The Evaluation and Treatment of Children with Acute Otitis Media

Between 1993 and 1995 more than 20 million visits were provided to children younger than 15 years for otitis media; 77% of these were for children aged 4 years and younger.¹ Acute otitis media (AOM) is the most frequent primary diagnosis in preschool children and accounts for almost 20% of ambulatory care visits in this age group. By the age of 3 months, 10% of children will be given at least 1 diagnosis of otitis media and more than 90% by the age of 2 years.² Peak incidence occurs between the ages 6 and 15 months, although there is a second peak at approximately age 5 years that is thought to be associated with entrance into school.³ In the mid-1990s, treatment of otitis media cost $3.8 billion per year4; 20% of the more than 110 million prescriptions for oral antibiotics are for otitis media.⁵

The most important contributor to AOM is a dysfunction of the eustachian tube, allowing reflux of fluid and bacteria into the middle ear space from the nasopharynx.⁶ This dysfunction is usually multifactorial and is likely a combination of anatomy (shorter and more flexible eustachian tubes) and function (inefficiency at clearing secretions and equilibrating negative intratympanic pressures) in younger children.⁷ Acute viral upper respiratory infections create inflammation and secretions that magnify this eustachian tube dysfunction and predispose to or induce AOM.

The 3 most common bacteria in AOM are Streptococcus pneumoniae, Haemophilus species, and Branhamella catarrhalis. A recent study showed that both bacteria and viruses were isolated in the middle ear fluid of 65% of children with otitis media. In fact, 35% had viruses isolated as the sole middle ear pathogen.⁸ Other studies have failed to identify a specific infectious agent in a significant number of middle ear fluid aspirates.⁹

Diagnosis

The diagnosis of AOM in children is often based on a combination of symptoms and physical findings. It is usually defined as bulging or opacification of the tympanic membrane with or without erythema, middle ear effusion, marked decrease or absence of tympanic membrane mobility, and accompanied by at least one of the following signs and symptoms of acute infection: fever, otalgia, irritability, otorrhea, lethargy, anorexia, vomiting, or diarrhea.10 Although the best reference standard for the diagnosis of AOM is myringotomy or tympanocentesis, no published studies were identified in which this reference was performed in all study patients. Most published studies use pneumatic otoscopy combined with tympanocentesis or myringotomy as the reference standard when middle ear effusion is suspected.

Most symptoms are not specific for AOM. In a survey of patients seeing general practitioners in Finland,11 the symptoms that most increased the likelihood of diagnosing AOM were earache (relative risk [RR]=5.4; 95% confidence interval [CI], 3.3-8.9), rubbing of the ear (RR=5.0; 95% CI, 2.9-8.6), and excessive crying (RR=2.8; 95% CI, 1.8-4.3). Although fever, earache, or excessive crying were present in 90% of children considered to have AOM, one or more of these symptoms were also present in 72% of children who did not have otitis media. In another survey of children aged younger than 4 years with a diagnosis of AOM, 40% did not have otalgia, and 30% did not have fever.¹²

Physical examination findings are of variable reliability. Findings that physicians rely on to diagnose AOM, such as a bulging or erythematous tympanic membrane, may occasionally be found in normal ears.13 One study compared the 3 most commonly documented otoscopic findings (color, position, and mobility of the tympanic membrane) with those of pneumatic otoscopy and myringotomy.14 Only 65% of patients with a distinctly red tympanic membrane and 16% with a slightly red tympanic membrane had AOM. A cloudy tympanic membrane was the most predictive color change, with an 80% positive predictive value (PPV), the percentage of patients with the symptom who have AOM. A bulging tympanic membrane was most predictive of AOM (PPV=89%), despite its 27% false-negative rate. Retraction was found in only 19% of children with AOM and had a PPV of only 50%. Distinctly impaired mobility was predictive of otitis media (PPV=78%), but diminished mobility was also found in 30% of children without middle ear effusion. These data and those presented in Table 1 show that each of these otoscopic examination elements (color, position, mobility) alone is inadequate for discriminating between cases in which the diagnosis of AOM is uncertain.

However, combining these signs can be useful.¹⁵ A cloudy (opaque), bulging, and immobile tympanic membrane on pneumatic otoscopy was nearly 100% predictive of otitis media in children with acute symptoms. In addition, 94% of children with the combination of distinctly red erythema, bulging, and immobility had AOM. No combination of findings that included only slight redness was more than 53% predictive of AOM.

In children aged younger than 1 year in whom otoscopy can be quite difficult, tympanometry can be a useful tool for detecting a middle ear effusion.¹⁶ An abnormal type B tympanogram (flat curve with no distinct peak) in infants presenting with acute symptoms is strong evidence in favor of AOM, although a normal test is not helpful in ruling out the diagnosis.

