Clinical-histopathological correlations in experimental otitis media: implications for silent otitis media in humans

Clinical-histopathological correlations were sought in an experimental animal model of otitis media. Among 20 chinchillas inoculated intranasally with wildtype influenza A/Alaska virus (H3N2) and type 7F Streptococcus pneumoniae, 15 animals (18 ears) developed otoscopic and tympanometric signs of otitis media with middle ear effusion. Middle ear inflammation was most intense 10 days after virus inoculation. Twenty-two days after virus inoculation, eight ears showed diffuse middle ear histopathology and contained effusion, which cultured pneumococcus, five ears showed focal histopathology, and four of the five contained no effusion. Clinical manifestations of otitis media had disappeared in four of the 13 ears with pathology at sacrifice; otoscopy was normal in all four ears, tympanometry was normal in three ears, and both otoscopy and tympanometry were normal in one ear. All four of these ears with clinically "silent" middle ear histopathology had shown abnormalities of ear drum appearance or tympanometry between 7 and 14 days after inoculation. Discordance between histopathology and the clinical examination performed at sacrifice was greatest for ears with focal pathology.     

Tympanometry in acute otitis media: prognostic implications

Impedance tympanometry was performed on children with acute otitis media. Most acute tympanograms were classified as either type B (no peak pressure) or positive-pressure tympanograms. A striking difference in outcome was noted between these two groups: the patients with positive-pressure tympanograms were more likely to have normal results with examination at the two-week follow-up than were those with type B tympanograms. There was no difference in outcome between antihistamine-decongestant and placebo regimens evaluated concurrently.     

Validity of acoustic reflectometry in detecting middle ear effusion

Pneumootoscopy, tympanometry, and acoustic reflectometry were performed in 256 middle-class children seen in a surburban pediatric office. The results demonstrated that relectometry, when validated by otoscopic findings, detected middle ear effusion with 88% sensitivity and 83% specificity when a cut-off of 5 linear units was used. Corresponding values for tympanometry were 87% and 77.5%. These results are in keeping with those of earlier studies on acoustic reflectometry and demonstrate the usefulness of this simple technique in detecting chronic and acute otitis media with effusion.     

Sulphamethoxazole prophylaxis in the otitis-prone child.

A bedtime dose of sulphamethoxazole was effective in preventing ear infections in otitis-prone young children. Thirty-three such children were studied by means of a random, double-blind, placebo-controlled, cross-over protocol. Nine (27%) of 33 children treated with sulphamethoxazole experienced 10 episodes of acute suppurative otitis media or otitis media with effusion while 19 (58%) of 33 children given a placebo experienced 27 episodes of acute otitis media or otitis media with effusion. No new episode of otitis media was observed in 11 children in whom serial urine samples uniformly had a positive response to Micrococcus lutea bioinhibition test, the method we chose to monitor compliance. Otitis media with effusion (secretory otitis media) was detected less often in the children who were given sulphamethoxazole; this fact suggests that prophylaxis with sulphamethoxazole may prevent persistent middle ear effusion in otitis-prone young children.     

Oral prednisolone is an effective adjuvant therapy for acute otitis media with discharge through tympanostomy tubes

OBJECTIVE: To determine the efficacy of a short course of oral prednisolone as an adjuvant therapy for acute otitis media draining through tympanostomy tubes. STUDY DESIGN: In a randomized, double-blind, placebo-controlled study, children with acute discharge (<48 hours) through tympanostomy tubes received either prednisolone (2 mg/kg/d; n = 23) or placebo (n = 27) for 3 days. All children received amoxicillin/clavulanate (40/10 mg/kg/d) for 7 days. The children were examined daily at the study clinic until the drainage ceased. RESULTS: The median duration of otorrhea in the prednisolone group was 1.0 days (25% to 75% range, 1.0 to 2.0 days), compared with 3.0 days (25% to 75% range, 2.0 to 4.0 days) in the children receiving placebo (P <.001). The duration of otorrhea was 相似文献   

Homeopathic treatment of acute otitis media in children: a preliminary randomized placebo-controlled trial

