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STAPHYLOCOCCUS SPECIES INFECTIONS
occurring within 3 months of surgery), septic
arthritis, and pyomyositis
CONS (S. epidermidis)
Infections caused by CONS are generally more
indolent than those caused by S. aureus, sometimes
only presenting with low-grade fever
Intravascular catheter and device/material-related
infections
Most common cause of bloodstream infections
(associated with intravascular catheters)
Infection of vascular grafts are also most
commonly caused by CONS
CONS accounts for ~ 25% of pacemaker-associated
infections
Stage II prosthetic joint infections (occurring
between 3 months and 2 years after surgery) are
often caused by CONS, and follow an indolent
course (pain without fever or drainage)
Endocarditis
Usually occurs on prosthetic valves and occurs at
time of placement (manifests within 12 months)
Heart failure occurs in 54% of cases, with abscess
and valve dysfunction occurring frequently
Neonatal infections
CONS is responsible for 31% of all nosocomial
infections and 73% of bacteremias in United
States NICUs
Neonates are more likely to develop wider
range of disease (wound abscess, pneumonia,
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
urinary tract infection, meningitis, enterocolitis,
omphalitis)
Infections are usually nosocomial (not acquired
from mother)
Other species of CONS
S. saprophyticus frequently (2nd to Escherichia coli)
causes urinary tract infections in young, sexually
active women
S. lugdunensis is distinguished by causing similar
spectrum and severity of infections to S. aureus
Endocarditis caused by S. lugdunensis follows more
virulent course than that of other CONS and often
results in valve dysfunction and abscess formation
(mortality 50-70%)
Also frequent cause of SSTIs below waist (where it
resides among skin flora)
S. hemolyticus is common cause of bacteremia and is
often pan resistant
Laboratory Tests
Serological testing for antistaphylococcal antibodies
does not play role in diagnosis due to lack of
specificity
Treatment
Surgical approaches
S. aureus: Necrotizing fasciitis (emergent drainage
and debridement)
CONS: Removal of infected hardware &/or devices
Drugs
II
MRSA can account for 50-60% of staphylococci in
USA hospitals
2
Vancomycin and linezolid are often used to treat
infections in these settings
CA-MRSA tends to carry fewer resistance
determinants to other drugs than HCA-MRSA does
CONS antibiotic susceptibility varies by species
(most are resistant to multiple drugs)
Prognosis
Variable by species and site of infection
S. aureus
Toxin-mediated disease mortality can range from
very low in food poisoning to quite high in adult
SSSS (> 50%) or CA-MRSA necrotizing pneumonia
(60%)
CONS
Mortality is highest with S. lugdunensis endocarditis
(50-70%) and is generally low with most other
manifestations
MICROBIOLOGY
Morphological/Biochemical
Gram-positive cocci arranged in clusters
Culture
Staphylococci are usually isolated on blood agar plates
S. aureus appears as smooth, creamy, yellowish
to orange colonies while CONS are often
nonpigmented
S. aureus usually demonstrates beta-hemolysis while
CONS are generally nonhemolytic (except for S.
