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Acute otitis media in children: Prevention of recurrence

Acute otitis media in children: Prevention of recurrence
Authors:
Stephen I Pelton, MD
Paola Marchisio, MD
Section Editors:
Sheldon L Kaplan, MD
Glenn C Isaacson, MD, FAAP
Deputy Editor:
Mary M Torchia, MD
Literature review current through: Dec 2022. | This topic last updated: Apr 13, 2022.

INTRODUCTION — Prevention is an important part of the management strategy for the child with severe and recurrent acute otitis media (AOM) and the child who is at risk for severe and recurrent AOM.

The prevention of AOM will be reviewed here. Other topics related to otitis media are presented separately:

(See "Acute otitis media in children: Epidemiology, microbiology, and complications" and "Acute otitis media in children: Clinical manifestations and diagnosis" and "Acute otitis media in children: Treatment".)

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

(See "External otitis: Pathogenesis, clinical features, and diagnosis" and "External otitis: Treatment".)

(See "Malignant (necrotizing) external otitis".)

DEFINITION — Recurrent AOM is usually defined as ≥3 distinct and well-documented episodes of AOM within six months or ≥4 episodes within 12 months [1,2]. Children with recurrent AOM are also referred to as "otitis prone" [3].

PREVALENCE — In a claims data study of AOM and recurrent AOM in the United States between 2001 and 2011, the prevalence of recurrent AOM in children <6 years declined from 17 to 11 percent after introduction of the 13-valent pneumococcal conjugate vaccine [4]. In a prospective, longitudinal study in the postpneumococcal conjugate vaccine era (2006-2016), the reported prevalence of recurrent AOM in children <2 years in the Rochester community varied depending on how the diagnosis was made and who made the diagnosis [3]. Among children seen by community clinicians, 27 percent were diagnosed with recurrent AOM, whereas 14 percent of children seen by validated otoscopists from a single practice met criteria for recurrent AOM, and only 6 percent when tympanocentesis was employed for diagnosis of AOM (although tympanocentesis is not routinely recommended for diagnosis of AOM in children).

OVERVIEW OF APPROACH

Interventions — Specific interventions that may be used in the prevention of recurrent AOM include [5-9]:

Interventions that should be introduced early in life for all infants:

Identification and treatment of predisposing conditions (eg, exposure to tobacco smoke, use of pacifier)

Parental education about risks posed by early and large day care settings

Education about the protective impact of breast feeding

Administration of influenza virus annually and/or pneumococcal conjugate vaccines (PCVs)

Expectant management (ie, observation with episodic antimicrobial therapy for recurrent episodes)

Interventions that are discussed in the context of share decision-making after the child meets criteria for recurrent AOM:

Antibiotic prophylaxis

Surgery (myringotomy and placement of tympanostomy tubes)

Factors influencing choice — Decisions regarding strategies for prevention of recurrent AOM are made on a case-by-case basis. Factors to be considered in the decision include [10,11]:

Age at first episode – Infants who have their first episode of AOM before six months of age are at risk for severe and recurrent AOM [12,13]. It is uncertain whether early disease damages the Eustachian tube or middle ear leading to recurrent disease, selects those with anatomic or genetic predisposition to recurrent disease, or both [14].

Family history – The risk of AOM and recurrent AOM is increased in children whose other family members have a history of severe and recurrent AOM.

Age of the child – Children younger than two years appear to receive greater benefit from more aggressive interventions (eg, antibiotic prophylaxis, tympanostomy tube placement) as they have a higher incidence of AOM, and in most children, recurrent episodes begin to decline with increasing age.

In a multicenter randomized trial in children with recurrent AOM in the post-PCV era, the rate of occurrence of AOM in children age 6 to 11 months was two to three times the rate in children age 25 to 35 months, and the rate of occurrence of AOM among children age 12 to 23 months was approximately twice the rate in children age 25 to 35 months [11].

Time of year – Given the seasonality of viral respiratory pathogens, the child who has already had several episodes of AOM by late fall (ie, November in the northern hemisphere) is likely to have many more before the end of the winter, whereas the child who has recurrent episodes by late spring (ie, May in the northern hemisphere) could be expected to have fewer additional infections during the late spring and summer.

Attendance in large-group day care – Children in this setting are likely to have more respiratory infections, some of which will be accompanied by AOM.

Siblings – Children with siblings younger than five years or who attend day care are at increased risk for recurrent OM [15-18].

Birth history – Children born preterm have a modest increased risk of AOM; preterm birth seems to be more important than low birth weight in determining the risk of AOM in early life [19].

The developmental status of the child, particularly language development. Children with permanent hearing loss, suspected or confirmed speech or language delay or disorder, developmental delay, autism spectrum disorder, or blindness or uncorrectable visual impairment are at increased risk for speech, language, or learning sequelae from recurrent AOM [20] and therefore warrant special consideration as to timing of interventions.

Underlying medical conditions that predispose to AOM (eg, cleft palate, immotile cilia syndrome, immunoglobulin or subclass deficiency, Down syndrome).

The effects of recurrent AOM on the quality of life for the child and family [21].

Choice of intervention(s)

Choice between expectant management and more aggressive interventions – When all factors are considered, the balance of risks and benefits will favor less aggressive interventions for some children and more aggressive interventions for others.

Less aggressive interventions, including expectant management, may be warranted for immunocompetent children older than two years because the incidence of AOM rapidly declines after the second year of life [11]. (See 'Treatment of predisposing conditions' below and 'Education' below and 'Vaccines' below and 'Expectant management' below.)

More aggressive interventions include antibiotic prophylaxis and tympanostomy tube placement. They may decrease the frequency or delay the occurrence of AOM. More aggressive interventions may be warranted for children with:

Age <2 years (when optimal hearing is necessary for acquisition of language skills), particularly in children with early-onset disease

Multiple risk factors, especially if the risk factor cannot be modified (eg, time of year, size of day care) (see "Acute otitis media in children: Epidemiology, microbiology, and complications", section on 'Risk and protective factors' and 'Factors influencing choice' above)

Underlying medical conditions that predispose to recurrent AOM (eg, cleft palate, immotile cilia syndrome, immunoglobulin or subclass deficiency, syndromes with craniofacial abnormalities, including Down syndrome, persistent Eustachian tube dysfunction)

Have known or suspected language delays or comorbid conditions associated with developmental or language delays (the conductive hearing loss associated with middle ear effusion may persist for weeks to months after the acute signs of AOM have resolved and are potentially an additional burden in children with existing delays or deficits)

Recurrent spontaneous perforation of the tympanic membrane, which may be associated with chronic suppurative otitis media [22]

More severe episodes (eg, moderate or severe ear pain, ear pain for ≥48 hours, temperature ≥39°C [102.2°F]) [7]

Continued recurrent episodes with expectant management

However, the ultimate decision about whether to use a more aggressive intervention and which intervention to use is made on a case-by-case basis after discussion of the potential benefits and risks with the caregivers.

Choice between antibiotic prophylaxis and tympanostomy tubes – The choice of antibiotic prophylaxis or tympanostomy tube placement is influenced by the level of concern about antibiotic-resistant bacteria in the specific community, language development, the risks of surgery and anesthesia, the age of the patient, and the values and preferences of the family. For children who have had frequent breakthrough episodes of AOM while receiving antibiotic prophylaxis or who have multiple drug allergies and continue to warrant more aggressive prevention strategies, tympanostomy tubes are preferred. The potential benefits and adverse effects of antibiotic prophylaxis and tympanostomy tubes are discussed below. (See 'Antibiotic prophylaxis' below and 'Tympanostomy tubes' below.)

