OTITIS MEDIA

OTITIS MEDIA

Current Diagnosis

•   History of acute onset of symptoms

•   Middle ear effusion

   •   Bulging tympanic membrane

   •   Limited mobility of tympanic membrane or air fluid level visible behind tympanic membrane

•   Middle ear inflammation

   •   Erythema of tympanic membrane or distinct otalgia

Current Therapy

• Watchful Waiting—appropriate for children:

    i.   Greater than 2 years of age with nonsevere illness

    ii.   Greater than 6 months of age with uncertain diagnosis and nonsevere illness

    iii. Greater than 2 years of age with severe illness, but uncertain diagnosis

  •   Need close follow-up in 48 hours

  •   Consider delayed prescription

•   Antibiotics

  •   First line should be amoxicillin (Amoxil) 80 to 90 mg/kg/day3

  •   Treat 10 days if child less than 6 years of age, 5 to 7 days if greater than 6 years of age

  •   Follow-up if not improving in 48 hours

•   Analgesia

  •   Acetaminophen (Tylenol), ibuprofen (Motrin, Advil)

  •   Benzocaine in combination with antipyrine (Allergen, Auroguard), benzocaine with antipyrine and acetic acid (Auralgan)

•   Antihistamines and decongestants are of no benefit

•   Surgery—consider tympanostomy tubes when:

   i.   First AOM episode at less than 6 months of age and child with 2 or more episodes in 6 months or 3 in 24 months

  ii.  First AOM episode at more than 12 months of age and child with 3 episodes in 6 months, 5 episodes in 12 months or 7 episodes in 24 months

3  Exceeds dosage recommended by the manufacturer

Epidemiology

Acute otitis media (AOM) is a common condition of childhood, with one in four children having at least one episode of AOM by age 10. In fact, 86% of children will have at least one episode of AOM within the first year of life. Younger children are more likely to be affected, with peak incidence noted between ages 6 and 20 months likely because of the relative immaturity of immune system and eustachian tube function. On average, 5 billion dollars are spent per year on office visits, lost productivity, and diminished parental quality of life due to AOM infections. As a result, research has focused on effective strategies both to prevent episodes of AOM and also to efficiently treat episodes that do occur.

Risk Factors

Identifying children at risk for AOM has been an important strategy to attempt to limit instances of AOM. Unfortunately, many of the risk factors associated with AOM are not modifiable, including male gender, Native American ethnicity, presence of siblings within the home, and a family history of recurrent AOM. Additional risk factors include low socioeconomic status, premature birth, attendance at out- of-home daycare, lack of breastfeeding, and history of poor maternal health during pregnancy. Limited studies have suggested that interventions such as avoiding supine feeding or bottle propping, reducing pacifier use after the first 6 months of life, and eliminating passive tobacco exposure can help to reduce incidence; however, the evidence in which these interventions demonstrate clear impact is limited. Public health programs that encourage breastfeeding and optimal maternal health during pregnancy, as well as those focused on reducing tobacco use, have perhaps the best opportunity to impact AOM incidence rates.

Not only are these identified risk factors for any episode of AOM, but children with these characteristics are also more likely to have recurrent AOM. Although many children will be affected in their lifetimes, those with recurrent disease are most at risk of complications leading to morbidity or mortality. Other risk factors specifically for recurrent AOM include an early onset of first episode and low parental education.

Pathophysiology

AOM has classically been associated with three bacteria; namely, Streptococcus pneumoniae, Moraxalla catarrhalis, and Haemophillus influenzae. Using data derived from middle-ear fluid analysis, M. catarrhalis is responsible for only 3% to 20% of AOM, while S. pneumoniae and H. influenzae are more common contributors at 25% to 50% and 15% to 30%, respectively.

The bacteria responsible for AOM become pathogenic in the setting of eustachian tube dysfunction. A relative obstruction of the eustachian tube develops most commonly secondary to secretions from an antecedent viral upper respiratory infection or allergies, but may result from neuromuscular conditions or abnormal anatomy.

Such relative obstruction creates a negative pressure within the middle ear leading to serous effusion and secondary infection of this collection of interstitial fluid. Thus, prevention of AOM is aimed at both reducing the presence of pathogenic bacteria and preventing upper respiratory infections that may create eustachian tube dysfunction.

Prevention

The successes of immunization programs in virtually eliminating childhood illnesses such as measles, polio, and varicella have led to great interest in the development of vaccines capable of eradicating the causative agents of AOM. Immunizations targeting the specific bacteria most commonly associated with AOM have had mixed success, however.

