Acute otitis media in children: Treatment

INTRODUCTION — 

Acute otitis media (AOM) is a common problem in children and accounts for a large proportion of pediatric antibiotic use.

The treatment of uncomplicated AOM will be reviewed here. The epidemiology, pathogenesis, diagnosis, complications, and prevention of AOM are discussed separately, as is otitis media with effusion (serous otitis media).

●(See "Acute otitis media in children: Epidemiology, microbiology, and complications".)

●(See "Acute otitis media in children: Clinical manifestations and diagnosis".)

●(See "Acute otitis media in children: Prevention of recurrence".)

●(See "Otitis media with effusion (serous otitis media) in children: Clinical features and diagnosis".)

●(See "Otitis media with effusion (serous otitis media) in children: Management".)

PAIN MANAGEMENT — 

Pain, which can be severe, is a common feature of AOM in children [1], and management of pain is a mainstay of treatment [2,3]. We provide analgesics to reduce ear pain in children whether or not they are treated with antibiotics.

●General pain management

•Oral and topical analgesics – We suggest oral ibuprofen or acetaminophen rather than other interventions for treatment of ear pain in children with AOM. If severe pain is unresponsive to either ibuprofen or acetaminophen alone, we provide a combination of both analgesics. (See "Pain in children: Approach to pain assessment and overview of management principles", section on 'Nonopioid analgesics'.)

Limited evidence from randomized trials suggests that ibuprofen and acetaminophen are effective in reducing ear pain compared with placebo or no treatment [4]. Ibuprofen and acetaminophen appear to be equally effective, although data are limited.

In children with intact tympanic membranes (TMs), topical procaine, lidocaine, or cinchocaine are reasonable alternatives, as they are effective in relieving ear pain [5-7]. However, these agents should not be used in children with TM perforation or ventilation tubes because, although rare, they increase the risk of arrhythmias, seizures, coma, and death. Topical benzocaine should not be used in children <2 years of age because of the risk of methemoglobinemia [8]. None of these agents are licensed for this indication in the United States. (See "Methemoglobinemia", section on 'Topical anesthetics'.)

We advise against applying heat or cold to the external ear or instilling olive oil or herbal extracts into the external auditory canal. The effectiveness of these therapies for the treatment of ear pain is unproven, and they may be harmful [2].

•Therapeutic tympanocentesis – Therapeutic tympanocentesis or myringotomy are rarely needed, but they may be helpful in children with severe pain that is unresponsive to both analgesia and proper antibiotic treatment [9], especially when AOM is caused by multidrug-resistant otopathogens. In a longitudinal prospective study, tympanocentesis with complete evacuation of middle ear fluid in combination with antimicrobial therapy was associated with decreased risk of treatment failure and tympanostomy tube placement [10,11]. Even without middle ear fluid evacuation, tympanocentesis creates a conduit that may permit drainage of otorrhea, which will reduce pressure and pain in the middle ear.

CONFIRM DIAGNOSIS BEFORE TREATING — 

Antibiotic therapy is reserved for patients with a confirmed diagnosis of AOM. Treatment is not warranted if the tympanic membrane (TM) cannot be visualized or if the child does not meet stringent diagnostic criteria for AOM (eg, visualization of a bulging TM (picture 1 and picture 2) or a perforated TM with acute purulent otorrhea). (See "Acute otitis media in children: Clinical manifestations and diagnosis", section on 'Clinical diagnosis'.)

In these circumstances, the TM should be reexamined if symptoms worsen or do not improve within 72 hours. In clinical practice, 30 to 50 percent of children diagnosed with AOM may not meet the stringent diagnostic criteria recommended by the American Academy of Pediatrics (AAP) [12-15]. In such cases, children are less likely to have bacterial infection, which diminishes the potential benefit of an antibiotic.

RISK FOR SEVERE INFECTION, COMPLICATIONS, AND/OR RECURRENCE — 

The choice between initial observation with analgesics and immediate treatment with antibiotics depends upon the level of risk for severe infection, complications, and/or recurrence (algorithm 1). Children with any of the following features are at increased risk:

●Age <6 months

●Immunocompromised

●Toxic appearance

●Craniofacial abnormalities (eg, cleft palate)

For these patients, we recommend immediate antibiotic therapy rather than initial observation. (See 'Children at increased risk' below.)

For children who are not at increased risk for severe infection, complications, and/or recurrence, treatment strategies include initial observation with delayed initiation of antibiotic therapy if the symptoms and signs worsen or fail to improve after 48 to 72 hours, or immediate treatment with antibiotics. (See 'Children not at increased risk' below.)

Our treatment recommendations are based upon clinical practice guidelines for the treatment of AOM from the American Academy of Pediatrics (AAP) [2], European countries and other regions [16,17], and evidence that has emerged since the last AAP update [18].