The 2013 American Academy of Pediatrics (AAP) and American Academy of Family Physicians (AAFP) clinical practice guideline for the diagnosis and management of AOM in children 6 months through 12 years of age recommends that clinicians not prescribe prophylactic antibiotics but "may offer" tympanostomy tubes to prevent recurrent AOM [7]. The 2013 AAP/AAFP guideline does not apply to children with underlying conditions that may alter the natural course of AOM (eg, anatomic abnormalities, genetic conditions with craniofacial abnormalities, immune deficiencies, or cochlear implants), whereas this topic review does not make such exclusions.

The 2013 American Academy of Otolaryngology-Head and Neck Surgery Foundation clinical practice guideline on tympanostomy tubes in children recommends against tympanostomy tube insertion for children with recurrent AOM unless they have unilateral or bilateral middle ear effusion at the time of assessment for placement of tympanostomy tubes [20].

TREATMENT OF PREDISPOSING CONDITIONS — The first step in the prevention of recurrent AOM is identification, and treatment if warranted, of underlying conditions that predispose the child to recurrent AOM. Such conditions include immune deficiencies and/or anatomic abnormalities.

Children who have had suppurative infections at multiple sites, including recurrent AOM, may have immunologic deficiencies. The most commonly identified immune abnormality in children with recurrent AOM is an IgG subclass deficiency. (See "IgG subclass deficiency", section on 'Clinical manifestations'.)

Children with recurrent AOM as their only manifestation of recurrent infection rarely have severe immunologic abnormalities. However, hypogammaglobulinemia, granulocyte defects, defective cell-mediated immunity, or HIV infection may present with recurrent AOM as part of the spectrum of either increased infections or infections that resolve more slowly than expected [23]. Additional information about when to suspect an immunodeficiency is provided separately. (See "Approach to the child with recurrent infections", section on 'Clinical features suggestive of a primary immunodeficiency' and "Primary humoral immunodeficiencies: An overview", section on 'Presentation of humoral immunodeficiency'.)

Children with palatal clefts also are predisposed to the development of recurrent AOM. This includes children with craniofacial abnormalities that are associated with submucous palatal clefts, such as micrognathia and glossoptosis (seen in Robin sequence and similar syndromes). (See "Congenital anomalies of the jaw, mouth, oral cavity, and pharynx", section on 'Jaw anomalies'.)

EDUCATION — Educating parents about ways to decrease exposure to risk factors (eg, cigarette smoke) and increase exposure to protective factors (eg, breast feeding) is an appropriate prevention strategy for all children with recurrent AOM [7]. Although the effectiveness of parental education in preventing recurrent AOM has not been proven, there is little risk of harm. The risk factors for AOM are discussed in detail separately. (See "Acute otitis media in children: Epidemiology, microbiology, and complications", section on 'Risk and protective factors'.)

Specific risk/protective factors to be discussed include [1,6]:

Day care – The fewer children in the day care group, the lower the exposure to respiratory pathogens and risk for AOM.

Exposure to smoke – Children exposed to cigarette smoke in the home have more episodes of AOM than children in smoke-free homes; methods of home heating, such as wood or coal burning stoves, also may be a risk factor. A suggested mechanism is increased colonization with bacterial otopathogens leading to greater risk for development of bacterial OM following viral respiratory tract infection. (See "Control of secondhand smoke exposure".)

Breastfeeding – Breastfeeding for at least three months protects against AOM during the first year of life. Although this knowledge may not prevent recurrent AOM in the index case, when family history suggests an increased risk of recurrent AOM, breastfeeding may help prevent recurrent AOM in subsequent children [24].

Pacifiers – The use of pacifiers after six months of age increases the risk of recurrent AOM [25].

VACCINES — The routine administration of pneumococcal conjugate vaccine (PCV) and influenza vaccine during infancy provides only a modest reduction in the frequency of AOM but appears to have greater downstream benefits in reducing the development of recurrent OM and the need for tympanostomy tube insertion [26]. These observations are consistent with the hypothesis that prevention of early episodes has subsequent benefit in prevention of subsequent recurrent and complex OM.

Pneumococcal conjugate vaccine

PCV included in routine schedule – In countries where PCV is part of the routine infant immunization schedule, we recommend that infants and children be immunized with PCV according to the recommended schedule (ie, at ages 2, 4, 6, and 12 through 15 months in the United States; the recommended schedule for other countries is available from the World Health Organization) [7,27]. In addition to preventing invasive pneumococcal disease (IPD), routine infant immunization against Streptococcus pneumoniae modestly reduces the incidence of AOM and is associated with fewer office visits for AOM, reduced progression to complex otitis media [14], and fewer tympanostomy tube placements. (See "Pneumococcal vaccination in children".)

In randomized trials, administration of the 7-valent pneumococcal conjugate vaccine (PCV7) beginning at age two months was associated with a modest reduction in AOM (6 to 8 percent) [28-30]. The efficacy of prevention of culture-confirmed pneumococcal AOM caused by a vaccine serotypes was 57 to 65 percent. However, given the reduction in nasopharyngeal colonization with vaccine serotypes (approximately 80 percent over time), the actual reduction in AOM caused by pneumococcal vaccine serotypes was estimated to be approximately 90 percent. Several subsequent studies noted a small increase in AOM caused by pneumococcal serotypes not included in PCV7 (ie, "replacement serotypes") [28,31,32].

In the United States, PCV7 was replaced by the 13-valent pneumococcal conjugate vaccine (PCV13) in 2010. The additional serotypes in PCV13 (table 1), particularly serotype 19A, provide further protection against AOM and recurrent AOM. In prospective surveillance from eight children's hospitals in the United States, the proportion of pneumococcal isolates from the middle ear or mastoid of children that were PCV13 serotypes decreased from 50 percent in 2011 to 29 percent in 2013 [33-38]; 19A isolates decreased from 34 to 10 percent. In another prospective study in the United States, completion of the primary series of PCV13 in healthy children was effective in reducing pneumococcal AOM, particularly AOM caused by the six serotypes not contained in PCV7 [35]. Compared with children immunized with PCV7, children immunized with PCV13 had an 86 percent relative reduction in isolation of the six serotypes from middle ear fluid and a 91 percent relative reduction in isolation of serotype 19A. Reports from Israel have also demonstrated declines in AOM due to PCV13 vaccine serotypes and overall AOM [37]. Continued monitoring is necessary to characterize the efficacy for prevention of vaccine serotype AOM and monitor for "replacement" serotypes.

In randomized and observational studies, receipt of PCV has also been associated with fewer medical visits for AOM and fewer tympanostomy tube placements [26,28-30,39-45]. Surveillance in the United States indicates that clinician office-based visits for AOM declined from 826 to 387 visits per 1000 children <2 years of age between 1997 and 2014, a decline of 51 percent (95% CI 42-53 percent) [33]. Among children two to four years of age, clinician office-based visits for AOM declined by 37 percent (95% CI 23-48). In a randomized trial, children who received the PCV7 during infancy had a 34 percent lower risk of tympanostomy tube insertion at age two through five years than those who received hepatitis B vaccine [26].

PCV not included in routine schedule – In countries where the PCV is not part of the routine immunization schedule, we suggest PCV for infants and young children at high risk for recurrent AOM (ie, first episode of AOM at <6 months of age, older siblings with severe and recurrent AOM), preferably beginning within the first few months of after birth.

Although PCV13 has not been specifically studied in children with recurrent AOM, a randomized trial of 96 infants with AOM onset at <6 months of age at high risk for recurrent AOM were assigned to receive or not receive PCV7 [46]. Receipt of PCV7 was associated with a 26 percent reduction in AOM, a 36 percent reduction in emergency department visits for suspected AOM, and a 50 percent reduction in placement of ventilation tubes, supporting the value of PCV13 for prevention of complex AOM/recurrent AOM when administered on an infant schedule.

