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CORYNEBACTERIUM SPECIES INFECTIONS
A gross photograph of the trachea from a patient who
died of diphtheria shows classic pseudomembranes .
(Courtesy R. Cooke, MD.)
TERMINOLOGY
Definitions
Greek: "korune" (club, club-shaped morphology)
Greek: "diphthera" (pair of leather scrolls, for
pseudomembrane appearance)
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
ETIOLOGY/PATHOGENESIS
Environmental Exposure
Many species are part of normal human skin and
mucous membrane flora
A particular species will often occupy a specific
anatomic site (e.g., nasopharynx or external auditory
canal)
Professions with a great deal of animal contact
may be at increased risk from some species (e.g.,
Corynebacterium pseudotuberculosis)
Infectious Agents
Corynebacteria are practically split between
Corynebacterium diphtheriae and all other species,
collectively known as diphtheroids
C. diphtheriae
Manifestations of disease are caused by a toxin,
encoded by TOX gene, encoded by a lysogenic
phage
Upon adherence of bacteria to epithelial cells
(particularly but not limited to respiratory
epithelium), toxin gains access to host cell
cytoplasm and inactivates EF-2, causing cell death
Widespread necrosis leads to characteristic thick,
adherent, leathery "membrane" of diphtheria,
composed of bacteria, necrotic epithelium, fibrin,
and inflammatory cells
Other systemic aspects of disease (e.g., myocarditis)
II
result from dissemination of toxin rather than
hematogenous spread of bacteria
2
Histologic examination of the pseudomembranes
associated with diphtheria reveals sheets of sloughed,
largely necrotic epithelium admixed with fibrin and
an inflammatory exudate . (Courtesy R. Cooke, MD.)
Corynebacterium ulcerans and C. pseudotuberculosis
are part of the C. diphtheriae group and may cause a
similar spectrum of disease
Diphtheroids
Major medically important species include:
Corynebacterium jeikeium, Corynebacterium
glucuronolyticum, Corynebacterium minutissimum,
Corynebacterium pseudodiphtheriticum, C.
pseudotuberculosis, Corynebacterium striatum,
Corynebacterium urealyticum, Corynebacterium xerosis
Mechanisms of pathogenicity are not well
characterized
CLINICAL ISSUES
Epidemiology
C. diphtheriae
Extremely uncommon in USA
Risk factors include extremes of age, nonvaccinated
status, migrant from endemic area (e.g., India)
Route of infection is by airborne respiratory droplets
or contact with respiratory excretions or skin lesions
Diphtheroids
Growing recognition as agents of device-associated
infection
Risk factors include extremes of age, compromised
immune system, residence in hospital
Presentation
C. diphtheriae (causative agent of diphtheria)
Respiratory disease often occurs 2-4 days after
exposure (cough, hoarseness, sore throat, dyspnea,
odynophagia)
Tonsils may be enlarged and associated with
grayish-white membranes
Cardiac involvement (due to toxin) manifests
1-2 weeks after infection with arrhythmias and
symptoms of CHF
10
CORYNEBACTERIUM SPECIES INFECTIONS
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
Etiology
Many species are part of normal human skin and
mucous membrane flora
Professions with animal contact at increased risk from
some species (e.g., C. pseudotuberculosis)
Corynebacteria are practically split between C.
