Chapter 28. Otitis Media

The term otitis media (OM) has been used to describe multiple disorders of the middle ear, including acute otitis media (AOM), otitis media with effusion (OME), chronic OME, and the umbrella designation including all of these terms. This chapter uses the term otitis media in its historic usage as an umbrella term including AOM and OME, and uses the terms AOM and OME as specific disease processes as defined below. The purpose of the chapter is to describe the contemporary approach to diagnosis and management of AOM and to discuss OME as it relates to AOM.

As few as 50% of pediatricians in the United States are aware of recent guidelines for diagnosis and management of AOM. Only 28% of those aware of these guidelines changed their practice as a result.1 University-affiliated pediatricians’ diagnoses of AOM complied with Centers for Disease Control and Prevention diagnostic criteria only 38% of the time during the winter of 1999–2000.2 Additionally, tympanometry as an adjunct to otoscopy did not improve diagnostic accuracy or decrease antibiotic usage.3 In Finland, implementation of a national guideline for OM resulted in health benefits and lower direct costs.4 One conclusion from the Finnish data is that adherence to such guidelines may improve care and reduce use of antibiotics.

OME is usually the result of AOM. Therefore, AOM and OME are pathologic processes along the same disease continuum. This relationship has resulted in diagnostic uncertainty and variations in the definition of AOM over time. However, establishing a uniform and appropriate definition is of utmost importance if AOM is to be diagnosed and managed appropriately. The most important distinction is that OME is not treated with antibiotics, whereas AOM may be treated with antibiotics. This difference exemplifies the need for uniform and appropriate definitions, diagnostic criteria, and management schema for AOM and OME.5,6

With the above caveat in mind, the American Academy of Pediatrics Subcommittee on Management of AOM and the Agency for Healthcare Research and Quality has established a definition of AOM.7–9 This definition requires the presence of three equally important elements8:

1. Acute onset (<48 hours) of signs and symptoms, and

2. Middle-ear effusion (MEE), and

3. Signs and symptoms of middle-ear inflammation.

Methods and criteria for the diagnosis of AOM pertaining to each of these diagnostic elements are included in the following sections and in Table 28–1.

In similar fashion the Agency for Healthcare Research and Quality has convened an expert panel to define and develop clinical practice guidelines for OME. OME is defined as the presence of middle ear fluid without signs or symptoms of AOM.5,10 Implicit in this definition is the absence of evidence of middle-ear inflammation. OME occurs without an inflammatory component as a result of Eustachian tube dysfunction or, alternatively, during the period following AOM in which inflammation has resolved but effusion persists.

AOM, OME, and other processes comprising the designation OM are second only to upper respiratory infections (URIs) as a reason for ambulatory care visits in patients younger than 15 years, and account for 13% of all emergency department visits.11 These data reflect a statistically significant decrease in the age-adjusted visit rate, reported by the National Ambulatory Medical Care surveys between the years 1993–1995 and 2001–2002.11,12 However, accurate data on the epidemiology of AOM are lacking because these surveys do not make the critical distinction among AOM, OME, or eustachian tube dysfunction.8 OM has previously been reported as the most frequent reason for antibiotic prescribing in childhood and accounted for $4.1 billion in the US expenditures in 1992.13,14

There is overlap of presenting signs and symptoms of AOM with those of other upper respiratory illnesses, and over recent decades there has been considerable variability in diagnostic criteria published for AOM. As a result, AOM is one of the most frequent diagnoses in infants and children.9 Age-specific rates of AOM since introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) (Prevnar®), in 2000, are lacking. Although previous studies have noted that as many as 60% of children have an episode before 1 year and 80% by 3 years of age, these rates may no longer be accurate.14,15 Paradise et al.16 followed a large cohort of infants from age 2 months until 2 years with frequent expert examinations, using pneumatic otoscopy and tympanometry. Middle ear effusion (MEE) was noted in 48%, 79%, and 91% by 6, 12, and 24 months, respectively. Although the investigators did not use strict criteria for defining AOM, these rates provide an indication of the frequency of MEE in the first 2 years of life.

The middle ear is a laterally compressed space within the temporal bone, bounded by the tympanic membrane (TM) and the eustachian tube.17 It is normally aerated and contains the ossicular chain, essential for transmission of sound energy to the inner ear. The eustachian tube is shorter and more horizontally oriented in children, thus allowing easier egress of nasopharyngeal secretions into the middle ear cavity.