Randomized trials and systematic reviews have not found administration of PCV to be beneficial in preventing AOM in older children (>2 years) with recurrent AOM [47-51]. This is primarily because the importance of pneumococcal disease decreases as children with recurrent AOM get older. We suggest PCV for older children with recurrent AOM who have not received PCV as much to prevent IPD and pneumococcal pneumonia as to prevent AOM because children prone to AOM are at increased risk for IPD and pneumococcal pneumonia.

Pneumococcal polysaccharide vaccine — For children older than two years who continue to have recurrent episodes of AOM, we suggest administration of the 23-valent pneumococcal polysaccharide (PPSV23) after completion of immunization with PCV13 to provide coverage for as broad a range of pneumococcal serotypes as possible (table 1). PPSV23 should be administered at least eight weeks after PCV13 [27].

A systematic review of randomized controlled trials evaluating pneumococcal vaccination for AOM in children younger than 12 years found a moderate effect of pneumococcal polysaccharide vaccine in the prevention of AOM in children older than 24 months who had documented AOM before vaccination (relative risk 0.74, 95% CI 0.62 to 0.90) [47].

Influenza vaccine — In the United States, annual influenza immunization is recommended for all children ≥6 months [52]. In countries where universal influenza immunization of infants is not routine, we suggest annual influenza vaccination for children who had onset of AOM before six months of age or recurrent episodes of AOM during the preceding winter [53]. (See "Seasonal influenza in children: Prevention with vaccines", section on 'Target groups'.)

In a 2017 meta-analysis of four randomized trials including 3134 children age six months to six years, influenza vaccine slightly reduced the risk of at least one episode of AOM over six months of follow-up (risk difference [RD] 4 percent, 95% CI 0 to 8; risk ratio [RR] 0.84, 95% CI 0.69 to 1.02) [54]. In meta-analysis of two trials (1223 children), influenza vaccine also appeared to reduce the number of antibiotic prescriptions (RD 11 percent, 95% CI 6-16; RR 0.70, 95% CI 0.59-0.83), but it is unclear whether this reduction was due to influenza vaccine or increased frequency of "watchful waiting" for AOM to avoid overuse of antibiotics. It is not surprising that influenza vaccine has only a modest impact on AOM episodes because infection with other respiratory viruses, such as respiratory syncytial virus, parainfluenzae, and human metapneumovirus, appear to have a much greater association with AOM. (See "Acute otitis media in children: Epidemiology, microbiology, and complications", section on 'Viral pathogens'.)

Influenza vaccination for children is discussed separately. (See "Seasonal influenza in children: Prevention with vaccines".)

EXPECTANT MANAGEMENT — Expectant management (also called "active monitoring") consists of observation with episodic antimicrobial therapy for recurrent episodes. Expectant management avoids the need for anesthesia and potential complications of tympanostomy tube placement and the adverse effects of prolonged antibiotic prophylaxis (eg, colonization with resistant pathogens, antibiotic associated diarrhea). (See 'Surgery' below and 'Antibiotic prophylaxis' below.)

In the context of shared decision-making, expectant management may be undertaken before or instead of more aggressive interventions. It is particularly attractive for children ≥2 years of age because the frequency of recurrent episodes declines with immunologic and physiologic maturation.

In the only randomized trial comparing expectant management and tympanostomy tube placement that was conducted after the introduction of pneumococcal conjugate vaccines, expectant management was not inferior to tympanostomy tube placement in reducing frequency of AOM [11]. However, among the 121 children in the expectant management group, 54 underwent tympanostomy tube placement: 35 (approximately 30 percent) for frequent AOM and 19 at parental request. Compared with the tympanostomy tube group, the expectant management group had shorter time to the first episode of AOM (2.3 versus 4.3 months), more days with otitis-related symptoms other than tube otorrhea (8.2 versus 2.0), and greater exposure to antibiotics (12.9 versus 8.8 days per year), although it did not increase nasopharyngeal colonization with resistant pathogens. The trial is discussed in detail below. (See 'Potential benefits' below.)

ANTIBIOTIC PROPHYLAXIS — Prophylaxis with a modified dose of an antimicrobial agent can be helpful in preventing recurrent AOM [55,56]. However, the protection afforded by prophylaxis is not sustained after discontinuation [57].

Indications — Antibiotic prophylaxis may be warranted for children with recurrent AOM (≥3 distinct and well-documented episodes within six months or ≥4 episodes within 12 months) despite education, alteration of environmental risks (ie, smoke exposure, large day care), and expectant management.

Earlier initiation of antibiotic prophylaxis (ie, before the child has ≥3 episodes within six months or ≥4 episodes within 12 months) may be warranted for children who (any of the following):

Are younger than two years

Have multiple risk factors for recurrent AOM (eg, first episode at age <6 months, day care attendance, family history of recurrent AOM, large number of siblings)

Have underlying conditions that predispose to AOM (eg, cleft palate, immotile cilia syndrome, IgG or subclass deficiency, Down syndrome, persistent Eustachian tube dysfunction), or

Have known or suspected developmental or language delays or comorbid conditions associated with developmental or language delays

Recurrent spontaneous perforation of the tympanic membrane, which may be associated with chronic suppurative otitis media [22]

More severe episodes (eg, moderate or severe ear pain, ear pain for ≥48 hours, temperature ≥39°C [102.2°F]) [7]

Continue to have recurrent episodes with expectant management

Decisions regarding the use of antibiotic prophylaxis should be made on a case-by-case basis. The potential benefits (20 to 50 percent fewer episodes) must be balanced with the risk of adverse events associated with long-term antibiotic exposure and that of development of nasopharyngeal colonization with antibiotic-resistant organisms [56,58]. Additional factors that influence the decision to use antibiotic prophylaxis are discussed above. (See 'Factors influencing choice' above.)

Potential benefits — In a meta-analysis, of 14 randomized trials (1461 children) comparing long-term antibiotics (>6 weeks) with placebo or no treatment for the prevention of acute and chronic suppurative otitis media, antibiotic prophylaxis [56]:

Reduced the occurrence of any episode of AOM (37 versus 56 percent; pooled risk ratio 0.65, 95% CI 0.53-0.79); approximately five children would need to be treated to prevent one child from experiencing AOM while on treatment.

Reduced the number of episodes of AOM while on antibiotics from 3 to 1.5 per year (incidence rate ratio 0.51, 95% CI 0.39-0.66).

The protection afforded by prophylaxis does not persist after discontinuation. Many children in whom antibiotic prophylaxis is discontinued will have recurrence of frequent AOM [57].

The findings of the meta-analysis must be interpreted with caution because the studies that were included had different entry criteria, used different drugs for different durations, and observed patients for various lengths of time. Most were conducted before the era of widespread penicillin-resistant pneumococci and the recommendation for routine immunization of infants with the pneumococcal conjugate vaccine (PCV).

Antibiotic prophylaxis compared with tympanostomy tubes — In the only trial comparing antibiotic prophylaxis and tympanostomy tube placement that excluded children with otitis media with effusion, antibiotic prophylaxis was more effective [59]. In this trial, 264 children 7 to 35 months of age with recurrent AOM (≥3 episodes within 6 months or ≥4 episodes within 12 months) were randomly assigned to three groups: amoxicillin prophylaxis, myringotomy and tympanostomy tube placement, or placebo, and followed for two years [59]. The average rate of new episodes of AOM or otorrhea was modestly decreased in the amoxicillin group (0.6 episodes per child-year) compared with the tympanostomy and placebo groups (approximately one new episode per child per year). These results must be interpreted with caution because the trial was performed before introduction of PCV.