diphtheriae and all other species, collectively known
as diphtheroids
C. diphtheriae
Causative agent of diphtheria: Respiratory disease,
cardiac involvement, muscle paralysis, and
ulcerative skin lesions
Manifestations of disease are caused by a toxin,
encoded by TOX gene, encoded by a lysogenic
phage
Neurological involvement can occur at any time and
typically begins with bulbar symptoms
These may progress to proximal then distal muscle
paralysis
Cutaneous infections present as vesicles that
progress to nonhealing ulcers
Size can range from a few millimeters to
centimeters
Diphtheroids
Community-acquired infections tend to include
pharyngitis, native valve endocarditis, genitourinary
tract infections, acute and chronic prostatitis,
mastitis, and periodontal infections
Nosocomial infections tend to include lineassociated infections, native and prosthetic valve
endocarditis, device-related infections, and surgical
site infections
Laboratory Tests
Direct examination of swabs or blood smear
Swabs should be taken from involved area
of nasopharynx and, if present, underneath
membranes
Gram staining will show gram-positive rods with
pleomorphic morphology
Many species are club shaped
May be arranged in palisades or v-shaped
arrangements
Neisser or Loeffler methylene blue staining
demonstrates metachromatic granules (limited
sensitivity)
Immunoassays
Elek test, using strips embedded with antitoxin,
detects TOX gene-producing strains on agar plates
Treatment
Drugs
C. diphtheriae
Prophylaxis
A vaccine is available consisting of formalin-
inactivated toxin
Boosters are recommended every 10 years
Key Facts
Diphtheroids
Since corynebacteria are so prevalent on skin, it is
always important to differentiate pathogens from
contaminants
Prognosis
C. diphtheriae
MICROBIOLOGY
Morphological and Biochemical
Characteristics
With 50 medically relevant species, there is a great
deal of diversity in the biochemical profile of
corynebacteria
Gram stain demonstrates gram-positive rods with a
slight curve and a club shape
Arrangement is in "V"s or palisades, with what has
been termed a "pile of matchsticks" appearance
Culture
Corynebacteria grow on 5% sheep blood agar and
can be selected for with fosfomycin due to innate
resistance of the genus to this compound
Other selective media include cysteine-tellurite
blood agar (CTBA) and Tinsdale media (differentiates
diphtheria group from diphtheroids by formation of
brown-black halos from tellurite reduction)
Microbiological Identification
API CORYNE system (bioMrieux) consists of a strip
of 20 reactions assaying enzymatic function and
Widespread necrosis leads to characteristic thick,
adherent, leathery "membrane" of diphtheria,
composed of bacteria, necrotic epithelium, fibrin,
and inflammatory cells
Community acquired infections: Pharyngitis,
native valve endocarditis, genitourinary tract
infections, acute and chronic prostatitis, and
periodontal infections
Nosocomial infections: Line-associated infections,
native and prosthetic valve endocarditis, devicerelated infections, and surgical site infections
Antisera
Diphtheria antitoxin (DAT) produced in horses
is administered as soon as possible to maximize
benefit
Antibiotics
Penicillin and erythromycin are preferred drugs
Diphtheroids
Preferred antibiotics differ by species; some are
highly resistant to multiple classes
Mortality ranges from 3.5-12%
Highest at extremes of age and in unvaccinated
individuals
II
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11
CORYNEBACTERIUM SPECIES INFECTIONS
carbohydrate analysis (90.5% sensitivity) that is based
on a library of 50 species
Gas chromatography of medium-length fatty acids
with Sherlock system (MIDI) can assist with genus and
possible species-level identifications
Sequencing of 16S rRNA gene can differentiate most
species of corynebacteria
Amplification of TOX gene can be applied to cultured
organisms as well as primary specimens
Some nontoxigenic strains, however, do possess
unexpressed TOX gene
MACROSCOPIC FEATURES
General Features
Diphtheria
Pharynx, larynx, trachea and main bronchi may be
covered by grayish pseudomembranes
In severe cases, lungs are hemorrhagic and
moderately solid
If there is cardiac involvement (mediated by
disseminated toxin, not bacilli) hearts may appear
dilated and pale
MICROSCOPIC PATHOLOGY
Histologic Features
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
II
C. diphtheriae
Respiratory
Forms a characteristic pseudomembrane on tonsils
and pharynx, which can descend further down
respiratory tree
C. diphtheriae proliferates on surface of the
pseudomembrane
Satellite infections may be found in lower airway
or upper GI tract
Cutaneous
Lesions have a diverse appearance due to
superinfection of corynebacteria of any number of
preexisting lesions
As a primary infection, it begins as a vesicle
and progresses to an ulcer with a punched-out
appearance and dense "cap" or membrane; lesions
commonly occur on lower legs, feet, or hands
Diphtheroids
Cause a wide variety of community and hospitalacquired infections
Erythrasma (C. minutissimum)
Appears as a brownish discoloration in axilla,
groin, and inframammary regions
Organisms often visible in stratum corneum;
minimal host response
Pitted keratolysis
Associated with multiple corynebacteria