The common pathway in AOM pathogenesis is dysfunction or edema of the eustachian tube, for instance from a viral URI or environmental smoke, that in turn results in development of negative middle ear pressure and MEE. The fluid may then become secondarily infected with viruses or bacteria, provoking an inflammatory response and resulting in AOM.18 Alternatively, the fluid may remain sterile and persist as OME.5

The relatively high incidence and spontaneous resolution of OME and AOM indicate these may be natural occurrences as the child's anatomy and immune system develop.18 However, environmental insults such as tobacco smoke lead to episodes that would otherwise not occur. Prevention of much of the disease burden of AOM in children is possible.

Although viral URIs appear to frequently initiate eustachian tube dysfunction and AOM, they have been reported as primary pathogens in only 0–13% of cases.19,20 At a minimum, viral–bacterial interaction appears to occur frequently in the cascade of events leading to AOM.20 Viral–bacterial coinfection of the middle ear is common, occurring in up to 30–60% of cases.19,20 The most frequently isolated viral agents are rhinoviruses; respiratory syncytial virus (RSV); influenza A and B; parainfluenza types 1,2, and 3; and adenovirus.19 Studies utilizing culture and antigen detection have noted RSV (41%) as the most common virus isolated from middle ear fluid, whereas those utilizing polymerase chain reaction have noted human rhinovirus (24%) as most prevalent with RSV (18%) less frequently isolated.21,22

When meticulous isolation technique (tympanocentesis) and bacteriologic isolation methods have been employed, bacteria were isolated from the middle ear in up to 95% of cases of AOM in the pre-PCV7 era.23,24 The major bacterial pathogens have been constant over time, and include Streptococcus pneumoniae, nontypable Haemophilus influenzae, and Moraxella catarrhalis. However, the relative frequencies of these pathogens subsequent to introduction of PCV7 appear to be changing (Table 28–2).

In a prospective cohort of children 7–24 months of age with severe or refractory AOM, Block et al.25 compared isolates from the pre-PCV7 era with those of vaccinated children in the post-PCV7 era in a rural setting. Statistically significant decreases in S. pneumoniae (48–31%) and increases in nontypable H. influenzae (41–56%) were noted, such that nontypable H. influenza had supplanted S. pneumoniae as the predominant bacterial pathogen. Casey and Pichichero26 conducted a prospective study of infants and children with persistent or treatment-failure AOM in a suburban practice. Similar post-PCV7 era decreases occurred in S. pneumoniae (44–31%) and increases in nontypable H. influenzae (43–57%) isolates.

The relative frequencies of major bacterial pathogens may change yet again as the prevalence of nonvaccine serotypes causing AOM increase.27 Of particular relevance in considering antibiotic treatment, a statistically significant increase of β-lactamase producing organisms (32–47%) occurred, and both investigations noted nonsignificant trends toward penicillin-susceptible S. pneumoniae in the post-PCV7 era.

The natural history of AOM has been intensely scrutinized in prospective studies and as part of randomized trials of antibiotic treatment.28 MEE is a natural consequence of AOM, and resolves in approximately two-thirds of children within 1 month and in 90% within 3 months. In the pre-PCV7 era, the mean cumulative proportion of days with MEE was 20% and 17% in the first and second years of life, respectively.16

Hereditary and Demographic Risk Factors

Genetic predisposition and premature birth are variables that contribute to anatomic and immunologic aspects of risk for AOM. The unique and developing anatomy of the middle ear system, as well as immunologic immaturity in infants and young children, are primary determinants of young age as a risk factor. Children of age 7–36 months are at greatest risk.14 Male gender appears to confer additional risk of AOM, although studies have not consistently demonstrated this risk.7,16

Although these associations are biologically plausible, investigations of race and ethnicity have inconsistently controlled for other statistically significant variables, including socioeconomic status, environmental tobacco smoke (ETS), and numbers of exposures to siblings and other infants and young children.16 There has also been variable diligence in observation for and diagnostic accuracy of middle ear disease in studies examining these variables.28 Native American, Inuit, and Native Alaskan children appear to have higher rates of middle ear disease than Caucasian children.7

Environmental Risk Factors

Exposure to older siblings or attendance at day care increases exposure to upper respiratory viruses, thereby influencing risk in infants and young children. Risk conferred by some exposures, in particular tobacco smoke, have been more difficult to assess because some studies have not controlled for other statistically significant variables, most importantly socioeconomic status. Importantly, the influence of certain of these risk factors may be changed through primary prevention.29

Aspects of breast feeding suggest that it might be protective against AOM. These include the upright positioning during feeding, resulting in less reflux of milk through the eustachian tube, and possible immune modulating and antimicrobial constituents of breast milk. This appears to be the case for exclusive breast feeding during the first 3–6 months. This protection continues until 1 year of age when the effect of breast feeding was adjusted for other variables.16

