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the middle ear mucosa can result in inammation in the middle ear if, for example,
esophageal contents regurgitate into the nasopharynx and middle ear via the ET [1].
Several factors, including changes in the ET throughout development, an underdeveloped immune system, and repeated infections of the upper respiratory mucosa
inuence the development of AOM in children. According to studies [2], bacterial
colonization and adherence in the nasopharynx and increased ETD may be linked to
an upper respiratory infection with resultant epithelial dysfunction. Infections with
specic viruses can trigger inammatory and immunological responses in the ET
mucosa, inviting microbes to invade the middle ear. Middle ear uid and AOM
symptoms result from the body’s inammatory and immunological reaction to
pathogens invading the middle ear [1]. Strong evidence suggests that virus contact
with the major pathogenic bacteria in AOM frequently causes more severe disease,
decreased responsiveness to antimicrobial treatment, and the development of OME
after AOM [1]. However, the exact mechanisms by which these interactions occur
remain unclear.
A. Budak et al.
16.3 Etiology
The development of OM is inuenced by a wide range of variables, including host
factors, infectious factors, and allergies and the environment [1].
16.3.1 Host Factors
16.3.1.1 Immune System
The development of OM may be inuenced by the immature immune systems of
infants or individuals with compromised immune systems due to congenital immunological abnormalities, HIV infection, or diabetes [3]. OM thrives when there are
weakened immune defenses because it is an infectious disease. Even when the
immune system is normal, disease development is inuenced by the dynamic
between infectious agents and the host’s immune system [1]. According to Patel
etal. [4], patients with OM who simultaneously had inuenza and adenoviral infections had greater interleukin (IL)-6 levels. In comparison, patients who got OM
after unspecied URIs had higher levels of IL-1β. In another investigation [5],
Skovbjerg etal. identied higher amounts of IL-1β, IL-8, and IL-10in middle ear
effusions harboring culturable pathogenic bacteria compared to sterile effusions.
16.3.1.2 Hereditary Susceptibility
Research has shown that OM tends to cluster in families, but the relative effects of
genetics versus environmental factors are difcult to disentangle. There is no evidence that any particular gene contributes to the risk of OM, but inherited craniofacial similarities may be related to Eustachian tube shape and size, in turn affecting
Eustachian tube function. Environmental factors on genetic expression likely inuence the pathophysiology of OM, as is the case with many disease processes [1].
16 Acute Suppurative Otitis Media
337
16.3.1.3 Mucins
Mucins are glycoproteins that cause the gel-like consistency of mucous discharge.
In contrast to the nasopharynx, the expression of mucin genes in the middle ear is
distinct. OME may be inuenced by abnormalities in this gene’s expression, particularly the overexpression of MUC5B in the ear [1].
16.3.1.4 Anatomic Abnormalities
Marked ETD and an increased risk of OM are characteristics of children with anomalies of the palate and related muscles, particularly the tensor veli palatini. Cleft
palate, Crouzon syndrome, Down syndrome, Treacher Collins syndrome, and Apert
syndrome are specic conditions that are associated with a high prevalence
of OM [1].
16.3.1.5 Physiologic Dysfunction
There is an increased risk of bacterial invasion of the middle ear and the subsequent
OME when there are abnormalities in the physiological function of the ET mucosa,
such as ciliary dysfunction and edema. There is an increased risk of OM, particularly chronic OM and cholesteatoma development, in children who have cochlear
implants. A study found a correlation between chronic OM (COM) and laryngopharyngeal reux; the authors recommended including a reux workup in COM investigations and starting reux medication alongside primary disease therapy if reux
was found [6].
16.3.2 Infectious Factors
16.3.2.1 Bacterial Pathogens
Over 99% of AOM cases are caused by bacteria. Streptococcus pneumoniae ranks
rst among the bacterial pathogens found in AOM, followed by Moraxella catarrh-
alis and nontypeable Haemophilus inuenzae [7].
Babies under six weeks old are also susceptible to AOM, with gram-negative
bacilli such as Escherichia coli, Klebsiella species, and Pseudomonas aeruginosa
accounting for 20% of cases. S. pneumoniae and H. inuenzae are also prevalent in
this age bracket. The ora in these early newborns may be similar to the typical
AOM in children older than six weeks. However, earlier studies did nd
Staphylococcus aureus as an additional pathogen in this age group [1].
Many specialists formerly thought that the MEE linked to OME was sterile
because middle ear uid cultures acquired during tympanocentesis rarely grew bacteria. Recent research has shown that patients with chronic MEE are more likely to
demonstrate positive results in middle-ear bacterial cultures (30–50% occurrence).
