Otitis Media

Otitis media (OM) is the second most common disease of childhood, after upper respiratory infection (URI). OM is also the most common cause for childhood visits to a physician's office. Annually, an estimated 16 million office visits are attributed to OM; this does not include visits to the emergency department.

OM is any inflammation of the middle ear, without reference to etiology or pathogenesis. It can be classified into many variants on the basis of etiology, duration, symptomatology, and physical findings.

Acute OM (AOM) implies rapid onset of disease associated with one or more of the following symptoms:

• Otalgia
• Fever
• Otorrhea
• Recent onset of anorexia
• Irritability
• Vomiting
• Diarrhea

These symptoms are accompanied by abnormal otoscopic findings of the tympanic membrane (TM), which may include the following:

• Opacity
• Bulging
• Erythema
• Middle-ear effusion (MEE)
• Decreased mobility with pneumatic otoscopy

AOM is a recurrent disease. More than one third of children experience six or more episodes of AOM by age 7 years.

OM with effusion (OME), formerly termed serous OM or secretory OM, is MEE of any duration that lacks the associated signs and symptoms of infection (eg, fever, otalgia, and irritability). OME usually follows an episode of AOM.

Chronic suppurative OM is a chronic inflammation of the middle ear that persists for at least 6 weeks and is associated with otorrhea through a perforated TM, an indwelling tympanostomy tube (TT; see the image below), or a surgical myringotomy.

Various tympanostomy tube styles and sizes.

The most important factor in middle ear disease is eustachian tube (ET) dysfunction (ETD), in which the mucosa at the pharyngeal end of the ET is part of the mucociliary system of the middle ear. Interference with this mucosa by edema, tumor, or negative intratympanic pressure facilitates direct extension of infectious processes from the nasopharynx to the middle ear, causing OM. Esophageal contents regurgitated into the nasopharynx and middle ear through the ET can create a direct mechanical disturbance of the middle ear mucosa and cause middle ear inflammation.

In children, developmental alterations of the ET, an immature immune system, and frequent infections of the upper respiratory mucosa all play major roles in AOM development. Studies have demonstrated how viral infection of the upper respiratory epithelium leads to increased ETD and increased bacterial colonization and adherence in the nasopharynx.[1]

Certain viral infections cause abnormal host immune and inflammatory responses in the ET mucosa and subsequent microbial invasion of the middle ear. The host immune and inflammatory response to bacterial invasion of the middle ear produces fluid in the middle ear and the signs and symptoms of AOM.

Although interactions between the common pathogenic bacteria in AOM and certain viruses are not fully understood, strong evidence indicates that these interactions often lead to more severe disease, lowered response to antimicrobial therapy, and OME development following AOM.

A multitude of host, infectious, allergic, and environmental factors contribute to the development of OM.

Host factors

Immune system

The immature immune systems of infants or the impaired immune systems of patients with congenital immune deficiencies, HIV infection, or diabetes may be involved in the development of OM.[2] OM is an infectious disease that prospers in an environment of decreased immune defenses. The interplay between pathogens and host immune defense plays a role in disease progression.

Patel et al found higher interleukin (IL)-6 levels in patients with OM who also had influenza and adenoviral infections, whereas IL-1β levels were higher in patients who developed OM following URI.[3] In another study, Skovbjerg et al found that middle ear effusions with culturable pathogenic bacteria were associated with higher levels of IL-1β, IL-8, and IL-10 than sterile effusions.[4]

Familial (genetic) predisposition

Although familial clustering of OM has been demonstrated in studies that examined genetic associations of OM, separating genetic factors from environmental influences has been difficult. No specific genes have been linked to OM susceptibility. As with most disease processes, effects of environmental exposures on genetic expression probably play an important role in OM pathogenesis.

Mucins

The role of mucins in OME has been described. Mucins are responsible for gel-like properties of mucus secretions. The middle ear mucin gene expression is unique compared with the nasopharynx. Abnormalities of this gene expression, especially upregulation of MUC5B in the ear, may have a predominant role in OME.

Anatomic abnormality

Children with anatomic abnormalities of the palate and associated musculature, especially the tensor veli palantini, exhibit marked ETD and have higher risk for OM. Specific anomalies that correlate with high prevalence of OM include cleft palate, Crouzon syndrome or Apert syndrome, Down syndrome, and Treacher Collins syndrome.

Physiologic dysfunction

Abnormalities in the physiologic function of the ET mucosa, including ciliary dysfunction and edema, increase the risk of bacterial invasion of the middle ear and the resultant OME. Children with cochlear implants have a high incidence of OM, especially chronic OM and cholesteatoma formation. One study described a relation between laryngopharyngeal reflux and chronic OM (COM); the authors concluded that reflux workup should be performed as part of COM investigations and that if reflux is confirmed, reflux treatment should be initiated in addition to treatment of primary disease.[5]

Other host factors

Vitamin A deficiency is associated with pediatric upper respiratory infections and AOM.

Obesity has been linked to an increased incidence of OM, although the causal factor is unknown. Speculations include alteration of intrinsic cytokine profile, increased gastroesophageal reflux with alterations of the oral flora, and/or fat accumulation; all of these have been linked with an increased incidence of OM. Conversely, OM may increase the risk of obesity by altering the taste buds.[6]

Infectious factors

Bacterial pathogens

The most common bacterial pathogen in AOM is Streptococcus pneumoniae, followed by nontypeable Haemophilus influenzae and Moraxella (Branhamella) catarrhalis. These three organisms are responsible for more than 95% of all AOM cases with a bacterial etiology.[7]

In infants younger than 6 weeks, gram-negative bacilli (eg, Escherichia coli, Klebsiella species, and Pseudomonas aeruginosa) play a much larger role in AOM, causing 20% of cases. S pneumoniae and H influenzae are also the most common pathogens in this age group. Some studies also found Staphylococcus aureus as a pathogen in this age group, but subsequent studies suggested that the flora in these young infants may be that of usual AOM in children older than 6 weeks.

Many experts had proposed that the MEE associated with OME was sterile because cultures of middle ear fluid obtained by tympanocentesis often did not grow bacteria. This view is changing as newer studies show 30-50% incidence of positive results in middle ear bacterial cultures in patients with chronic MEE. These cultures grow a wide range of aerobic and anaerobic bacteria, of which S pneumoniae, H influenzae, M catarrhalis, and group A streptococci are the most common.

M catarrhalis–induced AOM differs from AOM caused by other bacterial pathogens in several ways. It is characterized by higher a proportion of mixed infections, younger age at the time of diagnosis, lower risk of spontaneous perforation of the tympanic membrane, and an absence of mastoiditis.[8]

Further evidence for the presence of bacteria in the MEE of patients with OME was provided by studies using polymerase chain reaction (PCR) assay to detect bacterial DNA in MEE samples that were determined to be sterile with standard bacterial culture techniques. In one such study using PCR assay, 77.3% of the MEE samples had positive results for one or more common AOM pathogens (eg, S pneumoniae, H influenzae, M catarrhalis).

In chronic suppurative OM, the most frequently isolated organisms include P aeruginosa, S aureus, Corynebacterium species, and Klebsiella pneumoniae. An unanswered question is whether these pathogens invade the middle ear from the nasopharynx via the ET (as do the bacteria responsible for AOM) or whether they enter through the perforated TM or a TT from the EAC.

The role of Helicobacter pylori in children with OME has been increasingly recognized.[9] Evidence that this agent might be responsible for OME comes from its isolation from middle ear and tonsillar and adenoidal tissue in patients with OME.

Alloiococcus otitidis is a species of gram-positive bacterium that has been discovered as a pathogen associated with OME.[10, 11] This organism is the most frequent bacterium in AOM, as well as in OME. It has also been detected in patients who had been treated with antibiotics, such as beta-lactams or erythromycin, suggesting that these agents may not be sufficiently effective to eliminate this organism. Further investigation is needed to reveal the clinical role of the organism in OM.

Viral pathogens

Because acute viral URI is a prominent risk factor for AOM development, most investigators have suspected a role for respiratory viruses in AOM pathogenesis.

Many studies have substantiated this suspicion by showing how certain respiratory viruses can cause inflammatory changes to the respiratory mucosa that lead to ETD, increased bacterial colonization and adherence, and, eventually, AOM. Studies have also shown that viruses can alter the host-immune response to AOM, thereby contributing to prolonged middle ear fluid production and development of chronic OME.

The viruses most commonly associated with AOM are respiratory syncytial virus (RSV), influenza viruses, parainfluenza viruses, rhinovirus, and adenovirus. Human parechovirus 1 (HPeV1) infection is associated with OM and cough in pediatric patients.[12] OM developed in 50% of 3-month follow-up periods that yielded evidence of HPeV1 infection but in only 14% of the HPeV1-negative periods; in recurring OM, the middle ear fluid samples were positive for HPeV in 15% of episodes.

Factors related to allergies

The relation between allergies and OM remains unclear. In children younger than 4 years, the immune system is still developing, and allergies are unlikely to play a role in recurrent AOM in this age group. Although much evidence suggests that allergies contribute to the pathogenesis of OM in older children, extensive evidence refutes the role of allergies in the etiology of middle ear disease.

