Jurnal

DEPARTMENT OF
ANU LAULAJAINEN-HONGISTO Acute severe complications of otitis media in children and adults
OTORHINOLARYNGOLOGY
– HEAD AND NECK SURGERY
HELSINKI UNIVERSITY HOSPITAL
FACULTY OF MEDICINE
UNIVERSITY OF HELSINKI
ACUTE
SEVERE COMPLICATIONS
OF OTITIS MEDIA
IN CHILDREN AND ADULTS
ANU LAULAJAINEN-HONGISTO
ISBN 978-951-51-2169-1 (paperback)
ISBN 978-951-51-2170-7 (PDF)
Hansaprint
Vantaa 2016
Department of Otorhinolaryngology – Head and Neck Surgery
Faculty of Medicine
University of Helsinki
Helsinki, Finland
ACUTE
OF OTITIS MEDIA
ANU LAULAJAINENͳHONGISTO
Academic dissertation
To be presented for public examination with the permission of

the Medical Faculty of the University of Helsinki
at the University of Helsinki in Auditorium 107 at the Athena building,
Siltavuorenpenger 3 A, Helsinki,
on 27 May 2016, at 12 noon.
Helsinki 2016
Supervised by
Professor Jussi Jero

University of Helsinki and Helsinki University Hospital
Helsinki, Finland
Docent Antti A. Aarnisalo

Helsinki, Finland
Reviewed by
Professor Harri Saxén

Children’s Hospital
Helsinki, Finland
Docent Juha-Pekka Vasama

Department of Otorhinolaryngology
University of Tampere and Tampere University Hospital
Tampere, Finland
Opponent
Professor Olli-Pekka Alho

Department of Otorhinolaryngology
University of Oulu and Oulu University Hospital
Oulu, Finland
Layout: Tinde Päivärinta/PSWFolders Oy
ISBN 978-951-51-2169-1 (paperback)

ISBN 978-951-51-2170-7 (PDF)
http://ethesis.helsinki.fi
Hansaprint, Vantaa 2016

To Jonatan, Emil and Oskar
Education is not the learning of facts

but the training of the mind to think
Albert Einstein
ABSTRACT
Acute otitis media (AOM) is an infection that is particularly common in children. The bacterial
etiology of AOM, in both children and adults, affects its clinical picture. While in some cases
the infection can simply be carefully monitored without treatment, antimicrobials are often
prescribed. Caution is required, however, when prescribing antimicrobials as their excessive use
has led to antimicrobial resistance; this resistance has been seen among some of the causative
pathogens for these infections.
Before the development of antimicrobial treatment, complications due to middle ear infections
were common, potentially causing severe symptoms or even death. Some middle ear infections
spread into surrounding structures, leading to intratemporal or extratemporal (extracranial or
intracranial) complications. This thesis focuses on complicated otitis media and the causative
factors of its complications.
In the first two studies, we evaluated the medical records of all (n=100) children (0-16 years
old) hospitalized at the Department of Otorhinolaryngology in the Helsinki University Hospital
from 2003 to 2012 for acute mastoiditis (AM) or AOM, as well as the infection’s bacteriology
in relation to the patient’s clinical findings and treatment. Using this information, we analyzed
the differences in the etiologies and clinical pictures of those children hospitalized due to AOM
compared to AM.
In our third study, we examined the medical records of all (n=166) patients hospitalized at our
institution from 1970 to 2012 due to intracranial abscesses (IA), including those of otogenic
background (oIA).
In the fourth study, we evaluated the bacteriology in relation to the patients’ clinical findings
and treatment in all (n=160) adult patients treated at our institution from 2003 to 2012 for AOM
or acute mastoid infection. In adults, acute mastoid infection was subclassified into AM, latent
mastoiditis (LM), and AM following chronic middle ear infection (AMc).
The clinical picture of AM in children differed according to the causative pathogen. Streptococcus
pneumoniae (Pnc), especially its resistant strains, caused severe symptoms and often led to
mastoidectomies. Pseudomonas aeruginosa (Ps) typically affected older children with prior
tympanostomy tubes and generally caused milder symptoms. Furthermore, the bacteriological
etiology of hospitalized AOM and AM patients was different compared to outpatient AOM. Two
of the typical AOM pathogens, Haemophilus influenzae (Hi) and Moraxella catarrhalis (Mc),
were uncommon among the hospitalized patients. Pnc, especially its resistant strains, was less
common in children hospitalized for AOM compared to AM, and less common in adults than
children. Streptococcus pyogenes (StrA) and Ps were both linked to otorrhea and were found only
in older children.
Over our 42 year study period, oIAs became less common and typically developed following
chronic middle ear infections, often in connection with cholesteatoma.
4
In adults, the bacteriological etiology and clinical picture of AMc differed from AOM as well as
the other acute mastoid infection types (AM, LM). AOM and AM led to less surgical procedures
than the more prolonged forms of acute mastoid infection (LM, AMc).
In children, the hospitalized cases of AOM and AM differed from outpatient AOM. In adults,
severe AOM, AM, and LM seem to compose a continuum that may lead to chronic otitis media
and its acute complications, including oIAs. Otogenic IAs are quite rare, however, and became
less common over our study period.
5
TIIVISTELMÄ
Äkillinen välikorvatulehdus on yksi lasten tavallisimmista taudeista; aikuisilla se on lapsia
harvinaisempi. Vaikka pelkkä seuranta voi riittää äkillisen välikorvatulehduksen hoidoksi, usein
hoitona käytetään antibioottia. Välikorvatulehdus voi levitä välikorvaa ympäröiviin rakenteisiin
aiheuttaen vakaviakin komplikaatioita (esim. kartiolisäketulehdus, aivopaise). Ennen
antibioottien kehittämistä välikorvatulehduksen komplikaatioita esiintyi nykyistä enemmän.
Turhaa antibioottien käyttöä on vältettävä, mutta komplisoitunutta tautia sairastavat potilaat on
tunnistettava varhain ja hoidettava tehokkaasti. Tässä tutkimuksessa selvitettiin komplisoituneen
välikorvatulehduksen taustatekijöitä.
Äkillisen kartiolisäketulehduksen tai välikorvatulehduksen vuoksi HUS:n Korvaklinikalle

sairaalahoitoon vuosina 2003–2012 joutuneiden potilaiden (100 lasta, 160 aikuista)
sairauskertomustiedot käytiin läpi. Bakteereiden suhdetta taudinkuvaan ja hoitoon arvioitiin,
ja potilasryhmien tietoja vertailtiin keskenään. Kaikkien aivopaiseen vuoksi sairaalahoitoon
HUS:n Neurokirurgian klinikalle vuosina 1970–2012 joutuneiden potilaiden (166)
sairauskertomustiedot käytiin läpi. Aineistoon sisältyivät myös korvaperäiset aivopaiseet.
Streptococcus pneumoniae on tavallinen välikorvatulehduksen taudinaiheuttaja, myös tässä

tutkimuksessa. Erityisesti kartiolisäketulehdusta sairastavilla lapsipotilailla esiintyi muita
lapsia ja aikuisia enemmän tavallisille korvatulehduksen hoidossa käytettäville antibiooteille
vastustuskykyisiä Streptococcus pneumoniae -kantoja. Nämä johtivat muita taudinaiheuttajia
useammin kartiolisäkkeen puhdistusleikkauksiin. Kaksi tavallisimmista äkillisen
välikorvatulehduksen taudinaiheuttajista, Haemophilus influenzae ja Moraxella catarrhalis, olivat
sen sijaan harvinaisia komplisoitunutta välikorvatulehdusta sairastavilla potilailla. Aikuisilla
pitkäkestoisten välikorvatulehdusten äkillisiin komplikaatioihin liittyi enemmän leikkaushoidon
tarvetta kuin äkillisten välikorvatulehdusten komplikaatioihin. Korvaperäiset aivopaiseet
harvinaistuivat ajan kuluessa, ja ne liittyivät yleensä pitkäkestoiseen välikorvatulehdukseen ja
helmiäiskasvamaan.
Avohoidossa hoidettava välikorvatulehdus eroaa sairaalahoitoon johtaneesta

välikorvatulehduksesta ja kartiolisäketulehduksesta. Välikorvatulehduksen komplikaatiot
voivat johtaa pitkäkestoiseen välikorvatulehdukseen ja sen akuutteihin komplikaatioihin, myös
aivopaiseisiin. Korvaperäiset aivopaiseet olivat tutkimusaineistossa kuitenkin harvinaisia, ja
niiden määrä vähentyi tutkimusjakson kuluessa.
6
LIST OF ORIGINAL PUBLICATIONS
This thesis is based on the following publications, which are referred to by their roman numerals:
I Laulajainen-Hongisto A, Saat R, Lempinen L, Markkola A, Aarnisalo AA, Jero J.

Bacteriology in relation to clinical findings and treatment of acute mastoiditis in children.
Int J Pediatr Otorhinolaryngol. 2014;78(12):2072-8.
II Laulajainen-Hongisto A, Saat R, Lempinen L, Aarnisalo AA, Jero J. Children hospitalized

due to acute otitis media: how does this condition differ from acute mastoiditis? Int J
Pediatr Otorhinolaryngol. 2015;79(9):1429-35.
III Laulajainen-Hongisto A, Lempinen L, Färkkilä E, Saat R, Markkola A, Leskinen K,

Blomstedt G, Aarnisalo AA, Jero J. Intracranial abscesses over the last four decades;
changes in etiology, diagnostics, treatment, and outcome. Infect Dis. 2015 Nov 23:1-7
(Epub ahead of print)*
IV Laulajainen-Hongisto A, Jero J, Markkola A, Saat R, Aarnisalo AA. Severe acute otitis

media and acute mastoiditis in adults. (Submitted)
The original publications (I-III) have been reprinted here with the kind permission of their
copyright holders.
* This is the authors accepted manuscript of an article published as the version of record in Infectious Diseases,
Published online: 23 Nov2015, http://www.tandfonline.com/doi/pdf/10.3109/23744235.2015.1113557
7
CONTENTS
Abstract ......................................................................................................................................................4
Tiivistelmä .................................................................................................................................................6
List of original publications ...................................................................................................................7
Contents .....................................................................................................................................................8
Abbreviations......................................................................................................................................... 10
1 Introduction ................................................................................................................................... 11
2 Review of the literature ................................................................................................................ 12
2.1 Historical aspects ................................................................................................................ 12
2.2 Anatomy............................................................................................................................... 13
The ear and temporal bone ................................................................................................ 13
The brain and intracranial space in relation to the ear .................................................. 16
2.3 Otitis media ......................................................................................................................... 17
Definition, epidemiology and risk factors ....................................................................... 17
Etiopathogenesis ................................................................................................................. 18
Bacteriology ......................................................................................................................... 19
Vaccinations......................................................................................................................... 20
Diagnostics and treatment................................................................................................. 21
2.4 Complications of otitis media ........................................................................................... 23
Intratemporal complications ............................................................................................. 24
Mastoiditis ......................................................................................................... 24
Facial nerve paresis ........................................................................................... 26
Petrositis ............................................................................................................. 26
Labyrinthitis ...................................................................................................... 26
Extratemporal complications ............................................................................................ 27
Extracranial complications ...................................................................................... 28
Subperiosteal abscess........................................................................................ 28
Bezold’s abscess ................................................................................................. 28
Intracranial complications ....................................................................................... 28
Meningitis .......................................................................................................... 28
Intracranial abscesses ....................................................................................... 28
Brain abscess ............................................................................................ 30
Epidural abscess ....................................................................................... 30
Subdural abscess ...................................................................................... 30
Sinus thrombosis............................................................................................... 30
Otitic hydrocephalus ........................................................................................ 30
3 Aims of the study........................................................................................................................... 31
8
4 Patients and methods ................................................................................................................... 32
4.1 Diagnostic and inclusion criteria...................................................................................... 32
Acute otitis media (AOM) ....................................................................................... 32
Acute mastoiditis (AM) ........................................................................................... 32
Latent mastoiditis (LM) ........................................................................................... 32
Acute mastoiditis of a chronic ear (AMc).............................................................. 32
Intracranial abscesses ............................................................................................... 32
4.2 Patients ................................................................................................................................. 32
4.3 Methods ............................................................................................................................... 33
Children hospitalized due to AM (I) and AOM (II) ............................................ 33
Intracranial abscesses (III)....................................................................................... 33
Adults hospitalized due to AOM, AM, LM, or AMc (IV) ................................... 33
4.4 Statistics................................................................................................................................ 34
4.5 Ethical considerations ........................................................................................................ 34
5 Results ............................................................................................................................................. 35
Children hospitalized due to AM (I) ........................................................................................... 35
Children hospitalized due to AOM (II) ....................................................................................... 37
Comparison of children hospitalized due to AM and AOM (I,II) .......................................... 38
Intracranial abscesses (III) ............................................................................................................ 40
Adults hospitalized due to AOM, AM, LM, or AMc (IV)......................................................... 42
6 Discussion....................................................................................................................................... 46
Complications of otitis media ....................................................................................................... 46
Pathogens of complicated otitis media ........................................................................................ 46
Complicated otitis media in children and adults ....................................................................... 48
Intra- and extratemporal complications of otitis media............................................................ 49
Diagnostics of complicated otitis media...................................................................................... 49
Treatment of complicated otitis media ........................................................................................ 50
Future perspectives......................................................................................................................... 51
7 Conclusion...................................................................................................................................... 53
Acknowledgements ............................................................................................................................... 54
References ............................................................................................................................................... 56
Original publications ........................................................................................................................... 66
9
ABBREVIATIONS
AM acute mastoiditis
AMc acute mastoiditis in a patient with CSOM
AOM acute otitis media
CSOM chronic suppurative otitis media
CRP C-reactive protein (mg/l)
CT computed tomography
EAC external auditory canal
ENT ear, nose, and throat
ET Eustachian tube
Hi Haemophilus influenzae (non-encapsulated)
IA intracranial abscess
ICD-9 international classification of diseases, version 9
ICD-10 international classification of diseases, version 10
LM latent mastoiditis
Mc Moraxella catarrhalis
MEE middle ear effusion
MIC minimal inhibitory concentration (mg/l)
MRI magnetic resonance imaging
oIA otogenic intracranial abscess
OM otitis media
OME otitis media with effusion
PCV pneumococcal conjugate vaccine
Pnc Streptococcus pneumoniae
Ps Pseudomonas aeruginosa
Sa Staphylococcus aureus
StrA Streptococcus pyogenes
TM tympanic membrane
URTI upper respiratory tract infections
WBC leukocyte count (E9/l)
10
Introduction
1 INTRODUCTION
Acute otitis media (AOM), infection of the middle ear, is one of the most common infections
in children, though it affects adults as well. Middle ear infections, and the problems caused by
them, however, differ between children and adults. Children are prone to developing AOM due
to anatomical and immunological immaturity, whereas adult ear infections are typically chronic
in nature (Bluestone 2008). AOM is treated with antimicrobials, or in some cases by expectant
observation.
Viral upper respiratory tract infections (URTI) often precede bacterial AOM, especially
in children. The AOM-causing bacteria typically originate from the nasopharynx via the
Eustachian tube (ET). AOM caused by Streptococcus pneumoniae (Pnc) has been associated with
a severe form of the infection, with fever and earache, while AOM caused by non-encapsulated
Haemophilus influenzae (Hi) has been associated with conjunctivitis (Palmu et al. 2004). Hi and
Moraxella catarrhalis (Mc) rarely cause complications, whereas Streptococcus pyogenes (StrA) has
been associated with complicated AOM (Segal 2005). In prolonged middle ear infections, middle
ear mucosa swells, resulting in hypoxemia and metabolic changes which leads to the selection of
pathogens that survive in these conditions.
Tympanic membrane (TM) perforations and bone erosions may allow for the spreading of
infection to and from the middle ear, allowing for complications to arise. Complications of
otitis media (OM) can be classified into intratemporal and extratemporal (either intracranial
or extracranial). Anatomical or immunological conditions may predispose patients to these
complications. The thinner bony structures of children may more easily be resorbed by infection,
allowing for easier development of AOM complications (Stenfeldt et al. 2014).
Before the development of antimicrobial treatment, complications of OM were common and