For example, although the serotypes contained in the 7-valent pneumococcal conjugate vaccine (PCV, Prevnar) are responsible for approximately 66% of pneumococcal-related AOM, only moderate effectiveness has been noted in reducing AOM incidence among vaccinated children. After the introduction of the 7-valent PCV into practice in February of 2000, AOM incidence decreased only 6% to 7% among vaccinated children. The 9-valent and 11-valent PCVs2 have been shown to result in a risk reduction of S. pneumoniae isolates in children with AOM of 17% and 34%, respectively. An increase in serotype 19A has been noted that is not covered in the 7-, 9- or 11- valent PCVs2, but is included in the new 13-valent PCV (Prevnar 13). The 13-valent PCV was incorporated into the recommended childhood immunization schedule in February 2010. The effect of this change on AOM rates will be interesting to observe.

While the ability of the vaccine to prevent AOM episodes may be relatively small, recurrent disease has decreased 23% whereas the need for tympanostomy tubes has decreased nearly 25% in vaccinated children. Hence, the power of the vaccine may be in preventing recurrent disease requiring surgical intervention rather than in prevention of any AOM episodes.

Similar vaccines are in development for H. influenzae and M. catarrhalis as causative agents of AOM. The current H. influenzae b vaccine, or Hib, has had little impact on AOM, because less than 5% of episodes are caused by the type b strain of Haemophilius. Rather, non- typeable Haemophillus influenzae is a much more common cause of AOM.

Although the vaccines targeting specific bacteria that have been shown to cause AOM have been successful, so too has the influenza vaccine been shown to impact the course of AOM. In several studies, children who received seasonal influenza vaccine (Fluzone) were found to have fewer episodes of AOM than unvaccinated children.

Furthermore, those who did have an AOM episode were found to use fewer antibiotics and have shorter duration of middle-ear effusion compared with unvaccinated counterparts.

With evidence that reducing incidence of viral influenza may reduce the occurrence of secondary AOM, several other interventions aimed at reducing viral upper respiratory infection incidence have been studied for their impact on AOM rates. The use of zinc7 and propolis7 as agents to prevent viral upper respiratory infections, for instance, has been shown to have mixed benefit in reducing AOM in children. In multiple studies, zinc has been well tolerated with no contraindications to use identified. Zinc as a single agent has been shown to prevent AOM only when used in children under age five who are also malnourished. However, when combined with propolis, zinc was shown to be effective at reducing AOM episodes for children with a history of recurrent AOM. Of note, in several trials zinc did not reduce upper respiratory infection rates; rather, rates of secondary AOM alone were decreased. While not necessarily effective as a preventive measure for all children, zinc and propolis may be an option for children with recurrent infection.

Similarly, probiotics7 added to infant formula have been shown to be beneficial for some children. Although breastfeeding as compared to formula supplementation has been shown to be most beneficial in preventing AOM, infant formulas supplemented with Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb-12 (Enfamil Premium, Nestle Good Start) were shown to reduce incidence of AOM over the first 7 months and the first 1 year. Children who received placebo formula had an incidence of AOM of 50% in the first 7 months, whereas children who received the probiotic-supplemented formula had an incidence of only 22%.

Dietary supplementation to limit AOM is not limited to infant formulas, however. Xylitol7, a polyol sugar alcohol found in birch plants, plums, strawberries, and raspberries, has been demonstrated in several studies to be effective at preventing both dental caries and AOM, though its dosage forms make administration difficult. Xylitol is available as a chewing gum, which raises concern as a choking hazard in young children. Similarly, in its oral syrup form, xylitol must be administered five times daily to be effective. Studies of thrice daily dosing have not been able to demonstrate the same preventive effect as dosing five times daily despite a consistent total daily dose of 10 grams per day. Furthermore, emerging evidence suggests that xylitol must be given daily to remain effective at reducing AOM episodes, as prophylaxis only during winter months or use only during upper respiratory tract infections is ineffective. Of note, children who have already received tympanostomy tubes receive no prevention benefit from xylitol administration. Research is ongoing to increase physician awareness of xylitol as a possible prophylactic measure as current studies suggest less than one half of United States physicians are aware of xylitol and less than one fourth discuss or recommend its use to patients.