The following is a brief list of evidence for and against the etiologic role of allergy in OM:

• Many patients with OM have concomitant allergic respiratory disease (eg, allergic rhinitis, asthma)
• Many patients with OM have positive results to skin testing or radioallergosorbent testing (RAST)
• Although mast cells are found in the middle ear mucosa, most studies fail to show significant levels of immunoglobulin E (IgE) or eosinophils in the MEE of patients with OM
• OM is most common in the winter and early spring, yet most major allergens (eg, tree and grass pollens) peak in the late spring and early fall
• Most patients with concomitant OM and allergy show no marked improvement in middle ear disease with aggressive allergy management, despite marked improvements to nasal and other allergy-related symptoms

Environmental factors

Infant feeding methods

Many studies report that breastfeeding protects infants against OM. The best of these studies indicates that this benefit is evident only in children who are breastfed exclusively for the first 3-6 months of life. Breastfeeding of this duration reduces the incidence of OM by 13%. The protective effects of breastfeeding for the first 3-6 months persist for 4-12 months after breastfeeding ceases, possibly because delaying onset of the first OM episode reduces recurrence of OM in these children.

Passive smoke exposure

Many studies have shown a direct relation between passive smoke exposure and risk of middle ear disease.[13] A systematic review of 45 publications dealing with OM and parental smoking showed pooled odds ratios of 1.48 (95% confidence interval [CI], 1.08-2.04) for recurrent OM, 1.38 (95% CI, 1.23-1.55) for MEE, and 1.3 (95% CI, 1.3-1.6) for AOM.[14]

Group daycare attendance

Daycare centers create close contact among many children, which increases the risks of respiratory infection, nasopharyngeal colonization with pathogenic microbes, and OM.

Many researchers have used meta-analysis to confirm that exposure to other young children (including siblings) in group daycare settings is a major risk factor for OM.[15] A meta-analysis reported that care outside the home conferred a 2.5-fold risk for OM. Other critical reviews of studies on OM and group childcare show heightened odds ratios of 1.6-4.0:1 for center care versus home care.

Children who attend daycare centers frequently acquire antibacterial-resistant organisms in their nasopharynx, leading to AOM that may be refractory to antibacterial treatment. American Academy of Pediatrics (AAP) and American Academy of Family Physicians (AAFP) guidelines recommend high-dose amoxicillin-clavulanate as the antibiotic of choice in the treatment of AOM in children who attend daycare.

Socioeconomic status

Socioeconomic status encompasses many independent factors that affect both the risk of OM and the likelihood that OM will be diagnosed.[16]

In general, lower socioeconomic status confers higher risk for environmental exposure to parental smoking, bottle-feeding, crowded group daycare, crowded living conditions, and viruses and bacterial pathogens. Compared with children from middle-income and high-income families, children from lower socioeconomic groups use health care resources less frequently, which decreases the likelihood that OM cases will be diagnosed.

United States statistics

OM, the most common specifically treated childhood disease, accounts for approximately 20 million annual physician visits. Various epidemiologic studies report the prevalence rate of AOM to be 17-20% within the first 2 years of life, and 90% of children have at least one documented MEE by age 2 years. OM is a recurrent disease. One third of children experience six or more episodes of AOM by age 7 years.

International statistics

Incidence and prevalence in other industrialized nations are similar to US rates. In less developed nations, OM is extremely common and remains a major contributor to childhood mortality resulting from late-presenting intracranial complications. International studies show increased prevalence of AOM and chronic OM (COM) among Micronesian and Australian aboriginal children.

Age-related demographics

Peak prevalence of OM in both sexes occurs in children aged 6-18 months. Some studies show bimodal prevalence peaks; a second, lower peak occurs at age 4-5 years and corresponds with school entry. Although OM can occur at any age, 80-90% of cases occur in children younger than 6 years. Children who are diagnosed with AOM during the first year of life are much more likely to develop recurrent OM and chronic OME than children in whom the first middle ear infection occurs after age 1 year.

Sex-related demographics

Several studies have now shown equal AOM prevalence in males and females; many previous studies had shown increased incidence in boys.

Race-related demographics

For some time, the prevalence of OM in the United States was reported to be higher in black and Hispanic children than in white children. However, a study that controlled for socioeconomic and other confounding factors showed equal incidence in blacks and whites. Hispanic children and Alaskan Inuit and other American Indian children have higher prevalence of AOM than white and black children in the United States.

US mortality is extremely low in this era of antimicrobial therapy (< 1 death per 100,000 cases). In developing nations with limited access to primary medical care and modern antibiotics, mortality figures are similar to those reported in the United States before antibiotic therapy. A study that examined the causes of death in Los Angeles County Hospital from 1928-1933, years before the advent of sulfa, showed that 1 in 40 deaths was caused by intracranial complications of OM.

Morbidity from this disease remains significant, despite frequent use of systemic antibiotics to treat the illness and its complications. Intratemporal and intracranial complications of OM are the two major types.

Intratemporal complications include the following:

• Hearing loss (conductive and sensorineural)
• TM perforation (acute and chronic)
• Chronic suppurative OM (with or without cholesteatoma)
• Cholesteatoma
• Tympanosclerosis
• Mastoiditis
• Petrositis
• Labyrinthitis
• Facial paralysis
• Cholesterol granuloma
• Infectious eczematoid dermatitis

Intracranial complications include the following[17] :

• Meningitis
• Subdural empyema
• Brain abscess
• Extradural abscess
• Lateral sinus thrombosis
• Otitic hydrocephalus

The prognosis for almost all patients with OM is excellent[18] ; the exceptions are patients in whom OM involves intratemporal and intracranial complications (< 1%).

Data on cognitive and educational outcomes of OM in the literature are limited.[19] The impact of OM on child development depends on numerous factors. OM in infants younger than 12 months predisposes to long-term speech and language problems. OM has also been reported to negatively affect preexisting cognitive or language problems. Careful follow-up and early referral are key to management.

Patient education topics should include the following:

• Avoiding risk factors
• Appropriate use of antibiotics
• Understanding the implications of antibiotic-resistant bacteria in OM

Education for health care providers should focus on the following topics:

• Antibiotic-resistant bacteria and the need to avoid overprescribing antibiotics
• Importance of pneumatic otoscope examination to distinguish AOM from OME
• Treatment differences between AOM and OME

For patient education resources, see the Ear, Nose, and Throat Center, as well as Earache.

Acute otitis media (AOM), with or without effusion, should be suspected in children with a history of characteristic head-neck and general symptoms.

Common head and neck symptoms of AOM include the following:

• Otalgia - Young children may exhibit signs of otalgia by pulling on the affected ear or ears or pulling on the hair; otalgia apparently occurs more often when the child is lying down (eg, during the night, during nap time), which may be due to increased eustachian tube dysfunction (ETD) when the child is in a recumbent position
• Otorrhea - Discharge may come from the middle ear through a recently perforated tympanic membrane (TM), through a preexisting tympanostomy tube (TT), or through another perforation; for trauma patients, excluding a basilar skull fracture with associated cerebrospinal fluid (CSF) otorrhea is important
• Headache
• Concurrent or recent symptoms of upper respiratory infection (URI), such as cough, rhinorrhea, or sinus congestion

Common general symptoms include the following:

• Two thirds of children with AOM have a history of fever, although fevers greater than 40°C are uncommon and may represent bacteremia or other complications
• Irritability may be the sole early symptom in a young infant or toddler
• A history of lethargy, although nonspecific, is a sensitive marker for sick children and should not be dismissed

Gastrointestinal (GI) tract symptoms may include the following:

• Anorexia
• Nausea
• Vomiting
• Diarrhea

Otitis media (OM) with effusion (OME) often follows an episode of AOM. Consider OME in patients with recent AOM in whom the history includes any of the following symptoms:

• Hearing loss - Most young children cannot provide an accurate history; parents, caregivers, or teachers may suspect a hearing loss or describe the child as inattentive
• Tinnitus - This is possible, though it is an unusual complaint from a child
• Vertigo - Although true vertigo (ie, room-spinning dizziness) is a rare complaint in uncomplicated AOM or OME, parents may report some unsteadiness or clumsiness in a young child with AOM
• Otalgia - Intermittent otalgia tends to worsen at night

OM treatment varies widely, depending on the duration of symptoms, past therapeutic failures, and severity of current symptoms.

Exposure to environmental risk factors is another important aspect of the history and includes the following:

• Passive (ie, secondhand) exposure to tobacco smoke
• Group daycare attendance
• Seasonality - AOM prevalence is much higher in winter and early spring than in summer and early fall
• Supine bottle feeding (ie, bottle propping)

Pneumatic otoscopy remains the standard examination technique for patients with suspected OM. When performed correctly, it is 90% sensitive and 80% specific for diagnosis of AOM, and its findings are more accurate than those of myringotomy.

Proper pneumatic otoscopy technique is crucial to distinguish AOM from OME because recommended therapies for these entities are significantly different. Studies show that most practitioners improperly perform otoscopic examinations. Almost one half of physicians never use pneumatic compression of the TM during routine otoscopic examination, and almost 30% use otoscopes with inadequate light sources.

Tympanometry, acoustic reflectometry, and audiometry are important adjunctive techniques with which to evaluate patients with middle-ear effusion (MEE).