caused severe morbidity, and even death (Valentine 1924, Palva et al. 1959). Complications due
to OM have since become uncommon, but have not completely disappeared. Furthermore, the
clinical picture of complications has changed with antimicrobial treatment potentially masking
symptoms and leading to a prolonged, mild form of disease (Faye-Lund 1989).
Complications of OM can develop following untreated or incompletely treated infections as well as

cases with adequate antimicrobial treatment, and are also seen with infections caused by bacteria
that are resistant to antibiotics (Zapalak et al. 2002). Antimicrobial resistance of pathogens has
developed due to the excessive use of antibiotics. While patients with severe infections, or those
at risk of developing complications, should be effectively treated, antimicrobial treatment may be
unnecessary in patients with only mild infection.
We need to better understand which patients require antimicrobial treatment to achieve a

successful recovery, and which patient’s infections will resolve themselves - to be able to do this,
we must study complicated cases of OM; this study aims to do that.
11
Review of the Literature
2 REVIEW OF THE LITERATURE
2.1 Historical aspects
“Acute pain of the ear, with continual and strong fever, is to be dreaded; for there is
danger that the man may become delirious and die. Since, then, this is a hazardous spot,
one ought to pay particular attention to all these symptoms from the commencement.
Younger persons die of this disease on the seventh day, or still earlier, but old persons
much later; for the fevers and delirium less frequently supervene upon them, and on
that account the ears previously come to a suppuration, but at these periods of life,
relapses of the disease coming on generally prove fatal. Younger persons die before
the ear suppurates; only if white matter run from the ear, there may be hope that a
younger person will recover, provided any other favorable symptom be combined”
(Hippocrates, 400 BC).
Despite the immense advancements in medicine since Hippocrates’ time, his description
of complicated OM does not sound outdated to a modern otorhinolaryngologist. Not only
have the knowledge of anatomy and the understanding of the disease’s underlying conditions
advanced since his time, but fairly recent great developments have been made in the diagnostics,
and treatment of diseases. While living in the age of antimicrobials means we are often able to
prevent the most severe complications that Hippocrates saw, we still see patients, young and old,
presenting with OM and its complications.
Before the late 1800s, intracranial abscesses (IA) almost always led to death (Mathisen et al.
1997). Then antimicrobials arrived, with sulfonamides being introduced in the 1930s and
penicillin, streptomycin, chloramphenicol, and tetracyclins all being introduced in the 1940s
(Simpson 2013). Before antibiotics, complications due to OM were difficult to treat, with StrA
being the most common pathogen that led to AOM complications (Valentine 1924, Palva et al.
1959, Vergison 2008).
In less than 100 years since their introduction, however, the effectiveness of antimicrobials has
been reduced. Currently, bacterial resistance to antimicrobials is a growing global problem due,
in large part, to the often excessive use of antibiotics in the human medical field as well as in agri-
and aquaculture (Silbergeld et al. 2008, Heuer et al. 2009).
Thankfully, tools to aid in the diagnostics and treatment of OM and its complications have been
developed. Computed tomography (CT) imaging was introduced in the 1970s (Simpson 2013),
and magnetic resonance imaging (MRI) was utilized in clinical practice starting in the early
1980s (Ai et al. 2012).
12
2.1 Anatomy
The ear and temporal bone
The outer ear consists of the pinna (auricula) and the external auditory canal (EAC). At the end
of the EAC lies the TM, which forms the lateral border of the middle ear (Figure 1).
The middle ear is an air-filled cavity lined by mucous membrane; situated inside the temporal
bone it consists of the squamous, petrous, mastoid, tympanic, and styloid bones (Figure 2).
The uppermost part of the middle ear, the epitympanum or atticus, is superior to the TM. The
structure of the TM’s superior portion (pars flaccida, Schrapnell’s membrane) is less robust than
that of the main part (pars tensa). Negative pressure in the middle ear may lead to retractions
and perforations of the pars flaccida.
The middle ear connects to the nasopharynx by the ET, which helps in pressurizing the middle
ear and in removing middle ear secretion. The ET is shorter, softer, and has a more horizontal
course in children than adults. Running medially to the ET is the internal carotid artery.
The auditory ossicles - malleus, incus, and stapes - form a chain with the malleus attaching to the
TM in the umbo, while the stapes footplate is situated over the oval window. The whole chain is
attached to the roof of the middle ear via ligaments connected to the malleus and incus. Blood
supply to the middle ear mainly comes from branches of the internal maxillary artery. Infections
may cause bone resorption of the auditory ossicles, which may cause hearing problems. The
middle ear is inferiorly separated from the bulbus of the internal jugular vein by only a thin layer
of bone; if this bone is resorbed, an infectious thrombus may result.
The bony labyrinth consists of the cochlea, the vestibule, and the semicircular canals (Figure 1).
The membranous labyrinth, filled with endolymph, floats inside the bony labyrinth surrounded
by perilymph. These structures are involved in the sense of balance and hearing. The vestibule
connects to the saccus endolymphaticus situated within the dura mater. The vestibule connects to
the middle ear via the oval and round windows, while the cochlea connects to the subarachnoid
space via a cochlear aqueduct. The sensory organ of hearing, the organ of Corti, is situated within
the cochlea. Intracranial spreading of a middle ear infection may occur through the middle
cranial fossa bone at the roof of the middle ear (tegmen tympani), as well as through the saccus
endolymphaticus or the cochlear aqueduct.
The facial nerve travels through the internal acoustic meatus, along with the cochlear and
vestibular nerves. The facial nerve can be divided into sections: the meatal segment, the
labyrinthine segment, the tympanic segment, the mastoid segment, and the extratemporal
segment. The facial nerve may become infected if the bone covering it becomes dehiscent or
resorbed.
13
Figure 1. Anatomy of the ear (images by, and modified by, Helena Schmidt; from Laulajainen-
Hongisto et al. 2012, with permission of Duodecim)
14
Figure 2. The temporal bone and its surrounding structures (by Helena Schmidt)
The inner and middle ear structures develop before birth. The mastoid process, however, is
close to nonexistent in neonates and the position of the entire temporal bone is inferolateral
compared to adults. Due to the neonatal absence of the mastoid process, the facial nerve
exits the stylomastoid foramen on the lateral aspect of the skull, and, thus, is prone to injury
during operative treatment in young children. While the antrum is already present in infants,
and connects to the upper part of the middle ear through the aditus ad antrum, mastoid
pneumatization is not completed at birth. Air-filled cells, covered by mucous membrane, develop
as the bony structures are pneumatized, with the degree of pneumatization being affected by
middle ear ventilation, hereditary, environmental, nutritional, and infectious factors (Palva 1991,
Glasscock & Shambaugh 1990, Cinamon 2009).
15
The brain and intracranial space in relaƟon to the ear

The roof of the middle ear, the tegmen tympani, is situated under the brain. The middle ear and
the brain are separated by mucous membrane, periosteum, bone, and the meninges. Three layers
of meninges surround the brain: the dura mater, the pia mater, and the arachnoid mater. The
resulting epidural, subdural, and subarachnoid spaces are seen in Figure 3.
The cerebrum is situated above the tentorium cerebelli and it can be divided into temporal,
occipital, parietal, and frontal lobes. The cerebellum is located under the tentorium cerebelli.
The pons and the brain stem are located anterior to the cerebellum. The brain’s ventricular
system comprises four interconnected ventricles: two lateral ventricles and the third and fourth
ventricles. The fourth ventricle continues into the spinal cord.
The brain receives arterial blood from the internal carotid artery and the vertebral arteries.
The choroid plexuses of the lateral ventricles produce cerebrospinal fluid from arterial blood;
this fluid flows in the ventricular system and is gradually absorbed by the arachnoid villi of the
subarachnoid space (Purves et al. 2001). Dural venous sinuses (two sigmoid sinuses on either
side of the head, the transverse sinus connecting these two, and the superior sagittal sinus
extending superiorly) receive this absorbed cerebrospinal fluid, as well as blood from the veins
of the brain. The dural venous sinuses empty into the internal jugular veins. Additionally, venous
blood from extracranial structures may pass through the skull bone via emissary veins into the
dural venous sinuses.
Figure 3. The brain and meninges in relation to the mastoid air cells (image by Helena Schmidt; from
Laulajainen-Hongisto et al. 2012, with permission of Duodecim)
16
2.3 OƟƟs media

DeĮniƟon, epidemiology and risk factors
Otitis media is an inflammation of the middle ear with AOM being an acute inflammation of the
middle ear. The diagnosis of AOM should be based on acute symptoms, presence of middle ear
effusion (MEE), and signs of acute middle ear inflammation with a bulging of the TM (Lieberthal
et al. 2013). AOM is a common infection in children; by the age of three, 83% have had at least
one episode of AOM (Teele et al. 1989). On average, children experience five URTI episodes and
two AOM episodes per child-year during their first three years of life (Chonmaintree et al. 2008).
Some children suffer from glue ear (otitis media with effusion, OME) or recurrent AOM. OME
has been defined as inflammation of the middle ear with MEE, but without signs and symptoms
of infection; while recurrent AOM is defined as three or more documented, separate episodes
of AOM in the preceding six months, or four or more episodes in the preceding 12 months,
with at least one episode within the last six months (Lieberthal et al. 2013). OME and recurrent
AOM may lead to surgical interventions. A prolonged middle ear infection may lead to the
development of chronic suppurative otitis media (CSOM), which is defined as purulent otorrhea
persisting for more than 6 weeks in a patient with a chronic TM perforation (Gould et al. 2010).
Although problems caused by AOM predominate in the pediatric population, middle ear
infections also affect adults. The problems in children, however, are not the same in adults.
Adults have more prolonged ear problems, CSOM, and cholesteatoma than children. CSOM
and cholesteatoma have become less common over time in Finland, probably due to the more
efficient treatment of AOM (Alho et al. 1997). The annual incidence of cholesteatoma in Finland
was 9/100,000 in 1982-1991 (Kemppainen et al. 1999).
In Finland, 500,000 episodes of AOM occur annually (Niemelä et al. 1999). Globally, 709 million
cases of AOM occur annually, 51% of these in children under the age of five (Monasta et al.
2012). Additionally, 31 million cases of CSOM occur annually, of which 23% are children under
the age of five (Monasta et al. 2012). CSOM is uncommon in developed countries compared
to developing ones. The prevalence and severity of both acute and chronic OM in developing
countries is higher, along with deafness and severe suppurative complications (Bluestone 1998,
Vergison et al. 2010, Monasta et al. 2012).
AOM reduces the quality of life for children and their parents, and recurrent AOM may even
delay a child’s language development. AOM also burdens society through the cost of the medical
treatment for AOM, the use of medical care facilities, as well as loss of productivity due to
parental absence from work (Greenberg et al. 2003, Brouwer et al. 2005, Arguedas et al. 2010,
Haapala et al. 2014).
Children are prone to develop AOM due to anatomical factors (position of ET) and their under
developed immune system (Bluestone 2008). Innate immunity is already functioning at birth,
whereas adaptive immunity develops as pathogens are encountered (Mittal et al. 2014a).
OM is a multifactorial disease; environmental, bacteriological, host, immunological, and genetic