Echinacea7 and osteopathic manipulation have also been cited as potential prophylactic treatments, particularly for children at high risk of recurrence. However, little evidence exists that either are effective. In fact, one large study demonstrated an increased risk of AOM with Echinacea use during an upper respiratory tract infection episode and no benefit to manipulation treatment. Ongoing studies are examining the use of these modalities.

Clinical Manifestations

AOM presents with a rapid onset of symptoms that may include fever, chills, ear pain, or ear pulling. In fact, ear pulling and ear rubbing have been demonstrated to be quite sensitive for the diagnosis of AOM in the setting of a history consistent with AOM and middle ear effusion. Often, symptoms may be preceded by upper respiratory symptoms such as rhinorrhea, cough, or congestion.

Children who have had tympanostomy tubes placed will likely have a far different presentation, with fever and pain being quite unlikely; rather, a thin, yellow or milky discharge may be the only sign that AOM is present.

Diagnosis

The 2013 update of the guidelines of the American Academy of Pediatrics for the diagnosis and treatment of AOM acknowledged that no gold standard exists for the clinical diagnosis of AOM. History and physical examination should be consistent with rapid onset of inflammation in the middle ear. Both pneumatic otoscopy and tympanometry may be useful in the diagnosis of AOM. Tympanic membranes should be evaluated for position, mobility, color, and degree of translucency using pneumatic otoscopy to assess for presence of middle ear effusion and/or inflammation. Moderate to severe bulging of the tympanic membrane, new onset of otorrhea without other cause, or mild bulging of the tympanic membrane with intense erythema or ear pain should prompt diagnosis of AOM. Furthermore, tympanomtry may be useful in determining if an effusion is present if the diagnosis is otherwise unclear.

One concern of physicians has been accurately diagnosing middle ear inflammation after a child has been vigorously crying. A study of 125 healthy children, age less than 30 months, assessed the impact of crying on tympanic membrane color by performing otoscopy both before and after administering at least two immunizations. While crying can cause a pinkening of the tympanic membrane, it should disappear when the child quiets and should be less intense than what is observed with inflammation. True middle ear inflammation results in an angry, red eardrum, not the milder, pink flush seen with vigorous crying. The presence of effusion should also help to support a diagnosis of inflammation.

Differential Diagnosis

Otitis media with effusion is often misdiagnosed as an episode of AOM. Like AOM, OME is common, with 2.2 million episodes annually representing an estimated cost of 4 billion dollars. OME can also occur with a viral upper respiratory infection and may follow or precede an episode of AOM. OME differs from AOM, however, as fluid may be present in the middle ear with OME, but there are no signs of acute infection.

Although OME is not associated with acute infection, it is nonetheless critical to diagnose, as research has demonstrated that chronic OME is associated with hearing loss and subsequent developmental delay. In fact, OME in infancy has been shown to be associated with, on average, a 7-point reduction in IQ at age 7.

The cornerstone of treatment for OME is observation for 2 to 3 months to allow the effusion to clear. Avoidance of allergens and tobacco exposure that may worsen eustachian tube dysfunction is also important. Decongestants and antihistamines are not effective. If an effusion does not clear within 2 months, a single course of amoxicillin (Amoxil) or penicillin may be given.

Audiometry should be performed in all children with OME for greater than 3 months or, in the setting of language delay, learning problems or suspected hearing loss in a child with OME. If the effusion persists, or if a child has multiple episodes of OME or has hearing or learning difficulties as a result of OME, surgical intervention should be considered.

Initial surgical intervention for children with persistent OME should be myringotomy with placement of tympanostomy tubes. Tonsillectomy and myringotomy alone are not indicated for treatment of OME. However, adenoidectomy may have a role, particularly in children ages 4 to 8 years. Current recommendations include adenoidectomy only if repeat surgery for OME is needed. However, emerging evidence suggests adenoidectomy may decrease need for surgical retreatment, reduce ongoing hearing loss, and be of benefit during initial surgery for older children.

Treatment

The treatment of AOM has been controversial in recent years. As it is the most common childhood bacterial infection for which antibiotics are prescribed worldwide, debate continues about both the most effective regimen and appropriate time to treat AOM. On average, 2.8 billion dollars are spent per year on antibiotics for episodes of AOM, yet emerging evidence suggests that watchful waiting is appropriate for some children. Judicious use of antibiotic therapy remains key in the prevention of morbidity and mortality associated with otitis media, but is not an appropriate therapy for every child. All children require analgesia of some type as well as close, scheduled follow-up, but use of observation or antibiotic varies with severity of illness and age of the child. Treatment options are summarized in Table 1.