BACKGROUND: The use of antibiotics in the initial treatment of acute otitis media is currently being questioned. Homeopathy has been used historically to treat this illness, but there have been no methodologically rigorous trials to determine whether there is a positive treatment effect. METHODS: A randomized double blind placebo control pilot study was conducted in a private pediatric practice in Seattle, WA. Seventy-five children ages 18 months to 6 years with middle ear effusion and ear pain and/or fever for no more than 36 h were entered into the study. Children received either an individualized homeopathic medicine or a placebo administered orally three times daily for 5 days, or until symptoms subsided, whichever occurred first. Outcome measures included the number of treatment failures after 5 days, 2 weeks and 6 weeks. Diary symptom scores during the first 3 days and middle ear effusion at 2 and 6 weeks after treatment were also evaluated. RESULTS: There were fewer treatment failures in the group receiving homeopathy after 5 days, 2 weeks and 6 weeks, with differences of 11.4, 18.4 and 19.9%, respectively, but these differences were not statistically significant. Diary scores showed a significant decrease in symptoms at 24 and 64 h after treatment in favor of homeopathy (P < 0.05). Sample size calculations indicate that 243 children in each of 2 groups would be needed for significant results, based on 5-day failure rates. CONCLUSIONS: These results suggest that a positive treatment effect of homeopathy when compared with placebo in acute otitis media cannot be excluded and that a larger study is justified.     

Middle ear effusion among children diagnosed and treated actively for acute otitis media

We assessed the point prevalence of middle ear effusion among day care children in an area where acute otitis media is diagnosed, treated and followed actively. Minitympanometry was used to screen 850 day care centre attendants aged 0.6 to 6.9 years (mean 3.7 years). Tympanometry was performed by two trained nurses at the day care centres and pneumatic otoscopy was done by a paediatrician when effusion was suspected. We found 60 (7.1%) children to have middle ear effusion, which was bilateral in 23 (2.7%) cases. Of the children with bilateral effusion 13 had respiratory symptoms fulfilling the criteria of acute otitis media, 8 of them had experienced acute otitis media during the past 3 weeks and were diagnosed to have otitis media with effusion, and only 2 (0.2%) were asymptomatic children not identified earlier. Of the 37 (4.4%) children with unilateral effusion, 14 had acute otitis media and 23 otitis media with effusion, of whom 12 children (1.4%) had not been identified earlier. The point prevalence of acute otitis media was 3.2% and that of otitis media with effusion 3.9%. Conclusion We conclude that active diagnosis and treatment of acute otitis media practically eliminates such middle ear effusion that could cause significant hearing impairment. Received: 10 November 1997 / Accepted: 31 January 1998     

Comparative treatment trial of augmentin versus cefaclor for acute otitis media with effusion

A total of 150 children with acute otitis media were randomly allocated to treatment with amoxicillin-potassium clavulanate (Augmentin) or with cefaclor. Each drug was given in a daily dosage of approximately 40 mg/kg in three divided doses for ten days. Tympanocentesis done before treatment yielded specimens that contained pneumococcus or Haemophilus sp or both in 67% of specimens. Viridans group streptococci were isolated from 10% of specimens and Branhamella catarrhalis from 6%. Patients were scheduled for follow-up examinations at midtreatment, end of therapy, and at 30, 60, and 90 days. Of the 150 children, 130 were evaluable. Five of 60 patients (8%) treated with cefaclor were considered therapeutic failures because of persistent purulent drainage and isolation of the original pathogen or suprainfection. There were no failures among patients treated with Augmentin (P = .019). Rates of relapse, recurrent acute otitis media with effusion, and persistent middle ear effusion were comparable in the two groups of patients. Diaper rash, or loose stools, or both were significantly more common in children treated with Augmentin (34%) than in those taking cefaclor (12%), but in no case was it necessary to discontinue medication because of these mild side effects (P = .002). Cefaclor therapy was discontinued in one patient because of severe abdominal pain and vomiting. In this study, treatment with Augmentin was superior to treatment with cefaclor in the acute phase of acute otitis media with effusion, but Augmentin produced more adverse effects. The rates of persistent middle ear effusion and recurrent acute otitis media with effusion were comparable with the two regimens.     