In addition to a carefully documented examination of the external ear and TM, examining the entire head and neck region of patients with suspected OM is important. Several congenital syndromes, craniofacial anomalies, and systemic diseases have increased incidence associated with OM, including cleft palate, Down syndrome, Treacher Collins syndrome (ie, mandibulofacial dysotosis), hemifacial microsomia, diabetes mellitus, human immunodeficiency virus (HIV) infection, and many types of mucopolysaccharidosis.

Pneumatic otoscopy

Under direct visualization, first remove any cerumen, which causes a limited and sometimes inaccurate view of the TM and inaccurate and confusing results on tympanometry and audiometry.

To move the TM, the ear speculum must create an air seal against the external auditory canal (EAC), which is seldom possible with a standard disposable speculum. All otoscope manufacturers sell inexpensive cuffed ear speculums to perform insufflation. A rubber sleeve over the speculum may reduce patient discomfort during the examination.

Usually, the TM is in the neutral position (ie, neither retracted nor bulging), pearly gray, translucent, and unperforated. It responds briskly to positive and negative pressure, indicating an air-filled space. Many older texts emphasize a TM "light reflex" in an otherwise normal ear. Because this reflex may be absent in entirely normal ears and present in ears with MEE, the light reflex does not help confirm or exclude an OM diagnosis.

Every examination should include an evaluation and description of the following four TM characteristics:

• Color
• Position
• Mobility
• Perforation

Color

A normal TM is a translucent pale gray. An opaque yellow or blue TM is consistent with MEE. Dark red indicates a recent trauma or blood behind the TM. A dark pink or lighter red TM is consistent with AOM or hyperemia of the TM caused by crying, coughing, or nose blowing.

The color of the eardrum is less important diagnostically than its position and mobility. Redness of the TM alone does not necessarily suggest AOM because crying, removal of cerumen with associated irritation of the auditory canal, coughing, nose blowing, and fever can all cause redness of the eardrum without a middle ear infection. Note that most children cry when their ears are examined.

A study of 85 infants showed that the otoscopic finding most predictive of AOM was a poorly mobile, bulging, yellow, and opacified TM. However, this appearance was noted in only 19% of patients. In another analysis, a slightly red TM in a normal position and with normal mobility had a predictive value of only 7% for AOM.

Position

The position of the TM (ie, bulging, retracted, neutral, full) is key to differentiating AOM from OME.[20] In AOM, the TM is usually bulging. In OME, the TM is typically retracted or in the neutral position.

Mobility

Abnormal movement of the TM during pneumatic otoscopy can suggest various conditions or disorders. Movement during negative pressure only suggests ETD. A TM that moves only slightly with both positive and negative pressure applied indicates the probable presence of middle ear fluid. No movement occurs with a TM perforation or a TT.

Studies show that the most consistent physical finding in patients with OME is impaired mobility of the TM during pneumatic otoscopy. Pay special attention to movement of retracted segments of the TM because immobility of these sections may indicate middle ear cholesteatoma in the retraction pockets.

Perforation

Single perforations are most common, but some patients may have multiple perforations.

Note the location and cause of the perforation. Perforations in the posterosuperior quadrant, which are the most difficult to detect, are important because they occasionally are associated with cholesteatoma. Pus or other fluid may drain through a perforation. Multiple perforations and otorrhea that does not yield pathogens on culture may indicate tuberculosis.

Adjunctive screening techniques

Adjunctive techniques help identify patients with asymptomatic OME, which may account for 10% of cases.

Tympanometry

Tympanometry (ie, impedance audiometry), the most commonly used adjunctive technique, measures changes in acoustic impedance of the TM/middle ear system with air pressure changes in the EAC.

Current recommendations call for screening tympanometry at the beginning of school and 1 year later to identify children aged 4-6 years with asymptomatic OME. Tympanometry screening has a high degree of sensitivity (>90%) but is not specific for OME. The test may yield false-positive results in children with a retracted TM or a thickened TM without effusion. Screening tests may also yield invalid results in children who have cerumen obstructing the external canal or who are crying during the examination.

Middle ear pressure more than –200 daPa or a flat tympanometric curve is classified as a failure.

Further physician evaluation is indicated in a child in whom tympanometry screening fails in both ears and who has at least a 20-dB hearing loss at 1, 2, or 4 kHz.

After 2 months, retest any child in whom tympanometry screening fails in one ear and hearing loss occurs (>20 dB). Also retest children in whom tympanometry screening fails in both ears, even without marked hearing loss (ie, < 20 dB). A second screening failure should lead to physician evaluation. Assess the child's hearing, speech, and language and immediately start therapy to correct deficits.

Acoustic reflectometry

Acoustic reflectometry uses an acoustic otoscope to measure reflected sound from the TM; the louder the reflected sound, the greater the likelihood of an MEE. The breakpoint is defined as the level of sound reflectivity that correlates with the presence of MEE.

Acoustic reflectometry is rapid and easy to perform. Among its advantages over tympanometry is that an airtight seal of the EAC is unnecessary and that the test is unaffected by a crying patient or the presence of cerumen in the EAC. Despite these advantages, acoustic reflectometry has not been widely accepted by otolaryngologists because of the difficulty in setting standards to interpret test results.

Because no accepted breakpoint standards have been established, reported sensitivity and specificity vary according to the breakpoints set for each study. A low breakpoint leads to high sensitivity but low specificity. A high breakpoint leads to higher specificity but lower sensitivity.

Mastoiditis

Mastoid infections have two forms: acute coalescent mastoiditis[21] and chronic mastoiditis with osteitis. Treatment for both types consists of a mastoidectomy.

Acute coalescent mastoiditis occurs when obstruction of the aditus (the small opening between the epitympanum and the mastoid antrum) creates a sealed space in the mastoid antrum (the air space in the mastoid portion of the temporal bone that communicates with the tympanic cavity and mastoid air cells). Acute infection of the fluid in this space usually occurs as an extension of middle ear infection. Diagnosis is confirmed with a computed tomography (CT) scan of the head that reveals loss of septation between mastoid air cells.

Chronic mastoiditis occurs when acute mastoiditis remains undetected, with subsequent changes in the mucosal lining of the mastoid air cells. Granulation tissue filled with inflammatory cells replaces the air spaces of the mastoid and middle ear, and bone necrosis with erosion may result, leading to an extracranial Bezold abscess (see the image below) or intracranial complication. Chronic mastoiditis may not be depicted on CT. Magnetic resonance imaging (MRI) reveals regions of nonspecific bright signal, consistent with inflammation.

Acute coalescent mastoiditis with a Bezold abscess in a young girl who presented with chronic right ear pain and multiple untreated middle ear infections.

Cholesteatoma

Cholesteatomas are cystlike expanding lesions of the temporal bone, lined by stratified squamous epithelium and containing desquamated keratin and purulent material. Their etiology is controversial. Although cholesteatoma development is complicated and incompletely understood, contributing factors include ETD, increased negative pressures in the middle ear, repeated infection, chronic MEE, loss of collagen fibers and structural support of the TM, collapse of the TM, and formation of chronic retraction pockets.

Diagnosis is difficult but can be made by an experienced clinician using a pneumatic otoscopic examination in patients with chronic middle ear disease and progressive conductive hearing loss.

Treatment is surgical excision or exteriorization. In very rare cases (eg, when the patient is not a surgical candidate because the cholesteatoma is secondary to a comorbid disease), repeated cleansing under a surgical microscope may temporarily control the cholesteatoma.

Labyrinthitis

Inflammation of the labyrinth produces vestibular and auditory symptoms. In patients with chronic OM (COM), bacteria may infiltrate the bony labyrinth and produce a condition of suppurative labyrinthitis. Acute symptoms include hearing loss and vertigo, which usually improve after the body goes through a phase of central compensation for the damaged vestibular organs. Prolonged labyrinth infection leads to vestibular end-organ damage and permanent hearing loss.

Diagnosis of labyrinthitis in patients with COM is most often retrospectively confirmed. Vertigo and sensorineural hearing loss in these patients is presumptive evidence for labyrinthitis.

In patients in whom hearing or vestibular function recovers, labyrinthitis is classified as serous rather than suppurative; recovery indicates that the bacteria never truly invaded the labyrinth and that the symptoms were caused by severe inflammation of the vestibular organs without bacterial invasion.

Labyrinthitis treatment includes intravenous (IV) antibiotics directed against the common pathogens in COM to limit damage to vestibular organs. Vestibular suppressants are used in the acute period to relieve dizziness and nausea.

Facial paralysis

In patients with invasive OM (especially OM with cholesteatoma), infection and inflammation of the facial nerve leads to edema and nerve fiber compression that causes facial paralysis. The facial nerve courses through the temporal bone in the fallopian canal, protected by bone and epineurium. Naturally occurring bony dehiscences of the fallopian canal and reactive osteitis (often due to cholesteatoma) place the facial nerve at risk in invasive OM.

The combination of OM with concurrent ipsilateral facial paralysis suggests an obvious diagnosis, but other entities in the differential diagnosis for acute facial paralysis should be considered. Treatment is immediate administration of IV antibiotics and/or surgical treatment of the cholesteatoma involving the facial nerve.