Table 1

Treatment Options for Acute Otitis Media

 

* Severe symptoms include: toxic-appearing child, persistent otalgia for > 48 hours, temperature > 39 °C in past 48 hours, or uncertain access to  follow-up.

Treatment Options: Observation

For some children with AOM, observation has been shown to be an appropriate therapy that avoids the possible side effects of antibiotics with low risk of complications developing from an untreated otitis media. Evidence suggests that 78% of AOM episodes will spontaneously resolve within the first few days of infection. In fact, for every 100 otherwise healthy at-risk children with AOM, 80 will improve within 3 days without antibiotic therapy. If the same 100 children were all treated with amoxicillin or ampicillin, 92 would improve, though 3 to 10 would develop a rash and 5 to 10 would develop diarrhea. Thus, in a typical family medicine practice 16 children with AOM would need to be treated with antibiotics to prevent 1 child from experiencing ongoing otalgia, while 1 of every 24 children treated will experience harm related to therapy. Hence, the use of antibiotics is not without risk. Multiple studies have demonstrated that even in children as young as 2 months of age, many will improve without antibiotic therapy and delaying antibiotics may prevent undesirable side effects without exposing the child to undue risk. No studies have demonstrated a resurgence of either mastoiditis or meningitis with implementation of watchful waiting for AOM.

If observation is chosen as a management strategy for acute otitis media, it is important to re-evaluate the child in 48 to 72 hours to ensure that they are improving and that a rescue antibiotic is prescribed if symptoms are not resolving. Delayed prescriptions are one strategy that has been effective at reducing antibiotic use, maintaining parental satisfaction, and improving healthcare efficiency.

Physicians are often concerned that parental satisfaction will decrease if watchful waiting for an episode of AOM is recommended. Interestingly, satisfaction has been tied to the receipt of an antibiotic prescription, though not necessarily the administration of antibiotics to the child. Declines in satisfaction are noted when parents are advised to return to care in 2 to 3 days if the child is not improving while undergoing watchful waiting. By offering a delayed prescription, the parent can avoid the difficulties associated with needing to be re-seen if the child fails to improve and parental satisfaction is maintained even if the child never receives any medication. Parents should be educated that up to one third of children who initially are treated with observation will eventually need antibiotic therapy. While this suggests up to two thirds of children can avoid unnecessary antibiotics, parents should be aware that many children will go on to need antibiotic therapy. Clearly, however, not every child is a candidate for observation therapy.

Treatment Options: Antibiotic Therapy

Antibiotic therapy may be associated with less duration of pain, less analgesic use, and less absence for both children and parents from school and work, respectively. The American Academy of Pediatrics and the American Academy of Family Physicians in a joint position statement have recommended that, when a decision is made to use antibiotics, amoxicillin (Amoxil) be given as a first-line agent at a dose of 80 to 90 mg/kg/day.3 For penicillin-allergic children, cefdinir (Omnicef), cefpodoxime (Vantin), or cefuroxime (Ceftin) may be used. Although the cross reactivity of cephalosporins and penicillins is likely lower than previously believed, if concern exists about treating a child with a cephalosporin, clindamycin (30–40mg/kg/day) may be used. Macrolide antibiotics may have limited efficacy. Ceftriaxone (Rocephin) may be used as a single dose for a child unable to tolerate oral medications.

While amoxicillin continues to be the preferred first-line agent, 30% to 70% of strep pneumoniae strains have become penicillin and macrolide resistant while 20% to 40% of H. influenzae has beta- lacatamase–producing capabilities. Given the various resistance patterns of organisms, a child who fails to improve on amoxicillin should receive amoxicillin with clavulanate (Augmentin) or ceftriaxone as second-line therapy. Clindamycin (Cleocin) or tympanocentesis to identify a causative organism may also be considered.

Current evidence continues to suggest that a 10-day course is optimal for children under the age of 2 years. Less benefit to longer duration therapy is noted in older children, and therefore a shorter 5- to 7-day course is recommended for those older than 2 years.

If a child has a perforation of the tympanic membrane, treatment considerations may be slightly different. Oral antibiotics continue to be recommended if perforation is a result of the AOM episode; however, if a child has an episode of AOM with tympanostomy tubes in place topical 0.3% ciprofloxacin/0.1% dexamethasone (Ciprodex Otic) should be added to oral amoxicillin. See Table 2 for antibiotic dosing recommendations.