The diagnosis of AOM can be influenced by the physician’s perception of parental expectations for antibiotics.¹⁷ A study of children presenting with ear pain or other upper respiratory symptoms found that physicians diagnosed AOM 49% of the time when they perceived parents wanted antibiotics and only 13% of the time when they thought parents did not want antibiotics. Physicians were 23 times more likely to prescribe an antibiotic for an upper respiratory illness if they perceived that parents expected antimicrobials.

Treatment

A recent systematic review¹⁸ found that the symptoms of AOM (mainly otalgia) spontaneously resolved in two thirds of children by 24 hours and in 80% at 2 to 7 days. This was also observed in 2 earlier meta-analyses.^10,19 Seventeen children would need to be treated with antibiotics (vs placebo) for 1 child to have less pain at 2 to 7 days (number needed to treat [NNT]=17). There were no differences between antibiotic and placebo groups in other clinical outcomes, such as tympanometry findings, perforation, and recurrences. Also, children treated with antibiotics were almost twice as likely to have vomiting, diarrhea, or a rash.

Initially not treating uncomplicated AOM with antibiotics is an acceptable alternative. In a study by van Buchem and colleagues,²⁰ 90% of children with AOM recovered (symptoms resolved) in the first 4 days with nose drops and oral analgesics and without the use of antibiotics. Only 3% of the 4860 children in this study had a clinical course that required further treatment with antibiotics or myringotomy. A recent randomized controlled trial of 315 children demonstrated that children treated immediately with antibiotics had 1 less day of symptoms, but that 1 in 5 of these had diarrhea.²¹ The group not treated with antibiotics had no serious sequellae and used more analgesics. There were no differences in the number of missed school days, and more than 75% of the parents were satisfied with this “wait and see” approach. These studies also emphasize that antibiotics have a very modest effect on the clinical course of AOM and seem to decrease the duration of symptoms only to a small degree.

Physicians often recommend other symptomatic treatments for ear infections. Non–aspirin analgesics are effective in relieving pain,²¹ as are ibuprofen²² and Auralgan.²³ Antihistamine-decongestant preparations offer no added benefit in resolution of symptoms and have no effect on clinical outcomes when given with antibiotics.^24,25

If antibiotics are used, the meta-analysis by Rosenfeld and colleagues¹⁰ showed there were no differences in outcomes between treatment with cefaclor, cefixime, erythromycin, trimethoprim-sulfamethoxazole, amoxicillin clavulanate, or erythromycin sulfisoxazole, and treatment with amoxicillin or ampicillin. Broader spectrum and/or more expensive antibiotics therefore offer no advantage over amoxicillin for the initial treatment of AOM. In another meta-analysis, Kozyrskyj and coworkers26 showed that a 5-day antibiotic course was an acceptable alternative to a 8- to 14-day treatment course. There was a slightly increased risk of treatment failure at 1-month follow-up with the shortened course of antibiotics; the NNT to prevent 1 excess failure at 30 days was 17. There were no differences in long-term outcomes (2-3 months) or medication side effects (vomiting, diarrhea, rash) between the short and long antibiotic courses. The broader spectrum azithromycin and intramuscular ceftriaxone offered no advantage over amoxicillin. Children aged younger than 2 years deserve special mention, since they are at higher risk for treatment failures,^27,28 persistent symptoms,²⁹ and recurrent otitis media.³⁰ Few well-designed studies exist to guide treatment in this age group. Although children aged younger than 2 years were not excluded, neither review by Glasziou and colleagues¹⁸ or Rosenfeld and coworkers¹⁰ specifically examined this age group.

Another review demonstrated that (as with older children) routinely using antibiotics initially does not seem to add any clinical benefit.³¹ A recent randomized controlled trial of 240 children demonstrated that 8 children in this age group would have to be treated with amoxicillin for 1 child to have fewer symptoms (fever, crying, irritability) at 4 days (NNT=8).³² The major benefit of amoxicillin in this study was 1 day less of fever (P=.004). Adverse effects were almost twice as likely in the amoxicillin group, although this difference was not statistically significant. There were also no differences between the groups in clinical failure rates at 11 days or in the likelihood of recurrent otitis media, antibiotic use, specialist referrals, or surgery at 6 weeks. Effects on hearing were not measured. The authors conclude that “this modest effect does not justify prescription of antibiotics at the first visit, provided close surveillance can be guaranteed.” Also, Kozyrskyj and colleagues²⁶ demonstrated in their meta-analysis that as a subgroup there were no differences in clinical failures between 5 and 10 days of antibiotics in children aged younger than 2 years. However, there were only 118 children in this age group. Table 2 shows treatment options for AOM.