CHILDREN NOT AT INCREASED RISK

Initial observation — We suggest initial observation with analgesia rather than immediate antibiotics for children who are not at increased risk for severe infection, complications, and/or recurrent AOM (algorithm 1). The acute symptoms and signs of AOM often resolve within three days whether or not children are treated with antibiotics [1,19,20], and treatment with immediate antibiotics is associated with many disadvantages. These include a higher risk of side effects [13,19,21,22], disruption of the microbiome, and development of otopathogen antibiotic resistance [23].

In a meta-analysis of eight trials (2107 children), the risk of vomiting, diarrhea, or rash was higher in the group treated with antibiotics than in the placebo group (27 versus 20 percent; relative risk [RR] 1.38, 95% CI 1.16-1.63) [19].

Shared decision-making — We recommend that the decision be made collaboratively with caregivers based on their preferences and values because immediate antibiotic treatment also has some advantages [12,24-30]. These include earlier resolution of pain, reduced risk of tympanic membrane (TM) perforation, reduced occurrence of treatment failure, and fewer missed days of work for caregivers.

In a meta-analysis of 13 trials that included 3401 children with AOM, antibiotic treatment reduced the number of TM perforations (two versus five percent; relative risk [RR] 0.43, 95% CI 0.21-0.89; five trials, 1075 patients) [19]. Fewer children treated with antibiotics continued to have pain at two to three days compared with children receiving a placebo (12 versus 16 percent; RR 0.71, 95% CI 0.58-0.88; seven trials, 2320 patients). However, the difference in the proportion of children having pain at 24 hours (five trials, 1394 patients) and at five to seven days (seven trials, 1264 patients) was not clinically meaningful nor statistically significant.

We have found a tendency among caregivers to overestimate the benefits of antibiotics, overestimate the risk of serious complications if antibiotics are delayed, and underestimate the side effects and other risks associated with antibiotic use [31,32]. Thus, we focus on educating caregivers about the risks and benefits of each treatment so that they can make informed decisions about their child's care.

Children with the following characteristics are less likely to benefit from immediate antibiotics:

●≥2 years of age

●Temperature <39°C

●Mild-moderate pain improved with analgesia (ibuprofen or acetaminophen)

●Unilateral infections

●Absence of marked bulging of the TM

●Symptoms for <72 hours at presentation

Children with any of the following characteristics are more likely to benefit from immediate antibiotics (see 'Choice of antibiotic' below):

●<2 years of age

●Temperature ≥39°C

●Severe pain not improved with analgesia (ibuprofen or acetaminophen)

●Marked bulging of the TM (more likely to have bacterial etiology) [33-35]

●Otorrhea (ie, TM perforation)

●Bilateral AOM

●Symptoms for >72 hours at presentation

In a meta-analysis of individual patient data from six randomized trials (1643 children ages 6 months to 12 years) [1], antibiotics were most beneficial for children with AOM as well as otorrhea and for children <2 years of age with bilateral AOM. Other trials have reported similar results [1,36,37].

Children <2 years of age with unilateral AOM may also benefit from antibiotic therapy [34]. A pooled analysis of two trials reported increased rates of treatment failure among placebo recipients <2 years of age with nonsevere, unilateral AOM (40 versus 14 percent; risk ratio [RR] 0.34, 95% CI 0.18-0.65) [24]. Even so, the benefit of antibiotic therapy was greater in children with bilateral AOM and in children with severe, unilateral AOM (absolute risk reduction 31 to 34 percent).

Children with severe/marked bulging of the TM appear to benefit most from antibiotic therapy [34]. Bulging of the TM is more likely to be associated with a bacterial pathogen in the middle ear [33,35].

Strategies for initial observation — For all children, we recommend a plan for pain management with clear instructions on what to do if the child's symptoms worsen or if symptoms fail to improve within 72 hours. Strategies for initial observation can be tailored to meet patient needs and caregiver preferences.

●Observation without an antibiotic prescription – If observation without an antibiotic prescription is chosen, we recommend that clinicians clearly discuss contingency plans with caregivers. It is imperative that detailed instructions include the steps caregivers should take if their child's condition worsens outside of clinic hours. Caregivers should be provided with the phone number to call or the best way to reach the clinician if they have questions, including questions about how to obtain an antibiotic.

●Observation with a delayed antibiotic prescription – When observation with a delayed prescription is chosen, the clinician provides the caregiver with an antibiotic prescription to fill only if the child worsens or does not improve within 72 hours.

We have found that caregivers typically require more precise guidance than "worsening" to understand when to potentially start an antibiotic and/or seek follow-up care. We describe specific scenarios such as fever >39°C (102.2°F), pain that is not improved with use of ibuprofen or acetaminophen, symptoms that are not improving within 72 hours, drainage from the ear, and worsening fussiness.

Evidence from several trials suggests that most children with AOM do well with initial observation and analgesia, with or without delayed antibiotics, and that clinical outcomes and caregiver satisfaction are similar among children who are treated with initial observation or an immediate antibiotic [19,23,29,38-41].