Infection of stratum corneum of soles of feet,
which develop small pits
Cystic granulomatous neutrophilic mastitis with
diphtheroids demonstrable on Gram stain in cystic
spaces
DIFFERENTIAL DIAGNOSIS
Anthrax and Noninfectious Ulcers
Cutaneous diphtheria is differentiated by positive ID
of corynebacteria
Yeast Infections, Fungal Infections, Vitamin
B6 Deficiency
Erythrasma is differentiated by positive ID of
corynebacteria
Darier Disease
Can be found in many other regions, not associated
with bacteria (vs. pitted keratolysis)
DIAGNOSTIC CHECKLIST
Pathologic Interpretation Pearls
Since corynebacteria are so prevalent on skin, it is
always important to differentiate pathogens from
contaminants
The following guidelines have been proposed to
indicate true disease association
Isolation from normally sterile sites (if blood, from >
1 bottle of multiple bottles)
Isolation from adequately collected clinical material
if they are the predominant organism
Isolation from urine specimens if they are the only
organism isolated and their count is > 10/mL or if
they are the predominant organism and their count
is > 10/mL
Clinical significance is strengthened by
Isolate recovered from > 1 specimen
Organisms seen in direct Gram stains of tissue,
which also have an inflammatory response
No other pathogenic organisms observed in lesion
SELECTED REFERENCES
1. Bernard K: The genus corynebacterium and other
medically relevant coryneform-like bacteria. J Clin
Microbiol. 50(10):3152-8, 2012
2. MacGregor RR: Corynebacterium diphtheriae. In Mandell
G: Mandell, Douglas, and Bennett’s Principles and Practice
of Infectious Diseases. 7th Edition. Philadelphia: Churchill
Livingstone/Elsevier. 2687-93, 2010
3. Prieto-Granada CN et al: Skin infections. In Kradin R:
Diagnostic Pathology of Infectious Disease. Philadelphia:
Saunders Elsevier. 524-5, 2010
4. Hadfield TL et al: The pathology of diphtheria. J Infect Dis.
181 Suppl 1:S116-20, 2000
5. Funke G et al: Clinical microbiology of coryneform
bacteria. Clin Microbiol Rev. 10(1):125-59, 1997
6. Coyle MB et al: Coryneform bacteria in infectious diseases:
clinical and laboratory aspects. Clin Microbiol Rev.
3(3):227-46, 1990
7. Recurrent breast abscesses caused by Corynebacterium
minutissimum. S A Berger, A Gorea, J Stadler, M Dan, M
Zilberman J Clin Microbiol. 20(6): 12191220, 1984
8. Lipsky BA et al: Infections caused by nondiphtheria
corynebacteria. Rev Infect Dis. 4(6):1220-35, 1982
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Microscopic Features
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g
p
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
CORYNEBACTERIUM SPECIES INFECTIONS
(Left) A low magnification
of the pseudomembranes
associated with diphtheria
reveals sheets of sloughed
largely necrotic epithelium
admixed with fibrin and
an inflammatory exudate .
(Courtesy R. Cooke, MD.)
(Right) High-power image
of pseudomembranes from
a patient with diphtheria
reveals sheets of sloughed
epithelium admixed with
acute inflammation ,
entrapped in fibrin .
(Left) Diphtheria trachea
with coagulative necrosis
of the mucosa is shown
earlier in progression than
seudomembrane formation.
(Right) Diphtheria infection
in the spleen is characterized
by tight granulomas of
epithelioid histiocytes
with the relatively unusual
finding of pyknotic debris.
(Left) Cystic neutrophilic
ranulomatous mastitis is
a form of breast abscess
characterized by sheets of
neutrophils
unusual circumscribed
spaces surrounded by
neutrophils. (Right) The
morphology of diphtheroids
is best visualized on
Gram stain showing gram-
ositive club-shaped
organisms, which form
clumps reminiscent of a pile
of matchsticks.
with the
II
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13
LISTERIA SPECIES INFECTION
Section of skin from a fetopsy of maternal-fetal listerosis
shows mixed chronic inflammation involving superficial
dermis with focal erosion of the overlying epidermis.
ETIOLOGY/PATHOGENESIS
Environmental Exposure
Widely present in environment as a saprophytic
organism
Most infections are food-borne and have been
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
associated with fruits and vegetables, deli meats,
smoked meats, and unpasteurized milk and cheese
Infectious Agents
Clinically relevant species include Listeria
monocytogenes and Listeria ivanovii
CLINICAL ISSUES
Epidemiology
Disease is most severe at extremes of age, in
immunosuppressed, and in pregnant women
Presentation
Classified into 3 general syndromes: Febrile
gastroenteritis, maternal-fetal/neonatal listeriosis, and
bacteremia CNS involvement
Febrile gastroenteritis
Symptoms include diarrhea, fever, abdominal
pain, chills, and headache
Maternal-fetal/neonatal listeriosis
Generally presents as bacteremia (fever, chills,
headache) in mother
May induce stillbirth or abortion in ~ 20% of
pregnancies
Can also cause preterm delivery and neonatal
infection
Neonate can be exposed though placental
hematogenous seeding or through contact in birth
canal
Disease in neonate can be early or late
II
Early disease (infection before delivery) manifests
as pneumonia, meningitis, or bacteremia; signs
2
High-power Gram stain of Listeria in dermis from a fetus
that succumbed to maternal-fetal listerosis shows grampositive rods.