In recent years, there has been an increasing concern about worldwide bacterial resistance to antimicrobial drugs^33-35 by the World Health Organization³⁶ and the Centers for Disease Control and Prevention (CDC).³⁷ In response to the increasing antimicrobial resistance patterns seen in the common middle ear pathogens, especially S pneumoniae, the CDC Drug-resistant Streptococcus pneumoniae Therapeutic Working Group recommends doubling the dosage of amoxicillin to 80 to 90 mg per kg per day in the empiric treatment of AOM.³⁸ These recommendations are based on in vitro mean inhibitory concentration data of S pneumoniae cultures from middle ear fluid and nasopharyngeal swabs. However, there currently is no patient-oriented evidence to suggest that increasing the amoxicillin dosage actually decreases suppurative or invasive complications of AOM (meningitis, mastoiditis, and so forth), affects recurrence rates or treatment success, affects long-term outcomes of AOM, or even decreases the rate of drug-resistant S pneumoniae. Also, bacteriologic outcomes do not correlate with clinical outcomes. In the meta-analysis by Rosenfeld and coworkers,¹⁰ 89% of middle ear pathogens from treatment failures were susceptible in vitro to the antibiotic prescribed, and 13% of isolates from clinical cures were resistant in vitro to the prescribed antibiotic. We must use extreme caution in extrapolating the microbiologic findings to the clinical care of the child with AOM.

Prognosis

There are insufficient data to suggest that routine antibiotic use in AOM results in fewer cases of mastoiditis or meningitis. In the systematic reviews cited, the incidence of these suppurative complications was rare. In the Cochrane review by Glasziou and colleagues,¹⁸ only 1 case of mastoiditis developed in 2202 children, and this was in a child treated with penicillin. In the Netherlands among 4860 consecutive children with AOM, 2 experienced mastoiditis (both responded to outpatient antibiotic therapy), and there were no cases of meningitis.²⁰ In the meta-analysis by Rosenfeld and coworkers,¹⁰ there were no suppurative complications in the 5400 children studied. Although mastoiditis has been quoted as being more common in the preantibiotic era, it is unclear if the current rarity of this condition is due to antibiotic treatment, changes in organism virulence or host defenses, or the assertion that uncomplicated otitis media was often not reported, thus increasing the relative rate of mastoiditis.²⁷ In a recent review,³⁹ antibiotics did not seem to have an appreciable effect on complication rates, leading the authors to conclude that “antibiotic treatment for AOM cannot be considered as a safeguard against the development of complications.” Even in developing countries where the burden of otitis media is great, mastoiditis is quite rare, with a prevalence rate of much less than 1%.⁴⁰

Antibiotic use does influence bacterial resistance rates. In children previously treated with antibiotics for AOM, there is a 3-fold increased risk of isolating drug-resistant organisms from middle ear effusions with subsequent bouts of otitis media.^41,42 In the Netherlands and Iceland, routinely not treating AOM with antibiotics has resulted in a reduction in antibiotic resistance.^33,43 The most important risk factors for a poor outcome are age younger than 2 years and attendance at a daycare center.40 Children in daycare have a higher risk of requiring a hospital admission and up to a 50% increased risk of repeated or recurrent ear infections.^44,45 Children with chronic underlying illnesses or chronic otitis media with effusion have added risks of poor outcomes that are beyond the scope of this review.

Conclusions

Thus, the natural course of AOM in children is quite favorable. If left untreated, 80% will recover spontaneously within 2 weeks. The addition of antibiotics provides at best a modest reduction in symptoms, while adding cost, adverse drug effects, and increasing bacterial resistance in the patient and community. Minimizing the use of antibiotics in patients with AOM does not increase the risks of perforation, deafness, or contralateral or recurrent AOM.

Between 1993 and 1995 more than 20 million visits were provided to children younger than 15 years for otitis media; 77% of these were for children aged 4 years and younger.¹ Acute otitis media (AOM) is the most frequent primary diagnosis in preschool children and accounts for almost 20% of ambulatory care visits in this age group. By the age of 3 months, 10% of children will be given at least 1 diagnosis of otitis media and more than 90% by the age of 2 years.² Peak incidence occurs between the ages 6 and 15 months, although there is a second peak at approximately age 5 years that is thought to be associated with entrance into school.³ In the mid-1990s, treatment of otitis media cost $3.8 billion per year4; 20% of the more than 110 million prescriptions for oral antibiotics are for otitis media.⁵

The most important contributor to AOM is a dysfunction of the eustachian tube, allowing reflux of fluid and bacteria into the middle ear space from the nasopharynx.⁶ This dysfunction is usually multifactorial and is likely a combination of anatomy (shorter and more flexible eustachian tubes) and function (inefficiency at clearing secretions and equilibrating negative intratympanic pressures) in younger children.⁷ Acute viral upper respiratory infections create inflammation and secretions that magnify this eustachian tube dysfunction and predispose to or induce AOM.