Patients with respiratory illnesses (including AOM) that are managed with observation are less likely to ultimately use an antibiotic, and those managed with a delayed prescription are less likely to use an antibiotic than those managed with an immediate prescription [25,42].

CHILDREN AT INCREASED RISK — 

Our treatment recommendations are based upon clinical practice guidelines for the treatment of AOM from the American Academy of Pediatrics (AAP) [2], European countries and other regions [16,17], and evidence that has emerged since the last AAP update [18].

Initiate antibiotics — For patients with AOM who are at increased risk for severe infection, complications, and/or recurrent AOM, we recommend immediate antibiotic therapy rather than initial observation (algorithm 1). Although children in these groups generally were excluded from clinical trials, it is reasonable to expect that immediate antibiotic therapy would have similar effects and that the anticipated absolute benefit would be greater in these children than in lower-risk patients.

Choice of antibiotic

●Amoxicillin – We suggest high-dose (90 mg/kg per day) amoxicillin as the initial agent for most children with AOM. Although other agents have comparable efficacy [40], we prefer amoxicillin because it is effective, safe, relatively inexpensive, and has a narrow microbiologic spectrum [2,43-45].

●Amoxicillin-clavulanate – We suggest high-dose amoxicillin-clavulanate (90 mg/kg per day of the amoxicillin component) as the initial agent for children who have received a beta-lactam antibiotic in the previous 30 days or have a history of medically confirmed recurrent AOM unresponsive to amoxicillin. We also consider amoxicillin-clavulanate as the initial agent for children with concurrent infectious conjunctivitis because nontypeable Haemophilus influenzae (NTHi), including beta-lactamase producing strains, is the predominant pathogen in these infections.

The availability and widespread use of pneumococcal vaccines has caused a shift in the relative prevalences of the most common bacterial otopathogens (eg, NTHi, Streptococcus pneumoniae, and Moraxella catarrhalis) such that NTHi (including beta-lactamase-producing strains) has become the most common pathogen [46,47]. Nevertheless, we continue to prefer high-dose amoxicillin over amoxicillin-clavulanate for most children because gastrointestinal adverse effects (eg, diarrhea, disturbance of the microbiome) are more common with amoxicillin-clavulanate, and clinical failure rates are similar with amoxicillin [21,22,45,48,49].

Other experts suggest high-dose amoxicillin-clavulanate as the initial antibiotic for all children with AOM [48,50]. No trials have directly compared the efficacy of amoxicillin with amoxicillin-clavulanate since the introduction and widespread use of pneumococcal conjugate vaccines. (See "Acute otitis media in children: Epidemiology, microbiology, and complications", section on 'Bacterial pathogens'.)

Dosing and duration of treatment

●Dosing regimen for children prescribed amoxicillin (table 1):

•We suggest a dose of 90 mg/kg per day orally divided in two doses (and a maximum dose of 4 g/day); high doses are used to treat penicillin-nonsusceptible S. pneumoniae [19,51,52].

•Lower doses of amoxicillin (eg, 40 mg/kg per day orally divided in two or three doses [maximum dose: 1.5 g/day]) are appropriate in communities with low rates of penicillin-nonsusceptible S. pneumoniae.

Using a dose of 90 mg/kg per day (high-dose) rather than 40 mg/kg per day (standard dose) increases the concentration of amoxicillin in the middle ear, which provides activity against most strains of S. pneumoniae (ie, those with penicillin minimum inhibitory concentrations [MICs] of 2 to <4 mcg/mL) [53-55]. S. pneumoniae that are highly resistant to penicillin in the United States (ie, MIC ≥8 mcg/mL), which account for <2 percent of pneumococcal isolates, will not respond to high-dose amoxicillin [2,56,57]. Data on strains with MICs of 4 to <8 mcg/mL are limited.

The increasing prevalence of beta-lactamase-negative, ampicillin-resistant strains of H. influenzae in the community may limit future use of amoxicillin. These strains exhibit MICs for amoxicillin that may exceed what is achievable in the middle ear. Such isolates remain uncommon in the United States but have become common in France and Japan [58,59]. (See "Acute otitis media in children: Epidemiology, microbiology, and complications", section on 'Bacterial pathogens'.)

●Dosing regimen for children prescribed amoxicillin-clavulanate (table 1) [60-63]:

•We suggest a dose of 90 mg/kg per day of amoxicillin and 6.4 mg/kg per day of clavulanate orally divided in two doses (maximum dose: 4 g/day of amoxicillin component); high doses of the amoxicillin component are used to treat penicillin-nonsusceptible S. pneumoniae.

Adolescents ≥16 years of age who can swallow large tablets can be prescribed extended-release amoxicillin-clavulanate (1 to 2 g of amoxicillin and 62.5 to 125 mg of clavulanate) orally every 12 hours.