ETS is both biologically plausible and consistently demonstrated in numerous investigations to be associated with increased risk for both AOM and persistent MEE.16,30 Household members may underestimate the amount of ETS or deny smoking. Investigations using cotinine as a biomarker for ETS consistently demonstrate an association between cotinine levels and the risk of middle ear disease.31–33 Although the effect of ETS is confounded by socioeconomic status, a meta-analysis of prospective cohort studies adjusting for this and other potential confounders found a pooled RR (relative risk) of 1.19 (95% CI, 1.05–1.35, p < 0.01) for ETS and middle ear disease, and estimated that 13% of middle ear disease may be accounted for by ETS.30 Of the modifiable risk factors for AOM, ETS appears to be the most significant, and efforts are warranted to prevent exposure of infants and children to ETS.

Group day care and the number of older siblings both confer risk of AOM, although studies of the association between numbers of older siblings and middle ear disease have not consistently demonstrated such an association. What appears significant is not the location of exposure to other children (and upper respiratory viral illnesses), but rather the number and intensity of exposures.16

Immunoprophylaxis with the live trivalent intranasal influenza vaccine may prevent as much as 30% of AOM during the upper respiratory viral season and was 90–97% effective in preventing episodes of AOM associated with influenza.34,35 However, trivalent killed influenza vaccine did not decrease the incidence of AOM either during influenza season or during the subsequent 1-year period.36 PCV7 has been demonstrated to reduce the number of episodes of AOM from all causes by 6–8%, those episodes as a result of vaccine serotypes by 51–67%, and placement of tympanostomy tubes by 24%.37–39 In addition, a large study examining Medicaid and insurance databases found a decrease in AOM rates of 6% in Tennessee and 20% in upstate New York as a result of PCV7 use.40

Features of the medical history, signs, and symptoms of AOM are familiar to clinicians. Although some of these are relatively specific for middle ear disease (e.g., otalgia), many are nonspecific and are associated with other disease processes. If clinicians are to make an accurate diagnosis of AOM and, in turn, manage AOM and other upper respiratory illnesses appropriately, the various elements of the history and physical examination must be employed correctly. Of importance to clinicians are features of the history and physical examination found to be predictive of AOM using validated criterion measures such as tympanometry.41

A necessary first step in establishing the presence of relevant physical findings is a properly conducted otoscopic examination. This includes comfortable immobilization of the patient and the use of an otoscope with a bright light source and properly fitting speculum.9 An atraumatic examination is helpful because crying or irritation of the external auditory canal will cause redness of the TM.42

Cerumen in the external ear canal can be a significant diagnostic barrier for the clinician. Minimal-to-moderate cerumen in the external canal may not prevent the clinician from visualizing part of the TM, but impacted cerumen may need to be removed. Techniques for removal of cerumen include a soft speculum or gentle irrigation of the canal with warm sterile water or saline. Both procedures induce some risk of discomfort, pain, abrasion of the skin of the external canal (which may lead to bleeding) or traumatic perforation of the TM. An additional adjunct is the use of cerumenolytic agents such as docusate (Colace®) or triethanolamine polypeptide. The technique involves instillation of 1 mL of the agent into the ear canal for 15 minutes, followed by irrigation with saline if necessary. Trials of this technique have been of variable quality and have provided inconsistent evidence of efficacy.43–46 The examiner is more likely to be successful if the child's head is immobile while removing the cerumen. While no technique is always successful or risk free, it is nonetheless imperative that the clinician properly visualize the TM and assess mobility in order to confirm the presence or absence of an effusion in the middle ear space.

In addition to the position of the TM, the examiner should assess color, landmarks and mobility. For the latter, pneumatic otoscopy is invaluable, and may be supplanted with tympanometry or acoustic reflectometry. In this way, the examiner may achieve an examination approaching the validity of the criterion standard, tympanocentesis, although these individual elements of the otoscopic examination do not provide the diagnostic certainty of tympanocentesis and culture of middle ear fluid.

The normal TM has a pearl to pink color. Red coloration alone does not alone indicate inflammation, as crying will result in hyperemia with red coloration.42 The normal TM is neither retracted nor bulging. The TM is relatively translucent, allowing for visualization of some middle ear structures, including the handle and lateral process of the malleus, umbo, pars flaccida, long limb of the incus, chorda tympani nerve, as well as the light reflex (Figure 28–1). AOM is indicated by a red, bulging (with exudate), and immobile TM (Figure 28–2). A bluish or yellow coloration may indicate MEE, a finding supported by a TM that is bulging, retracted, or that has decreased mobility on pneumatic otoscopy (Figures 28–3 and 28–4). The TM may become perforated as a result of AOM, trauma, or prior PET insertion, and such perforations allow an avenue of egress for middle ear fluid (Figures 28–5 and 28–6).