The 3 most common bacteria in AOM are Streptococcus pneumoniae, Haemophilus species, and Branhamella catarrhalis. A recent study showed that both bacteria and viruses were isolated in the middle ear fluid of 65% of children with otitis media. In fact, 35% had viruses isolated as the sole middle ear pathogen.⁸ Other studies have failed to identify a specific infectious agent in a significant number of middle ear fluid aspirates.⁹

Diagnosis

The diagnosis of AOM in children is often based on a combination of symptoms and physical findings. It is usually defined as bulging or opacification of the tympanic membrane with or without erythema, middle ear effusion, marked decrease or absence of tympanic membrane mobility, and accompanied by at least one of the following signs and symptoms of acute infection: fever, otalgia, irritability, otorrhea, lethargy, anorexia, vomiting, or diarrhea.10 Although the best reference standard for the diagnosis of AOM is myringotomy or tympanocentesis, no published studies were identified in which this reference was performed in all study patients. Most published studies use pneumatic otoscopy combined with tympanocentesis or myringotomy as the reference standard when middle ear effusion is suspected.

Most symptoms are not specific for AOM. In a survey of patients seeing general practitioners in Finland,11 the symptoms that most increased the likelihood of diagnosing AOM were earache (relative risk [RR]=5.4; 95% confidence interval [CI], 3.3-8.9), rubbing of the ear (RR=5.0; 95% CI, 2.9-8.6), and excessive crying (RR=2.8; 95% CI, 1.8-4.3). Although fever, earache, or excessive crying were present in 90% of children considered to have AOM, one or more of these symptoms were also present in 72% of children who did not have otitis media. In another survey of children aged younger than 4 years with a diagnosis of AOM, 40% did not have otalgia, and 30% did not have fever.¹²

Physical examination findings are of variable reliability. Findings that physicians rely on to diagnose AOM, such as a bulging or erythematous tympanic membrane, may occasionally be found in normal ears.13 One study compared the 3 most commonly documented otoscopic findings (color, position, and mobility of the tympanic membrane) with those of pneumatic otoscopy and myringotomy.14 Only 65% of patients with a distinctly red tympanic membrane and 16% with a slightly red tympanic membrane had AOM. A cloudy tympanic membrane was the most predictive color change, with an 80% positive predictive value (PPV), the percentage of patients with the symptom who have AOM. A bulging tympanic membrane was most predictive of AOM (PPV=89%), despite its 27% false-negative rate. Retraction was found in only 19% of children with AOM and had a PPV of only 50%. Distinctly impaired mobility was predictive of otitis media (PPV=78%), but diminished mobility was also found in 30% of children without middle ear effusion. These data and those presented in Table 1 show that each of these otoscopic examination elements (color, position, mobility) alone is inadequate for discriminating between cases in which the diagnosis of AOM is uncertain.

However, combining these signs can be useful.¹⁵ A cloudy (opaque), bulging, and immobile tympanic membrane on pneumatic otoscopy was nearly 100% predictive of otitis media in children with acute symptoms. In addition, 94% of children with the combination of distinctly red erythema, bulging, and immobility had AOM. No combination of findings that included only slight redness was more than 53% predictive of AOM.

In children aged younger than 1 year in whom otoscopy can be quite difficult, tympanometry can be a useful tool for detecting a middle ear effusion.¹⁶ An abnormal type B tympanogram (flat curve with no distinct peak) in infants presenting with acute symptoms is strong evidence in favor of AOM, although a normal test is not helpful in ruling out the diagnosis.

The diagnosis of AOM can be influenced by the physician’s perception of parental expectations for antibiotics.¹⁷ A study of children presenting with ear pain or other upper respiratory symptoms found that physicians diagnosed AOM 49% of the time when they perceived parents wanted antibiotics and only 13% of the time when they thought parents did not want antibiotics. Physicians were 23 times more likely to prescribe an antibiotic for an upper respiratory illness if they perceived that parents expected antimicrobials.

Treatment

A recent systematic review¹⁸ found that the symptoms of AOM (mainly otalgia) spontaneously resolved in two thirds of children by 24 hours and in 80% at 2 to 7 days. This was also observed in 2 earlier meta-analyses.^10,19 Seventeen children would need to be treated with antibiotics (vs placebo) for 1 child to have less pain at 2 to 7 days (number needed to treat [NNT]=17). There were no differences between antibiotic and placebo groups in other clinical outcomes, such as tympanometry findings, perforation, and recurrences. Also, children treated with antibiotics were almost twice as likely to have vomiting, diarrhea, or a rash.

Initially not treating uncomplicated AOM with antibiotics is an acceptable alternative. In a study by van Buchem and colleagues,²⁰ 90% of children with AOM recovered (symptoms resolved) in the first 4 days with nose drops and oral analgesics and without the use of antibiotics. Only 3% of the 4860 children in this study had a clinical course that required further treatment with antibiotics or myringotomy. A recent randomized controlled trial of 315 children demonstrated that children treated immediately with antibiotics had 1 less day of symptoms, but that 1 in 5 of these had diarrhea.²¹ The group not treated with antibiotics had no serious sequellae and used more analgesics. There were no differences in the number of missed school days, and more than 75% of the parents were satisfied with this “wait and see” approach. These studies also emphasize that antibiotics have a very modest effect on the clinical course of AOM and seem to decrease the duration of symptoms only to a small degree.

