Eur J Clin Microbiol Infect Dis
Acute otitis media with spontaneous tympanic
membrane perforation
N. Principi1 & P. Marchisio1 & C. Rosazza1 & C. S. Sciarrabba1 & S. Esposito1
Received: 10 August 2016
/Accepted: 5 September 2016 #
Springer-Verlag Berlin Heidelberg
2016
Abstract The principal aim of this
review is to present the current
knowledge regarding acute otitis media
(AOM) with spontaneous tympanic
membrane perforation (STMP) and to
address the question of whether AOM
with STMP is a disease with specific
characteristics or a severe case of
AOM. PubMed was used to search for
all studies published over the past 15
years using the key words Bacute otitis
media^ and Bothorrea^
Bspontaneous tympanic membrane
perforation^. More than 250 articles
were found, but only those published in
English and providing data on aspects
related to perforation of infectious
origin were considered. Early
Streptococcus pneumoniae infection
due to invasive pneumococcal strains,
in addition to coinfections and biofilm
production due mainly to non-typeable
Haemophilus influenzae, seem to be
precursors of STMP. However, it is
unclear why some children have several
STMP episodes during the first years of
life that resolve without complications
in adulthood, whereas other children
develop chronic suppurative otitis
media. Although specific aetiological
agents appear to be associated with an
increased risk of AOM with STMP,
further studies are needed to determine
whether AOM with STMP is a distinct
disease with specific aetiological,
clinical and prognostic characteristics
or a more severe case of AOM than the
cases that occur without STMP.
Finally, it is important to identify
preventive methods that are useful not
only in otitis-
* S. Esposito
susanna.esposito@unimi.it
1
Pediatric Highly Intensive Care Unit, Department of
Pathophysiology and Transplantation, Fondazione IRCCS Ca’
Granda Ospedale Maggiore Policlinico, Università degli Studi
di
Milano, Via Commenda 9, 20122 Milan, Italy
or
prone children with uncomplicated
AOM, but also in children with
recurrent AOM and those who
experience several episodes with
STMP.
Introduction
Acute otitis media (AOM) is a common
disease in infants and young children.
In the first 3 years of life, almost all
children experience at least one episode
of this disease, and up to 50 %
experience recurrent episodes (i.e. at
least 4 AOM episodes in 1 year or at
least 3 AOM episodes in 6 months) [1].
AOM is mainly a bacterial disease
caused by Streptococcus pneumoniae,
non-typeable (nt) Haemophilus
influenzae, Moraxella catarrhalis and
Streptococcus pyogenes [2]. In the
majority of cases, even the most severe,

the tympanic membrane, although it
bulges and becomes highly hyperaemic,
remains intact. However, in a non-
negligible number of children,
spontaneous tympanic membrane
perforation (STMP) occurs. The
perforation is generally small and is
typically located in the anterior–inferior
quadrant and limited to the pars tensa
of the eardrum. STMP causes middle-
ear fluid to pass into the external ear
canal. Accumulation of a large amount
of pus in the middle ear cavity during
the first phase ofthe disease is
consideredthe cause ofSTMP. This pus
exerts pressure on the tympanic
membrane blood vessels, causing
ischaemia and necrosis of the eardrum,
and leads to perforation [3]. Because in
most cases, STMP is repaired
spontaneously within a few days
without any further clinical problems, it
is considered a mild AOM
complication.
In some recent guidelines for the
diagnosis and management of AOM,
STMP is considered a sign of severity,
indicating systemic antibiotic
prescription to prevent further clinical
problems [4–6]. On the other hand,
STMP accompanying AOM may be
considered a benign complication
because drainage of pus from the
middle ear results in a rapid and
marked improvement in symptoms and
enables the clinician to prescribe
tailored antimicrobial therapy as soon
as culture results are available. Many
ear–nose–throat (ENT) specialists
suggest middle ear perforation by
means of tympanocentesis for
diagnostic reasons in children at risk of
AOM due to uncommon pathogens or
with reduced sensitivity to
antimicrobials [7]. However, although
it has not been considered so in the
past, AOM with STMP may be a
disease with some specific
characteristics distinguishing it from
uncomplicated AOM. Some studies
suggest that AOM with STMP is
Eur J Clin Microbiol Infect Dis
mainly associated with specific
pathogens, although these studies are
not conclusive [8–11]. Moreover,
prevention of STMP in children with
recurrent AOM episodes is significantly
more difficult than the prevention of
uncomplicated AOM cases [12, 13].
