Periodontology 2000, Vol. 65, 2014, 178–189 © 2014 John Wiley & Sons A/S.
& Sons A/S. Published by John Wiley & Sons Ltd
Printed in Singapore. All rights reserved
Acute focal infections of dental
origin
I N G A R O L S E N & A R I E J. VAN WINKELHOFF
‘Dental focal infections are back with a bang’. This was
the title of an editorial in the Journal of American
Dental Association in January 1998 (21). Actually, den-
tal focal infections have never been absent, but our
attention is now being refocused on these infections.
Egyptian physicians knew, already in 1500 BC, that
tooth infections had to be treated carefully to prevent
life-threatening complications. In 1891, Miller (44)
published his theory on focal infection suggesting
that oral microorganisms and their products are able
to affect parts of the body adjacent to or distant from
the mouth. Hunter (25) reprimanded dentists who
allowed development of chronic abscesses in the oral
cavity, and he believed that necrotic teeth could rep-
resent foci of infection causing arthritis, heart disease
and other unexplained diseases. Billings (9) also spec-
ulated that infected teeth and tonsils could be
responsible for a number of focal infections such as
arthritis, rheumatism, nephritis, endocarditis and
other diseases. The bacteria and their products were
assumed to reach these sites through bone cavities,
blood or lymph vessels, and even along nerves. Tho-
den van Velzen et al. (61) suggested three different
ways by which oral bacteria can cause nonoral dis-
ease: (i) metastatic inflammation as a result of
immune injury; (ii) metastatic injury from microbial
toxins; and (iii) metastatic infection as a result of the
translocation of bacteria.
The focal infection theory was prevalent in the 19th
century and at the start of the 20th century, particu-
larly in the USA. It resulted in an orgy of tooth extrac-
tions, even in patients with the simplest forms of
gingivitis. The practitioners performing this ‘treatment’
were called ‘hundred percenters’ because they tended
to extract all teeth without considering the extent of
the disease (55). The theory fell into mistrust and was
gradually dismissed. Currently it is back, allegedly with
a bang, although in a new perspective (23). The main
reason for this is that a number of epidemiological
178
PERIODONTOLOGY 2000
studies have demonstrated the association between
chronic oral infections (particularly marginal peri-
odontitis) and systemic diseases, such as cardiovascu-
lar diseases, stroke, diabetes, low birthweight of babies
born prematurely, respiratory infections and rheuma-
toid arthritis (15, 33, 35). These issues are the realm of
periodontal medicine and will not be dealt with in the
current review which is focused on acute dental focal
infections. Thus, the association of dental infections
with systemic health is broad and is not covered to its
full extent in this article.
The oral cavity contains a wide variety of organisms,
including viruses, fungi and protozoa, but bacteria are
the most abundant. This article will focus only on bac-
teria. However, bacteria may occasionally cause sys-
temic disease in concert with viruses and yeasts,
particularly in the compromised host. These organ-
isms may also cause focal infection on their own.
Oral infections are among the most prevalent infec-
tious diseases of mankind. Being mostly chronic in
nature, they relatively rarely lead to acute or dramatic
consequences for the patient. However, medically
compromised subjects may be at risk even for chronic
oral conditions particularly if their immune system is
weak. In fact, translocation of oral bacteria to nonoral
sites may lead to an infectious process, even in
immunocompetent subjects.
Acute oral infections
Acute oral infections are diseases that have a rapid
onset, severe symptoms and a short course as
opposed to chronic oral infections.
Pulpitis
The pathogenesis of oral focal diseases has been
classically attributed to dental-pulp pathologies and

peri-apical infections (10). The main causes for
inflammation of the dental pulp (pulpitis) are bacte-
ria and their metabolites, which reach the connective
tissue of the pulp via small canals in the dentine. The
bacteria are located in caries lesions, in cracks along
tooth restorations or in tooth crowns. Pulp inflamma-
tion can also develop as a result of trauma, such as
following crown or bridge preparation. Toxic effects
from filling materials can also cause pulp inflamma-
tion. Acute pulpitis may induce almost intolerable
pain. At the onset, the pain is induced by external
influences such as sweets and acid food or cold. Later,
the pain can be provoked by heat. Acute intervention
involves excavation of carious lesions and removal of
the coronal part of the inflamed pulp tissue. Subse-
quently, extirpation of the remaining pulp and widen-
ing of the root canal are performed, resulting in filling
of the root canal and a coronal restoration. The root
canal is sealed off to prevent invasion of oral bacteria
and release of their products into the surrounding tis-
sues.
Apical periodontitis
Untreated pulpitis will sooner or later lead to pulp
necrosis. The necrotic tissues of the crown and root
pulp serve as a locus minoris resistentiae and allow
oral obligate anaerobic and facultative anaerobic bac-
teria to cause infection. Pulp necrosis will result in
inflammation of the tissue around the root apex.
Inflammatory mediators, produced by macrophages
and lymphocytes, will recruit and activate osteoclasts,
resulting in peri-apical bone loss. This process may
develop over years without overt clinical symptoms.
Histologically, the tissue around the apex can be
characterized as granuloma, abscess or cyst. The bal-
ance between organisms and the immune defense
can be altered by overgrowth of more virulent bacte-
ria, resulting in aggravation and acute pain. The pain
can, similarly to pulpitis, become severe, particularly
if pus from the apical focus accumulates below the
periostium. The succeeding sequence can be abscess
formation, perforation to the maxillary sinus and, in
serious cases, the infection can spread as a gravity
abscess or phlegmon with infiltration of neighboring
regions. In some cases a fistula will develop, which
may allow accumulated pus to drain and therefore a
decrease in symptoms will occur. Acute pain can also
develop during root-canal treatment if infected and
necrotic pulp/root-canal material is forced into the
peri-apical area. Maxillary sinusitis can cause otitis
and temporomandibular joint symptoms that may
resemble the pain from pulpitis and apical periodon-
Dental focal infections
titis. However, in sinusitis several teeth will be sensi-
tive to percussion and the pain is aggravated when
the patient bends forward.
Pericoronitis
A frequent acute condition in the mouth is pericoro-
nitis. Pericoronitis occurs around a partially erupted
third molar and frequently occurs in the mandible
of young individuals. As a result of the lack of local
dental hygiene, a biofilm containing predominantly
gram-negative anaerobic rods, spirochetes and cocci
develops in the pericoronary space. The acute condi-
tion is characterized by severe pain, rubor, swelling,
suppuration and problems with swallowing. Trismus
may also occur.
