronic otitis media with effusion (serous otitis media). Over 50% of the H. influenzae isolates from the middle ears belonged to biotype II. The incidence of beta-lactamase production was 17%. The results of this study indicate that future clinical or experimental investigations of chronic otitis media with effusion induced by serologically nontypable H. influenzae should focus on this clinically important biotype.