Knowledge of the aetiology,
pathogenesis and outcome of AOM
with STMP may be useful to better
understand the relevance of STMP and
plan adequate preventive and
therapeutic measures for children,
especially those with recurrent AOM.
The principal aim of this review is to
present the current knowledge on AOM
with STMP and to address the question
of whether AOM with STMP is a
distinct disease with specific
characteristics or a severe case of
AOM.
Materials and methods
PubMed was used to search for all
studies published during the last 15
years using the key words Bacute otitis
media^ and Bothorrea^ or
Bspontaneous tympanic membrane
perforation^. More than 250 articles
were found,and onlythose published in
English and providing data on
perforations of infectious origin were
included in the evaluation. In addition,
case reports on uncommon clinical
presentations were excluded. Analysis
of the literature did not permit a
systematic review to be performed
because the studies published from 1
January 2001, to 30 June 2016 covered
different aspects of AOM with STMP,
were heterogeneous, and were not
designed to answer our main question.
Incidence of infectious spontaneous
tympanic membrane perforation
Although the association of STMP with
AOM has been a known clinical
problem for centuries, its incidence has
Eur J Clin Microbiol Infect Dis
never been precisely quantified. Data
derived from epidemiological studies
carried out to evaluate the incidence,
clinical aspects and outcomes of AOM
are conflicting in this regard. Older
studies reported that STMP occurs in 0
% to approximately 30 % of AOMs
diagnosed in younger children [14–17].
A more recent evaluation carried out in
several European countries documented
a global incidence of STMP of
approximately 7 % [18]. However,
there were significant differences
among countries, ranging from 2.1 %
of episodes in Italy and 2.2 % in the
UK to 4.8 % in Spain, 6.8 % in
Germany and 17.2 % in Sweden.
Moreover, ear discharge was reported
in 16.9 % of episodes, ranging from
12.1 % in Italy and 12.7 % in Germany
to 17.3 % in the UK, 17.4 % in Spain
and 24.5 % in Sweden. These
differences may be explained by
differences in recommendations,
health-care-seeking behaviour, and the
diagnostic criteria of AOM [18].
Various factors such as the age and
genetic characteristics of the children
studied, the criteria used for AOM
diagnosis, use of antibiotics and
recording practices can significantly
influence the reported incidence of
OMA with STMP (Table 1). Pukander
[16] and Ingvarsson [17] found that
STMP was more common in children
under 2 years of age than in older
children, with the incidence gradually
declining from 50 % to 15 % in those
older than 8 years. Moreover, the
highest incidence values were found in
the studies with the most stringent
criteria for AOM diagnosis [15]. When
children with minor modifications of
the tympanic membrane leading to
uncertain diagnosis were enrolled, the
incidence of STMP was significantly
lower [16]. In addition, early and
extensive use of antimicrobials for
AOM treatment significantly reduces
AOM complications, including STMP
incidence [19]. Overestimation of
STMP frequency may occur when
epidemiological studies include mainly
otitis-prone children with histories of
previous STMP or patients suffering
from an underlying disease that may
favour AOM development. Similarly,
overestimation is common when studies
are mainly based on parents’ reporting.
In this case, ear discharge due to
external otitis could be considered
pathognomonic of AOM with STMP.
By contrast, underestimation is possible
when AOM with STMP without
significant otorrhoea is not adequately
diagnosed. Finally, the genetic
characteristics of the patients may play
a role in this regard. In a recent study
that evaluated potential associations
between variants in genes encoding for
factors of innate or adaptive immunity
and the occurrence of recurrent AOM
with or without STMP, Esposito et al.
found that the interleukin (IL)-10
rs1800896TC single nucleotide
polymorphism (SNP) and the IL-1α
rs6746923A and AG SNPs were
significantly more and less common
respectively among children without a
history of STMP than
Table 1 Factors associated with a high
incidence of acute otitis media
(AOM) with spontaneous tympanic membrane
perforation (STMP)
Factor
Age <2 years
Stringent criteria used for AOM diagnosis
No use of antimicrobials for AOM
management
Being an otitis-prone child
Specific genetic polymorphisms
among those who suffered from this
complication (odds ratio [OR] 2.17, 95
% confidence interval [CI] 1.09–4.41, p
= 0.02, and OR 0.42, 95 % CI 0.21–
0.84, p = 0.01) [20].
However, it has been demonstrated
that children suffering from a single
episode of AOM with STMP,
regardless of the aetiology, are more

prone than children with uncomplicated
AOM to experiencing recurrences.