Meningitis

Meningitis is among the most common intracranial complications of OM, occurring in children with either AOM or COM. Fever accompanied by neck stiffness should immediately prompt a search for an intracranial complication. As with all intracranial complications, perform contrast-enhanced CT or MRI.

Lumbar puncture and examination of the cerebrospinal fluid (CSF) is mandatory in patients in whom meningitis is suspected. CSF leukocytosis, with low glucose and high protein and lactate levels, is characteristic of meningitis. Studies of the CSF should include Gram staining, culturing, and testing for bacterial antigens.

The treatment of choice is immediate administration of broad-spectrum IV antibiotics, followed by directed therapy based on CSF culture results. Some experts have reduced neurologic and auditory sequelae resulting from meningitis by administering dexamethasone early in the treatment course.

Epidural abscess

Epidural abscesses secondary to OM occur near the temporal bone. Infection extends to the epidural space through venous channels in the bone or by bone erosion. The most common routes for extension are through the thin bone of the tegmen to the middle cranial fossa or through the bone adjacent to the sigmoid sinus and posterior cranial fossa. Most intracranial complications are accompanied by a concomitant epidural abscess because of the pathways involved in OM spread.

Diagnosis relies on high clinical suspicion and is confirmed using contrast-enhanced CT or MRI. Treatment requires surgical exploration, with a cortical mastoidectomy and thinning of the bone overlying the tegmen tympani, sigmoid sinus, and posterior fossa to allow the epidural space to be seen. If granulation tissue or purulent fluid is discovered in the epidural space, continue removing bone until noninflamed dura is encountered.

Lateral sinus thrombophlebitis

Lateral and sigmoid sinuses are relatively unprotected from direct extension of infections from the middle ear and mastoid. Direct extension occurs secondary to bone erosion from osteitis or necrosis. Indirect extension occurs via retrograde thrombophlebitis of the mastoid emissary veins.

Obstruction of venous drainage by thrombosis can produce elevated intracranial pressure (ICP) and headache. Otitic hydrocephalous can complicate the course of lateral sinus thrombosis, leading to vision changes and sixth cranial nerve (CN VI) palsy. Septic emboli can disseminate the infection to distant body sites, and the constant bacteremia produces febrile episodes.

The classic clinical picture of high spiking fevers, headache, and active ear disease is rare.

Diagnosis of this complication relies on high clinical suspicion and is confirmed by MRI or contrast-enhanced CT demonstrating the thrombosis. Early administration of IV antibiotics and surgical exploration are the mainstays of therapy. After exposing the sigmoid sinus, a needle may be used to aspirate the sinus. If free-flowing blood returns, no further surgery is needed. If no blood returns, open and drain the sinus.

Brain abscess

Brain abscess is the first or second most common intracranial complication of COM. Most abscesses form in the temporal lobe or cerebellum, supporting the theory that brain abscesses associated with OM are probably caused by direct extension of infection and not hematogenous spread of bacteria.

In addition to fever from the infectious process, symptoms and signs of brain abscess relate to abscess location and the overall mass effect of the abscess. Headache, vomiting, and lethargy may indicate increased ICP. Significant localizing signs include seizures, hemiparesis, cranial nerve palsies, and aphasia. Abscesses in the temporal lobe or cerebellum can exist with relatively few early localizing symptoms.

Contrast-enhanced CT or MRI is the diagnostic study of choice. The initial therapy of choice is administration of broad-spectrum antibiotics. Consult with a neurosurgeon for decisions about abscess drainage. In some patients, mastoid surgery can be performed with a neurosurgical procedure. Otologic surgery can be delayed in patients who are less stable until neurologic stability is established.

Laboratory evaluation is usually unnecessary, although many experts recommend a full sepsis workup in infants younger than 12 weeks who present with fever and associated acute otitis media (AOM).

Otitis media (OM) is associated with multiple systemic diseases and congenital syndromes. AOM may be the first presenting illness in some of these diseases; therefore, order appropriate laboratory studies to confirm or exclude possible systemic or congenital diseases.

Imaging studies are not indicated in patients with OM unless intratemporal or intracranial complications are suspected.

When an OM complication is suspected, the imaging study of choice is contrast-enhanced computed tomography (CT) of the temporal bones. CT findings help diagnose many complications (eg, mastoiditis, epidural abscess, sigmoid sinus thrombophlebitis, meningitis, brain abscess, and subdural abscess). Fine-cut CT sections through the temporal bone can reveal ossicular disease and cholesteatoma.

Magnetic resonance imaging (MRI) is more helpful in depicting fluid collections, especially small middle-ear collections. MRI is usually performed after CT if further information is needed for definitive diagnosis.

In clinical trials, the criterion standard in the diagnosis of AOM is tympanocentesis to determine the presence of middle-ear fluid, followed by culture of the fluid to identify causative pathogens. Because of the expense, effort, and lack of availability, no consensus guidelines call for routine use of tympanocentesis to manage AOM and OM with effusion (OME).

Tympanocentesis can improve diagnostic accuracy, guide treatment, and help eliminate unnecessary medical or surgical interventions in selected patients with refractory or recurrent middle ear disease.

Neonates, infants, and children with AOM who appear severely ill or toxic should undergo early tympanocentesis with culturing. Children with AIDS or those who are immunocompromised secondary to steroid therapy, chemotherapy, or immunosuppressive therapy after organ transplantation should undergo early tympanocentesis to exclude unusual organisms or nosocomial infection.

A report from the Centers for Disease Control and Prevention (CDC) working group on drug-resistant S pneumoniae (DRSP) included an option for tympanocentesis versus empiric second-line antibiotic therapy in patients in whom initial antibiotic therapy has failed.[22]

Tympanometry may help with diagnosis in patients who OME. Some practitioners also use acoustic reflectometry to evaluate for middle ear effusion (MEE) in patients with OM.

Medical management of otitis media (OM) is actively debated in the medical literature, primarily because of a dramatic increase in acute OM (AOM) prevalence over the past 10 years caused by drug-resistant S pneumoniae (DRSP) and beta-lactamase–producing H influenzae or M catarrhalis.

Beta-lactamases are enzymes that hydrolyze amoxicillin and some, but not all, oral cephalosporins, leading to in-vitro resistance to these drugs. Currently, 90% of M catarrhalis isolates and 40-50% of H influenzae isolates in the United States produce beta-lactamases. As a result, empiric antibiotic therapy for this disease has become more complex. Many opinions have been expressed regarding which drugs are best for first- and second-line therapy or whether antibiotics should be prescribed in all patients with AOM.

Medical therapy for acute otitis media

In 1999, the Centers for Disease Control and Prevention (CDC) therapeutic working group on DRSP published consensus recommendations for AOM management.[23] The recommendations supported the use of amoxicillin as the first-line antimicrobial agent of choice in patients with AOM. The group recommended increasing the dose used for empiric treatment from 40-45 mg/kg/day to 80-90 mg/kg/day because of concerns about increasingly resistant strains of S pneumoniae, which are theoretically susceptible to this higher dose.

The recommendations for second-line therapy were more controversial, despite their reasonableness from a scientific viewpoint. Stressing the importance of documenting true clinical failure of therapy after at least 3 days of treatment with high-dose amoxicillin, the working group suggested tympanocentesis for identification and susceptibility testing of the etiologic bacteria to guide alternate antibiotic therapy.

In cases where second-line therapy is empirically chosen (a common occurrence, because few primary care physicians routinely perform tympanocentesis in the office), the recommendations suggested administering the following three preparations:

• High-dose oral amoxicillin-clavulanate (80-90 mg/kg/day of amoxicillin component, 6.4 mg/kg/day of clavulanate component)
• Oral cefuroxime axetil (suspension, 30 mg/kg/day in divided doses; tablet, 250 mg twice daily)
• Intramuscular (IM) ceftriaxone (administered as a single IM injection of 50 mg/kg on 3 consecutive days)

The choice of these three preparations from among the 16 antimicrobials currently approved by the US Food and Drug Administration (FDA) for OM therapy was based on studies that reported that these drugs achieve sufficient concentrations in middle ear fluid for bactericidal action against the common pathogens in AOM, including DRSP and beta-lactamase–producing H influenzae. Similar studies for the other 13 approved agents either have not been completed or failed to show similar efficacy against resistant bacteria.

