Pediatric Otitis Media
CK CHOW, Y HUI, W WEI
Division of Otolaryngology, Department of Surgery, University of Hong Kong, HKSAR
Pediatric otitis media (OM) is the leading cause of hearing loss in children. It is a common healthcare concern in Hong Kong and worldwide, not only because of the distress it causes the patient and their family but also because of the substantial economic burden it imposes on the health care system. The direct and indirect costs of OM in the US were recently estimated at $5 billion annually. 1 Otitis media is also one of the most common reasons for visits to pediatricians.
Otitis media is defined as an inflammation of the middle ear, without reference to a specific etiology or pathogenesis. Classification of otitis media is based on the temporal sequence of the disease process. The terms acute and chronic are recommended. Acute otitis media (AOM) is an inflammation of the middle ear that presents with a rapid onset of signs and symptoms, such as pain, fever, irritability; a red bulging ear drum and middle ear effusion.2 Chronic disease implies middle ear fluid that has been present for three months or longer and has had many synonyms, including serous OM, secretory OM, and "glue ear".
The risk factors for AOM and OME appear to be the same. They include young age, male gender, bottle feeding, crowed living conditions (including child day care centers), smoking in the house, heredity, and a variety of associated conditions such as cleft palate, immunodeficiency, ciliary dyskinesia, Down syndrome, and cystic fibrosis.
The incidence of OM increases after the newborn period. Teele found that by age 12 months nearly two-thirds of all children had at least one episode of AOM. By three years, 46% of children had three or more episodes of AOM. In this study, the highest incidence of AOM for both sexes was found in children aged 6 to 11 months.3 There have also noted a second, lower peak between ages 4 and 5 years. 4 The onset of AOM during the first year of life is important because the majority of children with multiple recurrences of AOM have their first episode before the age of 12 months.
There is a high incidence of persistent middle ear effusion (MEE) occurring after an episode of AOM. A study has found that the mean duration of otitis media with effusion (OME) after AOM was 40 days. In a study by Shurin et al, it was shown that children who were less than 24 months of age were 3.8 times more likely to have persistent MEE than children who were older. They also found a higher incidence of persistent effusion in white children. 5
Factors involved in the development of otitis media include Eustachian tube abnormalities, impaired immunity, viruses, inflammation and inflammatory mediators, and allergy.
Eustachian tube abnormalities play a major role in the development of otitis media. The normal functions of the Eustachian tube are the regulation and equilibrium of pressure, protection and clearance of material from the middle ear. In many infants and children under the age of 7 years, there is an impaired opening mechanism in the Eustachian tube. In American Indians and Down syndrome patients, the Eustachian tube is always open and therefore, more prone to infection. In normal infants and children, Down syndrome patients, and in cleft palate, the Eustachian tube is shorter than in adults and, thus, bacteria do not have to travel so far to cause infection. Active clearance of the middle ear may be reduced if the ciliary function of the mucosal cells is impaired by viral infections, such as influenza A, or bacterial toxins, such as pneumolysin produced by Streptococcus pneumoniae.
Children are known to have poorer local antibody responses than adults and studies have shown that children who are prone to otitis media have lower IgG2 levels than normal children and respond less well to pneumococcal antigens. Compared with normal children, children with recurrent OM secreted low levels of cytokines, which are associated with the inflammatory response, into the nasopharynx. If dead bacteria are injected into the middle ear cavity, it has been shown that it will trigger the cytokines and the inflammatory response can still be detected in the middle ear fluid six weeks or more after effective antibiotic treatment. This may be one of the important mechanisms by which effusions persist in the middle ear following antibiotic treatment. 8
A role for allergy in the etiology of OM has long been postulated, however, proving this association has been difficult. The allergic response may, at least, predispose the patient to MEE by congesting and obstructing the Eustachian tube.
In the presence of an intact TM, the most likely source of the middle ear pathogens is the nasopharynx. Respiratory viruses may potentiate the possibility of nasopharyngeal colonization with bacteria, further increasing the incidence of OM. In most studies 25 to 30% of middle ear fluid cultures are negative for bacteria, some of which are positive for viruses, including rhinovirus, adenovirus, influenza virus, parainfluenza virus, and respiratory syncytial virus (RSV). Acute OM has been documented in 20 to 50% of hospitalized patients with laboratory-confirmed respiratory viral infection. 10 Heikkinen et al have found that RSV is the most commonly identified virus, being found in 74% of the middle ear isolates, followed by parainfluenza virus and influenza virus. 11 Also it has been shown that vaccination against influenza virus decreased the incidence of acute otitis media in infants and children.