include meconium staining, respiratory distress,
fever, lethargy, jaundice, and rash; may be
accompanied by microabscesses concentrated
in lungs, liver, and spleen (granulomatosis
infantiseptica)
Late disease (infection at time of delivery
from uncomplicated pregnancy) manifests as
meningitis
Bacteremia CNS involvement
CNS involvement is present in ~ 50% of patients
Manifestations include meningitis,
meningoencephalitis, brainstem encephalitis, and
brain abscess
Symptoms include fever, headache, and mental
status changes with meningeal signs in ~ 1/2 of
patients
Brainstem encephalitis (10% of infections) starts
with prodrome of headache, nausea, vomiting,
and fever followed by brainstem, cerebellar, and
long tract signs/dysfunction
Patients with abscess generally present with fever,
headache, and focal neurological signs
Cutaneous listeriosis is thought to result from contact
with infected animals (generally occupational) though
it may, in rare cases, result from bacteremia
Laboratory Tests
CSF analysis: With meningitis/meningoencephalitis,
Gram stain is positive in < 30% of cases, but cultures
are positive in 80%; with abscess, culture is positive in
< 1/2
Cervix, amniotic fluid, and placental cultures may
reveal organism in maternal listeriosis
14
LISTERIA SPECIES INFECTION
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
Etiology
Widely present in environment as a saprophytic
organism
Most infections are food-borne and have been
associated with fruits and vegetables, deli meats,
smoked meats, and unpasteurized milk and cheese
Clinically relevant species include Listeria
monocytogenes and Listeria ivanovii
Classified into 3 general syndromes
MICROBIOLOGY
Morphological and Biochemical
Characteristics
Gram-positive, non-spore-forming, facultative
anaerobe shaped as short rods arranged as singles or
short chains
Culture
Listeria are nonfastidious and typically isolated on
blood agar, where they demonstrate a small zone of
beta-hemolysis (sometimes difficult to appreciate) due
to bacterial production of hemolysin
MACROSCOPIC FEATURES
General Features
Placental infection can be indicated by yellowish
membranes with fruity odor and large abscesses
MICROSCOPIC PATHOLOGY
Histologic Features
CNS: Meningitis, encephalitis, and abscess
Liver: Granulomas and abscesses can be found in liver
with bloodstream sequestration followed by escape
and replication
Placenta: Fetal infection by hematogenous spread
from maternal circulation to placenta may
Key Facts
Strong tropism for central nervous system
Microscopic Pathology
CNS: Meningitis, encephalitis, and abscess
Liver: Granulomas and abscesses can be found in
liver as consequence of bloodstream sequestration
followed by escape and replication
demonstrate acute villitis, abscesses and granulomas
(granulomatosis infantisepticum), and necrotizing
acute chorioamnionitis
DIFFERENTIAL DIAGNOSIS
Abscess
Differentiate from other infectious causes of abscess by
culture or molecular diagnosis
Meningitis
Other common causes of bacterial meningitis include
Streptococcus pneumoniae and Escherichia coli
Differentiate by Gram stain, culture, &/or molecular
methods
SELECTED REFERENCES
1. Lorber B. Listeria monocytogenes. In Douglas et al: Mandell,
2. Cartwright EJ et al: Listeriosis outbreaks and associated
3. Cone LA et al: Multiple cerebral abscesses because of
Febrile gastroenteritis
Maternal-fetal/neonatal listeriosis
Bacteremia CNS involvement
Organisms can be identified by silver or Gram
staining
Douglas, and Bennett’s Principles and Practice of Infectious
Diseases. 8th ed. Philadelphia: Elsevier/Saunders. 2383-90,
2015
food vehicles, United States, 1998-2008. Emerg Infect Dis.