Phlegmon and abscess formation
Phlegmon (a spreading diffuse infectious process in
the connective tissue with formation of suppurative/
purulent exudate or pus) and abscess formation usu-
ally result from apical periodontitis but can also be
initiated by severe chronic periodontitis and pericor-
onitis. The symptoms can vary from local swelling
and rubor to more pronounced swelling with risk of
infection spreading to neighboring regions. Most of
these infections are drained through fistulas into the
oral cavity. However, infection may spread to neigh-
boring regions such as the maxillary sinus, the sublin-
gual, submandibular and infraorbital regions, orbit
and brain, and to the parapharyngeal space, ending
up in mediastinitis. In rare cases, so-called cervical
necrotizing fasciitis can develop.
Necrotizing ulcerative gingivitis and
periodontitis
Necrotizing ulcerative gingivitis is a form of necrotiz-
ing periodontal disease that affects the gingiva with-
out involving other tissues of the periodontium (4).
The infection is also known as ‘trench mouth’ and
Vincent’s angina or Vincent’s stomatitis (named after
the French physician, Henri Vincent). Another, older,
synonym is fusospirochetal gingivitis, referring to the
high numbers of fusiform bacteria and spirochetes
seen in the dental plaque using dark-field micros-
copy. Invasion of these organisms into the gingival
tissue explains the acute, necrotizing and ulcerative
nature of the infection. When other periodontal tis-
sues are involved in the infection and alveolar bone
loss occurs, the condition is called necrotizing ulcera-
tive periodontitis. A major risk factor for acute
179
Olsen & van Winkelhoff
periodontal infections is a compromised host
defense. These infections can occur in patients with
HIV infection and AIDS. Also, smoking and stress
have been identified as risk factors for necrotizing
ulcerative gingivitis and necrotizing ulcerative peri-
odontitis. Acute periodontal infections are discussed
in detail by Herrera et al. (24) in this volume of Peri-
odontology 2000.
Bacteremia
Microorganisms in the mouth are located on the
teeth and on dental restorations, in root apices,
mucosa, gingival epithelium, tongue and other oral
tissues and in saliva. Dental treatment, injuries and
infections cause bacteremia through breaches (50).
Even in healthy individuals, microbes of dental
plaque (biofilm) can cause ulceration of the gingival
crevicular epithelium (13). Patients with mucositis are
particularly prone to dissemination of bacteria
through their oral ulcers.
Even toothbrushing can cause bacteremia, which
may be serious in individuals at risk for infective endo-
carditis (36). The type of dental treatment also affects
the risk of bacteremia. Meurman & Ha €ma €la
€inen (43)
listed dental procedures and diseases associated with
bacteremia and reported that the incidence of bactere-
mia ranged from 100% after tooth extraction to 10% in
gingivitis. The intensity of bacteremia is related to the
magnitude of trauma, the density of the local micro-
bial deposits and the presence of inflammation or
infection at the site of mucosal injury (43).
Phenotypic and genetic methods were used to trace
microorganisms released into the blood during and
after endodontic treatment back to their presumed
source – the root canal (16). Microbiological samples
were taken from the root canals of 28 patients with
asymptomatic apical periodontitis of single-rooted
teeth. Blood was drawn during, and 10 min after, end-
odontic therapy. Microorganisms in the blood were
collected after anaerobic lysis filtration and anaerobic
culture. Biochemical and antimicrobial susceptibility
tests, sodium dodecyl sulfate–polyacrylamide gel elec-
trophoresis of whole-cell soluble proteins, gas chro-
matography of cellular fatty acids, DNA restriction
patterns and ribotyping showed identical phenotypic
and genetic characteristics of the root canal and blood
isolates, demonstrating that endodontic treatment can
be the cause of anaerobic bacteremia and fungemia.
Oral bacteria in the blood can deposit directly in
coronary vessels or in atherosclerotic plaques. These
bacteria are more diverse than previously thought
180
and include a number of anaerobes. Bahrani-
Mougeot et al. (5) identified oral bacterial species in
blood cultures following single-tooth extraction and
toothbrushing. Sequence analysis of 16S rRNA genes
detected 98 different bacterial species recovered from
151 bacteremic subjects. Forty-eight of the isolates
represented 19 novel species of Prevotella, Fusobacte-
rium, Streptococcus, Actinomyces, Capnocytophaga,
Selenomonas and Veillonella. This was not supported
in a review on oral organisms found in nonoral
diseases where most translocating oral species consti-
tuted commensals of low pathogenicity (64). How-
ever, this may have resulted from problems with the
culture and identification of the organisms. Probably,
bacteremias also contain not-yet-cultivated bacteria
from oral biofilms from which only half of the bacte-
ria can currently be cultured.
Usually, bacteremia has no consequences in
healthy subjects because bacteria are quickly elimi-
nated from the bloodstream by the reticuloendothe-
lial system of the host. Patients with artificial devices,
such as prosthetic heart valves, artificial joints and
other types of implants, and patients with a history of
infective endocarditis, may run a greater risk for com-
plications from bacteremia (52, 65). van Winkelhoff
et al. (65) described a long-standing symptomatic
bacteremia caused by Aggregatibacter actinomycetem-
comitans in a patient with a pacemaker. Attacks of
fever occurred for at least 1 year. The patient also had
mild periodontitis. Multiple isolates of A. actinomyce-
temcomitans from the oral cavity and the blood were
compared using DNA fingerprinting. The isolates
from the blood and the oral cavity were identical and
it was concluded that the oral cavity was the probable
source of the infection. Successful treatment included
systemic metronidazole and amoxicillin.
Invasive dental procedures can be associated with
a temporary increase in risk for stroke and myocardial
infarction, although the absolute risks are minimal
and the long-term benefits on vascular health would
probably outweigh the short-lived adverse effects.
This was recently shown in a study, carried out from
2002 to 2006, based on persons exposed to invasive
dental treatment with a primary hospital diagnosis of
ischemic stroke (n = 650) or myocardial infarction
(n = 525). The rate of vascular events significantly
increased after dental treatment (incidence ratio =
1.50; 95% confidence interval: 1.09–2.06) and gradu-
ally returned to baseline levels within 6 months. The
positive association persisted, even after exclusion of
persons with diabetes, hypertension or coronary
artery disease, or persons with prescriptions for anti-
platelet or salicylate drugs (45).