Physicians often recommend other symptomatic treatments for ear infections. Non–aspirin analgesics are effective in relieving pain,²¹ as are ibuprofen²² and Auralgan.²³ Antihistamine-decongestant preparations offer no added benefit in resolution of symptoms and have no effect on clinical outcomes when given with antibiotics.^24,25

If antibiotics are used, the meta-analysis by Rosenfeld and colleagues¹⁰ showed there were no differences in outcomes between treatment with cefaclor, cefixime, erythromycin, trimethoprim-sulfamethoxazole, amoxicillin clavulanate, or erythromycin sulfisoxazole, and treatment with amoxicillin or ampicillin. Broader spectrum and/or more expensive antibiotics therefore offer no advantage over amoxicillin for the initial treatment of AOM. In another meta-analysis, Kozyrskyj and coworkers26 showed that a 5-day antibiotic course was an acceptable alternative to a 8- to 14-day treatment course. There was a slightly increased risk of treatment failure at 1-month follow-up with the shortened course of antibiotics; the NNT to prevent 1 excess failure at 30 days was 17. There were no differences in long-term outcomes (2-3 months) or medication side effects (vomiting, diarrhea, rash) between the short and long antibiotic courses. The broader spectrum azithromycin and intramuscular ceftriaxone offered no advantage over amoxicillin. Children aged younger than 2 years deserve special mention, since they are at higher risk for treatment failures,^27,28 persistent symptoms,²⁹ and recurrent otitis media.³⁰ Few well-designed studies exist to guide treatment in this age group. Although children aged younger than 2 years were not excluded, neither review by Glasziou and colleagues¹⁸ or Rosenfeld and coworkers¹⁰ specifically examined this age group.

Another review demonstrated that (as with older children) routinely using antibiotics initially does not seem to add any clinical benefit.³¹ A recent randomized controlled trial of 240 children demonstrated that 8 children in this age group would have to be treated with amoxicillin for 1 child to have fewer symptoms (fever, crying, irritability) at 4 days (NNT=8).³² The major benefit of amoxicillin in this study was 1 day less of fever (P=.004). Adverse effects were almost twice as likely in the amoxicillin group, although this difference was not statistically significant. There were also no differences between the groups in clinical failure rates at 11 days or in the likelihood of recurrent otitis media, antibiotic use, specialist referrals, or surgery at 6 weeks. Effects on hearing were not measured. The authors conclude that “this modest effect does not justify prescription of antibiotics at the first visit, provided close surveillance can be guaranteed.” Also, Kozyrskyj and colleagues²⁶ demonstrated in their meta-analysis that as a subgroup there were no differences in clinical failures between 5 and 10 days of antibiotics in children aged younger than 2 years. However, there were only 118 children in this age group. Table 2 shows treatment options for AOM.

In recent years, there has been an increasing concern about worldwide bacterial resistance to antimicrobial drugs^33-35 by the World Health Organization³⁶ and the Centers for Disease Control and Prevention (CDC).³⁷ In response to the increasing antimicrobial resistance patterns seen in the common middle ear pathogens, especially S pneumoniae, the CDC Drug-resistant Streptococcus pneumoniae Therapeutic Working Group recommends doubling the dosage of amoxicillin to 80 to 90 mg per kg per day in the empiric treatment of AOM.³⁸ These recommendations are based on in vitro mean inhibitory concentration data of S pneumoniae cultures from middle ear fluid and nasopharyngeal swabs. However, there currently is no patient-oriented evidence to suggest that increasing the amoxicillin dosage actually decreases suppurative or invasive complications of AOM (meningitis, mastoiditis, and so forth), affects recurrence rates or treatment success, affects long-term outcomes of AOM, or even decreases the rate of drug-resistant S pneumoniae. Also, bacteriologic outcomes do not correlate with clinical outcomes. In the meta-analysis by Rosenfeld and coworkers,¹⁰ 89% of middle ear pathogens from treatment failures were susceptible in vitro to the antibiotic prescribed, and 13% of isolates from clinical cures were resistant in vitro to the prescribed antibiotic. We must use extreme caution in extrapolating the microbiologic findings to the clinical care of the child with AOM.