Adverse effects — Prolonged use of antibiotic prophylaxis for AOM may result in the selection of resistant bacteria in the nasopharynx and subsequent respiratory tract infection with resistant pathogens [56,58]. The treatment of AOM and other upper respiratory infections caused by antibiotic-resistant organisms is discussed separately. (See "Acute otitis media in children: Treatment", section on 'Initial antibiotic therapy' and "Acute bacterial rhinosinusitis in children: Microbiology and management", section on 'Empiric antibiotics'.)

Additional risks of prolonged antibiotic use include allergic reactions and diarrhea, as well as Clostridioides difficile-associated diarrhea (on rare occasions). (See "Clostridioides difficile infection in children: Microbiology, pathogenesis, and epidemiology", section on 'Risk factors'.)

Antibiotic choice and regimen — When the decision is made to use antibiotic prophylaxis, we typically use amoxicillin unless the child has a penicillin allergy. The dose for amoxicillin prophylaxis is 20 to 40 mg/kg orally once daily. The higher dose should be reserved for communities where the prevalence of penicillin-nonsusceptible S. pneumoniae is high. Sulfisoxazole 50 mg/kg orally once per day is an alternative if it is available. Cephalosporins usually are not used for prophylaxis because they have less activity against penicillin nonsusceptible S. pneumoniae, are broader spectrum and are more expensive. (See "Penicillin allergy: Immediate reactions".)

Antibiotic prophylaxis should be provided during the fall, winter, and early spring months, when respiratory infections are most prevalent, but for no longer than six months [60]. In a small randomized trial, administration every day was more effective than administration only during upper respiratory infections [61].

Breakthrough AOM — Breakthrough episodes of AOM in the child who is currently on amoxicillin prophylaxis increases the likelihood of a beta-lactamase producing nontypeable Haemophilus influenzae or a penicillin-resistant pneumococcus. Our initial choice is amoxicillin-clavulanate 90 mg/kg per day of amoxicillin and 6.4 mg/kg per day of clavulanate in two divided doses. Ceftriaxone 50 mg/kg intramuscularly once per day is an alternative. A single dose of ceftriaxone may be sufficient, but often a two- or three-dose regimen is necessary [62,63]. (See "Acute otitis media in children: Treatment", section on 'Initial antibiotic therapy'.)

Follow-up — During chemoprophylaxis, children should be examined whenever they have signs or symptoms of AOM. (See "Acute otitis media in children: Clinical manifestations and diagnosis", section on 'Diagnosis'.)

Children without signs of AOM should be examined approximately every two months to determine the presence and duration of middle ear effusion [6]. The 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'.)

SURGERY

Tympanostomy tubes — Myringotomy with placement of tympanostomy tubes permits drainage of the middle ear fluid, aeration of the middle ear space, and return of the middle ear mucosa to normal. An abscess does not form because the tube allows drainage of accumulated middle ear fluid. Nevertheless, recurrent infection may result in a mucositis that is usually identified by systemic signs and/or otorrhea. (See "Overview of tympanostomy tube placement, postoperative care, and complications in children", section on 'Tube otorrhea' and "Tympanostomy tube otorrhea in children: Causes, prevention, and management", section on 'Acute tympanostomy tube otorrhea'.)

The use of tympanostomy tubes in the prevention of recurrent AOM in otherwise healthy children has increased as the popularity of chemoprophylaxis has decreased due to concerns about antibiotic resistance among otopathogens. (See 'Adverse effects' above.)

Indications — Tympanostomy tube placement may be warranted for children who have had ≥3 distinct and well-documented episodes within six months or ≥4 episodes within 12 months. Decisions regarding the placement of tympanostomy tubes for recurrent AOM must be individualized after consideration of the risks and benefits. (See 'Factors influencing choice' above.)

We suggest tympanostomy tube placement for children who warrant more aggressive prevention strategies and (see 'Choice of intervention(s)' above):

Have had breakthrough episodes of AOM while receiving antibiotic prophylaxis, or

Have declined antibiotic prophylaxis (because of parental concerns), or

Have multiple drug allergies

Potential benefits — Tympanostomy tube placement may reduce the frequency and severity of episodes of AOM in children with recurrent AOM, but the evidence is limited. Episodes of AOM in children with tympanostomy tubes are accompanied by drainage of infected middle ear fluid into the external auditory canal (tympanostomy tube otorrhea). By permitting drainage of the infected fluid, tympanostomy tube placement may reduce the pain or severity of subsequent episodes of AOM. In addition, tympanostomy tube placement may simplify treatment because tympanostomy tube otorrhea often can be treated with ear drops. Tympanostomy tube otorrhea is discussed separately. (See "Tympanostomy tube otorrhea in children: Causes, prevention, and management".)

Only one randomized trial comparing tympanostomy tube placement and expectant management has been performed after the introduction of pneumococcal conjugate vaccine (PCV) [11]. In this multicenter trial, 250 children 6 to 35 months of age with recurrent AOM (with at least one episode confirmed by a validated otoscopist) were randomly assigned to tympanostomy tube placement (n = 129) or expectant management (n = 121) and followed for two years. Episodes of AOM were treated with amoxicillin-clavulanate followed by intramuscular ceftriaxone. Parents were permitted to request tympanostomy tubes after random assignment to expectant management. In the intention-to-treat analysis, no difference in the rate of episodes of recurrent AOM was detected (mean of approximately 1.5 per year). However, 13 children in the tympanostomy tube group did not receive tympanostomy tubes and 19 children in the expectant management group received tympanostomy tubes at parental request. In the per-protocol analysis, the tympanostomy tube group had slightly fewer mean episodes of AOM per year (1.5 versus 1.7, risk ratio 0.82, 95% CI 0.69-0.97). Approximately 30 percent of children in the expectant management group underwent tympanostomy tube placement for frequent AOM. Among secondary outcomes, the tympanostomy tube group had longer time to first episode of AOM (4.3 versus 2.3 months), less exposure to antimicrobial therapy (8.8 versus 12.9 days per year), fewer days per year with otitis-related symptoms other than tube otorrhea (2.0 versus 8.3), and more days per year with tube otorrhea (8.0 versus 2.8 days). Rates of other adverse effects (eg, diarrhea, diaper dermatitis, nasopharyngeal colonization with resistant pathogens), quality of life, and parental satisfaction were similar between groups. For each group, the rate of occurrence of AOM during the second year of follow-up was approximately one-half the rate during the first year.

A systematic review of randomized trials that were conducted before the introduction of PCV concluded that tympanostomy tubes may modestly decrease recurrence of AOM compared with expectant monitoring (approximately one less episode at 6 months and a less noticeable effect by 12 months), but the evidence was of low quality [64].

Comparison of tympanostomy tubes with antibiotic prophylaxis is discussed above. (See 'Antibiotic prophylaxis compared with tympanostomy tubes' above.)

Adverse effects — Myringotomy and placement of tympanostomy tubes are surgical procedures and parents should be informed about the potential adverse events associated with anesthesia and surgery. Complications and sequelae of tympanostomy tubes include intermittent and persistent otorrhea that may require removal of tympanostomy tubes in some children, persistent perforation of the tympanic membrane, tympanosclerosis, focal atrophy of the tympanic membrane, and cholesteatoma. (See "Overview of tympanostomy tube placement, postoperative care, and complications in children", section on 'Complications and sequelae'.)

Adenoidectomy or adenotonsillectomy — When the decision is made to proceed with a first set of tympanostomy tubes, concurrent adenoidectomy is indicated only for patients with moderate to severe nasal obstruction [1]. (See "Tonsillectomy and/or adenoidectomy in children: Indications and contraindications", section on 'Nasal obstruction'.)