•Lower doses of the amoxicillin component (eg, 40 mg/kg of amoxicillin and 5.7 mg/kg of clavulanate orally divided in two doses) are appropriate in communities with low rates of penicillin-nonsusceptible S. pneumoniae. However, the availability of amoxicillin-clavulanate formulations with this ratio (7:1) of amoxicillin to clavulanate varies geographically.

●Duration of treatment – In our clinical practice, one of us treats most children <2 years of age for 10 days and most children ≥2 years of age for five days. The other treats all children for five to seven days. This difference reflects the guidelines of the country in which we practice.

The AAP guideline suggests ten days of treatment for children <2 years of age, seven days of treatment for children ages 2 to <6 years, and five to seven days of treatment for children ≥6 years [2,18]. However, in many countries, shorter (five to seven days of treatment) courses are used for children of all ages including those <2 years of age [16].

Data comparing a five-day course with a seven-day course are lacking. Instead, nearly all studies have compared 5- versus 10-day durations [64-66]. Given the small difference in outcomes observed between children ≥2 years of age prescribed 5- versus 10-day antibiotic courses, a clinically meaningful difference in outcomes between five- and seven-day durations is unlikely.

In a trial comparing the effectiveness of 10 versus 5 days of amoxicillin-clavulanate to treat AOM in children ages 6 through 23 months, the failure rate was lower in the children randomized to receive 10 days of treatment versus those that received five days (16 versus 34 percent; difference 18 percent, 95% CI 9-25) [64].

In a meta-analysis of 49 trials (more than 12,000 participants ages 1 month to 18 years) that compared the failure rate of antibiotic durations of <7 days with durations of ≥7 days to treat a first episode of AOM, the failure rate was slightly higher for shorter durations (21 versus 18 percent, odds ratio [OR] 1.34, 95% CI 1.15-1.55) [66]. Of note, longer antibiotic durations were associated with increased rates of gastrointestinal adverse effects. Increased side effect rates were also reported in observational studies [49,67].

Children with penicillin reactions — Acceptable alternative antibiotic choices for children with penicillin allergy or for those who cannot otherwise tolerate penicillin antibiotics depend upon the type of the previous reaction to penicillin (table 2). Alternative regimens may provide less activity against common otopathogens. Clinical features and diagnosis of immediate and delayed penicillin allergy are discussed separately. (See "Penicillin allergy: Immediate reactions" and "Allergy evaluation for immediate penicillin allergy: Skin test-based diagnostic strategies and cross-reactivity with other beta-lactam antibiotics" and "Penicillin allergy: Delayed hypersensitivity reactions".)

Nearly 10 percent of children have a penicillin allergy documented in their medical record, though the true incidence of immune-mediated allergy is <1 percent [68,69]. Children who have experienced nonallergic drug events (eg, diarrhea, diaper rash) are often labeled as having an antibiotic allergy. Before considering an alternative regimen, clinicians should carefully obtain an allergy history to assess for the type and severity of reaction.

●Mild non-IgE-mediated reaction – For children with a mild non-immunoglobulin E (IgE)-mediated reaction to penicillin antibiotics, we suggest one of the following (algorithm 1 and table 1):

•Oral cephalosporins

-Cefpodoxime 10 mg/kg per day orally in two doses (maximum: 400 mg/day)

-Cefuroxime suspension 30 mg/kg per day orally divided in two doses (maximum: 1 g/day); no longer available in the United States

-Cefuroxime tablets 250 mg orally every 12 hours for children who weigh >17 kg and can swallow the tablet whole

-Cefdinir 14 mg/kg per day orally in one or two doses (maximum: 600 mg/day); the pharmacokinetics of this drug are less favorable than other oral cephalosporins

The duration of treatment for oral cephalosporins is the same as for amoxicillin. (See 'Dosing and duration of treatment' above.)

Oral cephalosporins should be reserved for children who are unable to take penicillin-containing antibiotics and should not be routinely used as first-line therapy for AOM. They do not achieve sufficient concentrations in the middle ear to eradicate penicillin-resistant S. pneumoniae and some penicillin-intermediate strains of S. pneumoniae. Oral cephalosporins have less activity against penicillin-resistant S. pneumoniae than amoxicillin or amoxicillin-clavulanate [70]. Cefuroxime has less activity against beta-lactamase-producing NTHi than amoxicillin-clavulanate [58].

•Intramuscular (IM) ceftriaxone – Ceftriaxone 50 mg/kg IM is administered once per day (maximum: 1 g/day) for one to three doses. If there is symptomatic improvement within 48 hours of the first dose, additional doses are not necessary [71].