Moreover, they are more prone to
developing new episodes with STMP.
Berger studied 271 patients up to 13
years old with AOM, among whom 80
(29.5 %) had STMP [3]. In the 3
months following the first episode, 20
(25 %) of those with STMP
experienced a new AOM episode in
comparison with 24 (12.5 %) of those
without. STMP occurred in 17 out of 20
children with previous perforation (85
%) and in 5 out of 24 of those with
previously intact tympanic membrane
(20.8 %). Similar findings were
reported by Van Cauwenberge et al.
[21]. These authors found that the
higher the number of AOM
recurrences, the higher the likelihood
that STMP might occur. A single
episode of AOM was accompanied by
STMP in 15 % of the children studied.
The frequency of STMP increased to 29
% during the second and third episodes
of AOM and to 40 % in children with
three or more recurrences.
Aetiology of AOM with STMP
The same four pathogens that are
considered the aetiological agents of
uncomplicated AOM can be found in
the external ear canal of patients with
STMP. However, the question remains
whether STMP occurs because some
ear pathogens are more aggressive than
others or because STMP is a
complication independent of the
pathogen that causes AOM.More over,
it is not known why new STMP
recurrences are frequent in children
with recurrent AOM: is it causality, or
are the same pathogens that caused the
first STMP the aetiological agents of
the new episodes? It is difficult to
answer these questions, although the
data seem to suggest that at least some
STMP cases are related to specific
aetiological agents. The evidence seems
particularly significant for S. pyogenes
Eur J Clin Microbiol Infect Dis
and S. pneumoniae, although the
evaluation of the final results of some
studies is complicated by a number of
factors. The first is the widespread use
of the pneumococcal conjugate
vaccines (PCVs) that, after inclusion in
the immunisation schedule of infants
and young children in most countries,
have caused worldwide changes in the
circulation of S. pneumoniae and the
frequency with which all the AOM
pathogens cause this disease. Ben-
Shimol et al. carried out a prospective,
population-based study in southern
Israel in which all AOM episodes
submitted for middle ear fluid (MEF)
culture in children aged <3 years from
2004 through 2015 were included [22].
The incidence of AOM cases due to S.
pneumoniae, ntH. influenzae, M.
catarrhalis and S. pyogenes, and those
that were culture-negative, was
calculated in the period before the
introduction of PCVs and after the
heptavalent PCV (PCV7) vaccine and
the thirteen-valent vaccine (PCV13)
became available. Both pneumococcal
and nonpneumococcal AOM episodes,
including those in which more than one
pathogen was cultured, declined
substantially following sequential
PCV7/PCV13 introduction. The
reduction in non-pneumococcal
episodes was ascribed by these authors
to early prevention of AOM episodes,
resulting in a lower rate of complex,
often nonpneumococcal AOM [22].
The second factor is the reduced
number of studies in which the
aetiologies of uncomplicated and
complicated AOMs have been
evaluated simultaneously.
Tympanocentesis is not routinely
recommended for ethical reasons [6],
and most recent studies of AOM
aetiology have included only cases with
STMP [23, 24]. This practice precludes
any possibility of comparing the two
types of AOM.
Eur J Clin Microbiol Infect Dis
STMP and the role of
Streptococcus pyogenes and
Streptococcus pneumoniae
Despite the above-mentioned
limitations, the available data on S.
pyogenes seem to indicate that this
pathogen is more common in AOM
complicated by STMP than in
uncomplicated cases. Segal et al.
studied 11,311 episodes of AOM,
including both uncomplicated (the great
majority) and complicated cases, and
found that S. pyogenes could be
identified in the
MEF in only 3.1 % of the cases
compared with 47.9%,43.2% and 4.1 %
of nt-H. influenzae, S. pneumoniae and
M. catarrhalis respectively [25].
However, the clinical features of S.
pyogenes AOM were significantly
different and generally more severe
than those of AOM caused by other
pathogens, suggesting that S. pyogenes
might cause faster and more significant
damage to the tympanic membrane.
Episodes of S. pyogenes AOM
occurred mainly with STMP and were
accompanied by high fever and other
systemic findings, such as upper- and
lower-respiratory infections. Similar
results were reported by Leibovitz et al.
in a study in which 5,247 culture-
positive patients with AOM were
enrolled [10]. In the 822 children with
STMP, S. pyogenes was found in a
significantly greater proportion than in
those without (47 out of 822, 5.7 % vs
44 out of 4425, 1 %, p < 0.01). Further
confirmation of the role of Spy in
causing STMP is provided by the data
collected by Grevers et al. [8] in a study
carried out in Germany and by
Marchisio et al. [9] with a retrospective
evaluation performed in Italy. Grevers
et al. studied 100 children with severe
AOM with and without STMP and
were able to detect S. pyogenes in 17 %
of otorrhoea samples and in none of the
tympanocentesis samples [8]. The same
prevalence of MEF samples positive for
S. pyogenes was reported by Marchisio
et al. in their study, in which 705 MEF
specimens were cultured.