Adenoidectomy, with or without tonsillectomy, does not appear to be an effective primary preventive measure for children with recurrent AOM [65-68]. Two randomized clinical trials run in parallel failed to demonstrate a substantial effect of adenoidectomy or adenotonsillectomy on the occurrence of AOM in patients 3 to 15 years of age with recurrent OM and no previous history of tympanostomy tubes, whether or not they had evidence of enlarged tonsils or adenoids [65].

The relative merits of adenoidectomy at the time of tympanostomy tube placement in children with recurrent AOM (more than three episodes in the past six months) or chronic otitis media with effusion were evaluated in a prospective trial [69]. A total of 217 children with no previous surgery (aged 12 to 48 months) were randomly assigned to adenoidectomy with insertion of tympanostomy tubes or insertion of tympanostomy tubes alone. There was no difference in the incidence of subsequent AOM between the two groups [69].

In contrast, adenoidectomy with or without tonsillectomy may be helpful in reducing the number of episodes of AOM in children who have recurrences after an initial placement of tympanostomy tubes [70]. A retrospective study suggested that adenoidectomy or adenoidectomy plus tonsillectomy at the time of tube reinsertion substantially reduced the incidence of subsequent hospitalizations and repeat tympanostomy tube insertion in patients ≥2 years of age [71]. (See "Tonsillectomy and/or adenoidectomy in children: Indications and contraindications", section on 'Otitis media'.)

INTERVENTIONS NOT ROUTINELY RECOMMENDED

Xylitol — We suggest against the use of xylitol to prevent recurrent AOM in children. Although there is some evidence from randomized trials to suggest that xylitol may be beneficial [72], additional information is necessary before it can be routinely recommended.

Xylitol is a five-carbon sugar alcohol that is used in place of sucrose as a sweetener. It has been shown to prevent dental caries by inhibiting the growth of Streptococcus mutans and has been studied as a means of preventing AOM in children attending day care [72-74].

In a 2016 meta-analysis of three randomized trials [75-77], two to three months of xylitol chewing gum, syrup, or lozenges prevented recurrent AOM among healthy children (mean age two to five years) attending day care (risk ratio 0.75, 95% CI 0.65-0.88) [72]. Although the results of the meta-analysis are promising, it has several limitations. The mean ages in the study populations were older than the age of peak incidence of AOM (2 to 5 years versus 6 to 18 months). In addition, it is not clear that the study conditions (eg, administration of xylitol five times per day) could be replicated in "the real world." In individual studies, administration of xylitol five times per day was effective [75,76], but three times per day was not [77,78]. In a separate randomized trial, xylitol syrup administered only during respiratory infections did not prevent AOM among children attending day care [79].

The optimal dose, dosing regimen, long-term benefits, and full range of adverse effects must be determined before xylitol can be recommended to prevent AOM [80].

Antiadhesive oligosaccharide — We suggest against the administration of oligosaccharides to prevent recurrent AOM in children. Administration of oligosaccharides may be helpful in the prevention of infection by inhibiting the binding of bacteria to epithelial cells [81-83]. In an animal study, intratracheal administration of antiadhesive oligosaccharides was effective in decreasing pneumococcal load and subsequent bacteremia [84]. However, in a randomized controlled trial, nasopharyngeal administration of oligosaccharides to children for three months did not affect nasopharyngeal carriage of S. pneumoniae, H. influenzae, or Moraxella catarrhalis or prevent AOM [85].

Probiotics — We suggest against the administration of probiotics to prevent recurrent AOM in children. In theory, administration of probiotics after treatment of AOM recolonizes the nasopharynx with bacteria that can hinder the growth of pathogenic bacteria [86]. However, studies evaluating probiotics for the prevention of recurrent AOM in otitis prone have inconsistent results and additional clinical evaluation is necessary before they can be recommended [87].

In two randomized trials, each including >200 otitis prone children, no benefit of oral probiotics in the prevention of recurrent AOM was detected [88,89]. Topical administration of probiotics via nasal spray has also been evaluated, with inconsistent results. Two randomized trials with various strains of alpha-hemolytic Streptococcus had promising results in otitis-prone children [90,91], but another trial did not find a benefit [92].

Vitamin D — We suggest against vitamin D to prevent recurrent AOM in children. Although vitamin D plays a role in immunity and infection [93], and a small randomized trial suggested that vitamin D supplementation (1000 international units per day) may reduce episodes of AOM [94], the evidence is insufficient to support a causative role of vitamin D deficiency in the etiology and pathogenesis of AOM. (See "Vitamin D and extraskeletal health", section on 'Immune system'.)

Other complementary therapies — Nearly one-half of families of children with recurrent AOM may try complementary, holistic, or integrative therapies (eg, herbal remedies; homeopathy; nutritional supplements, such as zinc) to prevent recurrent AOM [95]. Although some of these interventions have been evaluated in clinical trials, methodologic limitations preclude definitive conclusions about their safety or efficacy [7,96-98].

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 5th to 6th 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 10th to 12th 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 topic (see "Patient education: Ear tubes (The Basics)")

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

SUMMARY AND RECOMMENDATIONS

Recurrent acute otitis media (AOM) is defined as ≥3 distinct and well-documented episodes within six months or ≥4 episodes within 12 months. Infants who have their first episode of AOM before six months of age or who have siblings with severe and recurrent AOM are at risk for severe and recurrent AOM. (See 'Definition' above.)

Prevention strategies include identification and treatment of underlying conditions that predispose to recurrent AOM, parental education about the risk factors for AOM, vaccine administration, expectant management, chemoprophylaxis, and tympanostomy tube placement. (See 'Interventions' above.)

Factors that influence the choice of prevention strategy include the age of the child, the age at first episode of AOM, the time of year, day care attendance, family history, cognitive and language status, underlying conditions that predispose to AOM, and the effects of recurrent AOM on the quality of life for the child and family. (See 'Factors influencing choice' above.)

Treatment of predisposing conditions and parental education are reasonable strategies for all children with recurrent AOM. (See 'Treatment of predisposing conditions' above and 'Education' above.)

Children should receive pneumococcal conjugate vaccine (PCV) and annual influenza vaccine according to the routine childhood immunization schedule. (See "Seasonal influenza in children: Prevention with vaccines", section on 'Target groups' and "Pneumococcal vaccination in children", section on 'Routine immunization for children <5 years'.)

For children with recurrent AOM who are between two and six years of age and have not received any doses of the 13-valent PCV (PCV13) or the 10-valent PCV (PCV10), we suggest a single dose of PCV13 or PCV10 (Grade 2C). These children are at increased risk for invasive pneumococcal disease and pneumococcal pneumonia. (See 'Pneumococcal conjugate vaccine' above.)

For children ≥2 years of age with recurrent AOM, we suggest a single dose of the 23-valent pneumococcal vaccine (PPSV23) (Grade 2C). PPSV23 broadens the coverage against pneumococcal serotypes. PPSV23 should be given at a minimum eight weeks after the final dose of PCV13 or PCV10. (See 'Pneumococcal polysaccharide vaccine' above.)

Expectant management consists of observation with episodic antimicrobial therapy for recurrent episodes. In the context of shared decision-making, it may be undertaken before or instead of more aggressive interventions (eg, antibiotic prophylaxis, tympanostomy tube placement). Expectant management avoids the need for anesthesia, potential complications of tympanostomy tube placement, and the adverse effects of prolonged antibiotic prophylaxis and does not appear to be associated with increased colonization with resistant pathogens. Expectant management is particularly attractive for children ≥2 years of age because the frequency of recurrent episodes declines with immunologic and physiologic maturation. (See 'Expectant management' above.)

