Antibiotics for otitis media with effusion.

Otitis media with effusion (OME) is defined as asymptomatic middle-ear effusion, that is, without the signs and symptoms of acute otitis media (AOM), such as fever, otalgia, or otorrhea. OME can occur after an episode of AOM or may occur without any prior or concurrent symptoms and is often noted on a routine physical examination or screening. Because children with OME are usually not ill, there is a question of whether treatment is warranted for this condition. Also adding to the complexity of this problem is the high spontaneous cure rate of OME. This paper will review the many clinical trials of the efficacy of antimicrobial therapy for OME. We have grouped the studies into 4 major categories: antibiotic vs no treatment, antibiotic vs placebo, antibiotic vs antibiotic, and antibiotic prophylaxis. While study designs, definitions, and quality vary widely, these studies show a trend toward short-term efficacy of antimicrobial treatment, but long-term efficacy is doubtful. In this age of antimicrobial resistance, coupled with the high natural cure rate, routine antimicrobial treatment of OME is not warranted. It may be useful in selected patients, particularly those with chronic OME (3 months or longer of bilateral effusion or 6 months or longer of unilateral effusion) for whom surgery is being considered: a 1-time short course of antibiotic may allow cancellation or at least postponement of a surgical procedure, particularly in spring/summer when one would like to avoid placing tubes in the ears and placing the child at risk for otorrhea due to water exposure. Also, antimicrobial therapy may provide at least short-term relief for symptomatic children (hearing loss, developmental delay, etc.) for whom surgery must be postponed or is contraindicated.

The genetics of otitis media.

There is significant evidence from epidemiologic, anatomic, physiologic, and immunologic studies that susceptibility to recurrent episodes of acute otitis media (OM) and persistent OM with effusion is largely genetically determined. The genetics of OM are most likely complex, i.e., many genes are probably contributing to the overall phenotype. The knowledge of a hereditary component has important implications because closer surveillance of children at risk for OM could result in earlier detection and treatment. Further, once OM susceptibility genes have been identified it may be possible to develop molecular diagnostic assays that could enable the clinician to identify the child at high risk for OM and to develop more focused treatments in the future.

Past history of otitis media and balance in four-year-old children.

OBJECTIVES/HYPOTHESIS: To obtain normative data for a population of children 4 years of age with respect to standard vestibular and balance test protocols and to determine, in the absence of concurrent middle ear effusion (MEE), the possible changes caused by a history of recurrent or persistent MEE. STUDY DESIGN: Comparative studies of the results of vestibular and balance tests in a cohort of young children with and without a history of MEE. METHODS: Seventy-one children, 4 years of age, with a well-documented history since early infancy regarding the presence or absence of MEE were evaluated using pneumatic otoscopy, tympanometry, audiometry, and vestibular and balance (rotational and moving platform posturography) tests. For the results of the vestibular and balance tests, comparisons were made between the group of 31 children (43.7%) without and the group of 40 children (56.3%) with a history of recurrent or persistent MEE, when a positive disease history was defined as at least a 10% cumulative percentage of time with MEE between early infancy and time of testing. RESULTS: When compared with children with a negative history of significant MEE, children with a positive history had a lower average gain to a rotational stimulus of 0.1 Hz, 150 degrees/s (0.57 vs. 0.44; P = .007). There were no significant differences between groups with respect to other measures. CONCLUSIONS: These results suggest that a history of recurrent or persistent MEE affects the vestibular and/or balance function of 4-year-old children when tested in the absence of a concurrent episode of MEE. The possible sequelae of the disease should be weighed in future considerations of early intervention for MEE.

The heritability of otitis media: a twin and triplet study.