Other types of dissemination of
oral bacteria
Dissemination of oral bacteria to extra-oral body sites
may not necessarily occur through the blood. van
Winkelhoff et al. (63) described a case of conjunctivi-
tis with dacryopyorrhea in a patient with aggressive
periodontitis. The conjunctivitis had existed for
3.5 years on one eye only after the patient had suf-
fered from ocular trauma. The patient had used mul-
tiple medications, including topical antibiotics and
hydrocortisone, but without resolution of the infec-
tion. Anaerobic cultivation of pus exudate from the
conjunctival sac revealed multiple anaerobes, includ-
ing Prevotella intermedia and Parvimonas (formerly
Peptostreptoccoccus) micra. Restriction enzyme analy-
sis of the P. intermedia isolates from the conjunctival
sac and the oral cavity revealed the same clonal type,
suggesting translocation of the pathogen from the
oral cavity to the eye (Fig. 1). Systemically adminis-
tered metronidazole plus amoxicillin supported the
mechanical periodontal treatment and resolved the
conjunctivitis without recurrence of the disease. Oral
bacteria can also enter the immune system through
the gut and become processed in Peyer’s patches.
This may result in stimulation or suppression of the
immune system (13). Direct spread of dentoalveolar
abscesses (e.g. to the maxillary sinus, orbit and para-
pharyngeal spaces) can also occur (discussed later).
Dissemination of bacterial toxins
The two most important toxins of oral bacteria that
can be disseminated are lipopolysaccharide (endo-
toxin) and exotoxin. Lipopolysaccharide is released
Fig. 1. DNA fingerprints (PstI digest) of eight Prevotella in-
termedia isolates. Identical profiles are seen for isolates
from the conjunctive sac (lanes 4 and 5), the tongue (lanes
6 and 7) and the tonsils (lanes 8 and 9). Different profiles
are seen for the Prevotella intermedia isolates from the
periodontal pockets (lanes 2 and 3). Lanes 1 and 10 con-
tain a molecular weight DNA ladder.
Dental focal infections
from disintegrating, dead gram-negative bacteria, but
can also be released from the outer-membrane vesi-
cles of viable oral bacteria. Exotoxins are proteina-
ceous in nature and can be released from viable
gram-positive bacteria. An example of the harmful
effects of oral bacterial toxins involves orofacial gan-
grene (noma/cancrum oris) in which Fusobacterium
necrophorum displays a classic endotoxin, a der-
monecrotic toxin, a cytoplasmic toxin and a hemoly-
sin affecting hard and soft tissues of the oral and
para-oral structures (18). Aggregatibacter actinomyce-
temcomitans, the microorganism associated with
aggressive periodontitis, secretes a leukotoxin (LtxA)
that helps the bacterium evade the host immune
response during infection (26). LtxA is a membrane-
active toxin that specifically targets white blood cells.
The Streptococcus milleri group (Streptococcus con-
stellatus, Streptococcus intermedius and Streptococcus
anginosus) are important pathogens in deep neck
and brain abscesses. A massive release of cytokines
through a T-cell response to exotoxins produced by
the S. milleri group, as reported from the toxic shock-
like syndrome, has been suggested in the pathogene-
sis of abscess formation together with the production
of tissue-destroying enzymes such as collagenase and
hyaluronidase (22).
Dissemination of oral bacteria
owing to incompetence in immune
defense
An example of dissemination of oral bacteria as a
result of immune incompetence is the immunologic
changes caused by anticancer drugs. The antineoplas-
tic therapy interferes with the turnover of epithelial
cells; this is followed by mucosal injury and later by
infection as a result of invasion with gram-negative
bacteria and fungal species. Up to 37.2% of all
patients receiving cancer chemotherapy develop
acute oral complications, and up to 31.1% of all
patients receiving cancer radiotherapy experience
acute oral manifestations, which may result in signifi-
cant morbidity, treatment delays and dose reductions,
affecting the prognosis of the primary disease (49).
In infective endocarditis the colonizing bacteria of
morbid luxurious outgrowths on denuded areas of
the endocardium covering the valves of the heart
evade the actions of the adaptive immune system and
antibiotic therapy. This may lead to valvular
insufficiency. In immunocompromised individuals,
alpha-hemolytic oral streptococci cause disseminated
intravascular coagulation. Similarly to infective
181
Olsen & van Winkelhoff
endocarditis, the organisms here gain access to the
systemic compartment, most often through erosive
lesions of the oral and oropharyngeal mucosa, which
are known as mucositis (13). After translocation, the
organisms initiate disseminated activation of the
coagulation cascade. In both endocarditis and dis-
seminated intravascular coagulation, oral commen-
sals with low pathogenicity can cause life-threatening
disease.
During bacteremia, with, for example, Streptococ-
cus sanguinis, the concentration of bacterial heat
shock protein increases in the blood. Antibodies to
oral microbial heat shock proteins can cross-react
with antigens from host heat shock proteins. As a
result, immune complexes can form that activate the
complement system (13). This enables a role for heat
shock protein in some systemic diseases, such as
immune-mediated ulcers and eruptions of the
mucous membrane of the oral cavity, the eyes and
the genitals (Behcßet’s disease) through heat shock
protein mimicry.
Mention should also be made of bacterial mimicry
of host peptides (e.g. collagen fragments from the
platelet aggregation-associated protein epitope of
S. sanguinis). This may cause autorecognition and
autoimmune arthritis (13).