Otoscopic and tympanometric findings in acute otitis media yielding dry tap at tympanocentesis

BACKGROUND: The value of tympanometry in detection of middle ear effusion (MEE) has been widely studied in otitis media with effusion. There has been no direct comparison of tympanometric and tympanocentesis (TAP) findings in acute otitis media (AOM). We compared otoscopic, tympanometric and TAP findings in AOM including cases of AOM without effusion. METHODS: In a study of AOM treatment of 90 children, a tympanogram was obtained, and TAP was performed before and after 5 days of treatment. Subjects were followed with otoscopy and tympanometry every 2 weeks for 3 months or until the MEE cleared. RESULTS: In 130 AOM ears, otoscopic, tympanometric and TAP findings were available; MEE was obtained from 110 ears. Of 20 ears with a dry tap, 18 had abnormal tympanogram and otoscopic findings. With TAP findings as the standard, sensitivity and positive predictive value of type B tympanogram were 97 and 87%, respectively. Of 18 AOM ears yielding dry tap, 2 yielded MEE 5 days later, and 8 continued with evidence of MEE 5 days-12 weeks later. Five subjects with 8 AOM ears yielding dry tap were lost to follow-up; all had short duration of clinical symptoms. CONCLUSIONS: Although otoscopic and tympanometric findings suggested the presence of MEE in AOM, MEE was unobtainable by TAP in 14% of cases. Dry tap cases likely represent early AOM before accumulation of detectable MEE. However, technical difficulty in obtaining small amounts of or highly viscous MEE could not be excluded. Sensitivity and positive predictive value of abnormal tympanograms in detection of MEE in AOM cases are comparable with those in otitis media with effusion.     

Amoxicillin-clavulanate potassium compared with cefaclor for acute otitis media in infants and children

One hundred thirty-three infants and children with documented acute otitis media (OM) were randomized to receive the oral suspension of either amoxicillin-clavulanate potassium or cefaclor. Beta-lactamase-producing bacteria were found in 10.9 and 14.5% of subjects treated with amoxicillin-clavulanate potassium and cefaclor, respectively. Subjects were reexamined at 5, 10, 30, 60 and 90 days after the initiation of therapy and whenever signs/symptoms of acute otitis media recurred. All but two children had resolution of otalgia/otorrhea during the initial treatment period. The drug groups were not significantly different in the percentage of evaluable subjects with otitis media with effusion at each scheduled follow-up visit. Recurrence of acute OM/otorrhea [corrected] developed in a similar percentage of subjects in both treatment categories. Both subjects with and those without middle ear effusion at 10 days had approximately a 50% recurrence rate of subsequent middle ear disease. Adverse side effects/complaints, which occurred in significantly more children treated with amoxicillin-clavulanate potassium, were generally mild and primarily gastrointestinal.     

Comparative trial of cefprozil vs. amoxicillin clavulanate potassium in the treatment of children with acute otitis media with effusion

A total of 137 children with acute otitis media with effusion were randomly allocated to treatment with cefprozil (30 mg/kg/day divided into two equal doses), an investigational cephalosporin or amoxicillin clavulanate potassium (40 mg/kg/day divided into three equal doses) for 10 days. The most common pathogens obtained from middle ear cavities by tympanocentesis were Streptococcus pneumoniae (33%), Haemophilus influenzae (19.6%) and Moraxella catarrhalis (8.3%). Patients were scheduled for follow-up visits at midtreatment, at end of therapy and at 30 days. Of the 137 children 122 were evaluable. Five of 60 patients (8.3%) treated with cefprozil and 14 of 62 patients (22.5%) treated with amoxicillin clavulanate potassium were considered therapeutic failures because of persistence of symptoms and/or isolation of the original pathogen or superinfection (P = 0.05). Rates of relapse, reinfection and persistent middle ear effusion as documented by tympanogram were comparable in both groups. When persistent middle ear effusion was analyzed by pneumatic otoscopy, 64 of 103 affected ears (62.1%) treated with cefprozil and 80 of 105 affected ears (76.1%) treated with amoxicillin clavulanate potassium were abnormal (P = 0.04). Loose stools were more common in children treated with amoxicillin clavulanate potassium than in children treated with cefprozil (P = 0.0004). Based on the efficacy results from this study, the lower gastrointestinal side effects and the convenience of twice-a-day dosing, we believe that cefprozil in a dosage of 30 mg/kg/day divided every 12 hours represents a potential alternative for the treatment of acute otitis media with effusion in children.     