●IgE-mediated or serious delayed reaction – Alternative antibiotics for children with IgE-mediated or serious delayed reactions to penicillin include macrolides (eg, azithromycin, clarithromycin) and lincosamides (eg, clindamycin) (algorithm 1 and table 1). However, these agents generally are not effective for eradicating H. influenzae, and approximately 25 to 35 percent of S. pneumoniae isolates are resistant to macrolides and lincosamides [57,58,72,73].

The doses are as follows [74]:

•Azithromycin 10 mg/kg per day orally (maximum dose: 500 mg/day) as a single dose on day 1 and 5 mg/kg per day (maximum dose: 250 mg/day) on days 2 through 5

•Clarithromycin 15 mg/kg per day orally divided into two doses (maximum dose: 1 g/day)

•Clindamycin 30 mg/kg per day orally divided into three doses (maximum dose: 1.8 g/day)

The duration of treatment for azithromycin is five days for children of all ages. The treatment duration for clarithromycin and clindamycin is the same as for amoxicillin. (See 'Dosing and duration of treatment' above.)

Trimethoprim-sulfamethoxazole (TMP-SMX) may be useful in regions where pneumococcal resistance to TMP-SMX is not a concern, but TMP-SMX should not be used if group A Streptococcus (GAS) is suspected (eg, when there is an associated otorrhea from tympanic membrane [TM] rupture). Local pneumococcal susceptibility data may be obtained from state or local health departments or local hospitals. (See 'Persistent tympanic membrane perforation' below.)

Special circumstances

Recurrent episode of AOM — There are no trials to guide acute treatment of recurrent episodes of AOM in children. Our approach is based upon the microbiology of recurrent AOM in children. Antibiotic therapy must include coverage for resistant S. pneumoniae, NTHi, and M. catarrhalis.

●Recurrence within 15 days of completing antimicrobial therapy – When recurrence occurs within 15 days of completing the antibiotic course, it is most often due to persistence of the original pathogen [75].

For children who were initially treated with amoxicillin, we use amoxicillin-clavulanate. (See 'Dosing and duration of treatment' above.)

For children who were initially treated with an antibiotic other than amoxicillin, we suggest ceftriaxone 50 mg/kg per day (maximum: 1 g/day) IM or intravenously (IV) for three days.

Levofloxacin 10 mg/kg orally once per day (maximum: 750 mg/day) for 10 days is an alternative for children ≥6 months of age but is rarely used [76]. (See 'Antibiotic regimen changes' below.)

●Recurrence >15 days after completing antimicrobial therapy – A recurrence >15 days after completion of the antibiotic course is most often due to a different pathogen than the one that caused the previous episode. As such, it is treated as a new infection.

If the patient also has middle ear effusion and has had ≥3 distinct and well-documented episodes of AOM within six months or ≥4 episodes within 12 months, we refer to an otolaryngologist to discuss management options for recurrent AOM including tympanostomy tube insertion [77,78]. (See "Acute otitis media in children: Prevention of recurrence", section on 'Tympanostomy tubes'.)

Tympanic membrane perforation — For children with AOM and spontaneous TM perforation, we prefer amoxicillin or amoxicillin-clavulanate to other oral agents. Topical antibiotic therapy is not appropriate for the treatment of AOM with spontaneous TM perforation. (See 'Choice of antibiotic' above.)

●Amoxicillin 90 mg/kg per day orally divided in two doses (we suggest a maximum of 4 g/day) for 10 days.

●Amoxicillin-clavulanate 90 mg/kg per day of amoxicillin and 6.4 mg/kg per day of clavulanate orally divided in two doses (we suggest a maximum daily dose of the amoxicillin component of 3 g) for 10 days. Adolescents ≥16 years who can take large tablets can use extended-release amoxicillin-clavulanate (1 to 2 g of amoxicillin and 62.5 to 125 mg of clavulanate) orally every 12 hours.

For patients with acute otorrhea, 10 days of oral therapy is more effective than a shorter course [65].

Alternative agents for penicillin-allergic children with AOM and TM perforation are the same as those for children without perforation, except that TMP-SMX should be avoided. Although GAS is a relatively rare cause of AOM, it is among the most common pathogens isolated from the middle ear of children with TM perforation [79]. (See 'Children with penicillin reactions' above and "Acute otitis media in children: Epidemiology, microbiology, and complications", section on 'Group A Streptococcus'.)

Topical antibiotic therapy is not appropriate because the perforation is often small and can heal before the middle ear infection is resolved. Thus, it is not clear how much medication is reaching the middle ear, and this likely varies based on the degree of perforation and stage of healing. This contrasts with tympanostomy tubes, which maintain a patent opening. There is no known additional benefit to adding topical to oral antibiotics because the systemic antibiotics should be sufficient.

Persistent tympanic membrane perforation — Patients with perforation that persists for three months or longer (with or without suppurative drainage) should be referred to an otolaryngologist for further management [80]. Prevention of chronic suppurative otitis media (CSOM) entails promptly treating AOM, given that CSOM frequently begins with an episode of AOM [81]. (See "Chronic suppurative otitis media (CSOM): Clinical features and diagnosis" and "Chronic suppurative otitis media (CSOM): Treatment, complications, and prevention".)