factors affect its development (Rye et al. 2012). From twin and family studies, we know that
genetic factors play a major part in susceptibility to OM with heritability being approximately
40-70% (Hafrén et al. 2012, Mittal et al. 2014a). A family history of AOM is a risk factor for
17
development of AOM in a child (McCormick et al. 2011). Ciliary dysfunction, cleft palate,
craniofacial anomalies, and Down syndrome are additional known risk factors for AOM (Gould
et al. 2010).
As with AOM, CSOM is also a multifactorial disease (Bluestone 1998, Mittal et al. 2015).
Susceptibility to OM may, in adults, be affected by how well an individuals (innate) immunity
functions (Mittal et al. 2014b). Since CSOM is preceded by AOM or OME, prevention of the
earlier infections can reduce the cases of CSOM (Bluestone 1998).
Children who experience their first AOM before the age of six months are more prone to
additional AOM infections later in childhood (Gould et al. 2010). The amount of contacts with
other children (leading to increased exposure to viruses and bacteria) is a risk factor for the
development of AOM. Children with siblings and those in day-care have more AOM than others
(OR=1.8 for children in day care to become otitis-prone with ≥3 episodes of AOM) (Alho et
al. 1990, Uhari et al. 1996). Passive smoking and the use of a pacifier are additional risk factors
for AOM (Etzel et al. 1992, Uhari et al. 1996, Warren et al. 2001). Passive smoking is also a risk
factor for recurrent AOM after tympanostomy tube insertion (Hammarén-Malmi et al. 2007).
The presence of these risk factors, such as passive smoking and family history of AOM, are also
associated with a more severe clinical picture (McCormick et al. 2011). Breast-feeding for at least
three months, on the other hand, reduces the risk of AOM (Uhari et al. 1996).
EƟopathogenesis
AOM often develops as a complication of viral URTI. Many viruses can cause URTI: rhino-,
corona-, adeno-, entero-, and influenza viruses. The respiratory syncytial virus in particular has
been associated with AOM (Heikkinen et al. 1999). Viruses alone can cause acute middle ear
infection, but the interplay of viruses with bacteria is important in the development of AOM,
with the resulting AOM being a combination of a viral and bacterial infection (Chonmaitree et
al. 2008, Marom et al. 2012, Nokso-Koivisto et al. 2015).
Viral URTI results in inflammatory responses of the nasopharynx and ET, as well as an increased
bacterial colonization of the nasopharynx. ET dysfunction leads to negative pressure in the
middle ear, allowing bacteria and viruses to enter, which causes inflammatory changes in the
middle ear mucosa resulting in accumulation of MEE. Additionally, the mucous membrane
lining the mastoid air cells may become inflamed, swollen, and produce mucous secretion.
In some cases, a middle ear infection may continue despite antimicrobial treatment. Prolonged
inflammation results in inflammatory changes in the middle ear and its surrounding structures
(Palva et al. 1985). In OME, prolonged AOM leads to negative pressure in the middle ear,
trapping sterile MEE (Bluestone 1998). Middle ear infections may become chronic, and result
in CSOM or chronic mastoiditis. ET dysfunction and TM perforation are common mechanisms
for developing CSOM. Chronic infection and ET dysfunction may result in negative pressure in
the middle ear, creating conditions for the weaker part of the TM, the pars flaccida, to become
retracted and perforated.
18
Keratinizing stratified squamous epithelium may start to grow into the middle ear through a
TM perforation and accumulate in the middle ear or temporal bone, forming a cholesteatoma.
Most cholesteatomas are situated in the atticus and are acquired. Only 2% are congenital and
are thought to develop from epithelial rests of the middle ear. Cholesteatoma may erode bone,
become infected, and cause serious complications (Juliano et al. 2013, Prasad et al. 2013).
Additionally, a TM perforation may allow a bacterial infection to spread into the middle ear
from the EAC or from the nasopharynx through the ET, and lead to otorrhea.
In patients with CSOM, hearing loss may result from chronic MEE, as well as from bone erosion
leading to disruptions in the auditory ossicles.
Bacteriology
The most common bacterial pathogens of AOM in children are Pnc (23%-26%), Mc (18%-23%),
and Hi (16%-23%) (Virolainen et al. 1994, Kilpi et al. 2001, Palmu et al. 2004), while the most
common pathogens of AOM in adults are Hi (26%), Pnc (21%), and StrA (4%) (Celin et al. 1991,
Bluestone et al. 1992) (Figure 4). The bacteriological etiology of AOM changes over time and
is affected by environmental factors, vaccinations, and development of antimicrobial resistance;
these changes must be monitored, especially since the introduction of PCV vaccinations
(Vergison 2008, Jalava 2014).
The bacterial etiology of AOM affects its clinical picture. For example, Pnc causes severe
symptoms with fever, earache, and clear signs of infection of the TM (Rodriguez et al. 1999,
Palmu et al. 2004). It is reported to be the major pathogen present in 70% of infants with AM
(Stenfeldt et al. 2014), and is a common pathogen involved in complicated AOM. There is an
increasing trend of multi-drug resistant Pnc strains among complicated cases of AOM, which
may result in an overall rise in the number of AOM complications (Antonelli et al. 1999, Zapalac
et al. 2002, Mattos et al. 2014). Additionally, seasonal variation in penicillin susceptibility of Pnc
isolates has been reported, with more nonsusceptible strains seen as the winter months progress,
resulting in potential seasonal variation in the number of OM complications (Hoberman et al.
2005). In Finland, in 2014, Pnc resistance to penicillin was detected in the pus samples of 12%
of ≥ 5-year-olds and in 9% of < 5-year-olds, whereas in 2010-2011, 20% of Pnc were resistant to
penicillin. In 2014, Pnc resistance to trimethoprim-sulfonamide was 10%, whereas in 2009, up to
30% of Pnc were resistant to trimethoprim-sulfonamide. Pnc resistance to macrolides is reported
to be 14-27% (Jalava 2014).
Non-encapsulated Hi is a major pathogen of AOM and is associated with older age, recurrent
AOM, and bilateral AOM, but not with severe complications (Leibovitz et al. 2004, Segal 2005,
McCormick et al. 2007, Pichichero et al. 2008. Casey et al. 2010). Due to its relatively low
virulence, Mc is not common in complications of AOM and seldom causes AM (Leskinen & Jero
2003, Segal 2005). Some Hi, and almost all Mc, produce beta-lactamase, and thus have natural
resistance to penicillin and amoxicillin. This resistance can, however, be compensated for by the
19
Children, outpatient AOM Adults, outpatient AOM

S.
S.
Other/unknown pneumoniae
46% 21%
/mixed culture 23%
43%
H.
influenzae
16%
H.
influenzae
26%
S. pyogenes M. S.
0.4% catarrhalis pyogenes M. catarrhalis 3%
18% 4%
Figure 4. Pathogens of children with outpatient AOM (n=1819 AOM events) (Palmu et al. 2004) and
pathogens of adults with outpatient AOM (n=34 AOM events) (Celin et al. 1991).
addition of a beta-lactamase-inhibitor, clavulanic acid for example (Jalava 2014). Hi are resistant
to trimethoprim-sulfonamide in 30% of cases, and almost all Hi are intrinsically resistant to
macrolides (Leibovitz et al. 2004, Jalava 2014).
StrA is more common in older than younger children, and has been associated with complicated
infections, TM perforations, and mastoiditis (Katz et al. 2003, Segal 2005, Shulman et al. 2005).
As in other chronic infections, bacteria involved in CSOM infection may form biofilms that are
resistant to treatment (Lampikoski et al. 2012). Pseudomonas aeruginosa (Ps) and Staphylococcus
aureus (Sa) are common pathogens involved in CSOM, though Proteus vulgaris, Klebsiella
pneumoniae, Enterobacteriaceae, and anaerobes are also found in this group of patients (Brook
2005, Yeo et al. 2007, Mittal et al. 2015). Especially in children with prior recurrent AOM, Ps may
cause AM (Butbul-Aviel et al. 2003). Fucobacterium necroforum is a rare pathogen of complicated
AOM, that may lead to Lemierre’s syndrome with internal jugular vein thrombosis and septic
emboli (Gorphe et al. 2011, Wright et al. 2015).
VaccinaƟons
Vaccinations are hoped to reduce the burden caused by AOM, especially in developing countries
with less advanced health care facilities (Vergison et al. 2010). Influenza vaccinations have been
shown to prevent seasonal influenza and associated AOM (Block et al. 2011, Heikkinen et al.
2013). While AOM is sometimes caused by Hi, the Hi type b vaccinations do not protect against
it because AOM-causing strains are non-encapsulated (nontypable) (Leibovitz et al. 2004).
20
Pneumococcal conjugate vaccines (PCVs) reduce AOM episodes by 6% and the risk of
tympanostomy tube insertion in children (between ages 2 to 5) by 34% (Eskola et al. 2001,
Poehling et al. 2007, Sarasoja et al. 2013). PCVs are also effective against invasive pneumococcal
disease (Whitney et al. 2003, Palmu et al. 2013). Replacement of Pnc with other pathogens or
non-vaccination serotype Pnc, however, must be monitored (Hicks et al. 2007). Certain Pnc
serotypes may cause severe infections due to their virulence (e.g. 19A, not included in the 7
valent PCV), and some have a tendency to develop antimicrobial resistance (e.g. 19A and 35B,
which is included in the 13 valent PCV) (Hoberman et al. 2011b, Martin et al. 2014). Increased
antimicrobial resistance of Pnc has been reported after onset of pneumococcal vaccinations
(Farrell et al. 2007). Replacement of Pnc by these non-vaccination Pnc serotypes, may cause
more acute mastoiditis (Halgrimson et al. 2013, Koutouzis et al. 2016).
A large US insurance claims database study suggests that the incidence of AM has decreased
following the introduction of PCVs (Marom et al. 2014), however, several other studies found no
decrease in AM incidence after PCV introduction (Roddy et al. 2007, Leibovitz 2008, Choi et al.
2011, Daniel et al. 2013, Kordeluk et al. 2015).
Figure 5. The tympanic membranes of a healthy patient (A) and of a patient with acute otitis media
(B). © David P. McCormick, M.D., UTMB, with permission.
DiagnosƟcs and treatment

Patients with AOM often present with symptoms of URTI, earache, and fever. The diagnosis of
AOM cannot, however, rely solely on symptoms.
In the current Finnish guideline for treatment of AOM, the diagnosis of AOM is based on acute
symptoms of URTI, MEE, and impaired or absent mobility of the TM, or otorrhea (Heikkinen
et al. 2010). The fact that MEE can be a sign of OME, for which no antimicrobial treatment
is needed, or of AOM, is a diagnostic challenge. Pneumatic otoscopy and tympanometry are
important tools for detecting MEE. A healthy TM is translucent and pearl gray in color (Figure
5A). Changes in the translucency (from translucent to semiopaque or opaque) or color (from
gray to yellow, white, or red) of the TM are used to evaluate patients with AOM, however, a
bulging of the TM, in particular, has been found to be an important sign of AOM (Lieberthal
et al. 2013) (Figure 5B). The current clinical practice guideline from the American Academy of
21
Pediatrics advises that the diagnosis of AOM should be based on acute symptoms, the presence
of MEE, and signs of acute middle ear inflammation, especially with a bulging of the TM, to
differentiate between MEE caused by OME and AOM (Lieberthal et al. 2013). AOM causes
otorrhea in children with prior tympanostomy tubes, however, a spontaneous perforation of the
TM can be a sign of severe AOM.
Since decisions regarding surgeries for AOM are based on the number of AOM episodes in
individual patients, wrong diagnoses may lead to unnecessary tympanostomies and adenotomies.
Repetitive antimicrobial treatments may lead to the development of resistant pathogens, and
may cause adverse events (vomiting, diarrhea, rash, allergic reactions) (Venekamp et al. 2013).
Antimicrobial treatment also has effects on the intestinal microbiome, which may be associated
later in life with obesity (Saari et al. 2015).
Spontaneous resolution of AOM without antimicrobial treatment is common and occurs in

80% of patients within 2-3 days (Rosenfeld et al. 2003, Stevanovic et al. 2010, Venekamp et al.
2013). Antimicrobial treatment reduces the duration of MEE by two weeks and patients treated
with antimicrobials also have less persistent MEE (5% vs. 24% in placebo group), and less
resulting hearing impairment (Tapiainen et al. 2014). So called wait-and-see prescriptions of
antimicrobials have been shown to reduce their unnecessary use (Spiro et al. 2006).
Patients with bilateral AOM are more likely to have persistent symptoms if not treated with
antimicrobials, are more likely to have bacteria in the MEE, and are younger (McCormick et
al. 2007). Children under the age of two benefit from antimicrobial treatment of AOM by a
reduction of symptom burden, and shorter times to symptom resolution (Klein 2011, Tähtinen
et al. 2011, Hoberman et al. 2011a, Hoberman et al. 2013). The expectant observational approach
is accepted for most older children with mild disease in high-income countries (Venekamp et al.
2013).
National differences are seen in the prescription rates of antimicrobial treatment; in the
Netherlands, antimicrobial treatment is given to 31% of patients with AOM, whereas in most
other western countries, over 90% of patients with AOM receive antimicrobial treatment
(Schilder et al. 2004). In Sweden, no increase in the incidence of AM in children has been
reported following the introduction of watchful waiting as an alternative treatment for AOM
(Stenfeldt et al. 2010, Groth et al. 2011). Antimicrobial treatment halves the risk of mastoiditis;
the number needed to treat AOM to avoid one case of AM, however, is high (approximately
4,800) (Petersen et al. 2007, Thompson et al. 2009).
Pain medication is an important part of AOM treatment. Oral prednisolone has been shown
to be modestly effective as an adjuvant treatment of AOM with tympanostomy tube otorrhea
(Ruohola et al. 1999). This study alone, however, does not indicate regular use of steroids for
AOM. On the other hand, steroids have been proven efficient in other otological conditions such
as labyrinthitis and Bell’s palsy, and since they reduce tissue swelling, they are often used to treat
complicated OM (Hartnick et al. 2001, Salinas et al. 2010).
The treatment recommendations for AOM in Finnish current care guidelines have changed
over time. Much more active treatment was recommended in the 1970s than currently (Palva
22
et al. 1973, Puhakka et al. 1999, Heikkinen et al. 2010). These changes have most likely affected
our results, especially regarding otogenic intracranial abscesses. Currently, the following
treatment of AOM is recommended: adequate treatment of pain in all patients, antimicrobial
treatment (primarily with amoxicillin or penicillin) in most patients with a clear diagnosis of
AOM (especially in children under the age of two, in patients with bilateral infection, and in
patients with otorrhea), and the possibility of expectant observation with follow-up in 2-3 days
(Heikkinen et al. 2010).
Tympanostomy tubes reduce the risk of recurrent AOM by 1.5 episodes of AOM in the 6 months
following tube insertion (Gebhart 1981, McDonald et al. 2011, Kujala et al. 2012). Adenotomy
is beneficial in removing MEE, but has no additional value compared to tympanostomy tube
placement in reducing episodes of AOM (van den Aardweg et al. 2010, Kujala et al. 2012).
Tympanostomy tubes can also treat OME, having a beneficial effect on hearing for 6 months
in children with prolonged OME (>12 weeks) and hearing loss (Browning et al. 2010). It is
important to note, however, that tympanostomy tubes may lead to TM perforations, occurring
more often with longterm (several years) than short term (8-14 months) tympanostomy
tubes (17% vs. 2%, respectively) (Kay et al. 2001). TM perforations may lead to the need for
further surgical treatment. According to a recent Danish study, prolonged OM treated with
tympanostomy tubes was associated with a higher risk for operatively-treated cholesteatoma
(0.17%) than was the risk of completely healthy children (0.01%)(Djurhuus et al. 2015). At the
population level, however, the risk of cholesteatoma was lower in the children who had been
treated with tympanostomy tubes; each year prior to the first tympanostomy tube insertion
increased the risk of cholesteatoma by 54% (Djurhuus et al. 2015).
The treatment of CSOM consists mainly of aural toilet and topical antimicrobial treatment. If
these do not result in the resolution of infection, oral or parenteral antimicrobial treatment may
be needed. Reconstruction of a perforated TM may be attempted after the acute infection has
been treated. In uncomplicated CSOM, mastoidectomy has not been proven more effective than
conservative treatment, however, in cholesteatomatous CSOM, surgery is indicated (Mittal et al.
2015).
2.4 ComplicaƟons of oƟƟs media