These recommendations relied heavily on the pharmacodynamics model of drug efficacy. In this model, clinical cure is believed to correlate with demonstrated penetrance of the antibiotic into the middle ear at a level believed to be sufficient to kill the bacterial pathogens that cause AOM. Nevertheless, this model had the following shortcomings:

• Although bacteriologic eradication correlates with a successful clinical outcome, clinical success occurs in more than 60% of patients, even when bacteriologic eradication is not achieved; eventually, almost all patients improve
• Validation of the pharmacodynamic model relies on tympanocentesis to identify the causative bacteria and to measure antibiotic levels in middle ear fluid; some antibiotics (eg, azithromycin and clarithromycin) concentrate intracellularly, not in middle ear fluid, and are bacteriostatic rather than bactericidal; a model predicated on certain drug levels and bacterial eradication may underestimate the efficacy of these agents
• The drug levels used by the CDC to define bacterial killing were based on standards that changed 6 months after the CDC publication

The following crucial issues in AOM treatment were not clearly addressed by the CDC recommendations:

• Patient compliance and the associated factors of dosing frequency, duration of therapy, palatability, and drug cost
• Guidance for special situations (eg, allergy to penicillins, beta-lactam drugs, or both)
• Discussion of the option of withholding antibiotic therapy for 2-3 days in a subset of patients with AOM who are likely to experience spontaneous resolution of disease with only supportive care and analgesic therapy (a practice that is widespread in the Netherlands and Scandinavia but that has few proponents in the United States)

Compliance, duration of therapy, and cost are important issues in treating children with AOM. The primary determinants of compliance appear to be the following:

• Frequency of dosing
• Palatability of the agent
• Duration of therapy

Less frequent dosing (ie, once or twice daily) is more desirable than more frequent dosing, which interferes with daily routines. Shorter duration of therapy (ie, 5-7 days vs 10-14 days) increases compliance but should be used only when equal clinical efficacy can be assured. In many instances, palatability ultimately determines compliance in children.

In 2013, the American Academy of Pediatrics (AAP) and the American Academy of Family Practice (AAFP) published updated guidelines for the medical management of AOM (see Guidelines).[24]  Among other recommendations, these guidelines recommended antibiotics for bilateral or unilateral AOM in children aged at least 6 months with severe signs or symptoms and for nonsevere bilateral AOM in children aged 6-23 months. Amoxicillin was cited as the antibiotic of choice unless the child has received it within the previous 30 days, has concurrent purulent conjunctivitis, or is allergic to penicillin.

For children who are allergic to penicillin or beta-lactam, the only currently available products are cephalosporins, trimethoprim-sulfamethoxazole, and macrolides. Patients who are allergic to penicillin show 10-15% cross-reactivity when treated with cephalosporins. Levofloxacin has demonstrated higher efficacy in the treatment of AOM than amoxicillin-clavulanate has and can be used in patients who are allergic to penicillin.[25]

Pneumococcal resistance to trimethoprim-sulfamethoxazole is increasing and has become more common than penicillin resistance in some areas. Use this drug to treat AOM only in regions where it remains effective.

Of the macrolides, erythromycin-sulfisoxazole is a good choice, but many children refuse it because of its taste; a 5-day course of azithromycin or 10-day course of clarithromycin may be preferred. If DRSP is the suspected etiologic bacterium, do not use macrolides, because pneumococcal resistance is absolute with macrolides and, unlike the resistance seen with some beta-lactam antibiotics, cannot be overcome by increasing the dose.

Many children with AOM do not benefit from antimicrobial therapy, either because the illness is not of bacterial origin or because their immune system clears the infection without use of a drug. No clinical criteria currently distinguish which children do not require antibiotic therapy for AOM.

Until such criteria are available, many practitioners are unlikely to withhold initial antimicrobial therapy for proven cases of AOM. Increasing awareness of the pathophysiology of the disease among parents and healthcare providers has resulted in an increase in an observation-only approach in emergency departments with less parental anxiety.[26]

Medical therapy for otitis media with effusion

Most cases of OM with effusion (OME) occur after an episode of AOM, and 67% of patients develop a middle-ear effusion (MEE). The mean duration of the effusions is 23 days, but many persist much longer. Most cases of OME spontaneously resolve. Studies of the natural history of this disease report the following:

• An MEE is harbored in 50% of ears 1 month after an episode of acute OME
• An MEE is harbored in 20% of ears after 2 months
• An MEE continues to be harbored in 10-15% of ears after 3 months
• OMEs that persist longer than 3 months have spontaneous resolution rates of only 20-30%, even after years of observation

Most cases of chronic OME are associated with conductive hearing loss, averaging approximately 25 dB. Complications of hearing loss (eg, language delay, behavioral problems, poor academic performance) have led to investigations of multiple medical and surgical treatments for OME. The following are among the many strategies advocated for medical treatment in patients with OME:

• Antimicrobials
• Antihistamine-decongestants
• Intranasal and systemic steroids
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Mucolytics
• Aggressive management of allergic symptoms

Of these options, only antimicrobial therapy has provided measurable benefits. Steroid therapy (when administered in combination with a beta-lactam antimicrobial) has shown benefit in some studies and no benefit in others. All other medical therapies (ie, decongestants, antihistamines, mucolytics, and NSAIDs) have not provided measurable short- or long-term improvements in patients with OME.

Patients in whom OME is unresponsive to medical therapy and with an MEE that persists more than 12 weeks should be referred to an otolaryngologist to discuss surgical options in conjunction with further medical therapies.

Antimicrobial therapy

No clinical guidelines or consensus recommendations suggest which antimicrobials to use as first-line agents for OME. In this era of increasing antibiotic resistance, selection of an antibiotic agent should be individualized to the patient.

In each patient, consider prior experience with antibiotics, age, sex, and daycare attendance.

If penicillin allergy is not a concern and if the patient has no recent exposure to antibiotics, a reasonable choice for initial therapy is amoxicillin, administered at the same high dose recommended by the CDC for AOM (ie, 80-90 mg/kg/day). A reasonable first choice in a patient with antibiotic exposure during the prior month is trial administration of a beta-lactamase–stable agent (eg, amoxicillin-clavulanate) or a second- or third-generation cephalosporin.

As with antimicrobial selection, no recommendations have been made regarding duration of therapy; 10 days is reasonable for amoxicillin, amoxicillin-clavulanate, and cephalosporins. Studies of prolonged treatment in patients with OME show no advantage in therapies that last longer than 10 days.

Steroid therapy

The literature on steroid therapy is inconclusive. In 1994, the Agency for Health Care Policy and Research (AHCPR) reviewed more than 5000 articles on OME management and published a clinical practice guideline.[27] Although the review found that a combination of steroids and antibiotics improved MEE clearance in 25.1% of patients, the difference was not statistically significant, and the risks of steroids were felt to outweigh their potential benefits. The guideline stated that steroids were not recommended for OME treatment in children of any age.

After the publication of the AHCPR guideline, another investigation of steroids plus antibiotics to treat OME was published by Rosenfeld,[28] who reported that surgery was avoided or postponed for 6 months in 1 of 4 children treated with steroids. Therefore, steroid administration may have a role in patients who are not good surgical candidates.

The steroid regimen should be oral prednisone or prednisolone at a dosage of 1 mg/kg/day for 5-7 days, administered in combination with a beta-lactam antibiotic.

Steroids are contraindicated in patients with exposure to varicella who have not received the varicella vaccine because of the possibility of life-threatening disseminated disease.

Controversy continues over the optimal management of OME. The AHCPR guideline, although criticized for having a narrow scope, for favoring medical rather than surgical management of OME, and for minimizing the problem of drug-resistant bacteria, provides a framework within which to consider management options.

In 2016, the American Academy of Otolaryngology–Head and Neck Surgery Foundation, the AAP, and the AAFP issued updated guidelines for OME, including recommendations on the use of pneumatic otoscopy, tympanometry, routine screening, steroids, systemic antibiotics, antihistamines or decongestants, hearing tests, tympanostomy tubes, and adenoidectomy (see Guidelines).[29]

From the beginning, it is essential to integrate surgical management of AOM and OME with medical treatment. Early surgical interventions (eg, tympanocentesis) may be performed by primary care providers, but more invasive procedures (eg, myringotomy, TT insertion, and adenoidectomy) require an otolaryngologist.

In patients with intratemporal or intracranial complications of OM, surgical consultation is critical. Certain special patient populations, such as those with cleft palate, Down syndrome, or other craniofacial abnormalities, may require early surgical intervention to prevent OM.

Tympanocentesis

Indications for tympanocentesis are as follows:

• OM in patients who have severe otalgia, who are seriously ill, or who appear toxic
• Unsatisfactory response to antimicrobial therapy
• Onset of AOM in a patient receiving antimicrobial therapy
• OM associated with a confirmed or potential suppurative complication
• OM in a newborn, sick neonate, or patient who is immunologically deficient, any of whom may harbor an unusual organism

Tympanostomy tubes

In July 2013, the American Academy of Otolaryngology–Head and Neck Surgery Foundation (AAO-HNSF) issued the first evidence-based, multidisciplinary clinical practice guideline on the use of TTs in children aged 6 months to 12 years who have OM.[30]  These guidelines were subsequently updated in February 2022 (see Guidelines).[31]

Adenoidectomy and tonsillectomy

The performance of adenoidectomy, tonsillectomy, or both to treat patients with OM (in addition to myringotomy and TT placement) has generated extensive discussion and research, though potential benefits are controversial. Current literature supports the following recommendations from Bluestone[32] :

• Initial surgery - Myringotomy and TT placement are the initial surgical techniques (withhold adenoidectomy unless the patient has a nasal obstruction); some experts advocate simultaneous adenoidectomy in patients older than 3 years because this has been shown to improve eustachian tube (ET) function
• Repeat surgery (following extrusion of tubes and recurrence of chronic MEE unresponsive to antimicrobial therapy) - Myringotomy, with or without TT placement, and adenoidectomy, irrespective of adenoid size, are the techniques used
• Tonsillectomy - Although tonsillectomy is not indicated for treatment of OM (because it has not been shown to benefit ET function), it may be performed concurrently with surgery for OM if indications are present (eg, frequently recurrent tonsillitis, pharyngeal obstruction)

Surgery for children with cleft palate

Myringotomy and TT placement are warranted in most children with cleft palate because of inherent ET dysfunction (ETD) and increased risk of OM. In patients who also have a cleft lip, the TT may be placed at the time of initial lip repair, many months prior to palate repair. Consider performing TT placement or replacement at the time of palate repair.