Children at increased risk for more frequent, severe, or complicated AOM include (see 'Choice of intervention(s)' above):

Age <2 years

Children with multiple risk factors (eg, family history of recurrent AOM, attendance at large day care)

Underlying medical conditions that predispose to recurrent AOM (eg, cleft palate, immotile cilia syndrome, immunoglobulin or subclass deficiency, syndromes with craniofacial abnormalities, including Down syndrome, persistent Eustachian tube dysfunction)

Comorbid conditions associated with developmental or language delays

Recurrent spontaneous perforation of the tympanic membrane

More severe episodes (eg, moderate or severe ear pain, ear pain for ≥48 hours, temperature ≥39°C [102.2°F]) [7]

In the context of shared decision-making, for children at increased risk for more frequent or severe episodes and/or complications and sequelae of AOM, we suggest tympanostomy tube placement or antibiotic prophylaxis rather than continued expectant management (Grade 2C). These more aggressive interventions may modestly decrease the frequency or delay the occurrence of AOM. (See 'Choice of intervention(s)' above.)

The choice between antibiotic prophylaxis and tympanostomy tube placement is influenced by the age of the child, concern for development of antibiotic-resistant bacteria, the child's language development, the risks of surgery and anesthesia, and the values and preferences of the family. Tympanostomy tubes are preferred for children who have had frequent breakthrough episodes of AOM while receiving antibiotic prophylaxis or who have multiple drug allergies and who continue to warrant more aggressive prevention. (See 'Choice of intervention(s)' above and 'Tympanostomy tubes' above.)

When the decision is made to use antibiotic prophylaxis, we typically use amoxicillin 20 to 40 mg/kg orally once daily. The higher dose should be reserved for communities where the prevalence of penicillin-nonsusceptible S. pneumoniae is high. Sulfisoxazole 50 mg/kg orally once per day is an alternative if it is available. Antibiotic prophylaxis should be provided every day during the fall, winter, and early spring months. Children receiving antibiotic prophylaxis should be examined approximately every two months to determine the presence and duration of middle ear effusion. (See 'Antibiotic prophylaxis' above.)

Adenoidectomy is not an effective primary preventive measure for children with recurrent AOM but may be beneficial in those who continue to have recurrent AOM after extrusion of tubes and are undergoing repeat tympanostomy tube placement. (See 'Adenoidectomy or adenotonsillectomy' above.)

There is insufficient evidence of benefit to suggest using xylitol, antiadhesive oligosaccharide, vitamin D, or probiotics for the prevention of recurrent AOM in children. (See 'Interventions not routinely recommended' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge Jerome Klein, MD, who contributed to an earlier version of this topic review.