Sequelae of acute oral infections
Facial space infections
Orofacial infection can, in principle, spread to the
skull base or to the diaphragm. The route is largely
dependent on the location of infection in relation to
fasciae. A general rule is that infection spreads along
the route of least resistance in subcutaneous connec-
tive tissues (phlegmon) and along fascial planes with
separation of the fascial layers (30). Purulent exudates
collect at locations forming a space (the fascial
space). Fascial spaces communicate with each other
(Fig. 2), and spread of the infection can therefore pro-
gress extensively and rapidly. Affection of vital struc-
tures in the head and neck can cause airway
obstruction and mediastinitis. Despite modern ther-
apy, fascial space infection remains a significant
health problem and can potentially be fatal. Dental
infection is the most common cause, but also infec-
tions in the mouth, pharynx, tonsils and salivary
glands can be involved as well as trauma and surgical
infections. Biasotto et al. (8) and Cirino et al. (14),
reviewing the literature of descending necrotizing
mediastinitis, found that, despite prompt pharmaco-
182
Orbit
Canine space
Buccal space
Submasseteric space
Sublingual space
Submandibular space
Submental space
Lateral pharyngeal space
Retropharyngeal space
Danger space
Mediastinum
Fig. 2. Drawing showing possible pathways for dental
infection to spread. Courtesy of Wiley-Blackwell. From ref-
erence (30).
logic and surgical intervention, delayed diagnosis is
still responsible for a high mortality rate (about 40–
50%).
Sublingual space infection
Dental infection is most frequently the cause of sub-
lingual space infection, but also sialolith and sublin-
gual gland infection can be involved (30). Usually
sublingual space infections originate from the roots
of the mandibular anterior teeth and first molars.
They often expand bilaterally. A swollen tongue is a
significant clinical feature. There is communication
with the submandibular space posteriorly. In 240
patients treated for mouth-floor cellulitis from 2002
to 2006, 93.7% of the infections were of dental origin
(68). At the first examination the patients had exten-
sion of inflammation into the parapharyngeal and
pterygomandibular spaces and the neck. In 1.7% of
the patients, infection progressed to neck and para-
pharyngeal spaces (Fig. 3) despite treatment, and in
2% of the patients, infection resulted in mediastinitis.
Submandibular space infection
The submandibular space is frequently infected
(Fig. 4) through the second and third mandibular
molars because of the location of the mylohyoid mus-
cle. The boundary between the mandibular angle and
the neck can then become hard to distinguish as a
result of swelling (30). The masticatory muscles are

Fig. 3. Abscess in the neck with erysipelas reaction of the
skin. Courtesy of Geir Støre.
often affected. Infection can also include the mastica-
tor and lateral pharyngeal spaces.
Submental space infection
Submental space infection often involves an infected
mandibular incisor. As a result of the swelling the
chin may seem to protrude anteriorly. In addition,
the submandibular space is often affected (Fig. 5).
Ludwig’s angina
Ludwig’s angina involves infection in the sublingual,
submandibular and submental spaces. There is easy
communication from these spaces to the contralat-
eral side. Most cases of infection are of dental origin.
There is a firm swelling of the mouth floor and the
tongue is elevated. A cellulitis is present with no ten-
dency to abscess formation. Submandibular and sub-
lingual spaces become involved bilaterally. An
endodontic infection of a mandibular molar is often
the primary infection. The patient may develop signs
of toxicity, with high fever, tachycardia and malaise.
Dental focal infections
Fig. 4. Large submandibular abscess. Courtesy of Hans
Reidar Haanaes.
Fig. 5. Large submandibular abscess with spontaneous
drainage of pus. Severe caries is present in all tooth quad-
rants. Courtesy of Geir Støre.
It takes only 12–24 h from the start of the swelling to
the onset of symptoms of respiratory infection. Baq-
ain et al. (6) reported a case of Ludwig’s angina
caused by a dental infection that progressed to medi-
astinitis and pericarditis. The importance of early rec-
ognition and diagnosis of the source of deep cervical
infections must be emphasized (19, 37, 38). Staphylo-
coccus aureus and black-pigmented gram-negative
anaerobic rods may indicate a high risk for develop-
ing Ludwig’s angina (53). In one patient, facial celluli-
tis resulted from a painless dental abscess (37).
Other facial space infections
These may involve the buccal, canine, masticatory,
submasseteric (Fig. 6), pterygomandibular, temporal,
cervical fascial, lateral pharyngeal and retropharyn-
geal spaces (29). Bacterial infection of the mouth
occasionally spreads to these contiguous spaces.
These infections may also affect the orbital cavity (57)
(Fig. 7) and the brain (Fig. 8).
183
Olsen & van Winkelhoff

Fig. 6. Abscess in the masseter region with fistula. Cour-

tesy of Geir Støre.

Gas gangrene and necrotizing fasciitis Fig. 7. Abscess from previously traumatized tooth incised
in the labial fold. Courtesy of Geir Støre.
Dental infection is a common cause of gas gangrene
and necrotizing fasciitis. These infections may spread
downwards to the mediastinum, leading to mediasti-
nitis (8, 14), pericarditis, lung infection and sepsis.
They may also spread upwards to the skull base and
to the meninges, or through blood vessels to give sup-
purative thrombophlebitis, sepsis or disseminated
intravascular coagulation (30). Immunosuppressive
conditions and alcohol abuse may predispose but
these types of infections can also occur in healthy
individuals. Factors affecting mortality are diabetes,
alcohol abuse, delay of surgery and complicating
mediastinitis (62).

Osteomyelitis of the jaw

Both suppurative and nonsuppurative forms of jaw
osteomyelitis occur. The former are the most domi-
nant. They can be acute or chronic. Dental infections
are the most common cause of osteomyelitis in the
jaw, and the body of the mandible is the most com-
mon site. When there is chronically impaired blood
flow and when the bone contains fibrous marrow, the
jaw becomes sensitive to bacterial infection. Cranial
osteomyelitis was described, by Adams & Bryant (2),
to develop as a late complication of dental infection
that extended subtemporally.
Fig. 8. Computed tomography (CAT) scan of a patient with
multiple brain abscesses associated with Aggregatibacter
actinomycetemcomitans organisms and a poor periodontal
condition.
Osteoradionecrosis of the jaw
Osteoradionecrosis affects bone, particularly the
mandible that has been irradiated as part of cancer
treatment (Fig. 9). The radiation harms normal tissue
cells and affects the blood supply in bone, cartilage

184

Fig. 9. Irradiated mandible with osteoradionecrosis and
superinfection. Courtesy of Geir Støre.
and soft tissue. Such tissue is susceptible to infection
with oral bacteria. Until recently, a common view was
that the infection of the bone was superficial and
secondary (40). Several studies, using scanning and
transmission electron microscopy (59), DNA–DNA
hybridization (60) and 16S ribosomal DNA sequenc-
ing (1), have shown independently that the medullary
parts of bone in osteoradionecrosis are heavily
infected with a wide variety of facultative anaerobic
and strict anaerobic bacteria, some of which are not
yet cultivable.