Selection of antimicrobial agents for treatment of acute otitis media with effusion

Although a few studies suggest that symptomatic treatment alone may be sufficient for many children with acute otitis media with effusion, most investigators believe that clinical response is improved with antibiotic therapy. The first step in selecting an antimicrobial agent for treatment of acute otitis media with effusion is to determine in vitro susceptibilities of the most frequently isolated pathogens to commonly used antibiotics. Another important variable to consider is the degree to which the prospective agent penetrates and is concentrated in middle ear fluid. Although bacteriologic eradication of causative pathogens remains an objective of therapy, the desired result of any treatment regimen for both physician and patient is a satisfactory clinical response. Knowledge of geographic bacterial resistance patterns is essential to effective antibiotic therapy and continued successful clinical outcomes. The ideal antimicrobial agent for treatment of acute otitis media with effusion is safe, well-tolerated by infants and young children, is effective against the most frequently encountered pathogens and is affordable.     

Concentration of cefuroxime in serum and middle ear effusion after single dose treatment with cefuroxime axetil

Antimicrobial agents play an important role in the treatment of patients with acute otitis media and otitis media with effusion (OME). The study was undertaken to determine the concentrations of cefuroxime in the blood and middle ear effusions (MEE) of children between 6 and 12 years of age with acute otitis media and chronic OME after a single oral dose administration of cefuroxime axetil, the ester prodrug of cefuroxime. Cefuroxime axetil (250 mg) was administered 2 to 6 hours before either myringotomy for acute otitis media or myringotomy and tube insertion for chronic OME. Blood samples and middle ear aspirates were obtained from 31 children and the samples were analyzed by high performance liquid chromatography. Cefuroxime was recovered in measurable concentrations in all serum samples and in 15 (79%) of the 19 MEE specimens analyzed. No correlation was seen between cefuroxime MEE concentrations and effusion type, bacteriology or serum concentrations. This study shows that cefuroxime does penetrate into MEE when OME is present and that therapeutic concentrations can be achieved in some patients.     

Disappearance of middle ear effusion in acute otitis media monitored daily with tympanometry

BACKGROUND: Disappearance of middle ear effusion is one of the most important outcomes in the treatment of acute otitis media (AOM). AIM: To evaluate the duration of effusion in AOM treated by antimicrobials and to find factors influencing it. METHODS: Parents of 90 children with AOM monitored daily the disappearance of effusion with tympanometry. The children were randomly allocated to be treated with either oral amoxicillin or cefuroxime-axetil for 10 d. Daily monitoring lasted for 14 d or until the tympanogram was normal (curve A or C) in both ears. Pneumatic otoscopy was carried out every 2 wk. RESULTS: Normal tympanograms were obtained after a median time of 7.5 d (range 1-58 d) among 75 successfully monitored patients. In two-thirds (69%) of them, effusion resolved in 14 d. The median duration of effusion did not differ significantly between the two treatment groups (8 vs 7 days, p=0.7). The children who had unilateral AOM cured more rapidly than those with bilateral AOM (5 vs 19 d, p<0.001). In logistic regression analysis adjusted for age, bilaterality explained treatment failure at 2 wk with an odds ratio of 28.1 (95% CI 4.6-169.5, p<0.001). CONCLUSION: The choice of antimicrobials did not influence the duration of middle ear effusion, which was much shorter than had been thought previously. Children with unilateral AOM were cured much more quickly than those with bilateral AOM.     