Table 2

Antibiotic Selection for Specific Patient Populations

Abbreviation: AOM = acute otitis media.

1  Not FDA approved for this indication.

3  Exceeds dosage recommended by the  manufacturer.

Regardless of the decision to implement watchful waiting or antibiotic therapy, any child with AOM should be expected to improve within 48 to 72 hours. If improvement is not occurring, the child should be re-evaluated.

Treatment Options: Surgery

For some children, AOM will not be an isolated event. Rather, they will have recurrent infections and require multiple antibiotic courses throughout a year, prompting consideration of tympanostomy tube placement. Currently, referral for evaluation for tympanostomy tubes is recommended when a child has had three or more episodes of AOM within a 6-month period or more than four episodes within a 12-month period. Some have argued, however, that this recommendation should be considered within the context of the child’s age at first presentation. A child who has the first episode of AOM prior to 6 months of age is likely to go on to have many more episodes. Ultimately, they will likely meet the criteria for myringotomy and thus may warrant a more aggressive approach from the outset. Conversely, a child who presents with a first episode of AOM as an older child is less likely to have recurrent episodes and can therefore be treated in a more conservative manner.

Using an age-stratified approach, children who experience a first episode of AOM prior to 6 months of age should receive tympanostomy tubes if they have two episodes in a 6- or 12-month time period or three episodes in 24 months. Similarly, children who have a first episode of AOM after 1 year of age should receive tympanostomy tubes only if they have three episodes within 6 months, five within 12 months, or seven within 24 months.

Referral may also occur if a child has a history of AOM associated with meningitis, facial nerve paralysis, coalescent mastoiditis, or brain abscess. Tympanostomy tubes are also often placed due to prolonged OME resulting in hearing loss and language delay. Myringotomy without tube placement may be considered for either diagnosis of an infection that has not responded to numerous antibiotics or for relief of severe otalgia.

AOM episodes will continue to occur despite tympanostomy tube placement. However, episodes will likely be less severe, of shorter duration, and less frequent. In addition to ongoing AOM episodes, tympanostomy tubes can be problematic if they become clogged. New studies in animal models suggest that applying colchicine1 in the external ear may prevent this complication.

Treatment Options: Analgesia

Regardless of a decision to pursue watchful waiting or antibiotics, analgesics are an important component in the treatment of AOM. Multiple homeopathic interventions and home remedies including application of heat, ice, or mineral oil (Min-O-Ear)1 have been used for pain control, though no studies exist to verify their effectiveness.

Acetaminophen (Tylenol), ibuprofen (Motrin), narcotics, and tympanostomy have all been demonstrated to be effective at reducing pain. However, the side effects of altered mental status, gastrointestinal upset, and respiratory depression with narcotics as well as the skill needed to perform tympanostomy limit the usefulness of these interventions in primary care practice. Topical medications may help avoid the systemic effects of oral medication. Antipyrine and benzocaine are the only topical analgesics available in the United States. Topical benzocaine has been demonstrated to have minimal side effects and in patients over 5 years of age may offer more relief than acetaminophen alone. Benzocaine is available in combination with antipyrine (Allergen Ear Drops, Auroguard Otic). Benzocaine is also available with antipyrine and acetic acid (Auralgan) but may be expensive. In other countries, antipyrine, also known as phenazone, is available in combination with procaine and is effective.

Antihistamines have often been prescribed, as have decongestants, in an attempt to reduce the fluid volume in the middle ear and hence provide relief. Unfortunately, use of antihistamines and decongestants has been shown to result in a fivefold to eightfold increase in the risk of side effects with no benefits, including no decreased time to cure, no prevention of surgery or complications, and no increased symptom resolution. Therefore, antihistamines and decongestants have not been routinely recommended.

Conclusion

AOM continues to be one of the most costly and common childhood illnesses in developed nations throughout the world. Successful management of this condition requires much more than choosing amoxicillin at an appropriate dose and duration or appropriately timing a surgical referral. Vigilant attention to modifying risk factors when possible, promoting immunization, and limiting the spread of viral illnesses has been shown to prevent AOM instances.

Furthermore, adherence to diagnostic criteria to attempt to accurately distinguish between AOM and OME, as well as implementing observation when appropriate, can significantly reduce antibiotic usage, thereby minimizing side effects for patients and opportunity to develop resistance in pathogens.

2  Not available in the United  States.

7  Available as a dietary  supplement.

7  Available as a dietary supplement

1  Not FDA approved for this  indication.

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