19(1):1-9; quiz 184, 2013
Listeria monocytogenes: three case reports and a literature
review of supratentorial listerial brain abscess(es). Surg
Neurol. 59(4):320-8, 2003
IMAGE GALLERY
(Left) Maternal-fetal listerosis is typically characterized by acute villitis of the placenta. Less commonly, similar findings are present in the skin,
thought to be due to hematogenous dissemination. (Center) This section shows Listeria meningoencephalitis. (Courtesy Franz von Lichtenberg
Collection of Infectious Disease Pathology, BWH.) (Right) This section shows Listeria chorioamnionitis with focal villitis . (Courtesy Franz von
Lichtenberg Collection of Infectious Disease Pathology, BWH.)
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RHODOCOCCUS SPECIES INFECTION
This suppurative abscess cont ains numerous bacteria ,
which were identified as Rhodococcus rhodochrous.
TERMINOLOGY
Definitions
Greek: "Rhodon" (rose) + "kokkos" (berry, grain)
ETIOLOGY/PATHOGENESIS
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
Environmental Exposure
Rhodococci are widely present in environment
Rhodococcus equi is strongly associated with grazing
animals and their manure
Infection (of people and animals) can apparently
occur either by inhalation of contaminated dirt and
dust or by direct inoculation of wounds and mucous
membranes
Rare reports of nosocomial R. equi infections (VP
shunts and dialysis tubing) and person-to-person
spread (among immunocompromised individuals)
Infectious Agents
R. equi is an important veterinary pathogen and is also
associated with disease in humans
Virulence is based on ability to resist degradation
within phagosome of macrophages
Human disease may be modulated by a different
but overlapping set of poorly characterized
virulence factors
CLINICAL ISSUES
Epidemiology
While R. equi is a well-characterized pathogen of
horses, it is rarely reported in humans
85-90% of human cases occur in
immunocompromised patients, particularly those with
II
defects in cell-mediated immunity
Exposure to livestock, farming, or gardening increases
risk
2
This abscess demonstrates acid-fast bacilli , which
were identified as Rhodococcus rhodochrous.
Presentation
Pulmonary disease (cavitary upper-lobe pneumonia) is
most common manifestation of rhodococcal infection
(80% of cases)
Course of disease begins with fever over days to
weeks, along with dyspnea, chest pain, and cough
Disseminated disease can occur in
immunocompromised patients
Other reported manifestations include ophthalmitis,
colitis, and systemic disease following dissemination
from GI tract
Laboratory Tests
Culture
Treatment
Drugs
Combination of 2-3 drugs, often including
macrolides, rifampicin, aminoglycosides, linezolid,
or imipenem
Prognosis
Mortality ranges from ~ 11% in immunocompetent to
50% in HIV patients
IMAGE FINDINGS
Radiographic Findings
Imaging generally reveals upper lung lesions, which
can expand to cavitary lesions with air-fluid levels and
pleural effusions
MICROBIOLOGY
Morphological/Biochemical
Appear as gram-positive cocci (from solid media or
tissue) or pleomorphic rods (from liquid culture)
Colonies may be partially acid fast
16
RHODOCOCCUS SPECIES INFECTION
Etiology
Rhodococci are widely present in environment
Clinical Issues
While R. equi is a well-characterized pathogen of
horses, it is rarely reported in humans
85-90% of human cases occur in
immunocompromised patients, particularly those
with defects in cell-mediated immunity
Key Facts
Pulmonary disease (cavitary upper-lobe pneumonia)
is the most common manifestation of rhodococcal
infection (80% of cases)
Microscopic Pathology
Infection usually appears as a necrotizing,
granulomatous pattern
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
Microbiological Identification
Laboratory platforms that can be used to identify
rhodococci include API Coryne strip (bioMrieux),
MALDI-TOF, 16s rRNA sequencing, and medium-chain
fatty acid analysis (Sherlock System, MIDI Inc.)