Acute maxillary sinusitis
Maxillary sinusitis usually appears unilaterally and
constitutes approximately 10–12% of all cases of max-
illary sinusitis (12). The etiology includes most often
peri-apical dental abscesses, severe periodontitis,
peri-implantitis and postextraction infection. A num-
ber of other dentally related etiologies can occur (30).
Maxillary sinusitis may become chronic following the
acute phase or can manifest itself as a chronic inflam-
mation without acute episodes. Acute maxillary
sinusitis is caused by bacteria invading the sinus from
a focus of dental infection. Infection from maxillary
premolars and molars, peri-apical abscesses, severe
peri-implantitis, postextraction infection and cysts
are the most common causes (7). Signs and symp-
toms include dull or intense pressure, erythema,
swelling of cheek and anterior maxilla and the drain-
age of foul-smelling material. Acute maxillary sinusitis
can cause orbital abscess/cellulitis (41, 42), cavernous
sinus thrombosis, meningitis and intracranial
abscess. In cases where the origin is a peri-apical
abscess, there is toothache and swelling of the gingiva
and buccal vestibule. Bomeli et al. (11) examined the
frequency of a dental cause for acute maxillary sinusi-
Dental focal infections
tis and found that dental infections can cause acute
maxillary sinusitis, particularly if the radiographic
findings of sinusitis are severe. Many cases of recur-
rent acute sinusitis are caused by secondary rhinoge-
nous bacterial colonization of the antral mucosa that
has been weakened and degenerated by chronic den-
tal infection/inflammation (31).
Peritonsillar abscess
Extension of infection around the third molar may
result in peritonsillar abscess. It is usually seen unilat-
erally, with extreme soreness of the throat, odynopha-
gia, persistent pain in the peritonsillar area and
trismus (30). The uvula may be forced to the opposite
site. Fever, malaise and headache can follow. Of 311
abscesses of dental origin, the parapharyngeal and
peritonsillar abscesses were the rarest and the peri-
mandibular abscess the most common (58).
Suppurative arthritis of the
temporomandibular joint
Direct extension of an adjacent infection, such as
osteomyelitis of the jaw, traumatic and surgical
wound infection of the temporomandibular joint or
hematogenous spread of bacteria from a distal site
secondary to a systemic process may cause suppura-
tive arthritis of the temporomandibular joint (32).
Moses et al. (46) reported a case of septic arthritis of
the temporomandibular joint after removal of third
molars.
Orbital cellulitis/abscess
Dental infections, maxillary osteomyelitis and dental
extractions may cause orbital cellulitis (30). Compli-
cations can be loss of sight and fatal cerebral com-
plications. Orbital cellulitis starts with a painful and
erythematous swelling of the eyelid. The patients
may have severe orbital pain, fever, propoptosis,
conjunctivitis, chemosis, impaired movements of
the eye and optic nerve damage. Mun ~ oz-Guerra
et al. (47) reported a subperiosteal abscess of the
orbit that was an unusual complication of an
uneventful extraction of the left third maxillary
molar. It was probably caused by extension of the
infection to the pterygopalatine and temporal
regions progressing to the inferior orbital fissure.
Also, Sakkas et al. (57) and Kim et al. (28) reported
an orbital abscess after extraction of a maxillary wis-
dom tooth. Direct spread of a dentoalveolar abscess
of the maxillary first molar via the maxillary sinus
185
Olsen & van Winkelhoff
caused eye loss in a 42-year-old HIV-seropositive
woman (41). Allan et al. (3) reported a patient with
orbital cellulitis and a postseptal abscess secondary
to infection from a maxillary molar tooth. In this
patient the infection spread to the maxillary sinus
and then to the orbit via a defect in the orbital
floor.
Brain and liver abscess
Brain abscesses are rare but can be life-threatening.
They are sometimes caused by oral infection and
dental treatment (34). Oral infection with recurrent
bacteremia should always be considered in the path-
ogenesis of the so-called ‘cryptic’ intracerebral and
intraspinal infections (20). Ewald et al. (20) reported
six patients with intracerebral (n = 4) and intraspinal
(n = 2) infections. All patients had dental pathologies.
Clinical improvement was achieved in all patients
after decompression, evacuation of pus and targeted
antibiotics. Wagner et al. (66) described a patient
with brain and liver abscesses caused by oral infec-
tion with S. intermedius. A patient with generalized
periodontal disease, dental caries and peri-apical
pathology developed a cerebral abscess with right
hemiparesis and epileptic fits (48). The patient made
an uneventful recovery 29 months postoperatively
after immediate administration of intravenous antibi-
otics, craniotomy, resection of the abscess cavity and
removal of periodontally decayed and peri-apically
involved teeth. Another patient, with deep facial
space infection, developed a brain abscess (56).
Although a number of reports have suggested a dental
etiology for brain abscesses, few efforts have been
made to compare brain-abscess isolates with isolates
from the oral cavity using highly discriminative meth-
ods. Marques da Silva et al. (39) compared brain-
abscess isolates and oral isolates using phenotypic
and three genetic (restriction fragment length poly-
morphism, ribotyping and random amplification of
polymorphic DNA) fingerprinting techniques. The
phenotypic method and restriction fragment length
polymorphism showed identical profiles between
brain and periodontal isolates, while ribotyping and
random amplification of polymorphic DNA showed
very close similarity. It was suggested that gene trans-
fer by genetic recombination in the periodontal
pocket might have been responsible for the emer-
gence of a strain variant (of S. constellatus) that had
caused an abscess at a distant site.
Aggregatibacter actinomycetemcomitans in combi-
nation with Actinomyces meyeri were isolated from
the pus of multiple intracerebral lesions that were ini-
186
tially diagnosed as cerebral metastases of a suggested
lung carcinoma. Both species were also isolated from
multiple relapsing purulent skin lesions. The patient
had a poor dentition (29). This combination of oral
pathogens has been found more often in brain
abscesses (69), and both species may represent a syn-
ergistic pathogenic combination (65). It has been sug-
gested that a patent foramen ovale in patients with
severe periodontitis may be a risk factor for intracra-
nial infection caused by oral pathogens (27). Brain
abscesses have been confused with metastatic lesions
of a tumor of unknown origin. Rahamat-Langendoen
et al. (54) described a patient with a very poor denti-
tion, stomatitis and alcohol abuse; stereotactic biopsy
detected the presence of brain abscess, and pus was
collected from one of three lesions. Aggregatibacter
actinomycetemcomitans was detected in this patient
(Fig. 8).