Otorrhea in children with tympanostomy tubes — The treatment of otorrhea in children with tympanostomy tubes is discussed separately. (See "Tympanostomy tube otorrhea in children: Causes, prevention, and management", section on 'Treatment'.)

AOM in cochlear implant recipient — Management of AOM in children with cochlear implants is discussed separately. (See "Cochlear implant infections", section on 'Management'.)

Complications of AOM — Severe complications of AOM are rare. The management of intratemporal or intracranial complications of AOM is discussed separately:

●Cholesteatoma (see "Cholesteatoma in children", section on 'Surgical treatment')

●Mastoiditis, which may be complicated by petrositis (osteomyelitis of the petrous bone) (see "Acute mastoiditis in children: Treatment and prevention")

●Facial nerve palsy, which may be isolated or associated with osteomyelitis of the petrous bone (see "Facial nerve palsy in children", section on 'Treatment' and "Acute mastoiditis in children: Treatment and prevention", section on 'Complicated disease')

●Meningitis (see "Bacterial meningitis in children older than one month: Treatment and prognosis")

Neonatal AOM — The appropriate evaluation prior to administration of antibiotics to afebrile neonates with AOM is unclear, and clinical practice varies [82]. Antibiotics should not be administered if physical findings of AOM (eg, bulging TM (picture 1)) are not clearly present.

If oral antibiotics are initiated, clinicians should first critically weigh the possibility of an occult invasive bacterial infection and initiate an appropriate evaluation as indicated by the child's age and presentation. Although the absence of fever in such patients is reassuring, it does not exclude a systemic process. If cultures of blood, urine, and/or cerebral spinal fluid are deferred, initiating an oral antibiotic may mask an invasive bacterial infection. The effect on subsequent management decisions if the infant becomes febrile or ill appearing must be weighed. (See "The febrile neonate (28 days of age or younger): Initial management", section on 'Ill-appearing'.)

Neonates with AOM that are febrile require a complete sepsis evaluation. (See "The febrile neonate (28 days of age or younger): Initial management", section on 'Focal infection'.)

SUBSEQUENT MANAGEMENT BASED ON RESPONSE TO INITIAL TREATMENT

Persistent symptoms following initial observation — Children who worsen during observation with analgesic therapy or fail to improve after 72 hours of observation should be started on antibiotics. (See 'Strategies for initial observation' above and 'Initiate antibiotics' above.)

Persistent symptoms following initial treatment with antibiotics (treatment failure) — Treatment failure is defined by worsening symptoms or failure to improve after 72 hours of antibiotic therapy.

Etiology — Treatment failure suggests one of the following:

●Development of a complication (see "Acute otitis media in children: Epidemiology, microbiology, and complications", section on 'Complications and sequelae')

●Inadequate initial antimicrobial therapy, usually caused by a beta-lactam-resistant organism; less common organisms, such as S. aureus, also must be considered, particularly in children with tympanostomy tubes or perforation [83-89] (see "Acute otitis media in children: Epidemiology, microbiology, and complications", section on 'Microbiology')

●Signs and symptoms caused by another condition (see "Acute otitis media in children: Clinical manifestations and diagnosis", section on 'Differential diagnosis')

Antibiotic regimen changes — Our choice of second-line antimicrobial therapy following failure of a first-line antibiotic is based upon the initial agent (algorithm 1 and table 1):

●Amoxicillin – For children who fail initial treatment with high-dose amoxicillin, we prefer amoxicillin-clavulanate [2]. We do not advise the use of oral cephalosporins for children who have failed treatment with high-dose amoxicillin. The rationale for this advice is discussed above. (See 'Children with penicillin reactions' above.)

•Amoxicillin-clavulanate 90 mg/kg per day of amoxicillin with 6.4 mg/kg per day of clavulanate orally divided in two doses (maximum dose: 4 g/day of amoxicillin component).

Adolescents ≥16 years old who can take large tablets can use extended-release amoxicillin-clavulanate (1 to 2 g of the amoxicillin component and 62.5 to 125 mg of the clavulanate component) every 12 hours.

We treat for 10 days in children <2 years of age and children of any age with tympanic membrane (TM) perforation or recurrent AOM.

We treat for five days in children ≥2 years of age with intact TM and no history of recurrent AOM [64,66].

We prefer amoxicillin-clavulanate for children who fail treatment with amoxicillin because of amoxicillin-clavulanate's efficacy against beta-lactamase-producing H. influenzae and M. catarrhalis.

●Amoxicillin-clavulanate or oral cephalosporins – For children who fail initial treatment with high-dose amoxicillin-clavulanate or oral cephalosporins, we prefer parenteral ceftriaxone. Oral levofloxacin is an alternative. We do not advise the use of oral cephalosporins for children who have failed treatment with amoxicillin-clavulanate.