The rate of suppurative complications of AOM and OME has been reported to be 0.12-0.24%
(Rosenfeld et al. 2003). Complications of OM may develop following an untreated or incompletely
treated infection, following infection caused by resistant bacteria, or for unknown reasons.
Congenital malformations, and anatomical or immunological conditions may predispose a
patient to complications. The thinner bony structures of children may more easily be resorbed by
infection (Stenfeldt et al. 2014). Although complications of AOM may develop despite adequate
antimicrobial treatment, most patients with AOM have a very good prognosis. The common
use of antimicrobial treatment has changed the clinical picture of AOM complications and may
mask symptoms and lead to a prolonged, milder form of disease (latent mastoiditis) (Faye-Lund
1989). Thorough examination with bacteriological cultures should be performed, especially if a
patient with AOM does not recover and has high fever, severe general symptoms of infection,
23
secretion from the infected ear, retroauricular signs of infection, hearing problems, dizziness, or
neurological symptoms.
OM causes a severe burden in developing countries. According to the WHO, 51,000 deaths
occur annually in children under the age of five due to intracranial complications of AOM
(Berman 1995). CSOM has been reported as a major cause of hearing impairment in developing
countries (Berman 1995). Vaccinations and better treatment of infections are hoped to change
this situation.
CSOM with cholesteatoma has been associated with intracranial complications (Osma et al. 2000,
Juliano et al. 2013, Prasad et al. 2013). These complications are caused by the chronic infection
spreading through bone resorbed by cholesteatoma. In a previous Finnish study, however, more
complications were found in adult patients with acute, rather than chronic, OM (Leskinen & Jero
2005).
The complications of OM can be divided into intratemporal and extratemporal (extra- or

intracranial) complications.
Intratemporal complicaƟons
Intratemporal complications of OM, in order of their prevalence, are: mastoiditis, facial nerve
paresis, petrositis, and labyrinthitis (Bluestone 2000, Kitsko et al. 2007). Morbidity rates for the
intratemporal complications of OM are reported between 0.4% and 10%, with mortality being
extremely rare (Osma et al. 2000, Groth et al. 2012).
Mastoiditis
Mastoiditis develops when a middle ear infection spreads through the aditus to mastoid antrum
into the mastoid air cells causing mucosal swelling, local acidosis, ischemia, and resorption
of bone. Destruction of the bony mastoid septa occurs in coalescent mastoiditis. Coalescent
mastoiditis can have an acute, aggressive course of disease, or a prolonged, silent course of
disease known as latent mastoiditis (LM) (Vasquez et al. 2003, Juliano et al. 2013). LM may
be difficult to diagnose because the TM and middle ear may appear healthy due to a blocked
aditus to mastoid antrum, behind which the mastoid infection continues. The presence of MEE
with a simultaneous increase in attenuation of the mastoid cells upon CT, along with signs of
mastoiditis, is called incipient mastoiditis (Vasquez et al. 2003). Acute middle ear infections,
as well as sub-acute or chronic inflammation, may cause acute mastoid infections. CSOM with
cholesteatoma is a common etiology for intratemporal complications (Palva & Pulkkinen 1959,
Stahelin-Massik et al. 2008, Maranhao et al. 2014).
Because the diagnosis of mastoiditis is clinical, uniform and accurate diagnostic criteria are
essential; the most commonly used diagnostic criteria are: postauricular swelling, erythema,
tenderness, protrusion of the pinna, and a recent episode of (sub)acute OM (van den Aardweg
et al. 2008, Stalfors et al. 2013). High fever, and a high leukocyte count (WBC) and C-reactive
protein (CRP) levels may be signs of complicated AM and warrant close follow-up (Bilavsky et
al. 2009). Because the bacterial etiology of AM is more complicated than that of AOM, bacterial
cultures of the MEE must always be taken (Luntz et al. 2001, Benito et al. 2007).
24
Debate regarding the necessity of imaging in AM exists; currently imaging is used in cases
with suspected complications, in unclear cases, or in cases that do not respond to conservative
treatment (Psarommatis et al. 2012a, Marom et al. 2016). Because it is not always possible to
clinically rule out intracranial complications, some authors suggest CT imaging of all children
with AM (Luntz et al. 2012). CT has traditionally been the initial imaging technique for AM;
good visibility of the mastoid’s bony structures is achieved and intravenous contrast medium
is used for the better evaluation of soft tissues (Saat et al. 2015a) (Figure 6). The overall use
of MRI in clinical practice is rising, it is promising in otological conditions. MRI is good at
differentiating soft tissues, and at detecting possible intracranial complications (Saat et al. 2015a).
In patients with AM, MRI is suggested when intracranial complications are suspected (Dobben
et al. 2000, Vasquez et al. 2003, Minks et al. 2013). Incidental mastoid findings in MRIs of healthy
individuals are possible, and AOM patients (with no mastoid infection) can have intramastoid
fluid accumulation (Blomgren et al. 2003, Polat et al. 2011, Juliano et al. 2013). It is, however,
possible to distinguish between true mastoid infection and incidental MRI findings (Saat et al.
2015b).
Figure 6. Left: A child with acute mastoiditis of the left side, protrusion of the pinna, retroauricular
swelling, and redness. Right: CT image, in which a subperiosteal abscess is seen (red arrow) (From
Laulajainen-Hongisto et al. 2012, with permission of Duodecim)
Mastoidectomy used to be a common treatment for mastoiditis but, currently, more conservative
treatment is preferrable (Palva et al. 1959, Chesney et al. 2014). Antimicrobial treatment is often
combined with myringotomy or tympanostomy tube insertion, though, in some institutions,
retroauricular puncture may be attempted in patients with a subperiosteal abscess (Luntz et al.
2001, Bakhos et al. 2011, Psarommatis et al. 2012a, Psarommatis et al. 2012b). Mastoidectomy,
as the most reliable and efficient procedure, is suggested in patients who do not respond to
more conservative treatment, or those who have intracranial complications (Quesnel et al. 2010,
Psarommatis et al. 2012a, Psarommatis et al. 2012b) (Figure 7).
In our institution, patients with AM are treated with tympanostomy tube insertion and
antimicrobial treatment consisting of either intravenous cefuroxime or penicillin (penicillin
in infections caused by StrA), or of other antibiotics according to the results of bacteriological
cultures. Additionally topical ear drops (usually ciprofloxacin-hydrocortisone) are given, and
steroids are used to reduce inflammation and tissue swelling. Imaging is performed only in cases
with suspected complications, or those resistant to treatment in which case, mastoidectomy is
also considered (Kajosaari et al. 2014).
25
Figure 7. Intraoperative findings

of a patient with acute mastoiditis.
(From Laulajainen-Hongisto
et al. 2012, with permission of
Duodecim)
Facial nerve paresis

Complicated OM can result in facial nerve paresis, which is usually reversible (Kvestad et al.
2002). Its incidence is currently much lower (0.005%) than in the preantibiotic era (0.5%)
(Ellefsen et al. 1996). The tympanic segment of the facial nerve is most commonly affected,
especially in patients with dehiscence of the bone covering the facial nerve. Paracentesis or
tympanostomy tube insertion should be performed, and bacterial cultures of the MEE should be
taken, in patients with facial nerve paresis occurring as a complication of OM (Redaelli de Zinis
et al. 2003, Kitsko et al. 2007). Most patients can be treated with parenteral antibiotics (which
cover Hi, Streptococci, and Staphylococci). Mastoidectomy, with or without decompression of
the facial nerve, may be considered in complicated cases, or in cases not responding to other
treatment.
Petrositis
If infection spreads to the apex of the petrous part of the temporal bone (Figure 1) then
meningeal inflammation is often present, and due to their close proximity, cranial nerves V
(trigeminal nerve) and VI (abducens nerve) may be affected (Juliano et al. 2013). In Gradenigo’s
syndrome petrous apicitis is accompanied by orbital pain (trigeminal nerve), diplopia (abducens
nerve), and otorrhea (Heshin-Bekenstein et al. 2014). Treatment consists of antimicrobials,
tympanostomy tube insertion, and surgical treatment.
Labyrinthitis
In labyrinthitis, the inner ear is inflamed due to bacterial infections (suppurative), viral infections,
or autoimmune inflammation (serous). Suppurative labyrinthitis may result in permanent
hearing loss or vertigo. The infection usually spreads to the labyrinth through an intact round
window, or less commonly through the oval window, a congenital perilymphatic fistula, or
acquired bone defects. Labyrinthitis may also follow meningitis, in which case infection spreads
from the subarachnoid space (Kitsko et al. 2007).
26
Patients with labyrinthitis suffer from vertigo, nystagmus, and hearing loss. Diagnosis is based
on clinical and audiometric findings, though imaging is also useful. MRI is more effective than
CT in detecting signs of labyrinthine inflammation (Kitsko et al. 2007, Juliano et al. 2013).
In patients with labyrinthitis, paracentesis should be performed, tympanostomy tube should

be placed, and microbiological samples should be taken. Treatment consists of antimicrobials
(those covering the most common pathogens of AOM: Pnc, Hi, and Mc), topical ear drops, and
steroids; mastoidectomy may be considered in complicated cases or those unresponsive to other
treatment (Kitsko et al. 2007).
Labyrinthitis has three stages: acute, fibrous, and ossification (Juliano et al. 2013). The
inflammation can result in pathologic ossification of the labyrinth, which may be especially
severe after meningitis, and may complicate eventual later insertion of a cochlear implant
(Kitsko et al. 2007, Juliano et al. 2013). Steroids are used to prevent ossification in patients with
labyrinthitis (Hartnick et al. 2001).
Extratemporal complicaƟons
Extratemporal complications due to OM can be subdivided into intracranial and extracranial
categories.
Figure 8. Extratemporal complications of otitis media. (image by Helena Schmidt, from Laulajainen-
Hongisto et al. 2012, with permission of Duodecim)
27
Extracranial complicaƟons
Subperiosteal abscess
In AM, bone destruction may extend to the outer bone cortex through which infection may
spread and result in a subperiosteal abscess (Figure 6, Figure 8). If a middle ear infection spreads
temporally, it may form a subperiosteal temporal abscess (Luc’s abscess), which does not always
involve the mastoid (Weiss et al. 2010, Scrafton et al. 2014).
Bezold’s abscess
If a bone defect exists in the mastoid tip, mastoid infection can spread to the soft tissues of the
neck and form an abscess (Betzold’s abscess, Figure 8) (Jose et al. 2003, Vasquez et al. 2003).
Intracranial complicaƟons
Intracranial complications of OM are possible due to the close proximity of the brain to the ear.
Infection can spread to the intracranial space by direct spreading of infection, bone erosion,
retrograde thrombophlebitis, or hematogenous spreading. CSOM with cholesteatoma has been
associated with intracranial complications of OM (Penido et al. 2005, Szyfter et al. 2012, Sun et al.
2014). The pathogen that causes the initial, underlying infection would also be the one involved
in any resulting intracranial complication. Children with AM caused by anaerobic bacteria may
have a higher risk of developing intracranial complications (Zevallos et al. 2009).
Intracranial complications of OM are, however, rare. They include, in order of prevalence:

meningitis, dural venous sinus thrombosis, epidural abscess, subdural empyema, and IA
(Bluestone 2000). Carotid artery involvement is extremely rare (Vasquez et al. 2003).
The prognosis of patients with intracranial complications of OM, including IAs, has improved
over time. However, mortality rates ranging from 9-31% have been reported (Osma et al. 2000,
Sennaroglu et al. 2000, Penido et al. 2005, Dubey et al. 2010, Szyfter et al. 2012).
Meningitis
Meningitis is a common intracranial complication of OM. The annual incidence of otogenic
meningitis in adults in the United Kingdom is 0.42/100,000, with most cases being due to CSOM
(Ibrahim et al. 2010). Meningitis can lead to deafness, even when not caused by OM; thus, early
diagnosis is essential (Barry et al. 1999). If an otogenic infection is suspected in a patient with
meningitis, myringotomy with bacterial cultures of the MEE should be performed. CT imaging
of the ear should be performed if a suspicion of predisposing defects exists, in these cases
mastoidectomy should also be considered. Antimicrobial treatment is the first-line treatment
for all meningitis patients. Surgery of the ear should only be performed in patients who do not
respond to antimicrobial treatment within 48 hours (Slovic et al. 2007).
Intracranial abscesses
Intracranial abscesses (brain abscesses, subdural abscesses, and epidural abscesses) are rare, with
an annual incidence of 0.4-0.9/100,000 (Brouwer et al. 2014b). IAs may cause life threatening
sequelae, fortunately, however, the prognosis of IA patients has improved over time; case fatality
rates have decreased from 40% to 10%, and the rate of patients with full recovery has increased
28
from 30% to 70% between the 1970s and 2010s (Brouwer et al. 2014a). Predisposing factors can
be identified in most patients: immunosuppressive conditions, acquired or congenital disruptions
of anatomical borders of the surrounding structures, or a systemic source of infection (Brouwer
et al. 2014b). Although IAs are a rare complication of OM, and have become less common
with time, Brouwer et al. found in their recent meta-analysis that 32% of IAs were otogenic
(Tarkkanen & Kohonen 1970, Brouwer et al. 2014a). Otogenic IAs (oIA) usually develop as a
complication of (prolonged, chronic) middle ear infection via contiguous spreading (Figure 8).
The lifetime expectancy of a 30 year-old patient with CSOM developing an oIA is 1/200 (Nunez
et al. 1990). The bacteriological etiology of all IAs is affected by their underlying cause; the most
common pathogens of oIAs belong to Streptococcus spp, Bacteroides spp, Prevotella spp, and
Enterobacteriaceae (Brouwer et al. 2014b).
The most common symptom caused by IAs is headache; fever and an altered level of consciousness
are often absent, and though eventual other neurological signs become more common as the
abscess grows (Brouwer et al. 2014a; Brouwer et al. 2014b). The diagnosis is not always easy to
make since the differential diagnosis of IAs include many neurological and infectious conditions
(Brouwer et al. 2014b). Prompt treatment is necessary to ensure a better prognosis (Xiao et
al. 2005, Dubey et al. 2010). Otogenic IAs should be suspected in patients with prolonged ear
infection, headache, and neurological symptoms (Lildal et al. 2014).
CT imaging has resulted in improved diagnostics and has decreased the mortality of IA patients
(Mathisen et al. 1997, Ratnaike et al. 2011, Brouwer et al. 2014b). Since the clinical diagnosis of
oIAs is difficult, neuroimaging is important, preferably with MRI (Lildal et al. 2014), and imaging
of the ear should also be performed. MRI is excellent in differentiating between soft tissues and
is a valuable tool in differential diagnostics (Doebben et al. 2000, Lai et al. 2002, Prashanth et al.
2011) (Figure 9).
Antimicrobial treatment should be started as early as possible, usually after the IA puncture
(Brouwer et al. 2014b). The initial choice of antimicrobials should be based on the most likely
pathogen, often based on the predisposing condition, and should later be modified according to
the results of bacterial cultures (Hafidh et al. 2006, Brouwer et al. 2014b). Recommended, initial
broad-spectrum antimicrobials are cefotaxime or ceftriaxone with metronidazole; alternatively,
meropenem with vancomycin, if Sa is suspected (Brouwer et al. 2014b).
Glucocorticoids may also be needed to reduce cerebral edema (Brouwer et al. 2014b). In selected,
mild IA cases (also oIAs), only antimicrobial treatment may be attempted (Isaacson et al. 2010).
Neurosurgical treatment is needed to obtain bacteriological cultures, and to reduce the size of
the abscess; these can be achieved by puncture, but in some cases extirpation may be needed
(Brouwer et al. 2014b). The underlying cause of the infection must also be treated (Osborn et
al. 2011). The timing of the operations due to oIAs varies and depends on the clinical condition
of the patient (Seven et al. 2005, Wanna et al. 2010). Many authors report treating the ear and
IA simultaneously (Kurien et al. 1998, Sennaroglu et al. 2000, Hafidh et al. 2006, Syal et al.
2006, Morwani et al. 2009), with some suggesting treatment of the ear within the first 24 hours
(Kuczkowski et al. 2006). In our institution, the IA is usually treated first, followed by treatment
of the infected ear once the patient is stabilized.
29
Figure 9. Coronal T2 MR-image of a left-sided occipital