MICROSCOPIC PATHOLOGY
Histologic Features
Infection usually appears as a necrotizing,
granulomatous pattern dominated by macrophages,
which may contain coccobacillary organisms
(visualized by Gram, silver, or Gram-Weigert stain)
Can appear as an inflammatory pattern termed
malakoplakia
PAS(+) histiocytes with cytoplasmic globules and
inclusions called Michaelis-Gutmann bodies
Composed of mineralized remnants of
incompletely digested bacteria
Reported to produce pathologic changes similar to
Whipple disease, as well as pseudotumors of airway in
AIDS patients
Ocular tissues can demonstrate endophthalmitis and
keratitis
Organism is acid-fast and must be differentiated from
Mycobacterium
DIFFERENTIAL DIAGNOSIS
Other Bacterial and Fungal Infections
Pathologic tissue patterns (i.e., necrotizing
granulomas) are associated with several other members
of aerobic actinomyces, including Corynebacteria and
Mycobacteria
Histiocytic aggregates may also be caused by
Mycobacterium avium complex (MAC), Mycobacterium
genavense, Histoplasma capsulatum, and Cryptococcus
neoformans
Malakoplakia is most commonly associated with
coliform infections of GU tract
SELECTED REFERENCES
1. Meyer DK et al: Other coryneform bacteria and rhodococci.
In Mandell et al: Principles and Practice of Infectious
Diseases. 7th edition. Philadelphia: Livingstone/Elsevier.
2695-2706, 2010
2. Yamshchikov AV et al: Rhodococcus equi infection. Lancet
Infect Dis. 10(5):350-9, 2010
3. Verville TD et al: Rhodococcus equi infections of
humans. 12 cases and a review of the literature. Medicine
(Baltimore). 73(3):119-32, 1994
4. Prescott JF: Rhodococcus equi: an animal and human
pathogen. Clin Microbiol Rev. 4(1):20-34, 1991
IMAGE GALLERY
(Left) Granulomatous inflammation in a patient with Rhodococcus pulmonary infection is shown. Because of the organisms in the clinical
differential (Mycobacterium, fungi, other bacteria), culture is always required. (Center) Hemorrhagic lesions in a patient with Rhodococcus
pulmonary infection are shown. Diffuse alveolar damage may be present. (Right) A Gram stain demonstrates numerous gram-positive bacilli
in this patient with pulmonary R. rhodocrous infection.
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STAPHYLOCOCCUS SPECIES INFECTIONS
This gross photograph of hemorrhagic, necrotizing
staphylococcal pneumonia shows bronchial erosion
and empyema . (Courtesy Franz von Lichtenberg
Collection of Infectious Disease Pathology, BWH.)
TERMINOLOGY
Abbreviations
Methicillin-resistant S. aureus (MRSA)
Vancomycin-intermediate S. aureus (VISA)
Coagulase-negative Staphylococcus (CONS)
Definitions
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
Greek: "Staphyle" (grape) + "kokkus" (grain, seed)
ETIOLOGY/PATHOGENESIS
Environmental Exposure
Found widely on skin and mucous membranes of
humans and animals
S. aureus is usually confined to nares as colonizer
Coagulase-negative staphylococcal (CONS) species
often have trophism for distinct regions of host (i.e.,
axillae, head, etc.)
Most common organism isolated from human skin
Infectious Agents
Practically split into coagulase-positive (S. aureus)
and coagulase-negative (major species include
Staphylococcus saprophyticus, Staphylococcus epidermidis,
Staphylococcus capitis, Staphylococcus hemolyticus,
Staphylococcus hominis, Staphylococcus lugdunensis,
Staphylococcus saccharolyticus, and Staphylococcus
warneri)
Coagulase-positive staphylococci
S. aureus is the major pathogen
Coagulase-negative staphylococci
S. epidermidis is the major pathogen; others include
S. lugdunensis, S. saprophyticus, and S. hemolyticus
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Staphylococcal pneumonia demonstrates bronchial wall
necrosis and diffuse consolidation of adjacent
alveoli. (Courtesy Franz von Lichtenberg Collection of
Infectious Disease Pathology, BWH.)