CONTEXT: Anatomical, physiological, and epidemiological data indicate that there may be a significant genetic component to prolonged time with and recurrent episodes of otitis media in children. OBJECTIVE: To determine the genetic component of time with and episodes of middle ear effusion and acute otitis media (AOM) during the first 2 years of life. DESIGN: Prospective twin and triplet cohort study with enrollment from 1982 through 1995. SETTING: Otitis Media Research Center in the ear, nose, and throat clinic of Children's Hospital of Pittsburgh, Pittsburgh, Pa. PATIENTS: A total of 168 healthy same-sex twin and 7 triplet sets were recruited within the first 2 months of life; zygosity results were available for 140 sets; 138 (99%) of these were followed up for 1 year and 126 (90%) for 2 years. MAIN OUTCOME MEASURES: Proportion of time with middle ear effusion, episodes of middle ear effusion, and episodes of AOM by zygosity status. RESULTS: At the 2-year end point, the estimate of heritability of time with middle ear effusion was 0.73 (P<.001). The estimates of discordance for 3 or more episodes of middle ear effusion were 0.04 for monozygotic twins and 0.37 for dizygotic twins (P = .01). The estimate of discordance of an episode of AOM in monozygotic twins was 0.04 compared with 0.49 in dizygotic twins (P = .005). CONCLUSIONS: Our study suggests there is a strong genetic component to the amount of time with middle ear effusion and episodes of middle ear effusion and AOM in children.

Visual-induced postural sway in children with and without otitis media.

Children with otitis media with effusion (OME) have been shown to have a significantly higher velocity of sway than normal children. To further evaluate the effect of OME on balance, we studied visual dependency for balance by investigating the influence of optic flow on postural sway. The results of this preliminary study suggest that children with OME may be more visually dependent for balance than healthy age-matched controls. This was particularly evident for higher-frequency stimulus conditions (0.25 Hz) as opposed to lower-frequency stimulus conditions (0.10 Hz). These findings indicate that OME may affect vestibular function in children, thereby causing excessive reliance on other, nonvestibular sensory cues to maintain balance. Further studies are needed to define the role of vestibular function in the management of children with OME.

A role for otoacoustic emissions in screening for hearing impairment and middle ear disorders in school-age children.

OBJECTIVE: The primary purpose of this study was to investigate the potential role of transient-evoked otoacoustic emissions (TEOAEs) for screening for hearing impairment and middle ear disorders in school-age children. Because TEOAEs are present in ears with normal cochlear and middle ear function and typically are absent or reduced in ears with cochlear and/or middle ear disorders of even mild degree, TEOAE screening could serve as a first-stage screening to separate from the general population of school-age children those at greater risk for hearing impairment and/or middle ear disorder. There were two secondary objectives. First, the relationship between TEOAE measurement variables and measures of middle ear immittance in ears declared clinically normal was investigated. Second, the performance of TEOAEs in screening was compared with the performance of the pure-tone hearing and tympanometric screening protocol commonly used in the schools. DESIGN: Sixty-six children (ages 5 to 10 yr) participated. TEOAEs, pure-tone hearing screening, acoustic immittance (single-frequency and multi-frequency tympanometry), and an otoscopic exam by a pediatrician, who previously had been "validated" for identification of middle ear effusion, were done on each child under typical school hearing screening conditions. Performance of the TEOAE screening was determined based on the pediatrician's determination of middle ear status and the pure-tone hearing screening as the gold standards. RESULTS: Of the 66 subjects, 61 completed the study. Fifty-six children passed the hearing and otoscopic screenings bilaterally, and five children did not pass either or both the hearing screenings or otoscopic examination in at least one ear. A variety of TEOAE criteria were examined with respect to their ability to identify ears with either hearing impairment and/or middle ear disease. Several different otoacoustic emission criteria performed well according to our diagnostic criteria. Correlations between TEOAE variables and immittance measures of middle ear function were all low. In addition, tympenometric data were used to compare the TEOAE screening with the American Speech-Language-Hearing Association's (ASHA) recommended protocol for the same ears. The ASHA protocol, as recommended, did not do as well as the TEOAE screening. Using slightly modified criteria, the ASHA protocol did as well as TEOAEs. CONCLUSION: There were some screening criteria based on TEOAE measurement that produced good sensitivity and specificity. A TEOAE screening for hearing impairment and middle ear disease performed as well as or better than the ASHA-recommended protocol, which requires a minimum of two different tests, even when the ASHA protocol was modified to optimize performance. The results suggest that the TEOAE test has the potential to be incorporated successfully into hearing screening programs for school-age children and may have advantages over current screening protocols. Finally, no relationship between TEOAEs and middle ear function, as measured using single-frequency and multifrequency tympanometry, could be determined in ears with normal hearing and normal middle ear function.