The use of acoustic reflectometry in the study of middle ear effusion in children suffering from acute otits media,upper respiratory tract infection and in healthy children

This report focuses on the occurrence of middle ear effusion in children with acute otitis media (n = 62), upper respiratory tract infection (n = 81) as well as in healthy control children (n = 152). Data are reported in age categories 0–4 and 5–13 years. Middle ear effusion was found in 86% of children with acute otitis media, 49% of children with upper respiratory infection and 13% of healthy children. The younger the child, the more likely the presence of middle ear effusion in all groups. Acute otitis media and upper respiratory tract infection were clinically indistinguishable in infants. Conclusion Middle ear effusion is not generally a particularly significant clinical problem in children. Received: 31 January 1996 Accepted: 12 April 1996     

Respiratory virus infection as a cause of prolonged symptoms in acute otitis media

We studied respiratory viruses in 22 children with acute otitis media who had failed to improve after at least 48 hours of antimicrobial therapy. The mean duration of preenrollment antimicrobial therapy was 4.8 days. For comparison we studied 66 children with newly diagnosed acute otitis media. Respiratory viruses were isolated from middle ear fluid or from the nasopharynx, or both, significantly more often in the patients unresponsive to initial antimicrobial therapy than in the comparison patients (68% vs 41%, p less than 0.05). Viruses were recovered from the middle ear fluid in 32% of the study patients and from 15% of the comparison group. Bacteria were isolated from the middle ear fluid of four (18%) children in the study group; one child had an isolate resistant to initial antimicrobial therapy. All four children with bacteria in the middle ear fluid had evidence of concomitant respiratory virus infection. Our results indicate that respiratory virus infection is often present in patients with acute otitis media unresponsive to initial antimicrobial therapy, and may explain the prolongation of symptoms of infection. Resistant bacteria seem to be a less common cause of failure of the initial treatment.     

Five vs. ten days of therapy for acute otitis media

In a double blind study 175 patients with acute otitis media were randomized into 2 treatment groups: 10 days of therapy with cefaclor or 5 days of therapy followed by 5 days of placebo. The dosage of cefaclor was 40 mg/kg/day administered orally in equally divided doses at 12-hour intervals. Tympanocentesis before treatment yielded specimens that contained Streptococcus pneumoniae or Haemophilus influenzae or both in 55% of specimens. Branhamella catarrhalis was isolated from 21% of specimens. Culture of material from the ear canal of patients with spontaneous perforation of the tympanic membrane of less than 24 hours duration yielded pneumococci or H. influenzae or both in 38% of specimens and staphylococci in 31%. Patients were scheduled for follow-up examinations at 5 or 6, 10, 30, 60 and 90 days. Of the 175 children 151 were evaluable at 10 days. There were 123 patients with both tympanic membranes intact at the time of diagnosis. There were 6 (10%) treatment failures of therapy in the 59 patients assigned to 5 days of therapy and 4 (6%) failures and 1 (2%) early relapse in the 64 assigned to 10 days of therapy (difference not significant). There were 28 evaluable patients with spontaneous perforation. There were 8 (53%) failures in the 15 children assigned to 5 days of therapy and only 1 (8%) failure in the 13 children assigned to receive 10 days of therapy (P = 0.016, Fisher exact test). Rates of reinfection and persistent middle ear effusion at 10, 30, 60 and 90 days follow-up were not significant different in patients assigned to 5 to 10 days of therapy. In patients with acute otitis media with intact tympanic membranes we have not been able to show any advantage of the standard duration of 10 days of therapy over a shortened course of 5 days. A 5-day course of antibiotic therapy does not appear to be sufficient for children with acute otitis media and spontaneous purulent drainage.     

Prevention and therapy of serous otitis media by oral decongestant: a double-blind study in pediatric practice.