CLINICAL ISSUES
Epidemiology
S. aureus
MRSA is common in both hospital and community
(59% in ICU patients, 55% in non-ICU patients,
48% in outpatients)
Carriage is most important predisposing factor for
infection
Carried by large percentage of population (> 50%),
some persistently and some intermittently
Higher carriage rates in diabetics, injection drug
users, HIV-positive patients, and those undergoing
dialysis
Community-acquired (CA-MRSA) and healthcareacquired (HCA-MRSA) S. aureus strains are
responsible for distinct clinical syndromes
Epidemiology of specific manifestations
Toxic shock syndrome (TSS): In children, tampon
use, postoperative wound, or soft tissue infections
Staphylococcal scalded skin syndrome (SSSS):
Infants or young children
Gastroenteritis: Improperly stored prepared food,
particularly dairy; toxin can remain active under
conditions that kill organism
CONS
Strongly associated with intravascular catheters and
other devices
S. saprophyticus infection is often diagnosed in
sexually active younger women
Presentation
S. aureus
Causes wide spectrum of disease
Toxin-mediated diseases include: TSS, SSSS, and food
poisoning
TSS clinical course: High fever, hypotension,
and diffuse rash that eventually desquamates
(involvement of 3 organ systems)
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STAPHYLOCOCCUS SPECIES INFECTIONS
Etiology
Staphylococci are found widely on skin and mucous
membranes of humans and animals
Divided into coagulase-positive (S. aureus) and
coagulase-negative (major species: S. epidermidis)
S. aureus is usually confined to nares as a colonizer
S. aureus causes wide spectrum of disease
Skin and soft tissue infections
Bloodstream infection
Endocarditis
Pneumonia
Osteomyelitis
Toxin-mediated diseases include TSS, SSSS, and
food poisoning
Coagulase-negative staphylococcal (CONS) species are
most common skin isolates
Key Facts
CONS infections
General features of S. aureus infections include more
virulent course of disease with more suppurative
infection than those caused by CONS or other grampositive cocci
Microscopic Pathology
Useful stains include tissue Gram stain (demonstrates
gram-positive cocci in pairs or clusters) and
methenamine silver stain
Additional tests on tissue include PCR for 16S
rRNA gene, as well as rpoB for improved species
discrimination
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
Intravascular catheter and device-/material-related
infections
Endocarditis
SSSS is a bullous exfoliative dermatitis, which
can take diffuse (Ritter disease) or localized
(pemphigus neonatorum) forms; manifests as
bright red skin, generally on head, which then
spreads downward toward extremities (with
constitutional symptoms)
Food poisoning: Nausea, vomiting, diarrhea,
and abdominal pain, generally 2-6 hours after
ingestion
Skin and soft tissue infections (SSTI)
1/3 of SSTI
Can be relatively superficial (folliculitis,
furuncles, carbuncles, and impetigo in epidermis
and dermis) or deep (cellulitis, fasciitis, and
pyomyositis in dermis and subcutaneous tissues)
Folliculitis appears as nodule centered on hair
follicle, which may have apparent pus
Furuncles are deeper form of folliculitis
Carbuncles are collections of furuncles and may
demonstrate several openings to discharge pus
Impetigo often appears on face as pustules or
bullae with honey-colored crusting and negative
Nikolsky sign; often occurs as complication of
other dermatoses
Cellulitis presents as painful, bright red macules
or plaques, which can demonstrate scaling and
ulceration over time
Necrotizing fasciitis often presents subsequent
to trauma with pain out of proportion to clinical
findings
Fever, malaise, and myalgias follow and pain can
eventually progress to anesthesia
Bloodstream infection (BSI)
2nd most common cause of bacteremia
Community-associated BSI generally occurs in
patients without other major risk factors and
often can be traced to distinct focus of infection
(i.e., endocarditis)
Healthcare-associated or nosocomial BSI is
often related to intravascular catheters or other
instrumentation and surgical site infections
Carries risk of metastatic foci, particularly
endocarditis (risk: 10%)
Endocarditis
Usually presents acutely with fever, tachycardia,
and hypotension
Common symptoms include dyspnea, myalgias,
and pleuritic pain
Clinical signs include murmur, petechiae and
Janeway lesions (from septic emboli), and CNS
findings
Pneumonia
Causes 10% of community-acquired and 25% of
hospital-acquired pneumonia
Can be initiated by airway exposure or
hematogenous seeding and often follows severe
course
Community-acquired pneumonia can often be
preceded by influenza-like illness
Signs and symptoms include marked dyspnea,
hemoptysis, fever, leukopenia, hypotension, and
elevated C-reactive protein
Chest x-ray demonstrates multilobar cavitating
alveolar infiltrates
Sequelae can include abscess and empyema
Osteomyelitis
S. aureus is most common causative organism,
responsible for 50-70% of cases
Infection can be result of hematogenous or
contiguous spread
Hematogenous spread usually results in acute
picture with chills, fever, malaise, pain and
swelling
Contiguous spread (usually from complications
of diabetes, vascular disease, or prosthesis) often
follows chronic, subacute course with low-grade
inflammation, necrosis, and fistulas
May be painless due to neuritis
Other
S. aureus causes host of other clinical
manifestations including meningitis, pericarditis,
prosthetic joint infections (usually stage I,
II
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