Efficacy of antimicrobial prophylaxis for recurrent middle ear effusion.

OBJECTIVES: This trial compared the efficacy of amoxicillin prophylaxis with that of placebo for the management of recurrent middle ear effusion (MEE) in children. METHODS: Children between 7 months and 12 years of age who were effusion-free at entry but had histories of chronic or recurrent MEE were randomly assigned to receive either amoxicillin (20 mg/kg once daily) or placebo for 1 year. They were examined monthly and when there were symptoms of ear, nose or throat disease. Acute otitis media (AOM) and new episodes of otitis media with effusion (OME) were treated with amoxicillin-clavulanate; tympanocentesis was performed when possible for episodes of AOM. Throat cultures were obtained at entry; 4, 8 and 12 months after entry; and with new episodes of AOM and OME. Tympanometry was performed at each visit and audiometry was performed at entry and 4, 8 and 12 months after entry. RESULTS: One hundred eleven children were entered in this study. The rates per person year of new episodes of disease in the amoxicillin and placebo groups, respectively, were: MEE, 1.81 vs. 3.18 (P < 0.001); AOM, 0.28 vs. 1.04 (P < 0.001); and OME, 1.53 vs. 2.15 (P = 0.016). Subjects in the amoxicillin group had less time with MEE than the placebo group (19.7 and 33.2%, respectively; P = 0.002). Middle ear and throat cultures did not reveal any increase in beta-lactamase-producing organisms or in Streptococcus pneumoniae attributable to daily use of amoxicillin. CONCLUSIONS: Amoxicillin prophylaxis lowered the rates of occurrence of MEE, AOM and OME and decreased the percentage of time with MEE. However, because of present day concerns regarding antibiotic resistance, management should be individualized.

Efficacy of ceftibuten compared with amoxicillin for otitis media with effusion in infants and children.

OBJECTIVES: This trial compared the efficacy of ceftibuten with that of amoxicillin in resolving otitis media with effusion. METHODS: Two hundred ten children with otitis media with effusion were randomly assigned to receive either ceftibuten (9 mg/kg/day in one daily dose) or amoxicillin (40 mg/kg/day divided into 3 daily doses) for 14 days. Outcome was assessed at 2 and 4 weeks in all subjects; those without middle ear effusion at the 4-week visit were examined at 8, 12 and 16 weeks. Middle ear status was determined by pneumatic otoscopy and by an algorithm combining pneumatic otoscopy with tympanometry. RESULTS: The percentages of subjects who were effusion-free in the ceftibuten and amoxicillin groups at 2 weeks by otoscopy were 29.8 and 27.2%, respectively (P = 0.59), and by the algorithm, 23.4 and 20.4%, respectively (P = 0.47). In children who were effusion-free at 2 weeks, recurrence of effusion by 16 weeks was noted in approximately 60% of the ceftibuten group and 67% of the amoxicillin group. No medication side effects were reported by 88% of subjects in the ceftibuten group and by 93% of subjects in the amoxicillin group. We found no significant differences between the ceftibuten and amoxicillin groups with respect to resolution of middle ear effusion, rate of recurrence or side effects. CONCLUSIONS: Amoxicillin remains the drug of first choice for treatment of otitis media with effusion when treatment is deemed advisable, but ceftibuten may be an alternative drug in selected situations.

Otitis media in a population of black American and white American infants, 0-2 years of age.