Among many aerobic and anaerobic bacteria that can be grown in these cultures, the
most prevalent ones are S. pneumoniae, H. inuenzae, M. catarrhalis, and group A
streptococci [1].
Compared to AOM caused by other bacterial infections, M. catarrhalis-induced
AOM differs in various respects. There is no mastoiditis, a decreased incidence of
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A. Budak et al.
spontaneous perforation of the tympanic membrane, a higher proportion of mixed
infections, and a younger age at diagnosis [8].
Researchers found bacterial DNA in MEE samples previously found to be sterile
using regular bacterial culture techniques. This nding lends credence to the idea
that bacteria are present in the MEE of OME patients. A PCR experiment showed
that 77.3% of MEE samples tested positive for at least one prevalent AOM pathogen, such as S. pneumoniae, H. inuenzae, or M. catarrhalis I [1].
P. aeruginosa, S. aureus, Corynebacterium species, and Klebsiella pneumoniae
are the most commonly found organisms in chronic suppurative OM.It is unclear if
these infections reach the middle ear through the perforated TM or a TT from the
EAC or if they enter by the ET from the nasopharynx (as do the microorganisms
responsible for AOM) [1].
It is now widely acknowledged that Helicobacter pylori plays a role in children
with OME [9]. Its isolation from tonsillar and adenoid tissue in patients with OME,
as well as from the middle ear, provides evidence that this agent might be the cause
of OME [1].
One of the pathogens linked to OME is the gram-positive bacteria Alloiococcus
otitidis [10, 11]. This particular organism has also been suspected to be one of the
most common bacteria implicated in AOM and OME. It has also been found in
individuals who have taken antibiotics like erythromycin or beta-lactams. Additional
research is required to uncover the organism’s pathogenic function in OM [1].
16.3.2.2 Viral Pathogens
Many researchers have hypothesized that respiratory viruses have a role in the etiology of AOM due to the high prevalence of acute viral URI as a risk factor for this
condition [1].
Much research supports this theory by demonstrating how specic respiratory
viruses can induce mucosal inammation, which causes ETD, enhanced bacterial
colonization and adherence, and, ultimately, AOM.Viruses can change how the
body reacts to AOM, which can cause chronic otitis media elongation, and changes
in the host immunological response [1].
Viruses that are often linked to acute otitis media include the following: adenovirus, respiratory syncytial virus (RSV), inuenza, parainuenza, rhinovirus, and
inuenza. Children contracting human parechovirus type 1 (HPeV1) may experience OM and cough [12]. Half of the 3-month follow-up periods with HPeV1 infection developed OM, compared to 14% without infection; 15% of episodes of
recurrent OM had positive HPeV results in the middle ear uid [1].
16.3.2.3 Factors Related toAllergies
• It is still not known how OM relates to allergies in the pediatric population.
Because their immune systems are still maturing, children under the age of two
to four years are not likely to have allergies as a cause of recurrent AOM.Despite
abundant evidence linking allergies to the development of OM in older children,
a large body of research suggests that allergens do not cause middle ear ill-
ness [1].
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339
Some arguments in favor of and against allergy’s etiologic role in OM [1] are as
follows:
• Many patients with OM also have allergic respiratory diseases, such as asthma or
allergic rhinitis.
• Skin or radio allegro-sorbent testing (RAST) returns positive for many patients
with OM.
• Middle ear mucosa contains mast cells. However, most studies do not demon-
strate signicantly elevated eosinophils and immunoglobulin E (IgE) levels in
the MEE of OM patients.
• Although most major allergens, like tree and grass pollens, peak in the late spring
and early fall, OM is most common in the winter and early spring.
• Aggressive allergy management improves symptoms related to the nose and
other body parts, but it does little to help with middle ear disease in patients with
allergies and OM [1].
16.3.3 Environmental Factors
16.3.3.1 Infant Feeding Methods
Numerous studies have documented the protective effects of breastfeeding against
OM.According to the strongest of these studies, only infants nursed exclusively for
the rst three to six months of life show this advantage. This period of breastfeeding
results in a 13% decrease in the occurrence of OM.Nursing is believed to have a
protective effect for the rst three to six months and lasts for four to twelve months
after breastfeeding stops [1].
16.3.3.2 Involuntary Exposure toSmoke
Multiple studies [12] have shown that exposure to secondhand smoke increases the
likelihood of developing middle ear illness. According to a systematic evaluation of
45 articles that addressed OM and parental smoking, the pooled hazard ratios for
recurrent OM, MEE, and AOM were 1.48 (95% CI, 1.08–2.04), 1.38 (95% CI,
1.23–1.55), and 1.3 (95% CI, 1.3–1.6), respectively [13].