•Ceftriaxone 50 mg/kg intramuscularly (IM) or intravenously (IV) once per day (maximum dose: 1g/day) for two or three doses.

Parenteral ceftriaxone 50 mg/kg achieves high antibiotic levels in the middle ear and is effective for the treatment of AOM [2]. Results of an open-label prospective study suggest that three doses are superior to a single dose in eradicating penicillin-resistant S. pneumoniae from the middle ear [90].

•Levofloxacin [76]

-Age 6 months to 5 years – 10 mg/kg orally every 12 hours for 10 days

-Age >5 years – 10 mg/kg orally once daily (maximum dose: 750 mg/day) for 10 days

Levofloxacin should be reserved for children with contraindications to ceftriaxone or AOM refractory to other drugs. It should only be used in children who have had levofloxacin-susceptible S. pneumoniae serotype 19A isolated from the middle ear [84]. If levofloxacin is considered, we recommend consulting a pediatric infectious diseases specialist first.

We do not recommend trimethoprim-sulfamethoxazole (TMP-SMX), macrolides (eg, azithromycin, clarithromycin), or lincosamides (eg, clindamycin) for the treatment of AOM that fails to respond to high-dose amoxicillin or amoxicillin-clavulanate. Pneumococcal surveillance studies indicate that resistance to these agents is substantial [91,92]. Furthermore, macrolides and lincosamides have limited activity against nontypeable Haemophilus influenzae (NTHi).

●Initial macrolides, clindamycin, parenteral ceftriaxone, or persistent treatment failure – Persistent treatment failure is defined by failure to improve after 72 hours of starting a second antibiotic.

For children who fail initial treatment with macrolides, clindamycin, or parenteral ceftriaxone and children with persistent treatment failure, we suggest referral to an otolaryngologist for tympanocentesis (if available) to obtain middle ear fluid for culture and susceptibility testing to guide antimicrobial selection.

Tympanocentesis will also provide relief of ear pain. A discussion of the tympanocentesis procedure is beyond the scope of this topic review [93]. Concomitant placement of a tympanostomy tube may be warranted. (See "Acute otitis media in children: Prevention of recurrence", section on 'Tympanostomy tubes'.)

If tympanocentesis is not available, we prescribe levofloxacin [76]:

•Age 6 months to 5 years – 10 mg/kg orally every 12 hours for 10 days

•Age >5 years – 10 mg/kg per orally once daily (maximum: 750 mg/day) for 10 days

The most common pathogens in this category are multidrug-resistant S. pneumoniae and NTHi (beta-lactamase positive or negative). Most NTHi are susceptible to TMP-SMX, but susceptibility of S. pneumoniae varies geographically. TMP-SMX may be an option in areas with high rates of susceptibility.

We suggest consultation with a pediatric infectious diseases expert and/or pediatric otolaryngologist in patients with persistent treatment failure (algorithm 1 and table 1).

Resolution of symptoms — Most children do not require routine follow-up after symptoms have resolved [94]. However, children with language or learning problems and those at higher risk of conductive hearing loss should be reexamined to assure resolution of the middle ear effusion.

●For children with recurrent ear infections, chronic hearing loss, or language or learning problems, we suggest follow-up otoscopy 8 to 12 weeks after diagnosis of AOM.

By 8 to 12 weeks after the diagnosis of AOM, the middle ear effusion will have resolved in 80 to 90 percent of children (figure 1). (See "Otitis media with effusion (serous otitis media) in children: Management", section on 'Natural history'.)

Persistent middle ear fluid alone is not an indication of treatment failure or an indication for additional antibiotic therapy [95]. However, if present for more than 8 to 12 weeks, referral to an otolaryngologist is indicated. Management of persistent middle ear effusion is discussed separately. (See "Otitis media with effusion (serous otitis media) in children: Management", section on 'Approach to management'.)

●For children without recurrent ear infections, chronic hearing loss, or language or learning problems, we provide follow-up at the next health maintenance visit, or sooner if there are concerns regarding persistent hearing loss.

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute otitis media, otitis media with effusion, and external otitis".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)

●Basics topics (see "Patient education: Ear infections in children (The Basics)" and "Patient education: Ruptured eardrum (The Basics)")

●Beyond the Basics topic (see "Patient education: Ear infections (otitis media) in children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Confirm diagnosis before treating – Antibiotic therapy is reserved for patients with a confirmed diagnosis of acute otitis media (AOM); treatment is not warranted if the tympanic membrane (TM) cannot be visualized or if the child does not meet stringent diagnostic criteria for AOM (eg, bulging TM or perforation of TM with otorrhea). In these circumstances, the TM should be reexamined if symptoms worsen or do not improve within 72 hours. (See 'Confirm diagnosis before treating' above.)