As previously reported, the real
importance of S. pneumoniae as a direct
cause of STMP is difficult to ascertain.
However, Palmu et al., in a study
performed before the introduction of
PCVs, reported that initial episodes of
AOM with STMP were mainly due to
this pathogen [11]. Bacterial cultures of
the 74 MEF samples obtained through
STMP revealed a higher proportion of
pneumococci (35 %) and lower
proportions of M. catarrhalis (3 %) and
mixed cultures (3 %) than did the other
MEF cultures. However, pre-existing
perforations that, according to Dagan et
al., suggest recurrent disease [26] were
more likely to contain nt-H. influenzae
(30 %) and mixed pathogens (18 %)
and were less likely to be culture
negative (16 %). On the other hand,
several studies have shown that S.
pneumoniae is an extremely common
cause of early AOM [11, 27, 28], and
many cases are particularly severe
because they are associated with a
significant increase in inflammatory
markers and high fever, intense otalgia,
and, rarely, bacteraemia [29–32]. Early
severe pneumococcal AOM is caused
by the most aggressive serotypes, most
of which were included in PCVs. The
mucosal damage they cause may favour
infections by bacteria with lower
pathogenicity, such as the less invasive
pneumococcal serotypes and nt-H.
influenzae [33]. Mixed infection due to
the pneumococcal serotypes most
commonly carried by healthy subjects
in association with nt-H. influenzae
alone or in combination with other
pathogens were significantly more
common in older children with bilateral
AOM, recurrent episodes, and previous
tympanocentesis. The association
between colonisation with nt-H.
influenzae and recurrent AOM is well
known, but the reason for it is unclear.
By contrast, cases due to single S.

pneumoniae infections were associated
with serotypes shown to have higher
pathogenicity. The type of damage
caused by the invasive pneumococcal
serotypes and whether STMP can occur
as a consequence of this damage are
presently unsolved problems. However,
several experimental model systems
have demonstrated that cell-wall
components of S. pneumoniae play a
major role in generating inflammation
[34–37]. The wall matrix strongly
activates the alternative pathway of the
complement cascade and induces
platelet-activating factor and the
secretion of cytokines [38, 39].
Inflammation and direct effects of
pneumolysin cause changes in the hair
cells. However, the ability to penetrate
the round window is the main proof of
pathogenicity. Moreover,
pneumococcal strains deficient in some
of these cellular components can cause
less damage than normal strains,
supporting the hypothesis that S.
pneumoniae is important in
pathogenesis. The ability of S.
pneumoniae to penetrate the round
window membrane is strictly related to
the presence of pneumococcal surface
protein A (PspA) and pneumococcal
surface antigen A (PsaA) [40].
Moreover, strains defective in PspA
have reduced virulence in the inner ear
[41].
Non-typeable Haemophilus
influenzae, Moraxella
catarrhalis and other pathogens, and
the development
of STMP
Data suggesting a direct relationship
between ear infection with pathogens
other than S. pyogenes and S.
pneumoniae and the development of
AOM with STMP are lacking.
However, there is evidence of the
dominance of ntH. influenzae in ear
discharge from indigenous Australian
children with AOM and STMP [42].
Eur J Clin Microbiol Infect Dis
Similar findings were reported by
Grevers et al. [8], who found that ntH.
influenzae was the most common
aetiological agent both in the group of
patients with STMP and in the group of
children who underwent
tympanocentesis (18 % and 13 % of
samples respectively). Generally, non-
pneumococcal AOMs develop in
children older than those due to S.
pneumoniae or, if they are diagnosed
during infancy, they occur after a first
severe pneumococcal AOM. The main
pathogens associated with these AOM
episodes are nt-H. influenzae alone or a
mixture of ear pathogens. As has
already been reported, associations
between the less aggressive S.
pneumoniae and ntH. influenzae are
common. However, co-infections with
M. catarrhalis or S. pyogenes can also
be detected, particularly when
molecular methods of bacterial
identification are used [24]. In most of
the cases, these infections are clinically
mild. Palmu et al. reported that nt-H.