16.3.3.3 Attendance at aGroup Daycare
The high prevalence of respiratory infections, nasopharyngeal colonization with
pathogenic microorganisms, and OM among daycare attendees is likely due to tight
quarters and interpersonal transmission of microbes.
A large body of meta-analysis has established that being around other young
children, even siblings, in a group daycare setting signicantly increases the likelihood of OM [14]. According to a meta-analysis, the risk for OM increased 2.5-fold
when care was provided outside of the house. Odds ratios for center care against
home care range from 1.6 to 4.0:1, according to other critical reviews of research on
OM and group childcare [1].
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A. Budak et al.
16.4 Classification
Although many classications exist, it is generally agreed upon that there are several subtypes of OM, as follows [1]:
• Acute OM (AOM)
• OM with effusion (OME)
• Chronic suppurative OM
• Adhesive OM [1]
16.5 Signs andSymptoms
AOM implies rapid onset of disease associated with one or more of the following
symptoms [1]:
• Otalgia
• Otorrhea
• Headache
• Fever
• Irritability
• Loss of appetite
• Vomiting
• Diarrhea
OME often follows an episode of AOM.Symptoms that may be indicative of
OME include the following [1]:
• Hearing loss
• Tinnitus
• Vertigo
• Otalgia
Chronic suppurative otitis media is a persistent ear infection that results in tearing or perforation of the eardrum [1].
Adhesive otitis media occurs when a thin, retracted ear drum is adhered onto the
cochlear promontory, narrowing the middle ear space [1].
16.6 Diagnosis
At least one of the following is necessary for a clinical diagnosis of AOM [15–17]:
• Antibiotic treatment seems most effective for children with signicant or notice-
able tympanic membrane erythema and bulging [18]. When bacteria in the mid-
16 Acute Suppurative Otitis Media
341
dle ear cause the tympanic membrane to bulge, it is most likely due to a bacterial
infection [19, 20].
• It can be difcult for young children to pinpoint ear pain caused by acute inam-
mation. Still, symptoms such as fever, prominent reddening of the tympanic
membrane, and middle ear effusion without bulging can indicate early acute oti-
tis media. Manipulation of the pinna may be another sign that AOM is present.
• Acute purulent otorrhea with perforation of the tympanic membrane, unless
acute otitis externa is not the cause [15].
16.7 Treatment
16.7.1 Antibiotic Therapy Versus Observation
Antibiotics should be administered immediately to children with AOM, and if the
symptoms and signs worsen or do not improve after 48–72hours, antibiotic therapy
should be changed. While antibiotic-related side effects (such as diarrhea and rash)
are more common when started quickly, the benets outweigh the risks.
Caregiver preference, the child’s age, the severity of the sickness, and any cooccurring disorders should be considered while considering management options.
In patients between the ages of six months and twelve years, our approach generally
aligns with the American Academy of Pediatrics and American Academy of Family
Physicians protocols [16, 21].
The likelihood of severe infection, sequelae, and recurring AOM is higher in
children. The following patients are at a higher risk of developing severe infection,
complications, or a recurrence: patients with craniofacial deformities, such as a cleft
palate, individuals with impaired immune systems, infants less than six months, and
patients with a toxic appearance are also at risk.
We advise starting antibiotic treatment proactively for these patients at higher
risk. Immediate antibiotic treatment is likely to have comparable effects and a larger
predicted absolute benet in these groups of children compared to lower-risk children, even though these children were typically not included in randomized trials.
For most children who are not at a higher risk of severe infection, sequelae, and
recurring AOM, we recommend starting antibiotic treatment right away instead of
waiting through a period of initial observation [15].
There was less treatment failure and faster symptom resolution with antibiotic
therapy in randomized trials. Despite this, some consider these advantages to be
minimal, and antibiotic side effects can be problematic, including dermatitis and
diarrhea. Therefore, if the child is at least two years old and has unilateral AOM
without signicant symptoms or otorrhea, initial observation may be chosen over
antibiotic therapy if families prefer to do so. Patients aged 2years or younger, as
well as those older than two years old with severe symptoms such as chronic ear
pain for more than 48hours, a temperature of 39°C or higher in the past 48hours,
bilateral atypical or non-specic pain, otorrhea, or unclear follow-up, are more
likely to receive initial antibiotic therapy [15].
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A. Budak et al.
16.7.2 Initial Antibiotic Therapy
Antibiotic therapy for AOM should include the most prevalent bacterial pathogens,
including S. pneumoniae, non-typeable H. inuenzae (NTHi), and Moraxella
catarrhalis. The regimen should also reect the current local antimicrobial resistance patterns [15].