Prognosis

There are insufficient data to suggest that routine antibiotic use in AOM results in fewer cases of mastoiditis or meningitis. In the systematic reviews cited, the incidence of these suppurative complications was rare. In the Cochrane review by Glasziou and colleagues,¹⁸ only 1 case of mastoiditis developed in 2202 children, and this was in a child treated with penicillin. In the Netherlands among 4860 consecutive children with AOM, 2 experienced mastoiditis (both responded to outpatient antibiotic therapy), and there were no cases of meningitis.²⁰ In the meta-analysis by Rosenfeld and coworkers,¹⁰ there were no suppurative complications in the 5400 children studied. Although mastoiditis has been quoted as being more common in the preantibiotic era, it is unclear if the current rarity of this condition is due to antibiotic treatment, changes in organism virulence or host defenses, or the assertion that uncomplicated otitis media was often not reported, thus increasing the relative rate of mastoiditis.²⁷ In a recent review,³⁹ antibiotics did not seem to have an appreciable effect on complication rates, leading the authors to conclude that “antibiotic treatment for AOM cannot be considered as a safeguard against the development of complications.” Even in developing countries where the burden of otitis media is great, mastoiditis is quite rare, with a prevalence rate of much less than 1%.⁴⁰

Antibiotic use does influence bacterial resistance rates. In children previously treated with antibiotics for AOM, there is a 3-fold increased risk of isolating drug-resistant organisms from middle ear effusions with subsequent bouts of otitis media.^41,42 In the Netherlands and Iceland, routinely not treating AOM with antibiotics has resulted in a reduction in antibiotic resistance.^33,43 The most important risk factors for a poor outcome are age younger than 2 years and attendance at a daycare center.40 Children in daycare have a higher risk of requiring a hospital admission and up to a 50% increased risk of repeated or recurrent ear infections.^44,45 Children with chronic underlying illnesses or chronic otitis media with effusion have added risks of poor outcomes that are beyond the scope of this review.

Conclusions

Thus, the natural course of AOM in children is quite favorable. If left untreated, 80% will recover spontaneously within 2 weeks. The addition of antibiotics provides at best a modest reduction in symptoms, while adding cost, adverse drug effects, and increasing bacterial resistance in the patient and community. Minimizing the use of antibiotics in patients with AOM does not increase the risks of perforation, deafness, or contralateral or recurrent AOM.

Between 1993 and 1995 more than 20 million visits were provided to children younger than 15 years for otitis media; 77% of these were for children aged 4 years and younger.¹ Acute otitis media (AOM) is the most frequent primary diagnosis in preschool children and accounts for almost 20% of ambulatory care visits in this age group. By the age of 3 months, 10% of children will be given at least 1 diagnosis of otitis media and more than 90% by the age of 2 years.² Peak incidence occurs between the ages 6 and 15 months, although there is a second peak at approximately age 5 years that is thought to be associated with entrance into school.³ In the mid-1990s, treatment of otitis media cost $3.8 billion per year4; 20% of the more than 110 million prescriptions for oral antibiotics are for otitis media.⁵

The most important contributor to AOM is a dysfunction of the eustachian tube, allowing reflux of fluid and bacteria into the middle ear space from the nasopharynx.⁶ This dysfunction is usually multifactorial and is likely a combination of anatomy (shorter and more flexible eustachian tubes) and function (inefficiency at clearing secretions and equilibrating negative intratympanic pressures) in younger children.⁷ Acute viral upper respiratory infections create inflammation and secretions that magnify this eustachian tube dysfunction and predispose to or induce AOM.

The 3 most common bacteria in AOM are Streptococcus pneumoniae, Haemophilus species, and Branhamella catarrhalis. A recent study showed that both bacteria and viruses were isolated in the middle ear fluid of 65% of children with otitis media. In fact, 35% had viruses isolated as the sole middle ear pathogen.⁸ Other studies have failed to identify a specific infectious agent in a significant number of middle ear fluid aspirates.⁹

Diagnosis

The diagnosis of AOM in children is often based on a combination of symptoms and physical findings. It is usually defined as bulging or opacification of the tympanic membrane with or without erythema, middle ear effusion, marked decrease or absence of tympanic membrane mobility, and accompanied by at least one of the following signs and symptoms of acute infection: fever, otalgia, irritability, otorrhea, lethargy, anorexia, vomiting, or diarrhea.10 Although the best reference standard for the diagnosis of AOM is myringotomy or tympanocentesis, no published studies were identified in which this reference was performed in all study patients. Most published studies use pneumatic otoscopy combined with tympanocentesis or myringotomy as the reference standard when middle ear effusion is suspected.

Most symptoms are not specific for AOM. In a survey of patients seeing general practitioners in Finland,11 the symptoms that most increased the likelihood of diagnosing AOM were earache (relative risk [RR]=5.4; 95% confidence interval [CI], 3.3-8.9), rubbing of the ear (RR=5.0; 95% CI, 2.9-8.6), and excessive crying (RR=2.8; 95% CI, 1.8-4.3). Although fever, earache, or excessive crying were present in 90% of children considered to have AOM, one or more of these symptoms were also present in 72% of children who did not have otitis media. In another survey of children aged younger than 4 years with a diagnosis of AOM, 40% did not have otalgia, and 30% did not have fever.¹²