Surgery for children with Down syndrome

Children with Down syndrome often exhibit ETD, conductive and sensorineural hearing loss, external auditory canal (EAC) stenosis, and subtle immunologic deficiencies. These conditions create a high risk for OM, make diagnosis of MEE difficult, and can lead to profound language and learning difficulties. The essential elements of care in these patients include close monitoring, appropriate surgical interventions for EAC enlargement, and repetitive TT placements.

Tube selection is a critical issue. These patients may require prolonged external ventilation with TTs because of prolonged ETD. Unfortunately, TTs labeled as long-acting or permanent cause the greatest damage to the tympanic membrane (TM). These patients often require repeated TT insertions, even when long-acting or permanent TTs are used. The best procedure may be to anticipate early extrusion and reinsertion and to avoid these tubes in favor of ultrasmall TTs to prevent long-term TM damage.

Medical strategies to prevent OM include eliminating risk factors for AOM, immunologic interventions, and antibiotic prophylaxis. Surgical strategies to prevent recurrent OM include prophylactic myringotomy and TT insertion.

Elimination of risk factors

Risk factors include daycare attendance, secondary exposure to tobacco smoke, pacifier use, and breastfeeding for less than 3 months (breastfeeding for >3 months decreases risk).

Daycare attendance

A meta-analysis of studies of risk factors for AOM reported that care outside the home leads to an approximately 2.5-fold increase in the relative risk of recurrent AOM, probably because of greater exposure to respiratory infections. Children in daycare have an increased frequency of URIs, and their infections are often more prolonged.

AOM risk correlates with the number of contacts with other children rather than the absolute number of children enrolled in a center. Rates of respiratory infections, including AOM, are higher among children in daycare centers than among those receiving family care.

The risk of increased infection associated with group daycare is greatest in the first 2 years of life and particularly in the first year.

Tobacco smoke exposure

Tobacco smoke is an upper respiratory irritant, and multiple studies have shown that passive smoke exposure places children at increased risk for pneumonia, bronchitis, bronchiolitis, chronic MEE, and more frequent and severe asthma.

Most of the prior controversy regarding the relationship between tobacco smoke exposure and OM resulted from faulty study design and a failure to objectively quantify tobacco smoke exposure. Studies have controlled for confounding factors more carefully, and many have measured serum or urine concentrations of cotinine, a nicotine metabolite, to objectively determine exposure to passive tobacco smoke. These studies consistently establish a direct relationship between parental smoking and increasing risk of AOM.

A meta-analysis of risk factors determined that parental smoking increases the risk of AOM by 66%. The average duration of MEE in children with elevated cotinine levels was 28 days, compared with 19 days' duration in children without elevated levels.

Pacifier use

This clearly increases the risk for AOM in infants and small children, although the reason for this predisposition is uncertain. In one study, the relative risk for recurrent AOM was 1.6 in children younger than 2 years who used a pacifier and 2.9 in children aged 2 and 3 years who used a pacifier. According to one theory, the constant sucking action associated with pacifier use exacerbates ETD, leading to inoculation of the middle ear with pathogenic bacteria.

Breastfeeding for less than 3 months

Breastfeeding protects young infants from OM and GI tract illness. A meta-analysis reported that breastfeeding for at least 3 months resulted in a relative AOM risk of 0.87 and a relative risk of recurrent AOM of 0.69. Breastfeeding for at least 6 months reduced the risk of AOM even further. The risk reduction probably results from transferred immunoglobulins, cellular elements, and many nonspecific components in mother's milk that, collectively, exhibit antibacterial, antiviral, and antiparasitic properties.

Vaccines

Pneumococcal vaccine

In February 2000, the FDA approved use of heptavalent pneumococcal CRM197 conjugate vaccine (PCV7), composed of seven pneumococcal antigens (ie, polysaccharide serotypes 4, 6B, 9V, 14, 19F, 23F; oligosaccharide serotype 18C) conjugated to 20 μg of CRM197 by reductive amination. PCV7 has been replaced by vaccines with broader coverage and is no longer used. 

At the time, PCV7 provided potential serotype and serogroup cross-protection (eg, 6A) in 88% of cases of bacteremia, 82% of cases of meningitis, and 71% of cases of pneumococcal OM episodes in children younger than 6 years in the United States. It had decreased the number of episodes of S pneumoniae AOM caused by the serotypes included in the vaccine. It had reduced the nasopharyngeal carriage of vaccine-type S pneumoniae, particularly antibacterial-resistant organisms, and had also prevented the spread to contacts in the community.

After the introduction of the heptavalent pneumococcal vaccine in 2000, researchers found that nearly two thirds of invasive pneumococcal disease cases in young children were caused by six serotypes not covered by that vaccine. Those serotypes, along with the original seven, were incorporated into a 13-valent pneumococcal vaccine, which was approved in February 2010 and which supplanted PCV7.

As of 2023, the 13-valent and 20-valent pneumococcal vaccines are approved by the FDA for children aged 6 weeks through 5 years to prevent OM caused by S pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. 

Since 1985, pneumococcal polysaccharide vaccines have been recommended for children older than 2 years who are at high risk for invasive disease, but they were not recommended for younger children and infants, because of poor antibody response in children younger than 2 years.

Prymula et al described the effectiveness of a newer vaccine that contained pneumococcal capsular polysaccharides conjugated to H influenzae–derived protein D in the prevention of a first episode of AOM.[33] According to the data from this study, the full effectiveness of the vaccine in treating children was questionable, even in high-risk children.

Pneumococcal conjugate vaccines induce proposed protective antibody responses (>0.15 μg/mL) in more than 90% of infants after a series of three doses administered at ages 2, 4, and 6 months. Following the priming doses, significant booster responses (ie, immunologic memory) are apparent when additional doses are administered in patients aged 12-15 months. In efficacy trials, such vaccines were associated with a 7% decrease in OM and a 15-20% decrease in TT placement.

Most antibiotics are effective in treating AOM despite changed microbiology due to the use of PCV7.[34]

Influenza vaccine

Influenza is a highly infectious viral illness that is common during the winter months. A small proportion of AOM is directly caused by influenza viruses and may be directly prevented by immunization with influenza vaccine. In addition, any influenza infection of the upper respiratory tract leads to respiratory epithelial inflammation and associated ETD, which predisposes the host to bacterial AOM.

Influenza vaccine is strongly recommended for any person older than 6 months in whom age or an underlying medical condition creates increased risk for complications of influenza. It can be administered to any person who wishes to reduce the chance of infection by the virus. The vaccine can be administered to children as young as 6 months. Many experts recommend that children who are prone to OM receive the annual vaccine, particularly those in group daycare who have increased risk of upper respiratory infection (URI) and AOM.

A 2015 Cochrane review concluded that influenza vaccine yielded a small decrease in the incidence of AOM but noted that this benefit may not justify the use of the vaccine unless the vaccine's efficacy in reducing influenza and its safety data (limited at present) are taken into account.[35] Further research is warranted.

Antibiotic prophylaxis

Many studies in the 1970s and 1980s showed the effectiveness of antibiotic prophylaxis in children with recurrent AOM. The most common regimens were sulfisoxazole (35 mg/kg once or twice daily) or amoxicillin (20 mg/kg once or twice daily). These therapies were usually administered in patients who had three or more episodes of AOM within a 6-month period or four or more episodes within 12 months.

The use of antibiotic prophylaxis for AOM has become widely questioned because of the increasing antibiotic resistance among bacterial pathogens responsible for middle-ear infections. Even before the drastic rise in drug-resistant bacteria, the clinical effectiveness of antibiotic prophylaxis for AOM was unimpressive.

A meta-analysis of 1993 studies showed that a child must be treated for 9 months to prevent just one episode of AOM.[36] The meta-analysis was based on decade-old data that are almost irrelevant now because of the growing prevalence of drug-resistant bacteria. Most experts who once supported antibiotic prophylaxis no longer recommend routine antibiotic prophylaxis for all children with recurrent AOM.

Refer all patients who may require surgical interventions for complicated OM or who have recurrent AOM or chronic OME to an otolaryngologist. Primary care physicians who are uncomfortable performing tympanocentesis should refer patients who need this procedure to an otolaryngologist.

Children who present with subjective evidence of hearing loss should be referred to an otologist for a formal hearing test (ie, audiogram). Subjective evidence of hearing loss is often provided by a parent or caregiver in younger children or, possibly, by a school teacher in older children.

Referral to a speech therapist is indicated for patients in whom COM has caused speech and language delays because of hearing loss.

Inpatient care is indicated only in patients with intratemporal or intracranial complications of OM.