Rothman et al.9 have performed a systematic review of the literature pertaining to the precision and accuracy of the history and physical examination for diagnosis of AOM. Of 17 studies that specifically investigated signs and symptoms in the diagnosis of AOM, 5 met inclusion criteria. The presence of URI symptoms was sensitive (96%) for AOM but had low specificity (8–43%), and other signs and symptoms, including fever, cough, and excess crying had poor sensitivity and specificity.9 The presence of otalgia was 54–100% sensitive and 82–92% specific for AOM. However, although otalgia appeared to be the only symptom useful in establishing the diagnosis of AOM, 15% of children with otalgia did not have AOM in a well-performed prospective study.41 In addition, although it may appear that parental suspicion is highly predictive of the presence of AOM, 20% of parents suspected AOM in the presence of URI alone.41 The findings of this systematic review emphasize the need to fulfill all three diagnostic criteria in making a diagnosis of AOM (see section on “Definitions”).

The differential diagnosis for AOM is large and includes both common and uncommon entities encountered by the clinician (Table 28–3). Common diagnoses include foreign body in the external ear canal and otitis externa. Foreign body in the external ear canal may present with otalgia in the preverbal or developmentally delayed child. This diagnosis is usually confirmed with otoscopy. However, blood in the ear canal can obscure a foreign body. Otitis externa is more likely with a history of aural exposure to water. In this case, pain is usually produced with gentle movement of the pinna or with pressure on the tragus. An edematous external canal or a foul smelling exudate found within the canal seen via otoscopy helps confirm the diagnosis. Uncommon diagnoses include: brain abscess, accidental and nonaccidental trauma including perforation of the TM, Lemiere disease, Herpes zoster oticus (Ramsey Hunt Syndrome), peri-tonsillar abscess, sinusitis, mastoiditis (although usually associated with AOM) Wegener's granulomatosis, referred pain from oral cavity diseases, rhabdomyosarcoma of the ear and temporal bone, and cholesteatoma.

Otalgia is present in the majority of children that present with AOM, yet clinicians frequently prescribe antibiotics for AOM without addressing the pain often associated with this condition.47 A recent consensus practice guideline published by the American Academy of Pediatrics strongly recommends the assessment and treatment of otalgia in children diagnosed with AOM.7 However, there are few controlled studies that specifically evaluate the use of pain modalities for AOM. Table 28–4 describes the various medications used to treat pain associated with AOM.

Various home remedies, such as oils placed into the external canal, have been used for centuries. No controlled studies have demonstrated effectiveness of home remedies compared to placebo. Topical therapy applied directly to the TM using a combination of antipyrene as an analgesic agent and benzocaine as an anesthetic agent (Auralgan®) has been demonstrated in a small, randomized controlled trial to provide short-term relief of pain compared to the placebo olive oil.48 Auralgan® also contains glycerin, which may reduce middle ear pressure via fluid osmosis through the TM. This medication does not discolor the TM and will not alter otoscopic landmarks after application. Auralgan® may also facilitate the removal of cerumen but is contraindicated in children who have perforation of the TM.

Systemic medications such as acetaminophen and ibuprofen are the primary medications used to treat otalgia and also offer antipyretic relief, which is usually associated with AOM. Only ibuprofen has been shown to be superior to placebo in one randomized study.49 Combining ibuprofen and Auralgan® drops may be a beneficial combination to address otalgia in the outpatient setting.50 The effects of topical therapy are likely to be immediate whereas systemic therapy may take 30–60 minutes to relieve pain. Codeine and its analogs may be used for moderate-to-severe otalgia especially at night to help reduce pain when sleeping, although side effects of this pharmacologic class may limit its usefulness as a scheduled medication. Both ibuprofen and codeine may have adverse effects on the gastrointestinal system including nausea and emesis. Taking these medications with food may reduce these adverse effects.