Depending on the risk of beta-lactamase-producing NTHi, amoxicillin or amoxicillin-clavulanate are recommended as the initial medicines [15].
Potential dangers associated with NTHi that produce beta-lactamase include the
following:
• Use of a beta-lactam antibiotic during the past 30 days
• Coexisting purulent conjunctivitis (often caused by NTHi)
• Previous occurrences of AOM that have not responded to amoxicillin (NTHi is
more common in such cases)
Governmental and international public health and infectious disease control centers, such as the World Health Organization and the Centers for Disease Control and
Prevention in the United States, may provide specic references applicable to the
population being treated. Furthermore, the prevalence of pneumococcal vaccination
likely alters disease patterns [22–24].
Children with AOM without risk factors for beta-lactamase-producing NT in a
setting with increased prevalence of penicillin-nonsusceptible S. pneumoniae, such
as the United States, are typically treated with amoxicillin, at a dosage of 90mg/kg
daily, divided into two doses, orally, not to exceed 3g/day [25, 26].
Communities with low frequencies of penicillin-nonsusceptible S. pneumoniae
[15] may benet from lower dosages of amoxicillin, such as 40 mg/kg per day
orally divided into two or three doses, not to exceed 1.5g/day.
Amoxicillin-clavulanate is the chosen antibiotic for children with AOM who are
at an elevated risk for beta-lactamase-producing NTHi, as opposed to other antibiotics [15, 27–30].
For populations where penicillin-resistant Staphylococcus pneumoniae is more
common, the recommended dosage is 90mg/kg of amoxicillin and 6.4mg/kg of
clavulanate, taken orally twice daily (not to exceed 3g amoxicillin per day). Oral
administration of 1–2 g of amoxicillin and 62.5–125 mg of clavulanate every
12hours is recommended for adolescents ≥16years old who can swallow larger
tablets using extended-release amoxicillin–clavulanate [15].
Communities with a lower prevalence of penicillin-nonsusceptible S. pneu-
moniae should use lower doses of the amoxicillin component. For example, 40mg/
kg of amoxicillin and 5.7mg/kg of clavulanate, taken orally divided into two doses,
would be adequate. On the other hand, amoxicillin-clavulanate formulations with a
7:1 amoxicillin-to-clavulanate ratio are sometimes the only formulation available in
a given region [15].
Duration of treatment may vary. A standard duration of treatment is 14days.
Others have suggested that patients younger than two years old and children of any
16 Acute Suppurative Otitis Media
343
age with a history of recurrent auditory outow obstruction or tympanic membrane
perforation may be treated for 10days [15, 31].
Yet others have suggested a duration of treatment for children older than two
years old with a healthy tympanic membrane and no previous episodes of recurrent
AOM of ve to seven days [32].
Children aged 6–23 months had a decreased clinical failure rate (16%) when
treated with 10days of high-dose amoxicillin-clavulanate for AOM compared to
5days of therapy [31]. Children above the age of two years may be suitable for
shorter courses because the clinical failure rate is slightly lower with shorter courses
than longer ones (18% versus 21%) in a meta-analysis of randomized trials in children aged one month to 18years, with an increase in gastrointestinal side effects
with longer courses [32].
16.7.3 Supplemental Programs
The severity of any allergy to penicillin dictates which alternatives to amoxicillin or
amoxicillin-clavulanate may safe to use. Alternative regimens might be less effective against a broader range of standard pathogens [15].
Our recommendation for children who have a mild reaction to penicillin that is
not caused by an IgE-mediated reaction is one of the following [15]:
In children younger than two years old or those of any age with a perforated
tympanic membrane or recurring AOM, the recommended agent is cephalosporins
with a duration of treatment of 10days. In children older than two years of age with
a healthy tympanic membrane and no prior history of AOM recurrence, the recommended duration of treatment is 5–7days [31, 32]. Oral cephalosporin availability
may differ by region, and potential agents include the following:
• Cefdinir, taken orally once a day at a dose of 14mg/kg (not to exceed 600mg/day)
• Cefpodoxime, 10mg/kg orally twice daily (not to exceed 400mg/day)
• Cefuroxime, 30 mg/kg twice daily (not to exceed 1 g/day; no longer sold
in the US)
The aforementioned regimens did not eradicate penicillin-resistant or certain
penicillin-intermediate strains of S. pneumoniae because they failed to attain a high
enough concentration in the middle ear. Compared to amoxicillin or amoxicillinclavulanate, their effectiveness against penicillin-resistant S. pneumoniae is lower
[33]. Compared to amoxicillin-clavulanate, cefuroxime is less effective against
NTHi, which produces beta-lactamase [34].
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