●Pain management – Pain management is a mainstay of treatment for AOM in children. For children with AOM, we suggest treatment with oral ibuprofen or acetaminophen rather than other analgesics (Grade 2C). Alternative options for analgesia for children ≥2 years of age without TM perforation include topical procaine, benzocaine, or lidocaine preparations (where available). (See 'Pain management' above.)

●Risk for severe infection, complications, and/or recurrence – Patients at increased risk for severe infection, complications, and/or recurrence include (see 'Risk for severe infection, complications, and/or recurrence' above):

•Infants <6 months of age

•Patients who are immunocompromised

•Toxic-appearing patients

•Patients with craniofacial abnormalities (eg, cleft palate)

●Initial observation for children not at increased risk – For most children with AOM who are not at increased risk for severe infection, complications, and/or recurrent AOM (algorithm 1), we suggest initial observation with pain management rather than immediate antibiotic therapy (Grade 2A). In randomized trials, antibiotic therapy hastened symptom resolution and reduced the risk of TM perforation, but the absolute benefits were modest, and antibiotic-related side effects (eg, diarrhea, rash) were common. Additional downsides of antibiotic therapy include the disruption of the microbiome and development of otopathogen antibiotic resistance. (See 'Children not at increased risk' above.)

Because the trade-offs between observation and immediate antibiotic therapy are closely balanced, the choice depends on the values and preferences of the caregiver(s). The decision should be made collaboratively with the caregiver(s) after a discussion of the risks and benefits of antibiotic use. (See 'Shared decision-making' above.)

Young children (<2 years), those with more severe manifestations (eg, high fevers, severe pain, bilateral AOM, severe bulging of TM, otorrhea, or TM perforation), and those with symptoms for >72 hours at presentation are more likely to benefit from immediate antibiotic therapy.

●Immediate antibiotics for children at increased risk – For children with AOM who are at increased risk for severe infection, complications, and/or recurrent AOM (algorithm 1), we recommend immediate antibiotic therapy rather than initial observation (Grade 1B). Although children in these high-risk groups generally were excluded from clinical trials, it is reasonable to expect that immediate antibiotic therapy would have similar effects and that the anticipated absolute benefit would be greater in these children than in lower-risk patients. (See 'Children at increased risk' above.)

●Choice of antibiotic – The choice of antibiotic is based upon whether the child has penicillin allergy and whether there are risk factors for beta-lactamase-producing organisms:

•For most children, we suggest high-dose amoxicillin as the initial agent rather than other antibiotics (Grade 2C). At high doses, amoxicillin is highly effective, has a lower incidence of adverse events compared with amoxicillin-clavulanate, and provides a narrow spectrum of activity. Amoxicillin is given orally at a dose of 90 mg/kg per day (maximum dose: 4 g/day) divided twice daily. (See 'Choice of antibiotic' above.)

•For children who have received a beta-lactam antibiotic in the previous 30 days or have a history of recurrent AOM unresponsive to amoxicillin, we suggest high-dose amoxicillin-clavulanate as the initial agent rather than other agents (Grade 2C). Amoxicillin-clavulanate is given orally at a dose of 90 mg/kg per day (maximum dose: 4 g/day) of the amoxicillin component divided twice daily. (See 'Choice of antibiotic' above.)

•Alternative options for children with penicillin allergy are summarized in the table (table 1). (See 'Children with penicillin reactions' above.)

●Duration of treatment – In the United States, the duration of treatment depends on the age of the child. For children <2 years of age, the usual duration is 10 days; for children ≥2 years of age, the usual duration is 5 days. In many other countries, the duration of treatment is five to seven days regardless of the child's age.

●Subsequent management based on response to initial treatment

•Persistent symptoms after initial observation – Patients whose symptoms worsen or fail to improve after 72 hours of observation should receive antibiotics. (See 'Persistent symptoms following initial observation' above and 'Choice of antibiotic' above.)

•Persistent symptoms following treatment with antibiotics (treatment failure) – Patients whose symptoms worsen or fail to improve after 72 hours of antibiotic therapy should be switched to a second-line antimicrobial agent. The choice of agent depends upon the initial antibiotic used. (See 'Antibiotic regimen changes' above.)

Causes of treatment failure include the development of a complication, inadequate initial antimicrobial therapy, or a condition other than AOM. (See 'Etiology' above and "Acute otitis media in children: Clinical manifestations and diagnosis", section on 'Differential diagnosis'.)

•Resolution of symptoms – Most children do not require routine follow-up after symptoms have resolved. However, children with recurrent ear infections, chronic hearing loss, or language and/or learning problems should be reexamined 8 to 12 weeks after diagnosis to assure resolution of the middle ear effusion.

ACKNOWLEDGMENTS — 

The editorial staff at UpToDate acknowledge Jerome Klein, MD, and Stephen I Pelton, MD, who contributed to earlier versions of this topic review.