Discussion
S. intermedius abscesses have two presentations one of which being
monomicrobial associated with hematogenous spread or are deep-seated and
extensive compared with the other two species within its group which
were polymicrobial and often more superficial [4]. However, it has
been seen that when S. intermedius is found in conjunction with
anaerobes in an abscess, there is synergy between the organisms causing
enhanced growth [8]. SAG abscesses overall have a longer duration of
symptoms than other organisms and the majority of patients need surgical
or percutaneous drainage for cure [6]. Interestingly, there appear
to be no differences in mortality, duration of antibiotics, or
complications compared to non-SAG organisms [6]. Infection with S.
intermedius is very rare in previously healthy individuals without any
identifiable risk factors [9]. The two most common risk factors are
dental manipulation and sinusitis. Others include a history of diabetes,
heavy alcohol consumption, congenital heart disease, heart-related
conditions, malignancy, periodontal disease, preceding pneumonia,
neurological diseases, and COPD [1,5,9].
Infection and abscess formation is started with tissue damage and is
then followed by colonization [1]. S. intermedius has surface
proteins called Antigens I/II that bind to human lactoferrin,
fibronectin, and laminin components that subsequently induce monocytes
to release IL8, activating neutrophils leading to a pro-inflammatory
state that induces tissue damage and abscess formation [1,8,10].
Hydrolytic enzymes are then released to induce tissue liquefaction and
form pus [10]. Hyaluronidase, one of the hydrolytic enzymes released
by S. intermedius, has numerous effects. It decreases the viscosity of
ground substance and increases the permeability of connective tissue
allowing bacterial and toxins to spread while, along with
α-N-acetylmuramidase (sialidase), creating a source of nutrients for the
bacteria from the degradation products [1, 8]. It has been shown
that the higher the concentration of hyaluronidase, the deeper the
lesion [8]. It is also involved in biofilm formation, which
decreases the organism’s antibiotic susceptibility and protects it from
host immunological defenses [1]. It has signal molecules called
autoinducers that give it the ability to monitor the concentration of
bacterial signals and biofilm formation, allowing it to regulate its
pathogenic capabilities like proteolytic and hemolytic enzyme
activities, iron acquisition, antibiotic production, carbohydrate
metabolism, and biofilm formation [10]. S. intermedius thrives in
acidic environments causing the release of iron from host transferrin to
facilitate bacterial growth and infectious spread [8]. It also can
move to distant sites and rapidly decrease the pH, facilitating the
release of iron at this new location for its growth [10]. Some S.
intermedius have a polysaccharide capsule, which inhibits phagocytosis
and increases its tendency to form abscesses [1, 10]. Encapsulated
strains have larger abscesses, earlier spontaneous drainage, and a
higher lethality [8]. Superantigens also play an important role in
the S. intermedius’s virulence by stimulating the release of
proinflammatory mediators by activating glial cells and peripheral
immune cells, causing a positive feedback loop to recruit and activate
new inflammatory cells and glia to create a vicious cycle allowing
extensive damage to normal brain tissue [10]. S. intermedius is
unique to the other bacteria in SAG due to the expression of
intermedilysin (ILY), allowing it to cause cell necrosis with membrane
bleb formation [1, 10]. It is an important virulence factor in
causing deep-seated abscesses and its expression correlates with strain
pathogenicity or with the severity of infections [1, 8]. Isolates
found in deep-seated brain abscesses had a 6.2- to 10.2-fold higher
expression of ILY than those found in normal habitats like dental
plaques; and ily knockout strains showed greatly decreased
adherence, invasion, and cytotoxicity of human liver cells [10].
Because of its specificity to S. intermedius, the ILY gene is being used
as a specific marker detector via PCR [6,8].
Brain abscesses typically present with intermittent fever, constant
headaches, and/or mental status changes with elevated CRP and WBC count
[1, 6]. It can occur due to spread from the contiguous focus of
infection (sinus, teeth, or middle ear), hematogenous spread from
distant focus, or as a result of head trauma or neurosurgery [6,8].
An important primary source of S. intermedius is from a liver abscess,
but most patients have multiple risk factors for developing an invasive
intracerebral abscess including congenital heart disease, sinusitis,
otitis media, and dental caries [8,11]. The majority of brain
abscesses are solitary and occur in the frontal lobe [6]. Due to
newer antibiotics and earlier detection with CT scans and MRIs,
morbidity and mortality have decreased [6]. Pleuro-pulmonary
infections are uncommon and usually present with fever, cough, chest
pain, and dyspnea with elevated CRP and WBC count [12]. These
infections can present as pulmonary abscesses, pneumonia, pleural
effusions, pyopneumothorax, and pleural fistula [13]. It occurs due
to aspiration of oral secretions, which might be why it is more frequent
in the elderly [12]. Aspirate of the pleural fluid would show
exudate, with elevated protein, LDH, and WBC count [12]. The
prognosis of pleuro-pulmonary infections is generally favorable
[12]. Liver abscesses are generally associated with underlying
hepatobiliary or pancreatic disease, diabetes, liver transplantation,
and colorectal neoplasm [2]. The probable origin is a dental plaque
[2]. Symptoms depend on the size of abscesses and the general health
of the patient, but often include upper abdominal quadrant pain, high
fevers, nausea, and vomiting [13]; and most patients have an
elevated WBC count and liver function tests [2]. Less common
symptoms include loss of appetite, jaundice, ascites, pleural effusion,
and respiratory symptoms [13]. If liver abscesses are untreated,
major complications include sepsis and multiorgan dysfunction/failure,
rupture of abscess into peritoneal cavity, thrombosis of the portal or
hepatic veins, IVC occlusion of the pseudoaneurysm of the hepatic
artery, hemophilia, and fistula to the portal vein or suprahepatic veins
[2,13]; with a mortality rate of 100% [13]. When treated, these
numbers go as low as 2.5% - 14% [14]. Other possible infection
sites include the mouth, female genital tract, appendix, and blood
stream [11].