To determine the incidence of otitis media (OM) and the bacteriology of acute otitis media (AOM) in a clinic population of young children in Pittsburgh, 138 black infants and 60 white infants were followed from birth to 2 years of age, examined at monthly intervals and whenever an upper respiratory tract infection (URI) or OM intervened. By 24 months of age the cumulative incidence of episodes of AOM was 43% and 42%, and of episodes of middle-ear effusion (MEE) was 86% and 85% in black and white infants, respectively. The average rate of episodes of AOM was 0.41 and 0.39 and of episodes of MEE was 1.68 and 1.70 in black and white infants, respectively. Tympanocentesis was performed for episodes of AOM and the following organisms were isolated from black and white infants, respectively: Streptococcus pneumoniae 43% and 43% of episodes; Moraxella catarrhalis 24% and 24%; non-typable Haemophilus influenzae 18% and 24%; and Haemophilus influenzae type b 5% and 0%. In both black and white infants first born children had less ear disease. We found no difference in the incidence of otitis media during the first 2 years of life between black and white infants.

Effect of otitis media on the vestibular system in children.

Forty-one children with otitis media (OM) were evaluated by moving platform posturography (Equitest, NeuroCom) before and after insertion of tympanostomy tubes, and were compared to children with no ear disease (N = 50). Velocity of sway increased with increasing difficulty of test conditions (I-VI) for both groups of children (p < .001), and children less than 7 years of age had a higher velocity than children 7 years old or older (p < .001). Children with OM had a higher velocity than normal children (p < .05). For children tested less than 30 days after insertion of tympanostomy tubes, the velocity for condition VI was significantly lower than before insertion (p < .05). Also, that the 6 children who had fallen on all trials on condition V or VI were able to stand on these trials after insertion of tympanostomy tubes indicates an improvement. These findings indicate that episodes of OM may affect balance, leaving children more clumsy and accident-prone, and possibly impairing motor development.

Efficacy of 20- versus 10-day antimicrobial treatment for acute otitis media.

OBJECTIVE: The purpose of this trial was to determine whether 20 days of antimicrobial treatment is more efficacious than 10 days of treatment for acute otitis media (AOM) in clearing middle ear effusion and preventing recurrences of AOM, and whether changing to a beta-lactamase-stable antimicrobial agent after the initial 10-day treatment with amoxicillin for AOM is advantageous. METHODS: Children between 7 months and 12 years of age with AOM were randomly assigned to three treatment groups: (1) amoxicillin for days 1 through 10, then amoxicillin for days 11 through 20; (2) amoxicillin for days 1 through 10, then amoxicillin-clavulanate for days 11 through 20; and (3) amoxicillin for days 1 through 10, then a placebo for either amoxicillin or amoxicillin-clavulanate for days 11 through 20. Medication was dispensed in a double-blind manner. Children underwent tympanocentesis at entry and were re-examined on days 10, 20, 30, 60, and 90 after entry. RESULTS: Two hundred sixty-seven children entered the trial. At the 20-day visit, the percentages of children who were effusion free in the amoxicillin, amoxicillin-clavulanate, and placebo groups were 72.4%, 80.8%, and 52.5%, respectively. There was no statistically significant difference in the percentage of children who were effusion free between the amoxicillin and amoxicillin-clavulanate groups (95% confidence interval, -21.7, 4.9). Subsequent to the day 10 visit, the average proportions of time with middle ear effusion were not significantly different in the amoxicillin, amoxicillin-clavulanate, and placebo groups (0.29, 0.27, and 0.34, respectively), nor were there significant differences in the rates of recurrent episodes of AOM (0.56, 0.59, and 0.68, respectively). Regardless of treatment group, approximately 75% of children were effusion free at the time of their last visit. CONCLUSIONS: More children were effusion free by the day 20 visit if given antimicrobial treatment for 20 days rather than for 10 days, but this advantage was present for only a short time; by the end of the 90-day study period, the treatment groups were comparable with regard to effusion status. Recurrence of AOM during the study period was not prevented by the additional 10 days of treatment. Routine use of an additional 10-day course of antimicrobial treatment is therefore not recommended if a child is symptom free after the initial 10 days of treatment for AOM.