Most AOM cases resolve with antibiotic therapy, but recurrences are frequent. By the time children are aged 7 years, more than one third have experienced 6 or more episodes of AOM. In addition, many patients who are treated for AOM subsequently develop asymptomatic OME. Monitoring by otoscopic examination, acoustic reflectometry, and/or tympanometry is necessary to determine which children require further follow-up care and therapy to prevent hearing loss and resultant speech and learning disabilities.

Although the precise timing of follow-up visits is a matter of debate, examination after 4-6 weeks is reasonable. At the 4-week to 6-week follow-up visit, children in whom OME has not resolved should be rescheduled for a second follow-up appointment 4-6 weeks after the first.

If effusion persists as long as 12 weeks, perform a hearing test. Refer any child in whom the hearing loss in both ears exceeds 20 dB for surgical treatment with a bilateral myringotomy and TT placement. Children with a hearing loss of less than 20 dB and an MEE that persists beyond 12 weeks can be monitored, with the understanding that significant spontaneous improvement of the MEE after 12 weeks is unlikely, or they can receive antibiotic therapy using a beta-lactam–stable agent.

In February 2022, the American Academy of Otolaryngology–Head and Neck Surgery Foundation (AAO-HNSF) issued updated recommendations regarding tympanostomy tubes (TTs) in children.[31]

The following were listed as strong recommendations:

• Topical antibiotic ear drops alone, without oral antibiotics, should be prescribed for children with uncomplicated acute TT otorrhea.
• The child's ears should be examined within 3 months of TT insertion, AND families should be educated regarding the need for routine periodic follow-up until the tubes extrude.

The following were listed as recommendations:

• TT insertion should not be performed in children with a single episode of otitis media (OM) with effusion (OME) of < 3 months' duration from the date of either onset (if known) or diagnosis (if onset is unknown).
• A hearing evaluation is indicated if OME persists for ≥3 months or before surgery when a child becomes a candidate for TT insertion.
• Bilateral TT insertion should be offered to children with bilateral OME for ≥3 months and documented hearing difficulties.
• Children with chronic OME who do not receive TTs should be reevaluated at 3- to 6-month intervals until effusion is no longer present, significant hearing loss is detected, or structural abnormalities of the tympanic membrane or middle ear are suspected.
• TT insertion should not be performed in children with recurrent acute OM (AOM) who do not have middle-ear effusion (MEE) in either ear at assessment for TT candidacy.
• Bilateral TT insertion should be offered to children with recurrent AOM who have unilateral or bilateral MEE at assessment for TT candidacy.
• Efforts should be made to determine whether a child with recurrent AOM or with OME of any duration is at increased risk for speech, language, or learning problems from OM because of baseline factors.
• In children who meet criteria for TT insertion, long-term tubes should not be placed initially unless specifically warranted by anticipated need for prolonged middle-ear ventilation beyond what a short-term tube supplies.
• In the perioperative period, caregivers of children with TTs should be educated regarding expected duration of tube function, recommended follow-up schedule, and detection of complications.
• Antibiotic ear drops should not be routinely prescribed after TT placement.
• Routine prophylactic water precautions should not be encouraged for children with TTs.

The following were listed as options:

• TT insertion may be performed in children with unilateral or bilateral OME for ≥3 months (chronic OME) and symptoms likely to be attributable to OME, including (but not limited to) balance (vestibular) problems, poor school performance, behavioral problems, ear discomfort, or reduced quality of life.
• TT insertion may be performed in at-risk children with unilateral or bilateral OME that is likely to persist as reflected by a type B (flat) tympanogram or a documented effusion for ≥3 months.
• Adenoidectomy may be performed as an adjunct to TT insertion in children with symptoms directly related to the adenoids or in children aged ≥4 years as a potential means of reducing future recurrence of OM or need for repeat TT insertion.

In February 2016, the AAO-HNSF, the American Academy of Pediatrics (AAP), and the American Academy of Family Practice (AAFP) issued the following updated guidelines for OME[29] :

• The clinician should perform pneumatic otoscopy to assess for OME in a child with otalgia, hearing loss, or both
• Clinicians should obtain tympanometry in children with suspected OME for whom the diagnosis is uncertain after performing (or attempting) pneumatic otoscopy
• Clinicians should evaluate at-risk children for OME at the time of diagnosis of an at-risk condition and at 12-18 months of age (if diagnosed as being at risk prior to this time)
• Clinicians should not routinely screen children for OME who are not at risk and do not have symptoms that may be attributable to OME, such as hearing difficulties, balance (vestibular) problems, poor school performance, behavioral problems, or ear discomfort
• Clinicians should manage the child with OME who is not at risk with watchful waiting for 3 months from the date of effusion onset (if known) or 3 months from the date of diagnosis (if onset is unknown)
• Clinicians should recommend against using intranasal steroids or systemic steroids for treating OME
• Clinicians should recommend against using systemic antibiotics for treating OME
• Clinicians should recommend against using antihistamines, decongestants, or both for treating OME
• Clinicians should obtain an age-appropriate hearing test if OME persists for ≥3 months  or for OME of any duration in an at-risk child
• Clinicians should reevaluate, at 3- to 6-month intervals, children with chronic OME until effusion is no longer present, significant hearing loss is identified, or structural abnormalities of the eardrum or middle ear are suspected
• Clinicians should recommend TTs when surgery is performed for OME in a child aged < 4 years; adenoidectomy should not be performed unless a distinct indication (eg, nasal obstruction, chronic adenoiditis) exists other than OME
• Clinicians should recommend TTs, adenoidectomy, or both when surgery is performed for OME in a child aged ≥4 years

In February 2013, the AAP and the AAFP published updated guidelines for the medical management of AOM.[24]  Their recommendations are summarized as follows:

• AOM management should include pain evaluation and treatment
• Antibiotics should be prescribed for bilateral or unilateral AOM in children aged at least 6 months with severe signs or symptoms (moderate or severe otalgia or otalgia for 48 hours or longer or temperature 39°C or higher) and for nonsevere, bilateral AOM in children aged 6-23 months
• On the basis of joint decision-making with the parents, unilateral, nonsevere AOM in children aged 6-23 months or nonsevere AOM in older children may be managed either with antibiotics or with close follow-up and withholding antibiotics unless the child worsens or does not improve within 48-72 hours of symptom onset
• Amoxicillin is the antibiotic of choice unless the child received it within 30 days, has concurrent purulent conjunctivitis, or is allergic to penicillin; in these cases, clinicians should prescribe an antibiotic with additional beta-lactamase coverage
• Clinicians should reevaluate a child whose symptoms have worsened or not responded to the initial antibiotic treatment within 48-72 hours and change treatment if indicated
• In children with recurrent AOM, TTs—but not prophylactic antibiotics—may be indicated to reduce the frequency of AOM episodes
• Clinicians should recommend pneumococcal conjugate vaccine and annual influenza vaccine to all children according to updated schedules
• Clinicians should encourage exclusive breastfeeding for 6 months or longer

The FDA has approved more than a dozen antibiotics to treat otitis media (OM).

Some clinicians advocate administering corticosteroids in combination with a beta-lactam–stable antibiotic. Before prescribing such therapy, obtain a history of varicella, vaccination against varicella, and recent exposure to a patient with varicella to avoid the risk of disseminated varicella.

Studies of other adjunctive therapy for acute OM (AOM) and OME have shown that NSAIDs, decongestants, and antihistamines provide no obvious benefits.

The childhood immunization schedule includes pneumococcal vaccination to prevent OM caused by certain S pneumoniae serotypes.

Class Summary

These agents remove pathogenic bacteria from middle ear fluid.

Amoxicillin (Biomox, Amoxil, Trimox)

Mainly bactericidal. As with penicillins, inhibits third and final stage of bacterial cell wall synthesis by preferentially binding to specific PBPs located inside the bacterial cell wall.

PO semisynthetic aminopenicillin similar to ampicillin. Aminopenicillins are not stable in beta-lactamases of either gram-positive or gram-negative bacteria; more stable in gastric acid than penicillin and more bioavailable than PO ampicillin.

Amoxicillin is associated with a lower prevalence of diarrhea than is ampicillin administered PO because of the greater bioavailability of amoxicillin. Commonly used to treat infections (eg, OM, bronchitis, sinusitis, bacterial cystitis) caused by susceptible organisms. To increase efficacy against PRSP in OM or respiratory infections, higher dosing regimens have been recommended.

Amoxicillin and clavulanate (Augmentin)

As a beta-lactam antibiotic, amoxicillin is mainly bactericidal. Inhibits third and final stage of bacterial cell wall synthesis by preferentially binding to specific PBPs located inside the bacterial cell wall. As with all beta-lactam antibiotics, ability to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis.

Clavulanic acid is a beta-lactamase inhibitor that possesses weak antibacterial activity and acts as a competitive "suicide" inhibitor of many plasmid-mediated and chromosome-mediated bacterial beta-lactamases.

Excellent choice for second-line therapy in AOM or initial therapy in OME. Drug combination treats bacteria resistant to beta-lactam antibiotics. Combination with clavulanic acid reestablishes amoxicillin's activity against beta-lactamase-producing bacteria. Excellent for treating infections due to beta-lactamase-producing H influenzae and penicillinase-producing anaerobes.