Management of acute oral focal
infections
Some acute soft-tissue infections are potentially
lethal. Therefore, prompt diagnosis and treatment are
important. In patients where the infection has spread
to neighboring regions, surgical treatment under gen-
eral anesthesia and treatment with intravenous anti-
biotics may be necessary. Usually, abscesses are
drained by incision and antibiotics are given if the
general health condition is affected or if the host is
immunocompromised. C-reactive protein levels have
been shown to correlate well with the severity and the
resolution of acute dental infections and can thus be
used as a reliable parameter for monitoring the effec-
tiveness of therapy (17).
Fig. 10. Intra-orally incised dental abscess. Courtesy of
Hans Reidar Haanaes.

Surgery
Suppurative oral infections should mostly be surgi-
cally treated. This includes pulpectomy, tooth extrac-
tion and incision of abscesses in the oral cavity
(Fig. 10), the head and the neck (30). Surgery helps
to remove the cause of infection and promotes
access of antibiotics to the infected site. Even if anti-
biotics are used, failure of pus drainage may cause
further progression of disease and delay resolution.
Fluctuation is a clear indication of an abscess that
should always be drained, even if tooth extraction or
endodontic treatment is carried out. If cellulitis is
present, limited amounts of pus may be available by
incision, unless the cellulitis spreads widely. Irriga-
tion of the abscess cavity with saline can be useful
for large abscesses. In large abscesses, a drain may
prevent early closure of the incision. Drains should
be removed when drainage has ceased or is
minimal.
Root-canal opening
Drainage of root canals can be effective, but not if the
peri-apical area is unaffected. Opening of the root
canal can be convenient, even in cases of cellulitis
when the pus has not yet formed peri-apically. End-
odontic drainage may be difficult in cases of a
restricted root canal. The question of whether a root
canal should be left open for evacuation of pus has
not been resolved (67).
Tooth extraction
Mild infections do not usually require tooth extrac-
tion. In the case of a hopeless tooth, extraction will
remove the infectious source and provide drainage of
pus. If the tooth cannot be spared, early extraction is
preferable, even if this may aggravate the swelling.
Antibiotics
Systemic antimicrobial therapy should be considered
as an adjunct therapy to surgical intervention. Sys-
temic antibiotics are often necessary in acute orofacial
suppurative infections, osteomyelitis, acute maxillary
sinusitis, suspected actinomycosis, acute necrotizing
ulcerative periodontal infections, acute bacterial infec-
tion in an immunocompromised patient, facial space
infections, acute peritonsillar abscess and acute trau-
matic and surgical wound infections (30). Systemic
antibiotics may be indicated in immunocompromised
patients, even in mild infections. Antibiotic treatment
should preferably be based on microbial diagnosis and
Dental focal infections
bacterial sensitivity testing; however, as culture of
anaerobic bacteria may take a long time, empirical
antimicrobial therapy must be initiated based on the
knowledge and experience of the clinician (51). Usu-
ally, the most suitable antibiotic will be a penicillin,
which is generally considered as safe, even for preg-
nant women and for children with developing teeth
and skeleton. Broad-spectrum antibiotics should be
reserved for special occasions (e.g. serious cases with
multiple agents). Multidrug regimens are recom-
mended for severe infections, particularly when the
drugs have a synergistic effect. The possibility of inter-
action with other medicines used by the patient
should always be taken into account. For acute infec-
tions in immunocompromised patients bactericidal
antibiotics are preferred over bacteriostatic antibiotics.
Supportive care
Usually dental infections do not require hospitaliza-
tion. Exceptions are when there is a need for urgent
life-saving care; a high risk of a fatal condition or sus-
pected serious complications; considerable fever,
malaise, trismus, dysphagia or dyspnea; severe, rapid,
progressive and extensively spreading infection; a
need for intravenous drug administration; significant
dehydration or malnutrition; reduced infection
resistance; and a need for surgery under general
anesthesia (30).
Acknowledgments
Professor Geir Støre (Section for Maxillo-Facial Sur-
gery, ENT Department, Rikshospitalet University
Hospital, Oslo) and Professor Hans Reidar Haanaes
(Section of Oral Surgery and Oral Medicine, Institute
of Clinical Dentistry, Faculty of Dentistry, University
of Oslo, Oslo) are acknowledged for generously sup-
plying clinical photographs.
References
1. Aas JA, Reime L, Pedersen J, Eribe ERK, Abesha-Belay E,
Støre G, Olsen I. Osteoradionecrosis contains a wide variety
of cultivable and non-cultivable bacteria. J Oral Microbiol
2010: 2: 5072.
2. Adams JR, Bryant DG. Cranial osteomyelitis: a late compli-
cation of a dental infection. Br J Oral Maxillofac Surg 2008:
46: 673–674.
3. Allan BP, Egbert MA, Myall RW. Orbital abscess of odonto-
genic origin. Case report and review of the literature. Int J
Oral Maxillofac Surg 1991: 20: 268–270.
187
Olsen & van Winkelhoff
4. Armitage GC. Development of a classification system for
periodontal diseases and conditions. Ann Periodontol 1999:
4: 1–6.
5. Bahrani-Mougeot FK, Paster BJ, Coleman S, Ashar J, Barb-
uto S, Lockhart PB. Diverse and novel oral bacterial species
in blood following dental procedures. J Clin Microbiol 2008:
46: 2129–2132.
6. Baqain ZH, Newman L, Hyde N. How serious are oral infec-
tions? J Laryngol Otol 2004: 118: 561–565.
7. Bertrand B, Rombaux P, Eloy P, Reychler H. Sinusitis of
dental origin. Acta Otorhinolaryngol Belg 1997: 51: 315–322.
8. Biasotto M, Chiandussi S, Costantinides F, Di Lenarda R.
Descending necrotizing mediastinitis of odontogenic ori-
gin. Recent Pat Antiinfect Drug Discov 2009: 4: 143–150.
9. Billings F. Focal infection: its broader application in the eti-
ology of disease. J Am Med Assoc 1914: 4: 899–903.