brain abscess, 2cm in diameter, surrounded by marked
edema. (Image from Antti Markkola)
Brain abscess
Brain abscesses are intracranial abscesses located
within the brain tissue. Otogenic IAs are typically
located in the temporal lobe, or are cerebellar
(Couloigner et al. 1998).
Epidural abscess
Epidural abscess formation usually follows bone destruction associated with coalescent
mastoiditis. These abscesses are situated in the epidural space, and patients may be silent of
symptoms for them (Vasquez et al. 2003).
Subdural abscess
Subdural abscesses are located in the restricted subdural space. Patients with subdural empyema
often have severe symptoms (Vasquez et al. 2003).
Sinus thrombosis
Dural venous sinus thrombosis usually results from an extradural abscess, but may also develop
following an epidural abscess, or via osteothrombophlebitis. Infection spreads to the sigmoid
sinuses or the transverse sinus, where an infectious thrombus may develop (Vasquez et al. 2003,
Stam 2005, Ropposch et al. 2011) (Figure 8). The infected thrombus may continue into the jugular
vein, to other dural sinuses, or to the subcutaneous tissue via emissary veins. Patients may have
no symptoms, only mild symptoms, or severe infection with neurological symptoms (Stam et
al. 2005). CT or MRI are used in the diagnostics of this complication (Vasquez et al. 2003, Stam
2005, Sharma et al. 2015). In otogenic sinus thrombosis, the underlying ear infection should be
examined and treated. Treatment of the sinus thrombosis itself, however, remains controversial;
ligation of the internal jugular vein and anticoagulants have been used.
Otitic hydrocephalus
If the contralateral sigmoid sinus is hypoplastic in a patient with otogenic sinus thrombosis,
absorption of the cerebrospinal fluid may become disturbed resulting in increased intracranial
pressure and otitic hydrocephalus. The pathogenesis of otitic hydrocephalus is, however, not
completely understood. Symptoms include headache, drowsiness, nausea, blurred vision, diplopia
and photophobia; in patients with such symptoms, imaging with MRI should be performed. Both
the underlying ear infection and the elevated intracranial pressure must be treated (with steroids,
hyperosmolar dehydrating agents, and/or neurosurgery) (Stam 2005, Sadoghi et al. 2007).
30
Aims of the Study
3 AIMS OF THE STUDY

The aim of this study was to evaluate the complications resulting from otitis media at our
institution.
The specific study aims were:
1. To evaluate the clinical picture of acute mastoiditis caused by different pathogens in children.
2. To study differences in the etiology and clinical picture between acute mastoiditis and
hospitalized acute otitis media in children.
3. To study the predisposing factors for the development of otogenic intracranial abscesses.
4. To analyze clinical characteristics of adults hospitalized due to acute otitis media or acute
mastoid infections.
31
Patients and Methods
4 PATIENTS AND METHODS
4.1 DiagnosƟc and inclusion criteria

Acute oƟƟs media (AOM)
Acute fever (≤14 days), earache, or respiratory symptoms. MEE, bulging, redness, or abnormal
mobility of the TM upon otomicroscopy. Recent onset of otorrhea not due to otitis externa.
Acute mastoidiƟs (AM)

Diagnosis of AOM, and at least two of the following symptoms: protrusion of the pinna;
retroauricular redness, swelling, pain, or fluctuation; and/or abscess in the EAC; and/or purulent
secretion or acute infection in the mastoid process upon mastoidectomy.
Latent mastoidiƟs (LM)

Symptoms of acute mastoid infection in adult patients (≥17 years old) who did not fulfil all the
study criteria for AM, or who had a prolonged (> 14 days) duration of symptoms.
Acute mastoidiƟs of a chronic ear (AMc)

Adult patients (≥17 years old) with a history of CSOM in the ear with AM.
Intracranial abscesses
The diagnosis was based on clinical findings, laboratory test results, microbiological cultures and
imaging studies, intra-operative findings, or findings upon a post-mortem autopsy.
4.2 PaƟents
Patient data for studies I, II and IV originated in a retrospective search of the hospital’s electronic
database for data of all patients hospitalized at the Helsinki University Hospital, Department
of Otorhinolaryngology between 2003 and 2012. The patients with AOM were hospitalized due
to complications, severe symptoms not responding to antimicrobial treatment, or difficulties in
outpatient treatment.
Patient data for study III originated in a retrospective search for all patients treated at the Helsinki
University Hospital, Department of Neurosurgery due to IA between 1970 and 2012 (Table 1).
Table 1. Patients included in studies composing this dissertation
Study Diagnosis Age, range (years) Number of paƟents
I AM 0-16 56
II AOM 0-16 44
III IA 0-83 166
IV AOM, AM, LM, or AMc 17-91 160
32
All diagnoses were re-evaluated by the study group according to the diagnostic and inclusion
criteria. For studies I and II, only one diagnosis was analyzed per patient; if the patient had both
AOM and AM (bilateral infection), they were analyzed as AM. For studies I and II, recurrence
after three months was considered a new infection. For study III, all immediate postoperative
infection cases were excluded, while favorable recovery was defined as recovery from this
infection without severe neurological deficits or health problems and the ability to return to
independent life. For study IV, only the first infection of each patient, and only one diagnosis
per patient, was analyzed. If a patient (in study IV) had a bilateral infection with both AOM and
mastoiditis (AM, LM, or AMc), they were classified as mastoiditis.
The patients were classified as children if they were under the age of 17. For studies I and II,
children under the age of two were classified as younger children and those older than two as
older children.
The mean age of the patients with IA was 42; 71% were male and 85% were adults. Of the 25
children with IAs, 60% were male (mean age of eight). The mean age of the patients with oIAs
was 44; 89% were male and two were children. The mean age of the adults hospitalized for AOM,
AM, LM, or AMc was 47 and 42% were male. The mean age of the children hospitalized for
AOM was 6 and 45% were male. The mean age of the children hospitalized for AM was 5 and
52% were male.
4.3 Methods
Children hospitalized due to AM (I) and AOM (II)
The medical records of all 56 AM and 44 AOM children were retrospectively evaluated. The
data analysis included age, gender, medical history, symptoms and signs of infection, pre-
and in-hospital medication, surgical treatment, outcome, and results of laboratory tests,
bacteriological cultures, and radiological examinations. The samples for bacteriological cultures
were taken from MEE through a tympanostomy tube, aspirated from the middle ear through a
paracentesis, or taken intraoperatively from the mastoid cavity. The samples were analyzed at the
Helsinki University Hospital’s laboratory of microbiology. The data from study I was compared
to that of study II.
Intracranial abscesses (III)

The study material consists of 166 patients. Patient data was analyzed according to age,
demographics, medical history, predisposing condition, symptoms, abscess location, treatment,
outcome, and results of bacteriological cultures, laboratory tests and radiological examinations.
The bacteriological samples were taken intraoperatively (via puncture or during craniotomy)
from the abscess cavity, and were analyzed at the Helsinki University Hospital’s laboratory of
microbiology.
Adults hospitalized due to AOM, AM, LM, or AMc (IV)

The study material consists of 160 patients. The data analysis included age, gender, medical
history, symptoms and signs of infection, pre- and in-hospital medication, surgical treatment,
33
outcome, and results of laboratory tests, bacteriological cultures, and radiological examinations.
Samples for bacteriological cultures were taken from MEE through a tympanostomy tube,
aspirated from the middle ear through a paracentesis, or taken intraoperatively from the
mastoid cavity. The samples were analyzed at the Helsinki University Hospital’s laboratory of
microbiology.
4.4 StaƟsƟcs
IBM SPSS statistics for Windows, Version 19.0 (IBM Corp., Armonk, NY, USA) was used for
studies I-III and IBM SPSS statistics for Windows, Version 22.0 (IBM Corp., Armonk, NY, USA.
Released 2013) for study IV.
Fisher’s exact tests and Chi-square tests, as appropriate, were used to determine the significance
between categorical variables. The Mann-Whitney U test was used to analyze the equality
of medians between continuous variables. A two-sided p-value of below 0.05 was considered
statistically significant.
4.5 Ethical consideraƟons

The studies were approved by the Research Ethics Committee of Helsinki University Hospital.
34
Results
5 RESULTS
Children hospitalized due to AM (I)
The annual incidence of AM in children was 1.88/100,000. The childrens’ clinical characteristics,
symptoms, findings, complications, surgeries, and outcomes are presented in Table 2. The most
common symptoms were otalgia, mastoid tenderness, retroauricular redness, and fever.
Antimicrobial treatment had been prescribed prior to hospital admission in 70% of patients
(typically amoxicillin, amoxicillin-clavulanate, and cephalosporines), 55% had been diagnosed
with a previous AOM.
The bacterial findings are presented in Figure 10. The bacterial cultures were negative in 29%
of cases. Of all Pnc (n=21) samples, 48% (n=10) showed reduced susceptibility to common
antimicrobials (Table 3); these were clearly overrepresented, relative to the background
population (19%, p<0.001). The children with Pnc had less otorrhea (5, 24% vs 19, 54% in others,
p=0.03) and more protrusion of the pinna (18, 86% vs 19, 34% in others, p=0.02) than others.
The children with StrA had less otalgia than others (3, 50% vs 46, 82%, p=0.004). The children
with Ps often had prior tympanostomy tubes (83%). Children with Ps had the lowest CRP values
(21) and while retroauricular swelling was not as common in them as others (1, 17% vs. 30, 54%,
p=0.04) they all had otorrhea (6, 100% vs. 24, 43% in all, p=0.003). The patients with negative
bacterial cultures had less otorrhea (3, 19% vs 21, 38%, p=0.02) and protrusion of the pinna (7,
44% vs 30, 54%, p=0.03), but more dizziness (3, 19% vs 1, 2%, p=0.03) than others.
All patients received intravenous antimicrobial treatment; the most common being cefuroxime
(91%), ceftriaxone (16%), and metronidazole combined with another antimicrobe (14%). Steroids
were administered to 73%, and topical ear drops to 95%. Oral antimicrobial treatment was
continued after hospital discharge in 98%; most commonly cefalosporins (49%) or amoxicillin-
clavulanate (33%).
Mastoidectomy was performed on 34% of patients. The children who had been treated with
azithromycin prior to hospitalization were more likely to undergo mastoidectomy than others
(4, 80% vs 11, 28%, p=0.02). Mastoidectomy also tended to be more common in children with
resistant Pnc (6, 60% vs 13, 23%, not significant). No differences emerged in patient outcomes
regarding type of pathogen or mastoidectomy status.
35
Results
Table 2. Clinical findings, symptoms, surgeries, and outcome of children hospitalized due to AOM or AM.
AM (n=56) AOM (n=44) p- value

Females 27 (48%) 24 (55%)
Mean age 5.0 6.0
Age < 2 15 (27%) 14 (32%)
Median CRP (mg/l) 66 29 0.008
Bilateral infecƟon 9 (16%) 17 (39%) 0.013
Otalgia 49 (88%) 38 (86%)
Fever 40 (71%) 29 (66%)
Otorrhea 24 (34%) 22 (50%)
Dizziness 4 (7%) 11 (25%) 0.022
Nausea 4 (7%) 5 (11%)
Head ache 5 (9%) 2 (5%)
Hearing problem 5 (9%) 4 (9%)
Facial paresis 3 (5%) 12 (27%) 0.004
Retroauricular redness 44 (79%) 10 (23%) <0.001
Retroauricular pain 45 (80%) 7 (16%) <0.001
Retroauricular swelling 31 (55%) 6 (14%) <0.001
Retroauricular ŇuctuaƟon 10 (18%) 0% 0.002
Protrusion of the pinna 37 (66%) 3 (7%) <0.001
Subperiosteal abscess 10 (18%) 0%
MeningiƟs 1 (2%) 0%
Gradenigo’s syndrome 2 (4%) 0%
Sinus thrombosis 4 (7%) 0%
Imaging performed 28 (50%) 5 (11%)
Tympanostomy performed 47 (84%) 26 (59%) <0.001
Paracentesis performed 13 (23%) 10 (23%)
Mastoidectomy 34% 0%
Median hospitalizaƟon, days 4.0 3.0 0.001
Residual TM perforaƟon 1 (2%) 1 (2%)
Residual hearing problem 3 (5%) 2 (5%)
Re-operaƟon performed 7 (13%) 8 (18%)
36
Results
Pathogens of all children, Pathogens of younger

AM children, AM
S. Other/unknown
36% 27%
38%
S. aureus
2% H. S.
P. S. influenzae pneumoniae
aeruginosa pyogenes 2% 73%
11% 11%
Figure 10. Pathogens of all children with acute mastoiditis (AM) (n=56) and pathogens of younger
children (age < 2) with AM (n=15)
Table 3. Resistant S. pneumoniae cases (n=10) in children with acute mastoiditis.