  1. Bluestone CD. Role of surgery for otitis media in the era of resistant bacteria. Pediatr Infect Dis J 1998; 17:1090.
  2. Marchisio P, Esposito S, Bianchini S, et al. Efficacy of injectable trivalent virosomal-adjuvanted inactivated influenza vaccine in preventing acute otitis media in children with recurrent complicated or noncomplicated acute otitis media. Pediatr Infect Dis J 2009; 28:855.
  3. Pichichero ME. Ten-Year Study of the Stringently Defined Otitis-prone Child in Rochester, NY. Pediatr Infect Dis J 2016; 35:1033.
  4. Marom T, Tan A, Wilkinson GS, et al. Trends in otitis media-related health care use in the United States, 2001-2011. JAMA Pediatr 2014; 168:68.
  5. Giebink GS. Otitis media prevention: non-vaccine prophylaxis. Vaccine 2000; 19 Suppl 1:S129.
  6. Klein JO. Nonimmune strategies for prevention of otitis media. Pediatr Infect Dis J 2000; 19:S89.
  7. Lieberthal AS, Carroll AE, Chonmaitree T, et al. The diagnosis and management of acute otitis media. Pediatrics 2013; 131:e964.
  8. Zhang Y, Xu M, Zhang J, et al. Risk factors for chronic and recurrent otitis media-a meta-analysis. PLoS One 2014; 9:e86397.
  9. Marchisio P, Nazzari E, Torretta S, et al. Medical prevention of recurrent acute otitis media: an updated overview. Expert Rev Anti Infect Ther 2014; 12:611.
  10. Paradise JL. Antimicrobial prophylaxis for recurrent acute otitis media. Ann Otol Rhinol Laryngol Suppl 1992; 155:33.
  11. Hoberman A, Preciado D, Paradise JL, et al. Tympanostomy Tubes or Medical Management for Recurrent Acute Otitis Media. N Engl J Med 2021; 384:1789.
  12. Megged O, Abdulgany S, Bar-Meir M. Does Acute Otitis Media in the First Month of Life Increase the Risk for Recurrent Otitis? Clin Pediatr (Phila) 2018; 57:89.
  13. de Hoog ML, Fortanier AC, Smit HA, et al. Impact of Early-Onset Acute Otitis Media on Multiple Recurrences and Associated Health Care Use. J Pediatr 2016; 177:286.
  14. Dagan R, Pelton S, Bakaletz L, Cohen R. Prevention of early episodes of otitis media by pneumococcal vaccines might reduce progression to complex disease. Lancet Infect Dis 2016; 16:480.
  15. Friedel V, Zilora S, Bogaard D, et al. Five-year prospective study of paediatric acute otitis media in Rochester, NY: modelling analysis of the risk of pneumococcal colonization in the nasopharynx and infection. Epidemiol Infect 2014; 142:2186.
  16. Gisselsson-Solén M, Henriksson G, Hermansson A, Melhus A. Risk factors for carriage of AOM pathogens during the first 3 years of life in children with early onset of acute otitis media. Acta Otolaryngol 2014; 134:684.
  17. Shimada J, Yamanaka N, Hotomi M, et al. Household transmission of Streptococcus pneumoniae among siblings with acute otitis media. J Clin Microbiol 2002; 40:1851.
  18. Kvaerner KJ, Nafstad P, Hagen JA, et al. Early acute otitis media and siblings' attendance at nursery. Arch Dis Child 1996; 75:338.
  19. Bentdal YE, Håberg SE, Karevold G, et al. Birth characteristics and acute otitis media in early life. Int J Pediatr Otorhinolaryngol 2010; 74:168.
  20. Rosenfeld RM, Schwartz SR, Pynnonen MA, et al. Clinical practice guideline: tympanostomy tubes in children--executive summary. Otolaryngol Head Neck Surg 2013; 149:8.
  21. Holl K, Rosenlund M, Giaquinto C, et al. The Impact of Childhood Acute Otitis Media on Parental Quality of Life in a Prospective Observational Cohort Study. Clin Drug Investig 2015; 35:613.
  22. Principi N, Marchisio P, Rosazza C, et al. Acute otitis media with spontaneous tympanic membrane perforation. Eur J Clin Microbiol Infect Dis 2017; 36:11.
  23. Avanzini AM, Castellazzi AM, Marconi M, et al. Children with recurrent otitis show defective IFN gamma-producing cells in adenoids. Pediatr Allergy Immunol 2008; 19:523.
  24. Kaur R, Morris M, Pichichero ME. Epidemiology of Acute Otitis Media in the Postpneumococcal Conjugate Vaccine Era. Pediatrics 2017; 140.
  25. Uhari M, Mäntysaari K, Niemelä M. A meta-analytic review of the risk factors for acute otitis media. Clin Infect Dis 1996; 22:1079.
  26. Sarasoja I, Jokinen J, Lahdenkari M, et al. Long-term effect of pneumococcal conjugate vaccines on tympanostomy tube placements. Pediatr Infect Dis J 2013; 32:517.
  27. Nuorti JP, Whitney CG, Centers for Disease Control and Prevention (CDC). Prevention of pneumococcal disease among infants and children - use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine - recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2010; 59:1.
  28. Black S, Shinefield H, Fireman B, et al. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group. Pediatr Infect Dis J 2000; 19:187.
  29. Eskola J, Kilpi T, Palmu A, et al. Efficacy of a pneumococcal conjugate vaccine against acute otitis media. N Engl J Med 2001; 344:403.
  30. Taylor S, Marchisio P, Vergison A, et al. Impact of pneumococcal conjugate vaccination on otitis media: a systematic review. Clin Infect Dis 2012; 54:1765.
  31. McEllistrem MC, Adams JM, Patel K, et al. Acute otitis media due to penicillin-nonsusceptible Streptococcus pneumoniae before and after the introduction of the pneumococcal conjugate vaccine. Clin Infect Dis 2005; 40:1738.
  32. Pelton SI, Loughlin AM, Marchant CD. Seven valent pneumococcal conjugate vaccine immunization in two Boston communities: changes in serotypes and antimicrobial susceptibility among Streptococcus pneumoniae isolates. Pediatr Infect Dis J 2004; 23:1015.
  33. Kawai K, Adil EA, Barrett D, et al. Ambulatory Visits for Otitis Media before and after the Introduction of Pneumococcal Conjugate Vaccination. J Pediatr 2018; 201:122.
  34. Cohen R, Levy C, Bingen E, et al. Impact of 13-valent pneumococcal conjugate vaccine on pneumococcal nasopharyngeal carriage in children with acute otitis media. Pediatr Infect Dis J 2012; 31:297.
  35. Pichichero M, Kaur R, Scott DA, et al. Effectiveness of 13-valent pneumococcal conjugate vaccination for protection against acute otitis media caused by Streptococcus pneumoniae in healthy young children: a prospective observational study. Lancet Child Adolesc Health 2018; 2:561.
  36. Kaplan SL, Center KJ, Barson WJ, et al. Multicenter surveillance of Streptococcus pneumoniae isolates from middle ear and mastoid cultures in the 13-valent pneumococcal conjugate vaccine era. Clin Infect Dis 2015; 60:1339.
  37. Ben-Shimol S, Givon-Lavi N, Leibovitz E, et al. Near-elimination of otitis media caused by 13-valent pneumococcal conjugate vaccine (PCV) serotypes in southern Israel shortly after sequential introduction of 7-valent/13-valent PCV. Clin Infect Dis 2014; 59:1724.
  38. Wiese AD, Huang X, Yu C, et al. Changes in Otitis Media Episodes and Pressure Equalization Tube Insertions Among Young Children Following Introduction of the 13-Valent Pneumococcal Conjugate Vaccine: A Birth Cohort-based Study. Clin Infect Dis 2019; 69:2162.
  39. Fireman B, Black SB, Shinefield HR, et al. Impact of the pneumococcal conjugate vaccine on otitis media. Pediatr Infect Dis J 2003; 22:10.
  40. Zhou F, Shefer A, Kong Y, Nuorti JP. Trends in acute otitis media-related health care utilization by privately insured young children in the United States, 1997-2004. Pediatrics 2008; 121:253.
  41. Poehling KA, Szilagyi PG, Grijalva CG, et al. Reduction of frequent otitis media and pressure-equalizing tube insertions in children after introduction of pneumococcal conjugate vaccine. Pediatrics 2007; 119:707.
  42. Sugino H, Tsumura S, Kunimoto M, et al. Influence of Pneumococcal Conjugate Vaccine on Acute Otitis Media with Severe Middle Ear Inflammation: A Retrospective Multicenter Study. PLoS One 2015; 10:e0137546.
  43. Lewnard JA, Givon-Lavi N, Weinberger DM, et al. Pan-serotype Reduction in Progression of Streptococcus pneumoniae to Otitis Media After Rollout of Pneumococcal Conjugate Vaccines. Clin Infect Dis 2017; 65:1853.
  44. Sigurdsson S, Eythorsson E, Hrafnkelsson B, et al. Reduction in All-Cause Acute Otitis Media in Children <3 Years of Age in Primary Care Following Vaccination With 10-Valent Pneumococcal Haemophilus influenzae Protein-D Conjugate Vaccine: A Whole-Population Study. Clin Infect Dis 2018; 67:1213.
  45. Marom T, Tshori S, Shefer G, Pitaro J. Pneumococcal Conjugated Vaccines Decreased Acute Otitis Media Burden: A Population-Based Study in Israel. J Pediatr 2021; 235:233.
  46. Gisselsson-Solén M, Melhus A, Hermansson A. Pneumococcal vaccination in children at risk of developing recurrent acute otitis media - a randomized study. Acta Paediatr 2011; 100:1354.
  47. Straetemans M, Sanders EA, Veenhoven RH, et al. Review of randomized controlled trials on pneumococcal vaccination for prevention of otitis media. Pediatr Infect Dis J 2003; 22:515.
  48. American Academy of Pediatrics. Committee on Infectious Diseases. Policy statement: recommendations for the prevention of pneumococcal infections, including the use of pneumococcal conjugate vaccine (Prevnar), pneumococcal polysaccharide vaccine, and antibiotic prophylaxis. Pediatrics 2000; 106:362.