influenzae cases had lower fevers and
lower concentrations of inflammatory
markers [11]. Nonetheless, nt-H.
influenzae infections were frequently
associated with a history of previous
perforation, increased risk of treatment
failure and a high number of
recurrences, including episodes with
STMP [11, 43]. The main driver of the
role played by nt-H. influenzae and
other pathogens in the determination of
recurrent AOM and treatment failures
seems to be their ability to form a
biofilm in the middle ear. All ear
pathogens are capable of forming
biofilm, although data for the biofilm-
forming phenotype of nt-H. influenzae
are more extensive, whereas those for
S. pneumoniae and M. catarrhalis are
evolving. Clinical isolates of ntH.
influenzae are able to form a well-
developed biofilm in the middle ear of
a chinchilla host within 5 days of a
direct challenge to the middle-ear
cavity [43]. Biofilms are detectable in
Eur J Clin Microbiol Infect Dis
the middle ear of children with
recurrent AOM and persist even after
treatment during clinical remission
[44]. Biofilms are highly organised
multicellular bacterial communities
encased in an extracellular polymeric
matrix [45]. Bacteria within biofilms
have reduced growth rates and distinct
transcriptomes [46]. Expression of
genes that encode proteins inducing
tissue damage, such as pneumolysin, is
downregulated [47], whereas that of
genes favouring colonisation, such as
the type IV pilus of nt-H. influenzae, is
increased [48]. Moreover, in
multispecies biofilms, synergistic
interactions can affect overall function,
further increasing in resistance and
virulence [49]. For example, in the
chinchilla model of AOM,
polymicrobial infection promoted
M. catarrhalis persistence beyond the
level seen in animals infected only with
M. catarrhalis [50]. Together with the
physical barrier provided by the matrix,
all these functional modifications
explain why bacteria within the biofilm
have increased resistance to the
humoral and cellular mechanisms of
host immunity and to antibiotics [51].
Moreover, these changes favour the
persistence of bacteria at the site of the
infection even after treatment, resulting
in recurrences and possibly in chronic
disease. It is not known whether
synergies between specific pathogens
can lead to STMP. Further evidence is
needed to explain why, despite
numerous recurrences, many children
never experience STMP, whereas
others with similar characteristics
develop STMP in association with
several new AOM episodes. Moreover,
it is not clear why some children are
prone to carrying S. pneumoniae,
whereas others have a preference for
nt-H. influenzae and this difference
could play a role in the pediatric
population at risk of AOM with STMP.
A different problem arises when the
role of Staphylococcus aureus is
analysed. This pathogen is not
considered a common cause of AOM,
because it was not usually detected in
studies evaluating the aetiology of
uncomplicated AOM [2]. By contrast,
in studies in which the microbiology of
AOM with STMP was evaluated, S.
aureus was cultured in a significant
number of cases. Marchisio et al.
detected S. aureus in 49 out of 487
(10.1 %) samples of MEF collected
from the ear canal of children with
STMP [9]. Interestingly, unlike other
common ear pathogens, which are
frequently found in co-infections, S.
aureus was almost always detected as a
single pathogen (48 out of 49, 97.9 %).
Moreover, it was mainly found in
children who had experienced previous
episodes of AOM with STMP,
suggesting a possible relationship
between the pathogen and the
development of this complication. More
recently, Yatsyshina et al. tested MEF
found in the ear canal by molecular
methods and reported that S. aureus
was detected in 30 out of 179 (16.8 %)
patients, although always in
coinfections with other common ear
pathogens [24]. S. aureus is a common
coloniser of the skin, and in the absence
of myringotomy its detection in the
MEF may be the result of sample
contamination during MEF collection.
However, given the potentially negative
course of S. aureus infection and the
increased circulation of community-
acquired strains resistant to drugs of
choice for AOM, further studies should
be aimed at clarifying its role in AOM
with STMP.
Prevention of spontaneous tympanic
membrane perforation in children with
recurrent AOM
Attempts to prevent new episodes of
AOM in otitis-prone children are
considered mandatory for several
reasons. Although a single episode is
generally mild, repeated episodes

increase the risk of complications [52].
To limit the incidence of new episodes
of AOM, several preventive methods
have been proposed and tested [53, 54].