10. Bindslev PH, Schou S. Akutte tilstande i mundhulen [Article
in Danish; English summary]. Ugeskr Laeger 2010: 172:
3018–3022.
11. Bomeli SR, Bransletter BF 4th, Ferguson BJ. Frequency of a
dental source for acute maxillary sinusitis. Laryngoscope
2009: 119: 580–584.
12. Brook I. Sinusitis of odontogenic origin. Otolaryngol Head
Neck Surg 2006: 135: 349–355.
13. Camp S, Lei Y, Costalonga M, Zhang Y, Zaia A, Vajna R, Ross
KF, Herzberg MC. Systemic disease and the oral microbiota.
In: Lamont RJ, Burne RA, Lantz MS, LeBlanc DJ, editors.
Oral microbiology and immunology, Chapter 16. Washing-
ton, D.C.: ASM Press, 2006: 361–375.
14. Cirino LM, Elias FM, Almeida JL. Descending mediastinitis:
a review. Sao Paulo Med J 2006: 124: 285–290.
15. Debelian GJ, Olsen I, Tronstad L. Systemic diseases caused
by oral microorganisms. Endod Dent Traumatol 1994: 10:
57–65.
16. Debelian GJ, Olsen I, Tronstad L. Anaerobic bacteremia and
fungemia in patients undergoing endodontic therapy: an
overview. Ann Periodontol 1998: 3: 281–287.
17. Drazi
c R, Jurisic M, Markovic A, Colic S, Gacic B, Stojcev-
Staj
ci
c L. C-reactive protein as an inflammatory marker in
monitoring therapy effectiveness of acute odontogenic
infections. Srp Arh Celok Lek 2011: 139: 446–451 [Article in
Serbian; Summary in English].
18. Enwonwu CO, Falkler WA, Idigbe EO. Oro-facial gangrene
(nomad/cancrum oris): pathogenetic mechanisms. Crit Rev
Oral Biol Med 2000: 11: 159–171.
19. Esquivel BD, Huerta AS, Molina MJL. Report of 16 cases of
Ludwig’s angina: 5-year review [Article in Spanish; English
summary]. Pract Odontol 1991: 12: 23–24, 28.
20. Ewald C, Kuhn S, Kalff R. Pyogenic infections of the central
nervous system secondary to dental affections – report of
six cases. Neurosurg Rev 2006: 29: 163–166.
21. Focal infection: back with a bang! Editorial. J Am Dent Assoc
1998: 129: 8–9.
22. Fujiyoshi T, Okasaka T, Yoshida M, Makishima K. Clinical and
bacteriological significance of the Streptococcus milleri group
in deep neck abscesses [Article in Japanese; English sum-
mary]. Nihon Jibiinkoka Gakkai Kaiho 2001: 104: 147–156.
23. Goymerac B, Woollard G. Focal infection: a new perspective
on an old theory. Gen Dent 2004: 52: 357–361.
24. Herrera D, Alonso B, de Arriba L, Santa-Cruz I, Serrano C,
Sanz M. Acute gingival and periodontal lesions. Periodontol
2000 2014: 65: 149–177.
188
25. Hunter W. Role of sepsis and antisepsis in medicine. Lancet
1910: 1: 79–86.
26. Kachlany SC. Aggregatibacter actinomycetemcomitans leu-
kotoxin: from threat to therapy. J Dent Res 2010: 89: 561–
570.
27. Kawamata T, Takeshita M, Ishizuka N, Hori T. Patent fora-
men ovale as a possible risk factor for cryptogenic brain
abscess: report of two cases. Neurosurgery 2001: 49: 204–
206; discussion 206–207.
28. Kim IK, Kim JR, Jang KS, Moon YS, Park SW. Orbital abscess
from odontogenic infection. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 2007: 103: e1–e6.
29. Kuijper EJ, Wiggerts HO, Jonker GJ, Schaal KP, de Gans J.
Disseminated actinomycosis due to Actinomyces meyeri
and Actinobacillus actinomycetemcomitans. Scand J Infect
Dis 1992: 24: 667–672.
30. Kuriyama T, Lewis MAO, Williams DW. Infections of the
oral and maxillofacial region. In: Andersson L, Kahnberg K-
E, Pogrel MA, editors. Oral and maxillofacial surgery, Chap-
ter 29. Chichester, UK: Wiley-Blackwell, 2010: 467–582.
31. Legert KG, Zimmerman M, Stierna P. Sinusitis of odonto-
genic origin: pathophysiological implications of early treat-
ment. Acta Otolaryngol 2004: 124: 655–663.
32. Leighty SM, Spach DH, Myall RW, Burns JL. Septic arthritis
of the temporomandibular joint: review of the literature
and report of two cases in children. Int J Oral Maxillofac
Surg 1993: 22: 292–297.
33. Leishman SJ, Do HL, Ford PJ. Cardiovascular disease and
the role of oral bacteria. J Oral Microbiol 2010: 2: 5781.
34. Li X, Tronstad L, Olsen I. Brain abscess caused by oral infec-
tion. Endod Dent Traumatol 1999: 15: 95–101.
35. Li X, Kolltveit KM, Tronstad L, Olsen I. Systemic diseases
caused by oral infection. Clin Microbiol Rev 2000: 13: 547–
558.
36. Lockhart PB, Brennan MT, Sasser HC, Fox PC, Paster BJ,
Bahrani-Mougeot FK. Bacteremia associated with tooth-
brushing and dental extraction. Circulation 2008: 117:
3118–3125.
37. Lo pez JP, Camacho AF. Facial cellulitis resulting from a
painless dental abscess. Pediatr Dermatol 2007: 24: 588–589.
38. Marcus BJ, Kaplan J, Collins KA. A case of Ludwig angina: a
case report and review of the literature. Am J Forensic Med
Pathol 2008: 29: 255–259.
39. Marques da Silva R, Caugant DA, Josefsen R, Tronstad L,
Olsen I. Characterization of Streptococcus constellatus
strains recovered from a brain abscess and periodontal
pockets in an immunocompromised patient. J Periodontol
2004: 75: 1720–1723.
40. Marx RE. Osteoradionecrosis: a new concept of its patho-
physiology. J Oral Maxillofac Surg 1983: 48: 283–289.
41. Masipa JN, Bouckaert M, Masureik C, Lemmer J, Meyerov
R, Feller L. Orbital abscess as a complication of odonto-
genic infection. A case report and review of the literature.