Commonly used to treat infections (eg, AOM, acute sinusitis, acute bacterial cystitis, uncomplicated gonorrhea, chancroid) caused by susceptible organisms.

For children >3 mo, base dosing protocol on amoxicillin content. Because of different amoxicillin/clavulanic acid ratios in 250-mg tab (250/125) vs 250-mg chewable tab (250/62.5), do not use 250-mg tab until child weighs >40 kg. Use the 7:1 formulation (ie, bid formulation) in higher doses to minimize GI tract effects.

Cefaclor (Ceclor)

Second-generation PO cephalosporin indicated for infections caused by susceptible gram-positive cocci and gram-negative rods. Has slightly improved activity against H influenzae compared to cephalexin. Although marketed after first-generation agents, causing some clinicians to consider it a second-generation agent, its spectrum more closely resembles first-generation cephalosporins. Clinically, used primarily to treat OM, sinusitis, and URIs caused by H influenzae that are resistant to ampicillin or amoxicillin.

Use higher doses for severe infections (eg, pneumonia, OM), less susceptible strains of pathogens, and in patients who are obese.

Cefprozil (Cefzil)

PO, semisynthetic, second-generation cephalosporin. Binds to one or more PBPs, which, in turn, inhibit cell wall synthesis and result in bactericidal activity. Possible second-line therapy for AOM or initial therapy for OME. Therapeutic uses include OM, soft tissue infections, and respiratory tract infections.

Cefuroxime (Ceftin)

Second-generation cephalosporin maintains the gram-positive activity of first-generation cephalosporins and adds activity against Proteus mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis.

Common clinical uses include severe upper and lower respiratory tract infections, skin infections, OM, and surgical prophylaxis.

Condition of patient, severity of infection, and susceptibility of microorganism determine proper dose and route of administration. Susp is less bioavailable than tab. Bioavailability is enhanced when administered with food or infant formula.

Cefixime (Suprax)

Third-generation cephalosporin available in an PO formulation. As with ceftriaxone, has enhanced antibacterial activity and increased stability against many beta-lactamases. By binding to one or more PBPs, it arrests bacterial cell wall synthesis and inhibits bacterial growth.

Commonly used to treat OM, respiratory tract infections, and URIs caused by susceptible organisms.

When treating OM, susp is preferred due to higher serum concentrations achieved with this dosage form compared with tabs.

Ceftriaxone (Rocephin)

Third-generation cephalosporin with broad-spectrum gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more PBPs. Has longest half-life of all cephalosporins, allowing once-daily dosing and making it a useful antibiotic for outpatient therapy.

In Dec 1997, the FDA approved IM ceftriaxone to treat bacterial AOM caused by H influenzae (beta-lactamase negative), H influenzae (beta-lactamase positive), M catarrhalis (including beta-lactamase producing strains), and S pneumoniae. Approval was based on the following data in children aged 5 months to 5 years: A prospective, randomized, double-blind, clinical trial compared the effectiveness of a 50 mg/kg single dose of IM ceftriaxone (n=116) with a 10-d course of PO amoxicillin (n=117). The authors concluded that a single IM injection of ceftriaxone is as effective as PO amoxicillin to treat uncomplicated OM in children.

The CDC's DRSP therapeutic working group suggests this dose for 3 consecutive days in cases of suspected resistant bacteria.

Cefpodoxime (Vantin)

Cefpodoxime proxetil is an PO prodrug for the extended-spectrum, semisynthetic, cephalosporin antibiotic cefpodoxime. Spectrum is similar to third-generation cephalosporins and primarily has gram-negative coverage but also covers some gram-positive organisms. Highly stable in the presence of beta-lactamase enzymes; as a result, many organisms resistant to penicillins and some cephalosporins (due to beta-lactamases) may be susceptible to cefpodoxime.

Indicated for treatment of upper and lower respiratory tract infections, UTIs, STDs, and skin and skin structure infections. Has long half-life, allowing twice-daily administration. Approved by the FDA in 1984.

Cefdinir

Cefdinir is a third-generation cephalosporin. It inhibits mucopeptide synthesis in the bacterial cell wall and is typically bactericidal, depending on organism susceptibility, dose, and serum or tissue concentrations. It is indicated for acute bacterial otitis media caused by H influenzae (including beta-lactamase-producing strains), S pneumoniae (penicillin-susceptible strains only), or M catarrhalis (including beta-lactamase-producing strains) in children aged 6 months or older. The typical dosage is 14 mg/kg/day PO once daily or divided q12h.

Clarithromycin (Biaxin)

PO macrolide antibiotic similar to erythromycin and azithromycin. Commonly used in infections of the respiratory tract, STDs, OM, and infections in patients with AIDS. As with other macrolides, binds to 50S subunit of the 70S ribosome, thereby blocking RNA-mediated bacterial protein synthesis. Can be bacteriostatic or bactericidal in action, depending on concentration and the particular organism and its inoculum. Also penetrates phagocytes and macrophages efficiently, and, as a result, is effective against a wide variety of organisms in respiratory infections.

Generally active against organisms that are usually susceptible to erythromycin, including most staphylococcal and streptococcal strains. In addition, clarithromycin is active against M catarrhalis, Mycoplasma pneumoniae, Legionella species, and Chlamydia pneumoniae. Beta-lactamase production should have no effect on activity. Most strains of methicillin-resistant and oxacillin-resistant staphylococci are resistant to clarithromycin.

Originally approved by the FDA in Oct 1991.

Azithromycin (Zithromax)

Semisynthetic antibiotic belonging to the macrolide subgroup of azalides. Similar in structure to erythromycin. Inhibits protein synthesis in bacterial cells by binding to the 50S subunit of bacterial ribosomes. Action is generally bacteriostatic but can be bactericidal in high concentrations or against susceptible organisms.

Although significantly more expensive, it can be administered as a once-daily dose and produces less GI tract intolerance than erythromycin. Apparent advantage over erythromycin is that it reaches higher intracellular concentrations, thus increasing efficacy and duration of action. These advantages are demonstrated in studies that show that single doses are effective for the treatment of STDs caused by chlamydial and gonorrheal organisms.

Approved by FDA in Nov 1991. PO susp was introduced in Apr 1995. In late 1995, was approved for treatment of pediatric OM and pharyngitis and, in mid 1996, was approved for MAC prophylaxis in patients with advanced HIV disease.

IV form is also available for initial treatment of community-acquired pneumonia and pelvic inflammatory disease.

Trimethoprim/sulfamethoxazole (Bactrim DS, Septra DS)

Also known as co-trimoxazole. Combination product of TMP and SMZ in a fixed 1:5 ratio. Ratio produces serum concentrations of 1:20, which optimize antibacterial activity against some organisms. Both TMP and SMZ are synthetic folate antagonists that are effective antimicrobials as individual agents. TMP is usually bactericidal and acts by inhibiting sequential enzymes of the folic acid–synthesis pathway. SMZ is a structural analog of PABA and competitively inhibits formation of dihydrofolic acid from PABA. TMP binds to and reversibly inhibits the enzyme dihydrofolate reductase, which prevents formation of THF from dihydrofolic acid.

THF is a metabolically active form of folic acid. Without THF, bacteria cannot synthesize thymidine, which leads to interference with bacterial nucleic acid and protein formation.

Combination of TMP with SMZ is synergistic against some bacteria. Usually active against Staphylococcus epidermidis, S aureus, S pneumoniae, Streptococcus viridans, most Enterobacteriaceae, Salmonella and Shigella species, H influenzae, M catarrhalis, and Stenotrophomonas maltophilia.Enterococcus species, Neisseria gonorrhoeae, P aeruginosa, and anaerobes are usually resistant or less susceptible. Also effective against Pneumocystis carinii, Listeria monocytogenes, many Nocardia species, Yersinia enterocolitica, and Legionella pneumophila.

Initially used in the treatment of UTIs but has since proved to be a versatile agent and is now widely used in the prevention and treatment of P carinii pneumonia. Approved by FDA in 1973.

Erythromycin (E-Mycin, Eryc, Ery-Tab, Erythrocin)

Macrolide antibiotic produced by Streptomyces erythraeus; first of several macrolide antibiotics now on the market.

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections. Effective against wide range of microorganisms and, as with other antibiotics that inhibit protein synthesis, is mainly bacteriostatic.

Activity against gram-positive organisms is usually greater than against gram-negative organisms because of superior penetration into gram-positive organisms.

Gram-positive organisms susceptible to erythromycin include S aureus, Streptococcus agalactiae, Streptococcus pyogenes, S pneumoniae, S viridans, and Corynebacterium diphtheriae. Gram-negative coverage is limited. In general, should not be used against H influenzae, although, in some cases, organism may be susceptible. Although erythromycin is active against many microbes, its clinical applications are relatively few.

In children, age, weight, and severity of infection determine proper dosage. When bid dosing is desired, half of the total daily dose may be taken q12h. For more severe infections, double the dose.

Class Summary

The 13-valent and 20-valent pneumococcal vaccines are approved by the FDA for children aged 6 weeks through 5 years to prevent OM caused by S pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. 

Pneumococcal vaccine 13-valent (Prevnar 13)

Contains S pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F.

Pneumococcal vaccine 20-valent (Prevnar 20)

Contains S pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F.