Among the preventive methods,
administration of influenza vaccine has
been considered because AOM is
almost always preceded by an upper
respiratory tract infection (URTI) and
because during winter, when the
incidence of AOM increases, a large
number of URTI are due to influenza
viruses [55]. Despite some negative
results, most studies have found that
vaccination is beneficial [56]. However,
Marchisio et al. reported that
intramuscular administration of
injectable trivalent inactivated
virosomal adjuvanted influenza vaccine
reduced AOMrelated morbidity in
children with a history of recurrent
AOM, but was significantly less
effective in children with a history of
recurrent STMP [13]. These authors
studied 180 children who had
experienced at least three episodes of
AOM in the last 6 months or four or
more in the last year and administered
the vaccine to 90 of them, whereas the
remaining 90 received a placebo.
AOM-related morbidity was monitored
every 4–6 weeks for 6 months. In this
period, the number of children
experiencing at least one AOM episode
was significantly smaller in the
vaccinated group (p < 0.001), as was
the mean number of AOM episodes (p
= 0.03), the mean number of AOM
episodes without perforation (p <
0.001), and the mean number of
antibiotic courses (p < 0.001). The only
factor that seemed to be associated with
a significant efficacy of the influenza
vaccine in preventing AOM was the
absence of a history of recurrent
perforation (crude OR, p = 0.01;
adjusted OR, p = 0.006). These results
support the concept that children with
recurrent AOM and STMP are in part
different from those with recurrent
AOM without STMP. Another
Eur J Clin Microbiol Infect Dis
possibility is that influenza vaccination
in children with recurrent AOM and
STMP is not able to reduce nt-
H. influenzae burden. On the contrary,
there are studies in animal models and
humans showing that influenza
vaccination can reduce the burden of
pneumococcal and staphylococcal
infections [57, 58].
Vitamin D (VD) also has is not very
effective in preventing recurrent AOM
with STMP. VD plays a strong
immunomodulatory role by acting on
the cells of the innate immune system
to inhibit proinflammatory cytokine
production and induce antimicrobial
peptide synthesis [59–64].
Administration of 1,000 IU/day of VD
to children with recurrent AOM
confirmed the general benefit of the
vitamin in children with
hypovitaminosis by restoring normal
serum values in most cases,
significantly reducing the risk of
uncomplicated AOM [12]. However,
when results were analysed according
to the characteristics of the new
episodes, it was shown that whereas
children treated with VD experienced a
significant difference in the number of
cases of uncomplicated AOM (p <
0.001), there was no difference in the
number of children
Table 2 Aetiological agents related to an
increased risk of AOM with STMP
Aetiological agent
Streptococcus pneumoniae infection due to
invasive pneumococcal strains
Infections due to Streptococcus pyogenes
Co-infections with pathogens including non-
typeable Haemophilus influenzae and
Moraxella catarrhalis
Biofilm production due to non-typeable
Haemophilus influenzae
experiencing at least one episode of
STMP. In comparison with untreated
controls, the mean number of AOM
episodes per child diagnosed in the
VD-treated group was significantly
Eur J Clin Microbiol Infect Dis
lower (0.7 ± 0.8 versus 1.4 ± 1.4; p =
0.003), with a marked difference in the
mean number of uncomplicated AOM
episodes (0.2 versus 0.9; p = 0.0001),
and no difference in the mean number
of AOM episodes with STMP (0.5
versus 0.3; p = 0.08) [12].
Conclusions
This review showed that specific
aetiological agents appear to be related
to an increased risk of AOM with
STMP (Table 2). An early S.
pneumoniae infection due to invasive
pneumococcal strains, in addition to
coinfections and biofilm production
mainly due to nt-H. influenzae, seem to
affect the severity of the disease.
However, further studies are needed to
elucidate whether AOM with STMP is
a distinct disease with specific
aetiological, clinical and prognostic
characteristics or a severe case of
AOM. It is unclear why some children
have several STMP episodes during the
first years of life that resolve without
problems in adulthood, whereas other
children develop chronic suppurative
otitis media. Furthermore, studies on
the best antibiotic treatment of STMP
are needed. Finally, it is important to
identify preventive methods that are
useful not only in otitis-prone children
with uncomplicated AOM, but also in
children with recurrent AOM who have
experienced several episodes of STMP.
Compliance with ethical standards
Conflict of interest
conflicts of interest to declare.
Ethical approval All the studies mentioned in
this review obtained approval from the Ethics
Committee.
Informed consent In all the studies mentioned
in this review, written informed consent was
obtained from patients or their parents or legal
guardians.
Funding This review was supported by a grant
from the Italian Ministry of Health
(Fondazione IRCCS Ca’ Granda Ospedale
Maggiore Policlinico Ricerca Corrente Grant
2016 850/02).
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