Patients with suspected infection by S. intermedius should have the
abscess drained and cultured along with blood cultures if there is
suspicion of hematogenous spread [4,6]. Abscess culture can be
negative due to antibiotic therapy. If there is a negative culture and
suspicion is high, gene amplification and sequencing tests may be used
to aid in diagnosis and allow for more targeted antibiotic therapy
[4]. S. intermedius can also be difficult to detect with
conventional microbiology, so a broad range PCR method targeting the 16S
ribosomal RNA genes is typically used [14]. Since the ILY gene is
specific to S. intermedius, this is the gene sequenced with PCR to
detect these S. intermedius infections [6,8]. Brain abscesses can be
evaluated with an MRI which would show ring-enhancing lesions [8]. A
lumbar puncture should not be done as CSF analysis does not contribute
to diagnosis and there is a risk of brain herniation with the increased
ICP caused by abscesses [4]. Pleuro-pulmonary infections should get
cultures of the pleural effusion via percutaneous lung needle aspiration
or transthoracic needle aspiration [12,15]. If pleural effusion is
negative, a lung sample can be taken for microscopy and culture
[16].
Management and treatment of these abscesses include drainage, surgery,
and antibiotics [1]. Antibiotic therapy is based on susceptibility.
All SAG are generally susceptible to the usual dose of penicillin,
amoxicillin, cefotaxime, or ceftriaxone and have variable susceptibility
to tetracycline, clindamycin, and erythromycin [14]. Of the
beta-lactams, ceftriaxone is preferred due to its excellent activity and
tissue penetration [12]. If the patient has a penicillin allergy,
vancomycin is typically used [12]. However, recent penicillin
strains have been reported and in cases of high risk of antibiotic
resistance, carbapenems, especially ertapenem, are very effective [14,
15]. Most strains are resistant to aminoglycosides and resistance to
macrolides and clindamycin are increasing [9,12]. Empiric therapy
should depend based on patients’ current condition and whether they have
been exposed to antimicrobials within the past three months [9]
Fluoroquinolones have also been shown to be efficacious against SAG, but
resistance develops quickly so these are not appropriate as empiric
therapy [12]. The most commonly used antibiotic regimens currently
used are a combination of ceftriaxone and metronidazole or a combination
of ceftriaxone, metronidazole, and vancomycin [1]. However, with the
use of multiple antibiotic regimens in patients, there is a concern for
the emergence of drug-resistant strains, especially with vancomycin and
carbapenems [1]. There also have been cases of clinical failure with
antibiotics that showed susceptibility in vitro studies. Potential
causes of clinical failure can include the inappropriate selection of
empiric therapy, inability to penetrate tissue spaces, and inadequate
dosing to reach therapeutic concentrations in infected areas [9].
Brain abscesses are managed with a combination of neurosurgical
intervention, antibiotics, and eradication of any primary foci [10].
Patients with significant risk factors for surgery or small cerebral
lesions <5mm on CT should undergo conservative management with
antibiotics [4,10]. In those who can tolerate surgery, CT-guided
stereotactic aspiration of abscess can be performed as it is minimally
invasive, rapid, and effective in surgical drainage especially if an
abscess is small and deep-seated [4]. CT-guided stereotactic
aspiration is associated with lower morbidity and mortality and has a
better overall prognosis [4]. A more superficial abscess can be
treated with craniotomy and excision of abscess [4]. The working
group of the British Society of Antimicrobial Chemotherapy recommended
that brain abscesses should be treated with a combination of beta-lactam
and metronidazole for three to four weeks if surgically resected or four
to six weeks if aspirated [10]. Pleuropulmonary infections are
managed via drainage of pleural fluid, pleurectomy, thoracotomy,
decortication, and debridement [12,13]. Reasons for clinical failure
seen in pneumonia complicated by empyema by S. intermedius species
include the inability to penetrate pleural space and the inability to
reach therapeutic levels in desired areas [17]. Early recognition
and timely intervention imp for successful treatment and better
prognosis [14]. Liver abscesses are treated with IV broad-spectrum
antibiotics, most commonly fluoroquinolones or third-generation
cephalosporin in combination with metronidazole, and percutaneous
drainage [13]. For abscesses less than 5cm, antibiotics alone can be
sufficient; for abscess between 5-7.3 cm with sustains fevers for more
than 23-48 hours or suggestion of perforation, a combination of
percutaneous drainage and systemic antibiotics should be used; and for
abscesses that are larger than 7.3 cm should be considered for surgical
drainable due to the risk of being multiloculated and spontaneous
rupture [13].