SADJ 2007: 62: 318–319.
42. Mehra P, Caiazzo A, Bestgen S. Odontogenic sinusitis
causing orbital cellulitis. J Am Dent Assoc 1999: 130:
1086–1092.
43. Meurman JH, Ha €ma€la
€inen P. Oral health and morbidity –
implications of oral infections on the elderly. Gerodontology
2006: 23: 3–16.
44. Miller W. The human mouth as a focus of infection. Dental
Cosmos 1891: 33: 689–713.

45. Minassian C, D’Aiuto F, Hingorani AD, Smeeth L. Invasive
dental treatment and risk for vascular events. A self-con-
trolled case series. Ann Intern Med 2010: 153: 499–506.
46. Moses JJ, Lange CR, Arredondo A. Septic arthritis of the
temporomandibular joint after the removal of third molars.
J Oral Maxillofac Surg 1998: 56: 510–512.
47. Mun  oz-Guerra MF, Gonza lez-Garcia R, Capote AL, Escorial
 LN. Subperiostal abscess of the orbit: an unusual
V, Gõas
complication of the third molar surgery. Oral Surg Oral
Med Oral Pathol Oral Radiol Endod 2006: 102: e9–e13.
48. Mylonas AI, Tzerbos FH, Mihalaki M, Rologis D, Boutsikakis
I. Cerebral abscess of odontogenic origin. J Craniomaxillo-
fac Surg 2007: 35: 63–67.
49. Neagu I, Tabarcea IC, Vataman R. Associated risk factors in
developing oral manifestations in patients with blood dys-
crasia [Article in Romanian; English summary]. Rev Med
Chir Soc Med Nat Iasi 2010: 114: 555–561.
50. Olsen I. Update on bacteraemia related to dental proce-
dures. Transfus Apher Sci 2008: 39: 173–178.
51. Olsen I, Solberg CO, Finegold SM. A primer on anaerobic
bacteria and anaerobic infections for the uninitiated. Infec-
tion 1999: 27: 159–165.
52. Pallasch TJ, Slots J. Antibiotic prophylaxis and the medically
compromised patient. Periodontol 2000 1996: 10: 107–138.
53. Patel M, Chettiar TP, Wadee AA. Isolation of Staphylococus
aureus and black-pigmented bacteroides indicate a high
risk for the development of Ludwig’s angina. Oral Surg Oral
Med Oral Pathol Oral Radiol Endod 2009: 108: 667–672.
54. Rahamat-Langendoen JC, van Vonderen MG, Engstro € m LJ,
Manson WL, van Winkelhoff AJ, Mooi-Kokenberg EA. Brain
abscess associated with Aggregatibacter actinomycetemcom-
itans: case report and review of literature. J Clin Periodontol
2011: 38: 702–706.
55. Rosan B, Rossman L. Endodontic microbiology. In: Lamont
RJ, Burne RA, Lantz MS, LeBlanc DJ, editors. Oral microbi-
ology and immunology, Chapter 15. Washington, D.C.: ASM
Press, 2006: 349–360.
56. Sakamoto H, Karakida K, Otsuru M, Arai M, Shimoda M. A
case of brain abscess extended from deep fascial space
infection. Oral Surg Oral Med Oral Pathol Oral Radiol En-
dod 2009: 108: e21–e25.
57. Sakkas N, Schoen R, Schmeizeisen R. Orbital abscess after
extraction of a maxillary wisdom tooth. Br J Oral Maxillofac
Surg 2007: 45: 245–246.
Dental focal infections
58. Schmieg E, Schmelzle R. Treatment of odontogenic
abscesses [Article in German]. Dtsch Zahnarztl Z 1975: 30:
54–57.
59. Støre G, Olsen I. Scanning and transmission electron
microscopy demonstrates bacteria in osteoradionecrosis.
Int J Oral Maxillofac Surg 2005: 34: 777–781.
60. Støre G, Eribe ERK, Olsen I. DNA-DNA hybridization dem-
onstrates multiple bacteria in osteoradionecrosis. Int J Oral
Maxillofac Surg 2005: 34: 193–196.
61. Thoden van Velzen SK, Abraham-Inpijn L, Moorer WR. Pla-
que and systemic disease: a reappraisal of the focal infec-
tion concept. J Clin Periodontol 1984: 11: 209–220.
62. Umeda M, Minamikawa T, Komatsubara H, Shibuya Y, Yo-
koo S, Komori T. Necrotizing fasciitis caused by dental
infection: a retrospective analysis of 9 cases and review of
the literature. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 2003: 95: 283–290.
63. van Winkelhoff AJ, Abbas F, Pavicic MJ, de Graaff J. Chronic
conjunctivitis caused by oral anaerobes and effectively trea-
ted with systemic metronidazole and amoxicillin. J Clin
Microbiol 1991: 29: 723–725.
64. van Winkelhoff AJ, Slots J. Actinobacillus actinomycetem-
comitans and Porphyromonas gingivalis in nonoral infec-
tions. Periodontol 2000 1999: 20: 122–135.
65. van Winkelhoff AJ, Overbeek BP, Pavicic MJ, van den
Bergh JP, Ernst JP, de Graaff J. Long- standing bactere-
mia caused by oral Actinobacillus actinomycetemcomitans
in a patient with a pacemaker. Clin Infect Dis 1993: 16:
216–218.
66. Wagner KW, Scho €n R, Schumacher M, Schumeizeisen R,
Schultze D. Case report: brain and liver abscesses caused
by oral infection with Streptococcus intermedius. Oral Surg
Oral Med Oral Pathol Oral Radiol Endod 2006: 102: e21–
e23.
67. Weine FS, Buchanan LS. Controversies in clinical endodon-
tics: part 3. Filling from the open position. Compend Contin
Educ Dent 1997;18:906–910, 912, 914, 916–918.
68. Zaleckas L, Rasteniene R, Rimkuviene J, Seselgyte R. Retro-
spective analysis of cellulitis of the floor of the mouth.
Stomatologija 2010: 12: 23–27.
69. Zijlstra EE, Swart GR, Godfroy FJ, Degener JE. Pericarditis,
pneumonia and brain abscess due to a combined Actino-
myces–Actinobacillus actinomycetemcomitans infection.
J Infect 1992: 25: 83–87.
189