(MIC = minimal inhibitory concentration, S=susceptible, I=intermediate, R=resistant)
Received 1st and 2nd 3rd generaƟon Sulfa- Macrolide Clinda- Mastoid-
anƟmicrobial Penicillin generaƟon cefalosporin trimetho- mycin ectomy
treatment (MIC mg/l) cefalosporin prim
1 Yes I (0.75) R S I I S Yes
2 No I (1) S S R S S No
3 Yes I (0.094) S S S R R No
4 Yes I (0.125) S S I R R Yes
5 Yes I (0.094) Missing Missing S S S No
6 Yes R (2) R S R R R No
7 Yes R (4) R I R R I Yes
8 Yes R (4) R I R R R Yes
9 Yes I (0.75) R S R R R Yes
10 Yes I (0.125) S S R S S Yes
Children hospitalized due to AOM (II)

The annual number of children hospitalized due to AOM was 1-9 (over the study’s 10 year period:
12 cases in spring, 7 in summer, 17 in autumn, and 8 in winter). Patient clinical characteristics,
symptoms, findings, complications, procedures, and outcomes are presented in Table 2. The most
common symptoms were otalgia, fever, and otorrhea.
Antimicrobial treatment had been prescribed to 57% (n=25) prior to hospital admission
(typically amoxicillin, penicillin, or cephalosporines).
37
Results
The bacterial findings are presented in Figure 11. Samples for bacteriological culture were
taken from 38 children (86%). Mixed flora was found in the cultures of five children (11%). The
cultures were negative in 11 children (25%), typically those who had received antibiotics prior to
hospitalization (38% vs 6% in those who had not received antibiotics, p=0.016). Antimicrobial
resistance was only seen in one of the Pnc cases (13%) (penicillin MIC (minimal inhibitory
concentration) 0.19 mg/l, all were susceptible to cefalosporins). Otorrhea via prior tympanostomy
tubes was more common in the children with Ps than others (71% vs 5%, p=0.000). Otorrhea
occurred in all children with StrA, which was much more than in children with other pathogens
(p=0.021).
All patients received antimicrobial treatment, typically intravenously (75%), with cefuroxime
(57%) and ceftriaxone (18%) being most common. Steroids were administered to 55% and
topical ear drops to 86%. Per oral antimicrobial treatment was continued after hospital discharge
in 95%; amoxicillin-clavulanate (33%), amoxicillin (26%) and cefalosporins (24%) were most
common.
Pathogens of all children, Pathogens of younger

hospitalized AOM children, hospitalized AOM
S.
Other/unknown pneumoniae Other/unknown S.
31% 18% 36% pneumoniae
43%
M.
catarrhalis
7%
S. pyogenes
14%
S. aureus
14% P. M.
S. aureus
aeruginosa catarrhalis
7%
16% 14%
Figure 11. Pathogens of all children hospitalized due to acute otitis media (AOM) (n=44) and
pathogens of younger children (age < 2) hospitalized due to AOM (n=14). Note: Hi was not found in
any sample.
Comparison of children hospitalized due to AM and AOM (I,II)

The annual number of hospitalized AOM and AM patients are shown in Figure 12. Prior health
problems (such as asthma, diabetes, developmental disorders, ear problems) were more common
in children with AOM than AM (48% vs 27%, p=0.037).
Retroauricular symptoms were more common in children with AM than AOM (Table 2), and
these signs of infection were rare in patients with facial nerve paresis compared to those without
it: retroauricular swelling (0% vs 44%, p=0.001), retroauricular redness (0% vs 64%, p=0.000),
38
Results
retroauricular pain (7% vs 60%, p=0.0001), and protrusion of the pinna (0% vs 47%, p=0.000).
All children with facial nerve paresis were treated with tympanostomies, while only 68% of those
without paresis had the surgery (p=0.009).
Pnc was more common in children with AM than AOM (38% vs 18%, p=0.046), especially the
resistant strains (48% vs 13% of all Pnc, p=0.021). Younger children were more likely than older
children to have infections due to Pnc (59% vs 17%, p=0.000) and its resistant strains (24% vs
6%, p=0.013). No significant differences were found in the prevalence of Ps or StrA between
children with AM and AOM. The younger children, however, did not have Ps (compared to 18%
in the older children, p=0.018) or StrA (compared to 17% in the older children, p=0.017). Sa was
less common in children with AM than AOM (2% vs 14%, p=0.042).
12
10
0
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
AOM AM
Figure 12. Annual number of children hospitalized for acute otitis media (AOM), or acute mastoiditis
(AM).
39
Results
Intracranial abscesses (III)

The total number of IAs was 166, with a mean annual number of four cases (range 1-8) (Figure
13). The annual incidence of IAs was 0.33/100,000 (2000-2012), and the proportion of children
decreased with time (24% in 1970-1989 vs 8% in 1990-2012, p=0.004). The etiology in 18 (11%)
patients was otological (Table 4); these oIA cases were most common in 1970-1979 (10 cases,
25%) and their incidence decreased over time (2000-2012: 3 otogenic cases, 5%) (Figure 13). The
annual incidence of oIAs (2000-2012) was 0.017/100,000. Over time, cardiac anomalies among
IA cases became less common (15, 20% in 1970-1989 vs. 6, 7% in 1990-2012, p=0.001), whereas
odontogenic infections became more common.
The median symptom duration of IA patients prior to hospitalization was 10.0 days (0-90
days), though it was shorter in patients with odontogenic infection (4.5 days, p<0.001). Prior
to hospitalization, 19% of all IA patients had received antimicrobial treatment; often these were
patients with ENT infections (49% vs 3% of all other patients, p<0.001). The most common
presenting symptoms were headache (48%), fever (28%), and some focal neurological symptom
(21%).
Nearly all IA patients (99%) underwent some imaging, with a singular abscess being found in
most cases (87%). Multiple abscesses were more common in children than adults (28% vs 11%,
p=0.048). Patients with ENT infections had more temporal abscesses than others (43% vs 12%,
p<0.001). Patients with sinusitis had more extra-axial abscesses (i.e. empyemas) than others
(40% vs 3%, p<0.001). Temporal abscesses were more common in patients with oIAs than in
those with other etiologies (78% vs 12%, p<0.001).
Pathogen results from bacteriological culture are shown in Table 5. Fusobacteria were more
common in patients with odontogenic infection than others (9, 38% vs 14, 10%, p=0.001). Gram-
negative enteric bacteria were more common in patients with oIA than others (4, 22% vs 4, 3%,
p=0.005).
Antimicrobial treatment was common during hospitalization (96%); the most common (2000-
2012) being: cephalosporins (95%), nitroimidazoles (72%), meropenem (31%), and vancomycin
(28%). Preoperative corticosteroids were administered to 74%. Nearly all IAs were treated with
surgery (99%).
A favorable recovery was seen in 66%, with 19% being able to return to their prior occupation
(12 % in 1970-1989 and 24% in 1990-2012). Those that could return to their prior occupation
were typically patients that had no predisposing conditions for their IA (52% vs 28% of others,
p=0.018) and were younger (mean age 29 vs. mean age 45).
Twelve patients (11 adults and one child) died due to the IA. Death due to abscess became less
common over time (12% in 1970-1989 vs 3% in 1990-2012, p=0.037).
40
Results
0
1980
2012
1970
1972
1974
1976
1978
1982
1984
1986
1988
1990
1992
1994
1996
1998
2000
2002
2004
2006
2008
2010
oIA other IA
Figure 13. The annual number of otogenic intracranial abscesses (oIA) and of intracranial abscesses
of other etiologies (other IA).
Table 4. Intracranial abscesses with ENT or dental predisposing conditions. (* p<0.01)
All (166) Adults (141) Children (25) 1970-1989 (74) 1990-2012 (92)
ENT infecƟon 37 (22%) 27 (19%) 10 (40%) 21 (28%) 16 (17%)
OƟƟs 18 (11%) 16 (11%) 2 (8%) 10 (14%) 8 (9%)
SinusiƟs 15 (9%) 8 (6%) 7 (28%)* 8 (11%) 7 (8%)
Dental infecƟon 24 (15%) 23 (16%) 1 (4%) 3 (4%) 21 (23%)*
Table 5. Pathogen findings of patients with otogenic intracranial abscesses (oIA) and of intracranial
abscesses of other etiologies (other IA). (* p<0.01)
oIA other IA
Streptococcus spp 33 % 42 %
Gram-negaƟve enteric bacteria* 22 % 5%
Bacteroides spp 11 % 4%
Fusobacterium spp 6% 14 %
Haemophilus spp 6% 4%
Staphylococcus spp 0% 8%
AcƟnomycetales 0% 8%
Other/unknown 22 % 15 %
NegaƟve culture 17% 14%
41
Results
Adults hospitalized due to AOM, AM, LM, or AMc (IV)

The annual incidence of AM in adults was 0.4/100,000, and that of all mastoid infections (AM,
LM, or AMc) was 0.8/100,000. The annual number of cases is shown in Figure 14; no significant
seasonal variation was seen. Patient clinical characteristics, symptoms, findings, complications,
procedures, and outcomes are presented in Table 6. The median duration of symptoms was 8
days and was longest in patients with LM (10 days).
Prior medical conditions (such as asthma, diabetes mellitus, cardiac disease, ear problems) were
seen in 99 patients (62%). Cardiac problems were most common in the AMc group (5, 25% vs.
10, 7% in others, p=0.024). While all patients with AMc had CSOM, most patients (73%) had
no prior ear problems; only five (3%) had a prior tympanostomy tube. A history of prior ear
problems was least common in patients with AM (5, 10% vs. 38, 35% in others, p=0.001), these
patients also had fewer general prior medical conditions (26, 50% vs. 73, 68% in others, p=0.036).
Prior antimicrobial treatment had been administered to 114 patients (71%) and ear drops to 40
patients (25%). Patients with AMc had received less prior antimicrobial treatment than others
(10, 50% vs 104, 74% in others, p=0.034).
Imaging was commonly performed on patients, with CT performed on 104 (65%) and MRI
on 35 (22%); AOM patients were least likely to have had imaging. The most common cultured
pathogens were StrA (19%), Pnc (14%), and Ps (11%); pathogens are shown according to groups
in Figure 15. Hi was only found in the samples of three patients. Of all Pnc cultures, four (18%)
had reduced susceptibility for common antimicrobials. Ps (30%, p<0.01), and Sa (25%, p<0.05)
were more common in patients with AMc than in others. The results of bacterial cultures were
negative for 65 patients (41%), making up 57% of AOM samples, 35% of AM samples, 25% of LM
samples, and 30% of AMc samples. Patients with infection caused by Pnc had a longer duration
of hospitalization (7 days vs 4 days in others, p=0.000), higher median CRP (216 vs 28 in others,
p=0.000) and median WBC levels (14.4 vs 10.5 in others, p=0.009), and more meningitis (5,
23% vs 4, 3% in others, p=0.003) compared to those with infections caused by other pathogens.
Otorrhea (83%), TM perforations (57%), hearing problems (83%), and post-infection hearing
problems (60%) were common in patients with infection caused by StrA. Additionally, dizziness
was relatively common in these patients (57%). Otorrhea (94%) and retroauricular signs of
infection were common in patients with infection caused by Ps.
Parenteral antimicrobial treatment was administered to most patients (98%) (cefuroxime 84%,
ceftriaxone 11%, and/or metronidazole 10%), as well as peroral antimicrobial treatment to (92%)
(cephalexin 55%, amoxicillin-clavulanate 22%, ciprofloxacin 18%). Additionally, topical ear
drops (88%) and steroids (79%) were commonly prescribed.
Mastoidectomy was performed on 44% of patients. The mean duration of hospitalization was
longer in patients who underwent mastoidectomy (8 days) compared with those who did not (5
days, p=0.001).
Outcomes were better in patients who did not need a mastoidectomy. Full recovery was
comparatively less common in patients with infection caused by Ps (24%). Post-infection hearing
problems were common in patients with infection caused by Sa (62%) or StrA.
42
Results
12
10
0
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
AOM AM LM AMc
Figure 14. Annual number of adults hospitalized for acute otitis media (AOM), acute mastoiditis
(AM), latent mastoiditis (LM), or AM in chronic ear (AMc).
43
Results
Table 6. Clinical findings, symptoms, surgeries, and outcomes of adults hospitalized due to AOM, AM,
LM, or AMc.
AOM (60) AM (52) LM (28) AMc (20)

Females 67% 60% 43% 45%
Median age 43 47 49 52
Median CRP(mg/l) 11 81 24 12
Otalgia 97% 100% 86% 95%
Fever 32% 44% 39% 35%
Otorrhea 43% 64% 64% 90%
Dizziness 53% 44% 43% 30%
Nausea 23% 21% 14% 5%
Head ache 13% 23% 18% 15%
Hearing problem 67% 69% 68% 25%
Facial nerve paresis 17% 12% 18% 5%
Retroauricular redness 2% 23% 4% 40%
Retroauricular pain 12% 65% 25% 60%
Retroauricular swelling 0% 23% 4% 45%
Retroauricular ŇuctuaƟon 0% 2% 4% 30%
Protrusion of the pinna 0% 12% 0% 20%
Subperiosteal abscess 0% 2% 10% 35%
MeningiƟs 0% 8% 11% 10%
LabyrinthiƟs 38% 15% 18% 5%
Sinus thrombosis 0% 4% 4% 0%
Tympanostomy 55% 73% 71% 45%
Paracentesis 75% 71% 79% 35%
Mastoidectomy 7% 37% 54% 50%
Median hospitalizaƟon, days 4 6 5 4
Residual TM perforaƟon 13% 13% 18% 30%
Residual hearing problem 37% 35% 32% 20%
Re-operaƟons 8% 13% 21% 25%
44
Results
Pathogens of adults, Pathogens of adults, AM

S.
hospitalized AOM Other/unknown 34%
pneumoniae
S. 19%
pneumoniae
10% H.
influenzae H.
2% influenzae
2%
S. pyogenes
15%
P.
aeruginosa
8%
Gram-
S. aureus negative S. pyogenes
Other/unknown 3% 27%
enteric
59% Gram-negative P.
bacteria 2%
enteric S. aureus aeruginosa
bacteria 3% 6% 10%
Pathogens of adults, LM Pathogens of adults, AMc