Physical examination findings are of variable reliability. Findings that physicians rely on to diagnose AOM, such as a bulging or erythematous tympanic membrane, may occasionally be found in normal ears.13 One study compared the 3 most commonly documented otoscopic findings (color, position, and mobility of the tympanic membrane) with those of pneumatic otoscopy and myringotomy.14 Only 65% of patients with a distinctly red tympanic membrane and 16% with a slightly red tympanic membrane had AOM. A cloudy tympanic membrane was the most predictive color change, with an 80% positive predictive value (PPV), the percentage of patients with the symptom who have AOM. A bulging tympanic membrane was most predictive of AOM (PPV=89%), despite its 27% false-negative rate. Retraction was found in only 19% of children with AOM and had a PPV of only 50%. Distinctly impaired mobility was predictive of otitis media (PPV=78%), but diminished mobility was also found in 30% of children without middle ear effusion. These data and those presented in Table 1 show that each of these otoscopic examination elements (color, position, mobility) alone is inadequate for discriminating between cases in which the diagnosis of AOM is uncertain.

However, combining these signs can be useful.¹⁵ A cloudy (opaque), bulging, and immobile tympanic membrane on pneumatic otoscopy was nearly 100% predictive of otitis media in children with acute symptoms. In addition, 94% of children with the combination of distinctly red erythema, bulging, and immobility had AOM. No combination of findings that included only slight redness was more than 53% predictive of AOM.

In children aged younger than 1 year in whom otoscopy can be quite difficult, tympanometry can be a useful tool for detecting a middle ear effusion.¹⁶ An abnormal type B tympanogram (flat curve with no distinct peak) in infants presenting with acute symptoms is strong evidence in favor of AOM, although a normal test is not helpful in ruling out the diagnosis.

The diagnosis of AOM can be influenced by the physician’s perception of parental expectations for antibiotics.¹⁷ A study of children presenting with ear pain or other upper respiratory symptoms found that physicians diagnosed AOM 49% of the time when they perceived parents wanted antibiotics and only 13% of the time when they thought parents did not want antibiotics. Physicians were 23 times more likely to prescribe an antibiotic for an upper respiratory illness if they perceived that parents expected antimicrobials.

Treatment

A recent systematic review¹⁸ found that the symptoms of AOM (mainly otalgia) spontaneously resolved in two thirds of children by 24 hours and in 80% at 2 to 7 days. This was also observed in 2 earlier meta-analyses.^10,19 Seventeen children would need to be treated with antibiotics (vs placebo) for 1 child to have less pain at 2 to 7 days (number needed to treat [NNT]=17). There were no differences between antibiotic and placebo groups in other clinical outcomes, such as tympanometry findings, perforation, and recurrences. Also, children treated with antibiotics were almost twice as likely to have vomiting, diarrhea, or a rash.

Initially not treating uncomplicated AOM with antibiotics is an acceptable alternative. In a study by van Buchem and colleagues,²⁰ 90% of children with AOM recovered (symptoms resolved) in the first 4 days with nose drops and oral analgesics and without the use of antibiotics. Only 3% of the 4860 children in this study had a clinical course that required further treatment with antibiotics or myringotomy. A recent randomized controlled trial of 315 children demonstrated that children treated immediately with antibiotics had 1 less day of symptoms, but that 1 in 5 of these had diarrhea.²¹ The group not treated with antibiotics had no serious sequellae and used more analgesics. There were no differences in the number of missed school days, and more than 75% of the parents were satisfied with this “wait and see” approach. These studies also emphasize that antibiotics have a very modest effect on the clinical course of AOM and seem to decrease the duration of symptoms only to a small degree.

Physicians often recommend other symptomatic treatments for ear infections. Non–aspirin analgesics are effective in relieving pain,²¹ as are ibuprofen²² and Auralgan.²³ Antihistamine-decongestant preparations offer no added benefit in resolution of symptoms and have no effect on clinical outcomes when given with antibiotics.^24,25

If antibiotics are used, the meta-analysis by Rosenfeld and colleagues¹⁰ showed there were no differences in outcomes between treatment with cefaclor, cefixime, erythromycin, trimethoprim-sulfamethoxazole, amoxicillin clavulanate, or erythromycin sulfisoxazole, and treatment with amoxicillin or ampicillin. Broader spectrum and/or more expensive antibiotics therefore offer no advantage over amoxicillin for the initial treatment of AOM. In another meta-analysis, Kozyrskyj and coworkers26 showed that a 5-day antibiotic course was an acceptable alternative to a 8- to 14-day treatment course. There was a slightly increased risk of treatment failure at 1-month follow-up with the shortened course of antibiotics; the NNT to prevent 1 excess failure at 30 days was 17. There were no differences in long-term outcomes (2-3 months) or medication side effects (vomiting, diarrhea, rash) between the short and long antibiotic courses. The broader spectrum azithromycin and intramuscular ceftriaxone offered no advantage over amoxicillin. Children aged younger than 2 years deserve special mention, since they are at higher risk for treatment failures,^27,28 persistent symptoms,²⁹ and recurrent otitis media.³⁰ Few well-designed studies exist to guide treatment in this age group. Although children aged younger than 2 years were not excluded, neither review by Glasziou and colleagues¹⁸ or Rosenfeld and coworkers¹⁰ specifically examined this age group.