Approximately 30 to 35% of cases are caused by Streptococcus pneumoniae, 20 to 25% by nontypable strains of Haemophilus influenzae and 10 to 15% by M. catarrhalis. The frequency of M. catarrhalis otitis appears to have increased in the last decade. The group A streptococcus causes acute middle ear infection in 2 to 4% of children and tends to occur in early spring. 9 Staphylococcus aureus, gram-negative enteric bacilli, and other bacteria are found consistently but less frequently. In infants younger than 6 weeks of age, gram-negative bacilli cause about 20% of the AOM episodes. These organisms include Escherichia coli, Klebsiella, and Pseudomonas aeruginosa. Even in these very young infants, however, the most common organisms are still S.pneumoniae and H.influenzae.
The trends in the bacteriology of AOM during the past decade have been a rise in the proportion of patients infected with drug-resistant S. pneumoniae and an overall increase in beta-lactamase-producing H. influenzae and M. catarrhalis. The incidence of penicillin-resistant S. pneumoniae was with an average of 5% from 1979 to 1987. Since 1992, however, the incidence of penicillin-resistant S. pneumoniae in younger children with invasive disease has dramatically increased to as high as 41% in some studies. 9 The majority of these penicillin-resistant strains were isolated from children younger than 24 months.
In the past, chronic MEE was thought to be sterile but studies have shown a 30 to 50% incidence of positive middle ear cultures in children with chronic MEE and polymerase chain reaction (PCR) testing has revealed that over 75% of the specimens are PCR positive for bacterial DNA. The most likely organisms are again, S. pneumoniae, H. influenzae, M. catarrhalis, and group A strep.
The diagnosis of otitis media usually depends upon the symptoms and also on the pneumatic otoscopic findings. The usual picture of acute otitis media is seen in a child who has an upper respiratory tract infection for several days and suddenly develops otalgia, fever, and hearing loss. Fever occurs in one-third to two-third of children with AOM. Other associated signs and symptoms include irritability, lethargy, anorexia, vomiting, and diarrhea. Hearing loss will not be a complaint of the very young or even noticed by the parents. Otorrhea may come from the middle ear through an acutely perforated TM. Less common signs and symptoms include tinnitus, vertigo, post-auricular swelling and facial paralysis. Older children more easily convey tinnitus and vertigo but parents may give a history of unsteadiness or clumsiness in the younger group.
Most children with chronic middle ear effusion are asymptomatic but some may complain of hearing loss and, less commonly, tinnitus and vertigo. In children the attention of an alert parent or teacher may be drawn to a suspected hearing loss. Older children will describe a frank hearing loss or, more commonly, a "plugged" feeling or "popping" in their ears.
In the diagnosis of both AOM and OME, pneumatic otoscopy continues to be the gold standard with a high degree of sensitivity and specificity of 75% and 90% respectively. The TM should be evaluated for color, position, and mobility. An abnormal TM is frequently opaque and may appear yellow or blue (indicating MEE), dark red (indicating recent trauma or hemorrhage). Hypomobility of the TM is suggesting middle ear fluid. Other pathology of the middle ear such as retraction pockets, atelectasis, perforations, tympanosclerosis, or cholesteatoma should also be looked for. Associated congenital syndromes and craniofacial anomalies that can predispose to OM including cleft palate, Down syndrome, Treacher Collins, and hemifacial microsomia are important for management. Nasal polyps, deviated nasal septum, or a nasopharyngeal mass should be sought.
Hearing should be evaluated in any child with recurrent or persistent OM or for Eustachian tube dysfunction for three reasons - 1) to document any sensorineural loss, 2) to document any conductive loss, and 3) to establish a baseline for later comparison and preoperative planning. Most children have screening audiograms before they enter school at age 4 to 5 years, but children who have recurrent or persistent disease, or in those with suspected hearing loss, should be evaluated earlier so that treatment and possible rehabilitation can begin as soon as possible. Tympanometry provides an objective assessment of middle ear status. The positive predictive value of a flat tympanogram for OME is 84%. This data should, of course, be correlated with physical examination. 3,4
The most common methods of managing acute otitis media, recurrent acute otitis media and otitis media with effusion will be discussed as they relate to the specific condition.