We studied the efficacy of (1) preventing the development of serous otitis media (SOM) by using an oral decongestant in children with acute otitis media and (2) treating SOM with an oral decongestant. In a randomized double-blind study, 190 children were treated for acute otitis media with antibiotics and either pseudoephedrine hydrochloride (Sudafed) or placebo. They were evaluated two weeks later by tympanometry and (independently) by clinical evaluation and pneumotoscopy. There were no significant differences between the two groups, except that males developed SOM significantly more often than did females. Use of decongestant and placebo was continued in 78 patients with SOM for up to four more weeks. Again, there were no siginificant differences between the treatment groups except that patients with an allergic history did significantly worse using a decongestant. Overall there was no benefit from pseudoephedrine in either the prevention or treatment of SOM.     

Middle ear effusion IL-6 concentration in bacterial and non-bacterial acute otitis media

BACKGROUND: The pathogenesis of acute otitis media is complex and multifactorial. It is characterized by inflammation of the middle ear with an infiltration of leukocytes, macrophages and mast cells. The resulting effusion contains a large amount of inflammatory mediators, among which are cytokines. OBJECTIVES: To test the role of IL-6 in the inflammatory process associated with acute otitis media. METHODS: We analyzed 20 middle ear fluid (MEF) sample pairs, obtained by aspiration before initiating antibiotic therapy (day 1) and during treatment (days 4-5), for the presence of IL-6. IL-6 concentrations were assayed with an ELISA kit (detection limit 5 pg/ml) and were correlated with bacterial etiology and bacterial eradication from the middle ear. RESULTS: IL-6 was detected in all middle ear effusions analyzed. We found decreased IL-6 concentrations in culture negative MEF compared to culture positive MEF on both days I and 4-5 (day 1, 1752.20+/-1001.31 pg/ml vs 1216.20+/-1015.44 pg/ml, p = 0.19; days 4-5, 1049.36+/-472.40 pg/ml vs 800.33+/-676.00 pg/ml, p = 0.23); however, differences did not achieve statistical significance. Overall, a marked and significant decrease in IL-6 concentration occurred following 72-96 h of antibiotic therapy (1618.15+/-1004.88 pg/ml vs 936.85+/-581.05 pg/ml, p = 0.04). While MEF IL-6 concentrations decreased in ears where bacteria persisted (1468.20+/-858.48 pg/ml vs 1044.80+/-514.16 pg/ml, p = 0.167) or were eradicated (2320.20+/-866.16 pg/ml vs 767.40+/-522.88 pg/ml, p = 0.029), a more prominent decline was demonstrated in the latter. CONCLUSIONS: These results strongly suggest the involvement of IL-6 in the ongoing inflammatory process in both bacterial and non-bacterial acute otitis media. Resolution of inflammation in the middle ear, especially where bacteria were eradicated, is reflected by low IL-6 levels.     

A randomized, placebo-controlled trial of the effect of antihistamine or corticosteroid treatment in acute otitis media

OBJECTIVES: To determine whether the adjunctive drugs antihistamine and corticosteroid improve immediate and long-term outcomes of acute otitis media (AOM). STUDY DESIGN: Children with AOM (3 mos-6 y) were enrolled in a randomized, double-blind, placebo-controlled trial. All 179 children received one dose of intramuscular ceftriaxone and were assigned to receive either chlorpheniramine maleate (0.35 mg/kg/d) and/or prednisolone (2 mg/kg/day) or placebo for 5 days. Main outcome measures were rate of treatment failure during the first 2 weeks, duration of middle ear effusion, and rate of recurrences of AOM to 6 months. RESULTS: Clinical outcomes and recurrence rates did not differ significantly with treatment. Children who received antihistamine alone had significantly longer duration of middle ear effusion (median, 73 days) than subjects in other treatment groups (median, 23 to 36 days, P=.04). Temporary normalization of tympanometric findings on day 5 occurred more frequently in the corticosteroid-treated group (P=.04). CONCLUSIONS: Five-day treatment with antihistamine or corticosteroid, in addition to antibiotic, did not improve AOM outcomes. Antihistamine use during an acute episode of OM should be avoided, since the drug may prolong the duration of middle ear effusion. The efficacy of 7- to 10-day treatment of AOM with corticosteroid, in addition to antibiotic, deserves further investigation.