S.
Other/unknown P.
31% 21%
25% aeruginosa
30%
H.
influenzae
4%
Gram-
negative
Gram-negative enteric
S. pyogenes bacteria
enteric 25%
bacteria 4% 20%
S. aureus P. aeruginosa S. aureus
11% 4% 25%
Figure 15. Pathogens of adults hospitalized for AOM (n=60), AM (n=52), LM (n=28), or AMc (n=20).
45
Discussion
6 DISCUSSION
ComplicaƟons of oƟƟs media

According to our results, complications of OM in children and adults are less common in Finland
than in other European countries. The annual incidence of AM among Swedish and Dutch
children is 2.5-3.8/100,000 (van Zuijlen et al. 2001, Groth et al. 2012). The annual incidence of
mastoiditis in Italian adults is 1.0/100,000 with 31% of those due to chronic OM (Palma et al.
2014). In our study, AM was more common in children than adults. The annual incidence of AM
in children was 1.9/100,000, whereas the annual incidence of acute mastoid infections (AM, LM,
or AMc) in adults was 0.8/100,000. Only 13% of our adult patients had AMc, possibly explaining
our lower incidence compared to the Italian study. One explanation for the lower incidence of
AM in Finnish children compared to Sweden or the Netherlands, might be the reduced use of
antimicrobial treatment in those countries.
Complications due to OM have recently become more common at our institution compared
with earlier reports (1990-2004) in which annual OM complication incidences of 1.1/100,000 in
children and 0.3/100,000 in adults were reported (Leskinen & Jero 2004, 2005). The diagnostics
of OM and its complications have not been altered over this time period, and thus do not explain
this change. Reasons for this rise in incidence may be due to changes in the treatment of OM or
pathogen virulence.
The annual incidence of IAs, according to a recent meta-analysis, is 0.4-0.9/100,000, with 32%
being oIAs (Brouwer et al. 2014a). Some of the studies included in this meta-analysis were old,
possibly skewing the incidence rates to appear higher than are currently seen in practice. In our
study, the annual incidence for oIA over 2000-2012 was much lower, 0.02/100,000. Our results
also show that the incidence of oIA has decreased over time, and that the prognosis of patients
with IAs has improved. In our patients, most oIAs were due to CSOM and cholesteatoma, and
ear symptoms were common in this group (17 patients, 94%) (unpublished data, Laulajainen-
Hongisto et al.). The decrease in the incidence of chronic OM may explain the simultaneous
decrease in the incidence of oIAs.
Pathogens of complicated oƟƟs media

The most common pathogens of outpatient AOM in children are Pnc (23%), Mc (18%), and Hi
(16%) (Palmu et al. 2004). Studies regarding the pathogens of AOM in adults are scarce, perhaps
because outpatient AOM is uncommon in adults; the most common pathogens in adults with
AOM have been reported to be Pnc (21%), Hi (26%), StrA (4%), and Mc (3%) (Celin et al. 1991,
Bluestone et al. 1992).
Our study results are in accordance with prior literature findings that the bacteriological etiology
of complicated OM differs from outpatient AOM (Luntz et al. 2001, Leskinen 2005, Benito et
al. 2007); our results show that this difference in bacteriological etiology of outpatient AOM
from hospitalized AOM and AM occurs in both children and adults. Therefore, bacteriological
cultures should always be taken in complicated cases of OM in order to determine the proper
46
Discussion
course of treatment as early as possible. We found that Pnc, StrA, and Ps were the most common
pathogens in both adults and children with complicated OM; StrA and Ps were, however, only
seen in adults and children older than two years.
Recent prior antimicrobial treatment was more common in adults (71%) than children (64%). In
children, it tended to be more common in AM (70%) than AOM (57%), and in adults it was least
common in AMc (50%). Our results show that culture negative bacterial findings were associated
with prior antimicrobial treatment; these findings were less common in children (27%) than
adults (41%), they were uncommon in adults with AMc (30%). Antimicrobial resistance
(especially of Pnc to penicillin) is more common in children who have had prior antimicrobial
treatment (Leibovitz et al. 1998, Del Castillo et al. 1998).
We found Pnc to be common in both outpatient AOM and complicated OM. In this study, Pnc was
found in 38% of childen hospitalized for AM, 21% of adults hospitalized for LM, 19% of adults
hospitalized for AM, 18% of children hospitalized for AOM, and in 10% of adults hospitalized
for AOM, but not in oIAs or adults with AMc. Pnc, including its resistant strains, were common
in children under two years of age. More Pnc strains with resistance to penicillin and 1st and
2nd generation cefalosporins were seen in children with AM (48% of Pnc) than in children with
AOM (13% of Pnc), or in adults (18% of Pnc). This might be due to the resistant, more virulent
Pnc strains being able to more easily cause complicated infections, or due to selection of resistant
strains due to prior antimicrobial treatment. Drug-resistant strains are not necessarily more
virulent, but may be treated with inefficient antimicrobials more often. Fortunately, a high and
frequent-enough dosage of antimicrobials can compensate for the intermediate resistance of Pnc
to penicillin (Del Castillo et al. 1998, Jalava 2014). Adults had less infections caused by these
resistant Pnc strains, even though they had received more preceding antimicrobial treatment
(71%) compared with children (64%). In children, pneumococcal infections (especially those
caused by the resistant strains) caused more severe symptoms and led to more mastoidectomies
than infections caused by other pathogens. Multi-drug resistant Pnc is, according to the literature,
common in complicated AOM (Mattos et al. 2014, Antonelli et al. 1999, Zapalac et al. 2002).
More antimicrobial resistance of Pnc to penicillin, macrolides, and trimethoprim-sulfonamide
was observed in Finland over the period 2009-2011, compared to 2014 (Jalava 2014). Our study
fell into this 2009-2011 period, but this does not explain why children with AM, in particular,
had such high rates of resistant Pnc strains.
In this study, Hi was a very rare finding (0-4%) in complicated OM among both children and
adults. Mc was most often found in children under the age of two who were hospitalized for
AOM (14%), but it was not seen in adults or children with AM. Our results confirm the findings
of earlier reports, that Hi and Mc rarely cause complications of OM (Katz et al. 2003, Leskinen &
Jero 2003, Segal 2005).
In our study, StrA was often found in adults and older children, but not in younger children.
It was common in adults hospitalized for AM (27%), LM (25%), and AOM (15%), but not in
adults with AMc. In adults, StrA caused otorrhea, TM perforations, disturbances in balance,
and hearing problems. To enable a faster diagnosis of infections caused by StrA, rapid detection
from MEE can be used. StrA is known to be virulent and locally invasive (Segal 2005, Shulman
et al. 2005). The incidence of invasive StrA infections in children has tripled within the last 15
47
Discussion
years in Finland (Tapiainen et al. 2016). Some strains of StrA have the ability to release bacterial
toxins that can, at worst, result in a cytokine storm leading to toxic shock syndrome with tissue
damage, disseminated intravascular coagulation, and multiorgan dysfunction (Lappin et al.
2009). Therefore, it is easy to understand how tissue damage caused by bacterial toxins entering
the labyrinth or cochlea can result in serious complications.
Ps has been reported to be a common pathogen in AM, especially in children with prior recurrent
AOM (Butbul-Aviel et al. 2003). Ps was found in adults with AMc (30%), children hospitalized
for AOM (16%) or AM (11%), and adults hospitalized for AM (10%) or AOM (8%), but it was
not among the most common pathogens in adults with LM. In our material, Ps caused otorrhea
and was found in older children, especially those with prior tympanostomy tubes, as well as
adults with chronic OM. In children, the clinical picture of AM caused by Ps was mild.
The bacteriological etiology of AMc was not like that of AOM, LM, or AM. As expected, the
bacteriological etiology of AMc - Ps (30%), Sa (25%), and Gram-negative enteric bacteria (20%)
- resembled the bacteriology of CSOM (Brook 2005, Yeo et al. 2007, Mittal et al. 2015).
In our material, most patients with oIAs had preceding CSOM with cholesteatoma. An association
of CSOM with cholesteatoma, with intracranial complications of OM has been seen previously
as well (Penido et al. 2005, Szyfter et al. 2012, Sun et al. 2014). According to the literature, the
most common pathogens of oIAs belong to Streptococcus spp, Bacteroides spp, Prevotella spp, and
Enterobacteriaceae (Brouwer et al. 2014b), which are similar to those seen in CSOM patients. In
our study, Gram-negative enteric bacteria were more common in patients with oIAs (22%) than
in others. The bacteriological etiology of oIA resembles that of chronic OM and AMc.
Complicated oƟƟs media in children and adults

In our study, the children with AM were generally younger than those with AOM. However,
there were more children under the age of two in the AOM group (32%) than AM group (27%).
AM causes a more severe clinical picture in younger children, compared to those who are
older (Katz et al. 2003). AM has been reported as very uncommon in infants under the age of
six months (17 cases in Sweden over a 15 year period) (Stenfeldt et al. 2014). In our material,
AM was clearly less common in children under the age of two than in a Swedish study (55%)
(Groth et al. 2012). Although the expectant observation approach for AOM in older children
is more clearly suggested in Sweden than Finland, antimicrobial treatment is recommended for
AOM in children under the age of two in both countries (Heikkinen et al. 2010, Stenfeldt et
al. 2010, Groth et al. 2011). The adults with AOM or AM were younger than those with more
prolonged infections (LM, AMc); this may be explained by the complications of OM being along
a continuum, starting from AOM, progressing to either AM or LM, which, if not treated, can
lead to CSOM and AMc. Most oIAs developed following CSOM, which is more common in
adults than children.
Underlying medical problems were more common in children hospitalized for AOM (48%) than
AM (27%), while adults with AMc had more prior medical conditions, including ear problems;
48
Discussion
this was most likely due to their older age compared with adults in other groups. The chronic ear
problems of adults with AMc persisted after the acute mastoid infection.
Intra- and extratemporal complicaƟons of oƟƟs media

In the present study, subperiosteal abscesses were more common in children with AM (18%)
than in adults (6%), probably due to the thinner bone structures in children than adults and
the immature immune system of children. Subperiosteal abscesses were more common in adults
with AMc than other types of acute mastoid infections or AOM. The patients with AMc probably
had more underlying bone destruction due to their chronic middle ear infection.
Facial nerve paresis was more common among children hospitalized due to AOM (27%) than
AM (5%). This can be explained by the spread of infection in the direction of least resistance. If
the infection spreads toward the mastoid, it causes less pressure on the facial nerve area. In our
study, 14% of adults had facial nerve paresis and 23% had labyrinthitis. AOM and AM patients
with facial nerve paresis typically have infected tissue and purulent effusion surrounding an
uncovered facial nerve.
In our patients, oIAs were usually due to CSOM with cholesteatoma. According to Zevallos et
al. (2009), 25% of pediatric patients with coalescent AM may have intracranial complications.
We found intracranial complications of AM to be much less common. Additionally, the rate of
intratemporal complications due to OM reported in a Brazilian study (0.8%) seems very high
compared to our results (Maranhao et al. 2014).
DiagnosƟcs of complicated oƟƟs media

The diagnosis of mastoiditis is based on symptoms and clinical findings (protrusion of the pinna,
retroauricular redness, swelling, pain, or fluctuation; and/or abscess in the EAC; and/or purulent
secretion or acute infection in the mastoid process upon mastoidectomy), not imaging or
laboratory tests. Since AOM, AM, LM, and AMc are part of a continuum of middle ear infection,
their symptoms overlap.
In our study, children with AM had more protrusion of the pinna than the children with AOM.
Also, retroauricular signs of infection were more common in children with AM than AOM. The
criteria we chose to use for the diagnosis of AM, therefore, seem appropriate.
Fever, otorrhea, and otalgia did not differ significantly in children with AOM and AM. In
our material, fever was more common in adults with AM than in other groups. According
to the literature, high fever and elevated infectious parameters (WBC, CRP) may be signs of
complicated AM and warrant close follow-up (Bilavsky et al. 2009). We also found that patients
with AM had higher CRP levels than those with AOM.
The necessity of imaging in AM has been discussed; currently, imaging is mainly performed
to detect complications in unclear cases, or in cases that do not respond to treatment. In
concordance with this, imaging was, in our study, less common in children with AOM (11%)
49
Discussion
than AM (50%), and less common in adults with AOM (CT 28%, MRI 5%) than LM (CT 93%,
MRI 43%). Imaging is crucial in the diagnostics of IAs, as well as in diagnosing the underlying
conditions of the ear. CT is efficient in evaluating bony structures, but MRI is superior in
evaluating soft tissues and intracranial structures; the choice of imaging technique should be
based on the type of anatomical structures in question. The availability of CT is better than
that of MRI, and its duration is shorter. Anesthesia may be needed when MRI is performed on
small children. All of these factors affect the choice of modality; nevertheless, imaging should
be considered in patients with acute infection of the middle ear and signs of mastoid infection
that do not respond to conservative treatment (within 48 hours), when surgical treatment is
considered, or when complications are suspected.
Treatment of complicated oƟƟs media