AOM is the most common condition for which antimicrobials are prescribed for children. Clinicians write an estimated 15 million antibiotic prescriptions annually in the United States for AOM alone.51 Most cases of AOM will resolve spontaneously. Therefore, the benefit of antimicrobials must be weighed against adverse reactions.52 Approximately 15 children need to be treated with antibiotics to reduce or eliminate otalgia in one child within a week of treatment. This statistic should temper enthusiasm for immediate treatment with antibiotics. Antimicrobial resistance is a major public health concern, which is strongly associated with the use of antibiotics.53

The clinician may choose to give a wait-and-see prescription (WASP) for the antimicrobial treatment of AOM. This alternative form of therapy empowers the parent to make a decision about filling or not filling the prescription based on whether the child has worsened or not improved 48 hours after the initial visit. This model has been evaluated both in the outpatient clinic and emergency department settings.50,54,55 Children older than 6 months who are well appearing, do not have another suspected bacterial illness, are nonimmunocompromised, have access to medical care and no recent treatment with antibiotics may be suitable for a WASP (see Figure 28–7). Approximately two-thirds of children given a WASP will not fill their antibiotic prescriptions. Outcomes are similar compared to immediate treatment with antibiotics.50 Widespread use of an optional prescription for antibiotics in the United States may lead to a reduction in antimicrobial resistance.

When the child is younger than 6 months, or optional therapy is not warranted, immediate treatment of AOM with an antibacterial agent may be prescribed (see Table 28–5). High dose amoxicillin (80–90 mg/kg/day) is recommended as the initial antibacterial medication for uncomplicated AOM.7 This recommendation is based on middle ear concentrations of high dose amoxicillin that exceed the minimum inhibitory concentration for most resistant forms of S. pneumoniae.56 Children who have completed a recent course of antibiotics are at a higher risk of resistance to amoxicillin.57 High-dose amoxicillin-clavulanate may be considered for children with high fever or as a second tier medication if high-dose amoxicillin fails, a reasonable option given the relatively high prevalence of β-lactamase producing organisms discussed in the “Pathogenesis” section.7 However, the addition of clavulanic acid to amoxicillin increases the likelihood of gastrointestinal side effects including diarrhea, and these adverse effects should be explained to the family prior to prescribing this medication. For patients unable to tolerate oral medications, ceftriaxone (50 mg/kg/day) intramuscularly or intravenously for 3 days may be considered.58 In patients with a history of type 1 allergy to penicillin, azithromycin, or erythromycin-sulfasoxizole should be considered; it should be noted that both medications have a high incidence of nausea and vomiting. The latter medication has a high incidence of drug eruptions associated with its use. In patients who fail both oral and intramuscular medications, either clindamycin or tympanocentesis (with culture) should be considered.

The clinician may consider various options for duration of antimicrobial therapy for AOM. A shortened course of antibiotics (5–7 days) compared to a standard course (10 days) may reduce the likelihood of resistance to antibiotics by reducing the total dose exposure. This may also reduce unwarranted side effects that are known to be associated with their use. Approximately 44 children would need to be treated with a long course of antibiotics to avoid one short-course treatment failure for uncomplicated AOM.59 Standard course antimicrobial therapy should be prescribed in children younger than the age of 2 years or those who present with severe AOM. Discharge instructions to the family should describe the expected clinical response to therapy with antibiotics in order to avoid unnecessary return visits to the office. During the first 24–48 hours of treatment, fever and or otalgia may persist or worsen. If by 72 hours the child's condition does not improve, treatment failure should be considered and the child should be promptly re-evaluated in the office.

Effusions of the middle ear are part of the natural resolution of AOM and are visualized in the majority of children, weeks after AOM is diagnosed (Figures 28–3 and 28–4).60 There is no need for a scheduled follow up examination if symptoms of AOM have resolved. In the children diagnosed with uncomplicated OME (with or without a recent diagnosis of AOM), there are no indications for the use of antibiotics.61 If OME is present for greater than 3 months referral for placement of tympanostomy tubes may be warranted, although recent evidence suggests that this practice may not alter long-term developmental outcomes.62

Mastoiditis is the most frequent suppurative complication of AOM with an estimated frequency in the United States of approxiamately 1–2 cases per 100,000 person-years.63 Rates of mastoiditis are similar in countries whose physicians regularly prescribe antibiotics for AOM, such as the United States, compared to countries where physicians do not routinely prescribe antibiotics immediately for AOM, such as the Netherlands.63 Clinical signs include erythema, warmth and edema over the mastoid space with protrusion of the auricle. Less common findings include cranial nerve palsies (VI and VII) with extension of the infection into the intracranial space. The bacterial pathogens isolated in children with acute mastoiditis include those commonly found in AOM. Other common bacterial organisms isolated with mastoiditis include Pseudomonas aeruginosa and Streptococcus pyogenes.64 The treatment of mastoiditis includes antimicrobial therapy directed against the most common bacterial pathogens and may also include myringotomy. Mastoidectomy is recommended with antimicrobial treatment failure, the presence of a cholesteatoma in the middle ear space or with intracranial extension.65