Another review demonstrated that (as with older children) routinely using antibiotics initially does not seem to add any clinical benefit.³¹ A recent randomized controlled trial of 240 children demonstrated that 8 children in this age group would have to be treated with amoxicillin for 1 child to have fewer symptoms (fever, crying, irritability) at 4 days (NNT=8).³² The major benefit of amoxicillin in this study was 1 day less of fever (P=.004). Adverse effects were almost twice as likely in the amoxicillin group, although this difference was not statistically significant. There were also no differences between the groups in clinical failure rates at 11 days or in the likelihood of recurrent otitis media, antibiotic use, specialist referrals, or surgery at 6 weeks. Effects on hearing were not measured. The authors conclude that “this modest effect does not justify prescription of antibiotics at the first visit, provided close surveillance can be guaranteed.” Also, Kozyrskyj and colleagues²⁶ demonstrated in their meta-analysis that as a subgroup there were no differences in clinical failures between 5 and 10 days of antibiotics in children aged younger than 2 years. However, there were only 118 children in this age group. Table 2 shows treatment options for AOM.

In recent years, there has been an increasing concern about worldwide bacterial resistance to antimicrobial drugs^33-35 by the World Health Organization³⁶ and the Centers for Disease Control and Prevention (CDC).³⁷ In response to the increasing antimicrobial resistance patterns seen in the common middle ear pathogens, especially S pneumoniae, the CDC Drug-resistant Streptococcus pneumoniae Therapeutic Working Group recommends doubling the dosage of amoxicillin to 80 to 90 mg per kg per day in the empiric treatment of AOM.³⁸ These recommendations are based on in vitro mean inhibitory concentration data of S pneumoniae cultures from middle ear fluid and nasopharyngeal swabs. However, there currently is no patient-oriented evidence to suggest that increasing the amoxicillin dosage actually decreases suppurative or invasive complications of AOM (meningitis, mastoiditis, and so forth), affects recurrence rates or treatment success, affects long-term outcomes of AOM, or even decreases the rate of drug-resistant S pneumoniae. Also, bacteriologic outcomes do not correlate with clinical outcomes. In the meta-analysis by Rosenfeld and coworkers,¹⁰ 89% of middle ear pathogens from treatment failures were susceptible in vitro to the antibiotic prescribed, and 13% of isolates from clinical cures were resistant in vitro to the prescribed antibiotic. We must use extreme caution in extrapolating the microbiologic findings to the clinical care of the child with AOM.

Prognosis

There are insufficient data to suggest that routine antibiotic use in AOM results in fewer cases of mastoiditis or meningitis. In the systematic reviews cited, the incidence of these suppurative complications was rare. In the Cochrane review by Glasziou and colleagues,¹⁸ only 1 case of mastoiditis developed in 2202 children, and this was in a child treated with penicillin. In the Netherlands among 4860 consecutive children with AOM, 2 experienced mastoiditis (both responded to outpatient antibiotic therapy), and there were no cases of meningitis.²⁰ In the meta-analysis by Rosenfeld and coworkers,¹⁰ there were no suppurative complications in the 5400 children studied. Although mastoiditis has been quoted as being more common in the preantibiotic era, it is unclear if the current rarity of this condition is due to antibiotic treatment, changes in organism virulence or host defenses, or the assertion that uncomplicated otitis media was often not reported, thus increasing the relative rate of mastoiditis.²⁷ In a recent review,³⁹ antibiotics did not seem to have an appreciable effect on complication rates, leading the authors to conclude that “antibiotic treatment for AOM cannot be considered as a safeguard against the development of complications.” Even in developing countries where the burden of otitis media is great, mastoiditis is quite rare, with a prevalence rate of much less than 1%.⁴⁰

Antibiotic use does influence bacterial resistance rates. In children previously treated with antibiotics for AOM, there is a 3-fold increased risk of isolating drug-resistant organisms from middle ear effusions with subsequent bouts of otitis media.^41,42 In the Netherlands and Iceland, routinely not treating AOM with antibiotics has resulted in a reduction in antibiotic resistance.^33,43 The most important risk factors for a poor outcome are age younger than 2 years and attendance at a daycare center.40 Children in daycare have a higher risk of requiring a hospital admission and up to a 50% increased risk of repeated or recurrent ear infections.^44,45 Children with chronic underlying illnesses or chronic otitis media with effusion have added risks of poor outcomes that are beyond the scope of this review.

Conclusions

Thus, the natural course of AOM in children is quite favorable. If left untreated, 80% will recover spontaneously within 2 weeks. The addition of antibiotics provides at best a modest reduction in symptoms, while adding cost, adverse drug effects, and increasing bacterial resistance in the patient and community. Minimizing the use of antibiotics in patients with AOM does not increase the risks of perforation, deafness, or contralateral or recurrent AOM.