Ideally, we would be able to identify those AOM patients who are at risk for development of
complications as early as possible and treat their infections efficiently before complications
develop. Antimicrobial treatment is not only used to avoid complications of AOM, but also to
reduce symptoms, shorten the duration of MEE, and to avoid hearing problems in children
(Tapiainen et al. 2014). According to Swedish publications, watchful waiting does not seem to
increase the incidence of AM (Stenfeldt et al. 2010, Groth et al. 2011). However, the incidence of
mastoid complications of AOM in Sweden and the Netherlands, where antimicrobial treatment
for AOM is less common, is much higher than in Finland (van Zuijlen et al. 2001, Groth et al.
2012). It is known that antimicrobial treatment reduces the risk of mastoiditis, but the number
of treated AOM patients needed to avoid one case of AM is very high (~4800) (Petersen et al.
2007, Thompson et al. 2009). Since spontaneous resolution of AOM is seen within 2-3 days of
symptom onset in 80% of patients, those with no known risk for complications can simply be
followed (Rosenfeld et al. 2003). Based on the literature and our results, antimicrobial treatment,
at least for AOM in children under the age of two, seems adequate (Klein 2011, Tähtinen et al.
2011, Hoberman et al. 2011a, Hoberman et al. 2013).
The factors leading to complications are not entirely known. Complications may develop
following untreated infections, incompletely treated infections (LM), or, in some cases, due
to unknown causes, despite effective treatment. Anatomical or immunological factors, as well
as age, may affect a patient’s predisposition for complications. Additionally, the virulence, or
antimicrobial resistance, of a pathogen may affect its ability to cause complicated infections
(Antonelli et al. 1999, Zapalac et al. 2002).
In our study, children with AM had received more antimicrobial treatment prior to hospitalization
(70%) than children with AOM (57%). Many of the pathogens of OM are naturally resistant to
macrolides. In our study, the children with AM who had been treated with macrolides underwent
more mastoidectomies (80%) compared to the whole group (34%). Macrolides should not be
used to treat AOM since almost all Hi strains, and 14-27% of Pnc, are resistant to them.
All study patients with AOM or mastoid infection received antimicrobial treatment; cefuroxime
was the most common, followed by ceftriaxone, clindamycin, and metronidazole. Ciprofloxacin-
hydrocortisone ear drops were commonly administered to the patients (~90%) to treat the
50
Discussion
infection and keep the tympanostomy tube open. In order to reduce inflammation and tissue
edema, oral or parenteral steroids were given to 55-73% of children and 79% of adults.
We advise that the antimicrobial treatment of complicated OM should always cover Pnc and
StrA. In the Finnish current care guidelines for treatment of AOM, the suggested amoxicillin
dose is 40mg/kg/day, whereas guidelines from the United States suggest an amoxicillin dose of
80-90mg/kg/day (Heikkinen et al. 2010, Lieberthal et al. 2013). Since antimicrobial resistance
of Pnc was common in our pediatric sample of AM, and most Pnc cases were intermediately
resistant to penicillin, a higher dose of antimicrobials should be considered for this group.
The patients with AM required longer hospitalization and more surgeries than those with AOM.
In adults, surgeries were more common in the patients with prolonged mastoid infections (LM,
AMc) than in those with AOM or AM. Paracentesis was performed more commonly in adults
(69%) than children (23%), and tympanostomies less commonly in adults (63%) than children
(73%). Tympanostomy was more common in children with AM (84%) than with AOM (59%).
Although the treatment of mastoiditis has become more conservative, mastoidectomy is still
required in AM resistant to conservative treatment (Chesney et al. 2014). Mastoidectomy was
performed on 34% of children with AM, and on 44% of all adult patients with AM, LM, or AMc.
In adults, mastoidectomy was most common in LM (54%). The adult patients that underwent
mastoidectomy had worse outcomes than those who did not, however, none had perioperative
complications. Patients requiring mastoidectomy had infections that were already severe prior
to the surgery. The overall outcomes across all patient groups in our study are similar to those
reported in prior literature (Osma et al. 2000, Sennaroglu et al. 2000, Penido et al. 2005, Dubey
et al. 2010, Groth et al. 2012). In our material, the outcome of children was better than that of
adults, probably because children have less chronic ear infections.
Since the acute infections of patients with CSOM may lead to serious complications (AMc, oIAs),
they must be efficiently treated. In patients with complicated CSOM, the common pathogens are
Ps, Sa, and Gram-negative enteric bacteria. Patients who have already developed chronic OM
should be efficiently treated and followed. Antimicrobial treatment of complicated chronic OM
should efficiently cover the most common bacterial pathogens of CSOM (Ps, Sa, and Gram-
negative enteric bacteria).
The treatment of oIAs was not specifically analyzed in this thesis. Most patients with IAs in this
study received antimicrobial treatment, the only exception were patients arriving at the hospital
in critical condition, dying before treatment was possible. Almost all patients (99%) with IAs
underwent surgery for their abscess. At our institution, the underlying (ear) infection is treated
when the patients are stable, usually after the initial treatment of the IA.
51
Discussion
Future perspecƟves
PCVs were added to our national immunization protocol in September 2010 and our data
collection period ended in 2012. Our aim, however, was not to evaluate the effect of PCVs on
OM complications. Although PCVs are effective against invasive pneumococcal disease, against
AOM caused by Pnc, and have resulted in a reduction in tympanostomies among children, they
seem not to have resulted in a reduced incidence of AM (Eskola et al. 2001, Poehling et al. 2007,
Sarasoja et al. 2013, Whitney et al. 2003, Palmu et al. 2013). Pnc replacement by non-vaccine
serotypes has been reported, some of these serotypes are virulent and have a tendency to develop
antimicrobial resistance (Casey et al. 2010, Hoberman et al. 2011b). Multivalent PCVs are
available, however, and may, in the future, change the prevention landscape. The effect of PCVs
on the development of AOM complications is important to monitor in the future.
Anatomical conditions may exist that predispose a person to developing complications from
OM. For example, the size of the mastoid might affect development of mastoid infections; this
too warrants further study. Genetic susceptibility for the development of complicated OM is also
an interesting issue for future research, as well as the use of steroids in the treatment of OM
complications.
52
Conclusion
7 CONCLUSION
Acute complications of OM are rare in Finland compared with other European countries.
However, their incidence has risen over the last decade.
1. The clinical findings in children with AM differ depending on the causative pathogen. Pnc,
particularly the resistant strains, often cause severe symptoms and lead to mastoidectomy.
Ps typically causes milder symptoms and affects mainly older children with prior
tympanostomy tubes.
2. Children hospitalized due to AOM or AM have a different bacteriological etiology than

those with outpatient AOM. The typical AOM pathogens, Hi and Mc, were uncommon
in the complicated (hospitalized) patients. Pnc, especially its resistant strains, was less
common among patients hospitalized due to AOM than AM. Children with AOM required
less surgical interventions and had a shorter hospitalization period than those with AM.
StrA and Ps were linked to otorrhea and were only found in older children.
3. Otogenic IAs have become less common over time and are usually due to CSOM, often in
connection with cholesteatoma.
4. In adults, the bacteriological etiology of hospitalized AOM, AM, and LM (Pnc, StrA, and
Ps) differs from that of AMc (Ps, Sa, and Gram-negative enteric bacteria). LM and AMc
lead to more surgical procedures than do the acute complications of AOM or AM.
53
Acknowledgements
ACKNOWLEDGEMENTS
These studies were carried out at the Department of Otorhinolaryngology – Head and
Neck Surgery, Helsinki University Hospital. They were performed in co-operation with the
Departments of Radiology and Neurosurgery. We began discussing this project in 2005, and
most of the work took place between 2008 and 2016. I wish to warmly thank all those that helped
and supported me during this time.
First and foremost, I wish to express my deepest gratitude to both my supervisors, Professor
Jussi Jero and Docent Antti Aarnisalo. Working with you has been a pleasure and I hope we can
continue to collaborate in the future. Thank you Jussi for always being positive and encouraging.
Your skills, intelligence, enthusiasm, innovativeness, humanity, fairness, and general interest in
life are qualities I admire. And thank you Antti for your energy, positive attitude, encouragement,
and for being exceptionally good at seeing the forest for the trees.
Thank you Docent Hans Ramsay, Director of the Helsinki University Hospital Head and Neck
Center, for enabling this research. I wish to kindly thank both Docent Erna Kentala, current Head
of the Department of Otorhinolaryngology, and Docent Heikki Rihkanen, retired Head of the
Department of Otorhinolaryngology, for encouraging and enabling research at the Department
of Otorhinolaryngology, and for your good and fair leadership. I sincerely thank Professors Anne
Pitkäranta and Antti Mäkitie for creating such an inspiring, yet warm, atmosphere for research.
My thesis committee, Docent Hannu Valtonen and Matti Seppälä, MD, PhD, are thanked for
their support. Thank you Professor Mika Mäkelä, Head of Skin and Allergy Diseases, for enabling
me, over the past almost three years, to combine working as a clinician with being a researcher,
while simultaneously learning new things in the field of allergology.
To the members of our research group: Laura Lempinen, MD, Antti Markkola, MD, PhD, and
Riste Saat, MD…it has been a pleasure to work with you! Riste and Laura, thank you for the
peer-support and all of your help. Antti, thank you for your radiological expertise and friendly
attitude.
I also wish to express my gratitude to co-authors Docent Göran Blomstedt, Esa Färkkilä, DDS,
MB, and Kimmo Leskinen, MD, PhD. Göran Blomstedt is especially thanked for his original
idea of the study on intracranial abscesses, and for his neurosurgical expertise. Kimmo Leskinen
is thanked for his initial work on the intracranial abscess study. Esa Färkkilä is appreciated for
his friendly help in the field of dental medicine. For statistical help, I thank Timo Pessi. For the
skillful medical drawings, a huge thank you goes to Helena Schmidt. Additionally, I wish to
warmly thank Alyce Whipp for the English language editing, and Katariina Ahtola-Rajala for the
Finnish language editing, of this thesis.
I respectfully thank the official reviewers of this thesis, Professor Harri Saxén and Docent Juha-
Pekka Vasama, for your time and effort, and the extremely valuable comments. And, for agreeing
to be my opponent, I wish to warmly thank Professor Olli-Pekka Alho.
54
Acknowledgements
To all my colleagues at the Department of Otorhinolaryngology I wish to extend my sincere

thanks for all your help and support, and for creating the exceptionally welcoming work
environment. I greatly value the friendship of our group of otorhinolaryngologists who have
helped and encouraged each other during our thesis projects. Working at the Skin and Allergy
Hospital has taught me a great deal, and I wish to express my gratitude to Docent Sanna Salmi
and Docent Paula Kauppi for this opportunity.
And to my friends and relatives, thank you, from the bottom of my heart, for all your help and
support. Thank you Hanna Malmi and Kristiina Nieminen for your friendship and the many
conversations over the years that have helped me, also during this thesis process. I thank my
cousins Annukka Harju and Tiina Suvanto for our lifelong friendship, it means so much to me.
Words cannot express my gratitude and love to my parents Tuula and Esa Laulajainen. You are
the best parents and grandparents imaginable, thank you for all your help, support, and love!
I also want to warmly thank my brilliant parents-in-law, Christina Mock-Hongisto and Pekka
Hongisto, for all your help and support, and for being such amazing grandparents. Tuula, Esa,
Christina, and Pekka – your practical help in our daily life is invaluable to our family! I also want
to thank my sister-in-law, Joanna Hongisto for your kindness, and for being there for the boys!
Most of all, I want to thank my family: my husband Jonatan and our sons Emil and Oskar. You
are the most important thing in my life, I love you! Jonatan, your love and support could carry
me through anything. Emil ja Oskar, te teette minut äärettömän onnelliseksi - Kiitos!
This project was financially supported by grants from Finska Läkaresällskapet, the Finnish
Research Foundation for Otology, and the research funds of the Helsinki University Hospital.
Helsinki, May 2016

Anu Laulajainen-Hongisto
55
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65
ORIGINAL PUBLICATIONS
66
DEPARTMENT OF
ANU LAULAJAINEN-HONGISTO Acute severe complications of otitis media in children and adults
OTORHINOLARYNGOLOGY
– HEAD AND NECK SURGERY
HELSINKI UNIVERSITY HOSPITAL
FACULTY OF MEDICINE
UNIVERSITY OF HELSINKI
ACUTE
OF OTITIS MEDIA
ANU LAULAJAINEN-HONGISTO
ISBN 978-951-51-2169-1 (paperback)
ISBN 978-951-51-2170-7 (PDF)
Hansaprint
Vantaa 2016

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To be presented for public examination with the permission of

Professor Jussi Jero

Docent Antti A. Aarnisalo

Professor Harri Saxén

Docent Juha-Pekka Vasama

Professor Olli-Pekka Alho

Layout: Tinde Päivärinta/PSWFolders Oy

ISBN 978-951-51-2169-1 (paperback)

Hansaprint, Vantaa 2016

Education is not the learning of facts

Äkillisen kartiolisäketulehduksen tai välikorvatulehduksen vuoksi HUS:n Korvaklinikalle

Streptococcus pneumoniae on tavallinen välikorvatulehduksen taudinaiheuttaja, myös tässä

Avohoidossa hoidettava välikorvatulehdus eroaa sairaalahoitoon johtaneesta

I Laulajainen-Hongisto A, Saat R, Lempinen L, Markkola A, Aarnisalo AA, Jero J.

II Laulajainen-Hongisto A, Saat R, Lempinen L, Aarnisalo AA, Jero J. Children hospitalized

III Laulajainen-Hongisto A, Lempinen L, Färkkilä E, Saat R, Markkola A, Leskinen K,

IV Laulajainen-Hongisto A, Jero J, Markkola A, Saat R, Aarnisalo AA. Severe acute otitis

Before the development of antimicrobial treatment, complications of OM were common and

Complications of OM can develop following untreated or incompletely treated infections as well as

We need to better understand which patients require antimicrobial treatment to achieve a

2 REVIEW OF THE LITERATURE

2.1 Historical aspects

The brain and intracranial space in relaƟon to the ear

2.3 OƟƟs media

OM is a multifactorial disease; environmental, bacteriological, host, immunological, and genetic

Children, outpatient AOM Adults, outpatient AOM

DiagnosƟcs and treatment

Spontaneous resolution of AOM without antimicrobial treatment is common and occurs in

2.4 ComplicaƟons of oƟƟs media

The complications of OM can be divided into intratemporal and extratemporal (extra- or

Figure 7. Intraoperative findings

Facial nerve paresis

In patients with labyrinthitis, paracentesis should be performed, tympanostomy tube should

Intracranial complications of OM are, however, rare. They include, in order of prevalence:

Figure 9. Coronal T2 MR-image of a left-sided occipital

3 AIMS OF THE STUDY

The specific study aims were:

4 PATIENTS AND METHODS

4.1 DiagnosƟc and inclusion criteria

Acute mastoidiƟs (AM)

Latent mastoidiƟs (LM)

Acute mastoidiƟs of a chronic ear (AMc)

Table 1. Patients included in studies composing this dissertation

Study Diagnosis Age, range (years) Number of paƟents

Intracranial abscesses (III)

Adults hospitalized due to AOM, AM, LM, or AMc (IV)

4.5 Ethical consideraƟons

AM (n=56) AOM (n=44) p- value

Pathogens of all children, Pathogens of younger

Table 3. Resistant S. pneumoniae cases (n=10) in children with acute mastoiditis.

Children hospitalized due to AOM (II)

Pathogens of all children, Pathogens of younger

Comparison of children hospitalized due to AM and AOM (I,II)

Intracranial abscesses (III)

Table 4. Intracranial abscesses with ENT or dental predisposing conditions. (* p<0.01)

Adults hospitalized due to AOM, AM, LM, or AMc (IV)

AOM (60) AM (52) LM (28) AMc (20)

Pathogens of adults, Pathogens of adults, AM

Pathogens of adults, LM Pathogens of adults, AMc

ComplicaƟons of oƟƟs media

Pathogens of complicated oƟƟs media

Complicated oƟƟs media in children and adults