Acute otorrhea: bacteriology of a common complication of tympanostomy tubes.

We prospectively followed 246 children with tympanostomy tubes and observed acute otorrhea through a functioning tube at least once in 50% of subjects. Pathogens typical of acute otitis media (Streptococcus pneumoniae, Hemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes) were found in 42% of all episodes; Pseudomonas aeruginosa or Staphylococcus aureus was found in 44% of all episodes. Pathogens of acute otitis media were found in 50.0% of subjects under 6 years old versus 4.4% of subjects 6 years or over at the first episode (p < .001). Pseudomonas aeruginosa was found more often in children 6 years or older (43.5% versus 20.5% at the first episode, p = .052). Pathogens typical of acute otitis media were less prevalent in the summer months (14.7% versus 52.2% for the first episode, p = .001), while P aeruginosa was more prevalent in summer (44.1% versus 16.4% for the first episode, p = .006). This suggests that while many younger children with acute otorrhea may respond to treatment with oral antimicrobials alone, outpatient therapy of older children may involve use of topical antipseudomonal agents that may be complicated by the question of the safety of such medications.

A comparative evaluation of cefaclor and amoxicillin in the treatment of acute otitis media.

In an earlier study of 214 children with acute otitis media (AOM) randomly assigned to a 14-day course of either cefaclor or amoxicillin, 55.7% of cefaclor-treated subjects were effusion-free compared with 41.2% of amoxicillin-treated subjects at the end of treatment. The present study was conducted to determine whether, in a 1-year period, subjects treated with cefaclor for each episode would have middle ear effusion for significantly less time than those treated with amoxicillin for each episode. One hundred fifty-seven subjects with AOM were enrolled. No statistically significant differences were found between the cefaclor-treated and amoxicillin-treated groups in number of subjects effusion-free immediately after first treatment (47.9% vs. 42.3%, respectively), average percent of time with effusion (22.2% vs. 23.4%, respectively), or in rate of new episodes of AOM (3.05 vs. 3.26, respectively). We conclude that there is no clinically significant advantage to the use of cefaclor rather than amoxicillin as the routine first line drug in the treatment of AOM.

Efficacy of myringotomy with and without tympanostomy tubes for chronic otitis media with effusion.

In a previous trial involving 109 children with chronic otitis media with effusion of at least a 2 months' duration that had been unresponsive to medical treatment, we compared the efficacy of myringotomy with tube insertion, myringotomy alone and no surgical intervention with regard to time with middle ear effusion, hearing status and other indices over a 3-year period. Because interpretation of the results was rendered difficult by certain complexities of study design, the present trial with a revised protocol was carried out in an additional group of 111 children. As in the previous trial, myringotomy with tube insertion resulted in less time with effusion and better hearing than did either myringotomy alone or no surgery. However, acute and chronic otorrhea and tympanic membrane perforation developed not uncommonly after tube insertion. Myringotomy alone offered no advantage over no surgery regarding the percent of time with effusion or the number of episodes of acute otitis media. Currently for children with long-standing middle ear effusion, we recommend either watchful waiting with periodic hearing assessment or myringotomy with tube insertion, individualizing the recommendation for each child.

Comparative efficacy of erythromycin-sulfisoxazole, cefaclor, amoxicillin or placebo for otitis media with effusion in children.