Acute Otitis Media
Antimicrobials are the mainstay of therapy for acute otitis media. However, children older than 2 years age with low grade or no fever and minimal or early signs of middle ear infection can be managed expectantly as long as follow-up evaluation can be assured at 24 to 72 hours. Since most clinicians rarely perform a tympanocentesis or myringotomy initially, the organism causing the otitis is usually not known with certainty before treatment begins. The recommended therapeutic dose of the antimicrobial should be administered for 10 days. During this period, the parents should be instructed to notify the clinician if the child fails to show a satisfactory clinical improvement. If there is persistence or recurrence of otalgia or fever, or both, then the child should be reexamined before the completion of the antibiotic course.
Factors to consider in choosing an appropriate agent for treatment of acute otitis media include activity of the drug against the usual otitic pathogens, safety, tolerance, ease of administration, the physician's experience, and cost. There is no one preferred treatment for all infants and children with acute OM. Amoxicillin is favored by many for initial treatment because of its long history of safety and effectiveness. In communities where penicillin-resistant pneumococci are prevalent, larger dosages of amoxicillin (i.e. 60 to 90 mg/kg daily in two or three doses) should be effective. When disease is caused by beta-lactamase producing organisms, amoxicillin may not be clinically effective, in which case, amoxicillin-clavulanate (Augmentin), a cephalosporin, trimethoprim-sulfamethoxazole, or erythromycin-sulfa could be used. Second generation cephalosporins provide good in vitro activity against penicillin-susceptible S. pneumoniae and group A streptococcus. In patients who fail to respond adequately to initial antibiotic therapy or have recurrent disease, amoxicillin-clavulanate (Augmentin), cefuroxime axetil (Zinnat) or possibly one of the newer macrolides - clarithromycin (Klacid) can be considered for treatment. 10
After an appropriate course of a usually effective antimicrobial therapy, most children are clinically well, but up to 50% will have persistent middle ear fluid. Several options can be considered, although many of them have not proved to be consistently significantly more effective than observation. These options include 1) another course of the same antimicrobial but for a longer time, 2) another course of a different antimicrobial, 3) topical or systemic decongestants and/or antihistamines, 4) topical or systemic steroids, 5) Eustachian tube/middle ear inflation, and 6) observation. If the patient is asymptomatic, the effusion can be followed because it may take up to three months to resolve. 4
Recurrent Acute Otitis Media
Children who experience recurrent AOM but who do not have persistent middle ear fluid can be considered for the following options. Chemoprophylaxis with an antimicrobial agent, Sulfisoxazole, amoxicillin, ampicillin, and penicillin has been used and studied. This option appears to be employed less frequently due to the increased rate of penicillin-resistant S. pneumoniae and beta-lactamase producing organisms. A recent meta-analysis showed a trend for better efficacy with sulfisoxazole than the other antibiotics in studies with a high recurrent AOM rate. Intermittent antibiotic prophylaxis for recurrent AOM during upper respiratory tract infections is controversial. A US study with amoxicillin showed less efficacy for intermittent than continuous use, and a Finnish study showed a lack of efficacy for a 7-day course of amoxicillin-clavulate given at the onset of an upper respiratory tract infection. 12
Myringotomy and tube insertion can be used to improve the ventilation of the middle ear. Many parents choose not to employ a daily antimicrobial and may instead favor it. As long as the tubes are patent, studies have shown a decrease in the number and severity of episodes of AOM. There is however the risk of persistent TM perforation and otorrhea, TM scarring, plugging of the tube, early extrusion, extrusion of the tube into the middle ear, and secondary infection around the tube. For children with particularly severe recurrent AOM, both prophylaxis and tube placement may be necessary. Myringotomy tubes are indicated in recurrent AOM, especially when antimicrobial prophylaxis fails to reduce the frequency, severity, and duration of attacks. The minimum frequency of three or more episodes in 6 months or four or more episodes in 12 months with one being recent is an indication of myringotomy tube insertion. 13
Adenoidectomy may improve the Eustachian tube function and eliminate a nasopharyngeal source of infection. Paradise et al found a significant difference in the attack rate of acute OM in children who had been randomized to receive adenoidectomy in addition to tube placement in comparison to those who received tube placement alone. He found that during the first and second years of follow-up, 28% and 35% fewer episodes of AOM occurred in the study group versus the control. 4
Otitis Media with Effusion
Treatment of middle ear effusion should generally be considered for children with MEE of 3 months or longer since many studies have shown asymptomatic MEE associated with upper respiratory tract infections and resolving AOM. In addition to chronic MEE, the decision to treat can be affected by the following - 1) hearing loss, 2) discomfort, 3) frequent OME episodes, 4) vertigo or unsteadiness, 5) TM changes, 6) middle ear pathology, and 7) associated upper respiratory tract disease.