  49. Hoberman A, Marchant CD, Kaplan SL, Feldman S. Treatment of acute otitis media consensus recommendations. Clin Pediatr (Phila) 2002; 41:373.
  50. Veenhoven R, Bogaert D, Uiterwaal C, et al. Effect of conjugate pneumococcal vaccine followed by polysaccharide pneumococcal vaccine on recurrent acute otitis media: a randomised study. Lancet 2003; 361:2189.
  51. de Sévaux JL, Venekamp RP, Lutje V, et al. Pneumococcal conjugate vaccines for preventing acute otitis media in children. Cochrane Database Syst Rev 2020; 11:CD001480.
  52. Grohskopf LA, Blanton LH, Ferdinands JM, et al. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022-23 Influenza Season. MMWR Recomm Rep 2022; 71:1.
  53. Pappas DE, Owen Hendley J. Otitis media. A scholarly review of the evidence. Minerva Pediatr 2003; 55:407.
  54. Norhayati MN, Ho JJ, Azman MY. Influenza vaccines for preventing acute otitis media in infants and children. Cochrane Database Syst Rev 2017; 10:CD010089.
  55. Williams RL, Chalmers TC, Stange KC, et al. Use of antibiotics in preventing recurrent acute otitis media and in treating otitis media with effusion. A meta-analytic attempt to resolve the brouhaha. JAMA 1993; 270:1344.
  56. Leach AJ, Morris PS. Antibiotics for the prevention of acute and chronic suppurative otitis media in children. Cochrane Database Syst Rev 2006; :CD004401.
  57. Teele DW, Klein JO, Word BM, et al. Antimicrobial prophylaxis for infants at risk for recurrent acute otitis media. Vaccine 2000; 19 Suppl 1:S140.
  58. Brook I, Gober AE. Prophylaxis with amoxicillin or sulfisoxazole for otitis media: effect on the recovery of penicillin-resistant bacteria from children. Clin Infect Dis 1996; 22:143.
  59. Casselbrant ML, Kaleida PH, Rockette HE, et al. Efficacy of antimicrobial prophylaxis and of tympanostomy tube insertion for prevention of recurrent acute otitis media: results of a randomized clinical trial. Pediatr Infect Dis J 1992; 11:278.
  60. Dowell SF, Marcy SM, Phillips WR, et al. Otitis media--principles of judicious use of antimicrobial agents. Pediatrics 1998; 101 Suppl 1:165.
  61. Berman S, Nuss R, Roark R, et al. Effectiveness of continuous vs. intermittent amoxicillin to prevent episodes of otitis media. Pediatr Infect Dis J 1992; 11:63.
  62. Barnett ED, Teele DW, Klein JO, et al. Comparison of ceftriaxone and trimethoprim-sulfamethoxazole for acute otitis media. Greater Boston Otitis Media Study Group. Pediatrics 1997; 99:23.
  63. Leibovitz E, Piglansky L, Raiz S, et al. Bacteriologic and clinical efficacy of one day vs. three day intramuscular ceftriaxone for treatment of nonresponsive acute otitis media in children. Pediatr Infect Dis J 2000; 19:1040.
  64. Venekamp RP, Mick P, Schilder AG, Nunez DA. Grommets (ventilation tubes) for recurrent acute otitis media in children. Cochrane Database Syst Rev 2018; 5:CD012017.
  65. Paradise JL, Bluestone CD, Colborn DK, et al. Adenoidectomy and adenotonsillectomy for recurrent acute otitis media: parallel randomized clinical trials in children not previously treated with tympanostomy tubes. JAMA 1999; 282:945.
  66. Koivunen P, Uhari M, Luotonen J, et al. Adenoidectomy versus chemoprophylaxis and placebo for recurrent acute otitis media in children aged under 2 years: randomised controlled trial. BMJ 2004; 328:487.
  67. van den Aardweg MT, Schilder AG, Herkert E, et al. Adenoidectomy for otitis media in children. Cochrane Database Syst Rev 2010; :CD007810.
  68. Kujala T, Alho OP, Luotonen J, et al. Tympanostomy with and without adenoidectomy for the prevention of recurrences of acute otitis media: a randomized controlled trial. Pediatr Infect Dis J 2012; 31:565.
  69. Hammarén-Malmi S, Saxen H, Tarkkanen J, Mattila PS. Adenoidectomy does not significantly reduce the incidence of otitis media in conjunction with the insertion of tympanostomy tubes in children who are younger than 4 years: a randomized trial. Pediatrics 2005; 116:185.
  70. Paradise JL, Bluestone CD, Rogers KD, et al. Efficacy of adenoidectomy for recurrent otitis media in children previously treated with tympanostomy-tube placement. Results of parallel randomized and nonrandomized trials. JAMA 1990; 263:2066.
  71. Coyte PC, Croxford R, McIsaac W, et al. The role of adjuvant adenoidectomy and tonsillectomy in the outcome of the insertion of tympanostomy tubes. N Engl J Med 2001; 344:1188.
  72. Azarpazhooh A, Lawrence HP, Shah PS. Xylitol for preventing acute otitis media in children up to 12 years of age. Cochrane Database Syst Rev 2016; :CD007095.
  73. Mäkinen KK, Bennett CA, Hujoel PP, et al. Xylitol chewing gums and caries rates: a 40-month cohort study. J Dent Res 1995; 74:1904.
  74. Knuuttila ML, Mäkinen K. Effect of xylitol on the growth and metabolism of Streptococcus mutans. Caries Res 1975; 9:177.
  75. Uhari M, Kontiokari T, Niemelä M. A novel use of xylitol sugar in preventing acute otitis media. Pediatrics 1998; 102:879.
  76. Uhari M, Kontiokari T, Koskela M, Niemelä M. Xylitol chewing gum in prevention of acute otitis media: double blind randomised trial. BMJ 1996; 313:1180.
  77. Hautalahti O, Renko M, Tapiainen T, et al. Failure of xylitol given three times a day for preventing acute otitis media. Pediatr Infect Dis J 2007; 26:423.
  78. Vernacchio L, Corwin MJ, Vezina RM, et al. Xylitol syrup for the prevention of acute otitis media. Pediatrics 2014; 133:289.
  79. Tapiainen T, Luotonen L, Kontiokari T, et al. Xylitol administered only during respiratory infections failed to prevent acute otitis media. Pediatrics 2002; 109:E19.
  80. Mitchell AA. Xylitol prophylaxis for acute otitis media: tout de suite? Pediatrics 1998; 102:974.
  81. Beachey EH. Bacterial adherence: adhesin-receptor interactions mediating the attachment of bacteria to mucosal surface. J Infect Dis 1981; 143:325.
  82. Zopf D, Roth S. Oligosaccharide anti-infective agents. Lancet 1996; 347:1017.
  83. Lingwood CA. Oligosaccharide receptors for bacteria: a view to a kill. Curr Opin Chem Biol 1998; 2:695.
  84. Idänpään-Heikkilä I, Simon PM, Zopf D, et al. Oligosaccharides interfere with the establishment and progression of experimental pneumococcal pneumonia. J Infect Dis 1997; 176:704.
  85. Ukkonen P, Varis K, Jernfors M, et al. Treatment of acute otitis media with an antiadhesive oligosaccharide: a randomised, double-blind, placebo-controlled trial. Lancet 2000; 356:1398.
  86. Santagati M, Scillato M, Patanè F, et al. Bacteriocin-producing oral streptococci and inhibition of respiratory pathogens. FEMS Immunol Med Microbiol 2012; 65:23.
  87. Scott AM, Clark J, Julien B, et al. Probiotics for preventing acute otitis media in children. Cochrane Database Syst Rev 2019; 6:CD012941.
  88. Hatakka K, Blomgren K, Pohjavuori S, et al. Treatment of acute otitis media with probiotics in otitis-prone children-a double-blind, placebo-controlled randomised study. Clin Nutr 2007; 26:314.
  89. Cohen R, Martin E, de La Rocque F, et al. Probiotics and prebiotics in preventing episodes of acute otitis media in high-risk children: a randomized, double-blind, placebo-controlled study. Pediatr Infect Dis J 2013; 32:810.
  90. Roos K, Håkansson EG, Holm S. Effect of recolonisation with "interfering" alpha streptococci on recurrences of acute and secretory otitis media in children: randomised placebo controlled trial. BMJ 2001; 322:210.
  91. Marchisio P, Santagati M, Scillato M, et al. Streptococcus salivarius 24SMB administered by nasal spray for the prevention of acute otitis media in otitis-prone children. Eur J Clin Microbiol Infect Dis 2015; 34:2377.
  92. Tano K, Grahn Håkansson E, Holm SE, Hellström S. A nasal spray with alpha-haemolytic streptococci as long term prophylaxis against recurrent otitis media. Int J Pediatr Otorhinolaryngol 2002; 62:17.
  93. Adams JS, Hewison M. Update in vitamin D. J Clin Endocrinol Metab 2010; 95:471.
  94. Marchisio P, Consonni D, Baggi E, et al. Vitamin D supplementation reduces the risk of acute otitis media in otitis-prone children. Pediatr Infect Dis J 2013; 32:1055.
  95. Marchisio P, Bianchini S, Galeone C, et al. Use of complementary and alternative medicine in children with recurrent acute otitis media in Italy. Int J Immunopathol Pharmacol 2011; 24:441.
  96. Bukutu C, Deol J, Vohra S. Complementary, holistic, and integrative medicine: therapies for acute otitis media. Pediatr Rev 2008; 29:193.
  97. Gulani A, Sachdev HS. Zinc supplements for preventing otitis media. Cochrane Database Syst Rev 2014; :CD006639.
  98. Marom T, Marchisio P, Tamir SO, et al. Complementary and Alternative Medicine Treatment Options for Otitis Media: A Systematic Review. Medicine (Baltimore) 2016; 95:e2695.
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References