We randomly assigned children with otitis media with effusion to receive either erythromycin-sulfisoxazole, cefaclor, amoxicillin or placebo for a 2-week period, primarily to determine whether either erythromycin-sulfisoxazole or cefaclor would have greater short term efficacy than that found previously for amoxicillin, and secondarily to supplement earlier data on outcomes in placebo-treated subjects. Interim analyses showed no statistically significant (P less than 0.05) differences between the three antimicrobial treatment groups in the primary outcome measures, i.e. the prevalence of middle-ear effusion 2 and 4 weeks after entry, and indicated that postulated differences favoring the erythromycin-sulfisoxazole and cefaclor groups over the amoxicillin group were unlikely to be found even if the originally calculated sample size were attained. Subject accrual was therefore terminated. Final analysis showed no significant between-group differences in other outcome measures as well. In antimicrobial vs. placebo comparisons neither erythromycin-sulfisoxazole nor cefaclor gave more favorable outcomes than placebo, whereas more children were effusion-free in the amoxicillin group than in the placebo group at 2 weeks (31.6% vs. 14.1%, P = 0.007), but not at 4 weeks. We conclude that when antimicrobial treatment for otitis media with effusion is deemed advisable, neither erythromycin-sulfisoxazole nor cefaclor should replace amoxicillin as first line treatment.

Systemic steroids for otitis media with effusion in children.

The role of oral steroids in the treatment of otitis media with effusion in children is the subject of ongoing debate. To critically evaluate the existing evidence, we performed a formal meta-analysis of six randomized clinical trials (n = 264 children) selected from 14 articles and abstracts. Children receiving steroids for 7 to 14 days were 3.6 times more likely than placebo-treated control subjects to have both ears free of effusion at the end of therapy (95% confidence interval, 2.2 to 4.1). This finding was essentially unchanged when the studies were weighted by a quality score, or stratified by use of concurrent antibiotic. The presence of significant heterogeneity among these studies suggests that additional trials will be needed to identify the specific subset(s) of children most likely to benefit from steroid therapy.

Myringotomy with and without tympanostomy tubes for chronic otitis media with effusion.

We studied 109 children with otitis media with effusion of 2 months' duration or longer that was unresponsive to medical management. Eighty-six subjects who had neither "significant" hearing loss nor defined symptoms were randomly assigned to receive myringotomy, myringotomy with tympanostomy tube insertion, or no surgery, and 23 subjects with significant hearing loss, defined symptoms, or both were randomly assigned to receive either myringotomy or myringotomy with tube insertion. Myringotomy with tube insertion provided more disease-free time and better hearing than either myringotomy alone or no surgery; however, some subjects who underwent myringotomy with tube insertion developed otorrhea or persistent perforation of the tympanic membrane. Myringotomy offered no advantage over no surgery regarding percent of time with middle-ear effusion, number of acute otitis media episodes, and number of subsequent surgical procedures. These results may not properly be extrapolated to less severely affected children.

A comparative study of amoxicillin-clavulanate and amoxicillin. Treatment of otitis media with effusion.

A double-blind randomized clinical trial was conducted at two sites comparing amoxicillin-clavulanate potassium (Augmentin) and amoxicillin trihydrate for the treatment of otitis media with effusion ("secretory otitis media"). One hundred eight subjects were randomly assigned to receive a ten-day course of either drug regimen. Clinical response was assessed at ten days and four weeks after entry. For those without middle ear effusion at four weeks, recurrence rates were measured at 8, 12, and 16 weeks after entry. At ten days following entry, 29 (51.8%) of 56 subjects in the amoxicillin-clavulanate-treated group were effusion free compared with 16 (32.0%) of 50 subjects in the amoxicillin-treated group (P = .06). At four weeks following entry, 26 (50.0%) of 50 subjects in the amoxicillin-clavulanate-treated group were effusion free compared with 23 (51.1%) of 45 subjects in the group given amoxicillin. By the 16-week visit, eight (36.4%) of 22 subjects in the amoxicillin-clavulanate-treated group who were effusion free at four weeks had recurrence of effusion, compared with 12 (63.2%) of 19 subjects in the amoxicillin-treated group. This study suggests that there was a favorable clinical response immediately following treatment in the amoxicillin-clavulanate--treated subjects as compared with those treated with amoxicillin, but this benefit was not sustained at the four-week end point.