Among the medical options, only antimicrobial agents have been consistently shown to be of benefit. Antibiotics can be used here because there is evidence of persistent bacterial organism by both standard culture techniques and PCR, therefore, eradication of the organism may lead to resolution of the fluid. 4 There is controversy surrounding administration of a corticosteroid with or without an antibiotic. There is data showing that combination therapy with an antibiotic plus a corticosteroid improved the rate of clearance of effusions by 21% compared to antibiotic alone, and by 25% compared to placebo. There is other conflicting data in the literature so decision on corticosteroid use will be a matter of personal preference until more data is available. If combination therapy is used, a corticosteroid (prednisone, 1 mg/kg per day, given orally in two doses) can be administered for 7 days along with an antibiotic for 14 to 21 days. Children without a history of varicella who have been exposed to the virus in the month prior to treatment should not receive prednisone because of the risk of disseminated disease. 2
Surgical options are usually reserved for patients who do not improve with medical therapy and include myringotomy with tube insertion with or without adenoidectomy. Studies have shown an improvement in conductive hearing loss secondary to OME and a decrease in the amount of time spent with MEE. Gates et al described a 47% reduction in time spent with recurrent effusion in children who received adenoidectomy and tympanostomy tube placement (compared to a reduction of 29% in the tympanostomy only group) in a group of 4 to 8 year old children with OME. 18
Although the intracranial suppurative complications of otitis media are relatively rare today except in neglected cases, awareness of the less serious sequelae is essential in management and to improve the quality of life of children with otitis media. The aural and intratemporal complications and sequelae of otitis media include hearing loss, perforation of the TM, chronic suppurative otitis media, retraction pocket, acquired cholesteatoma, mastoiditis, petrositis, labyrinthitis, adhesive OM, tympanosclerosis, ossicular discontinuity and fixation, facial paralysis, cholesterol granuloma, infectious eczematoid dermatitis, and necrotizing otitis externa.
There is much interest in the development of methods to prevent otitis media. Prevention rather than treatment would go a long way toward relieving human suffering and reducing its great financial impact on the health care system. At present, the vaccine approach seems to hold the greatest promise for ultimate prevention of OM. In addition to the bacterial vaccines, vaccines against the most common viruses predisposing to OM may also prove valuable in the prevention of OM. The multifactorial etiology of AOM constitutes a serious problem in the development of a vaccine. It is not certain whether even a highly effective vaccine against the main pathogens responsible for AOM would decrease its overall incidence when there are so many contributing factors to the pathogenesis of AOM. Despite these concerns there is much interest and hope in the development of these vaccines. S. pneumoniae is the most common bacterial agent in AOM, so several pneumococcal vaccine trials of AOM prevention have been reported.
The well-established role of viruses in the pathogenesis of AOM justifies the consideration of viral vaccines in the prevention of AOM. The most common viruses predisposing to AOM include respiratory syncytial virus, influenza A virus, adenovirus and parainfluenza viruses. Several investigators have studied the role of influenza vaccine and shown a decrease in the incidence of OM during the influenza season. Influenza vaccine starting at 6 months of age to those at higher risk of OM are now recommended by some authorities. Recent work found that RSV is the principal virus invading the middle ear during AOM. Intranasal RSV vaccines to protect both the upper and lower respiratory tract are being developed. 1,11,16
Finally, xylitol, a widely used sweetening substitute for sucrose has been shown to inhibit the growth of S. pneumoniae in growth media. Using xylitol chewing gum, syrup, and lozenges versus controls, it was found that all three decreased the number of days that the study children were on antimicrobials secondary to OM. They also found that the xylitol chewing gum and syrup led to a significant reduction in the occurrence of AOM among the children at day care centers (40% reduction for gum and 30% reduction for syrup, respectively). These effects are thought to be explained by its local inhibitory effects on the growth of pneumococci and the inhibition of the adhesion of both pneumococci and H. influenzae in the nasopharynx. 17
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