hemolyticus and S. lugdunensis)
Microbiological Identification
Organisms can be presumptively identified as
staphylococci if they are catalase-positive, grampositive cocci
Coagulase production differentiates S. aureus from
most CONS (except S. lugdunensis: Coagulase positive,
clumping factor negative)
Within CONS, pathogenic S. saprophyticus is
differentiated by resistance to novobiocin
MICROSCOPIC PATHOLOGY
Histologic Features
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
Staphylococcus aureus
Skin findings (from toxin- and organism-mediated
disease)
SSSS: Mediated by toxin, so organisms are not
present
Stratum corneum is sloughed off
Keratinocytes are regular and smooth with
occasional acantholytic cell
Inflammation is not present
20
STAPHYLOCOCCUS SPECIES INFECTIONS
TSS: Like SSSS, mediated by toxin, so no
organisms present
Spongiotic reaction with neutrophils and scattered
necrotic keratinocytes over edematous dermis
as well as a superficial perivascular and mixedcell infiltrate with neutrophils and possibly
eosinophils
Pustular or necrotic vasculitis may also be seen
and neutrophilic abscesses may be present
Impetigo consists of subcorneal pustules with
variable numbers of neutrophils and acantholytic
cells
Gram-positive cocci may be present on gram stain,
which confirm diagnosis
Folliculitis, furuncles, and carbuncles consist of
inflammatory cells, predominantly neutrophils,
centered on 1 or several hair follicles
Cellulitis is accompanied by edema in dermis and
subcuticular regions and dilated blood vessels and
lymphatics
Diffuse infiltrate of neutrophils is present
Organisms are very rarely observed and tissue
culture is usually essential
In chronic cases, there may be spongiosis of
epidermis with vesicles, pustules, ulceration, and
necrosis fibrosis
Necrotizing fasciitis occurs in fascia and deep soft
tissue where necrosis, hemorrhage, thrombosis,
and secondary vasculitis are prominent features
Endocarditis
S. aureus can colonize both defective/mechanical
and native valves (often damaging them)
Tends to form relatively large (> 1 cm) vegetations
Often results in septic emboli and mycotic
aneurysms
Pneumonia
Can occur as primary pneumonia or as sequelae of
influenza
Causes necrotic lesions, with abscess formation
Abscesses may metastasize to distant organs or
rupture into pleural space, causing empyema
Organisms may be seen in clusters on Gram stain
Osteomyelitis
Demonstrates neutrophils adjacent to bony
trabeculae with erosive changes
Organisms may be seen on Gram stain
CONS
General feature of CONS infections is that they are
not associated with same degree of pus and necrosis
as infections by S. aureus
Devices &/or catheters that are colonized by CONS
usually appear to be coated with tan, fibrinous
material and microscopically demonstrate clusters
of gram-positive cocci with acute inflammatory
infiltrates
DIFFERENTIAL DIAGNOSIS
Skin Manifestations
SSSS must be differentiated from toxic epidermal
necrolysis (TEN); former only involves stratum
corneum while latter affects entire epidermis
Impetigo must be differentiated from pemphigus
foliaceus (by presence of organism)
Many aspects of skin and soft tissue infection, i.e.,
cellulitis and necrotizing fasciitis, can be caused by
organisms other than Staphylococcus aureus (or as
copathogens)
Endocarditis
Streptococcal and enterococcal endocarditis:
Differentiated by more severe course, more
suppurative reaction, and culture
Noninfectious endocarditis: Differentiate by lack of
inflammatory reaction, no visible organisms, and lack
of culture results
SELECTED REFERENCES
1. Fine SM: Staphylococcus epidermidis and other coagulase
negative staphylococci. In Bennet JE et al: Mandell,
Douglas, and Bennett’s Principles and Practice of Infectious
Disease. 8th ed. Philadelphia: Elsevier/Saunders. 2272-82,
2015
2. Morrell DS: Staphylococcus aureus (including
staphylococcal toxic shock syndrome). In Bennet JE et al:
Mandell, Douglas, and Bennett’s Principles and Practice of
Infectious Disease. 8th ed. Philadelphia: Elsevier/Saunders.
2237-71, 2015
3. Becker K et al: Staphylococcus, Micrococcus, and other
catalase-positive cocci. In Versalovic et al: Manual of
Clinical Microbiology. 10th ed. Washington: ASM press.
308-330, 2011
4. David MZ et al: Community-associated methicillinresistant Staphylococcus aureus: epidemiology and clinical
consequences of an emerging epidemic. Clin Microbiol
Rev. 23(3):616-87, 2010
5. Prieto-Granada CN et al. Skin infections. In Kradin RL:
Diagnostic Pathology of Infectious Disease. Philadelphia:
Saunders Elsevier. 519, 2010
6. Otto M: Staphylococcus epidermidis--the ’accidental’
pathogen. Nat Rev Microbiol. 7(8):555-67, 2009
7. Rogers KL et al: Coagulase-negative staphylococcal
infections. Infect Dis Clin North Am. 23(1):73-98, 2009
8. Cooke RA: Bacterial Infections. In Cooke RA: Infectious
Diseases: Atlas, Cases, Text. Sidney New York: McGraw-Hill.
24-25, 2008
9. Morgan MS: Diagnosis and treatment of Panton-Valentine
leukocidin (PVL)-associated staphylococcal pneumonia. Int
J Antimicrob Agents. 30(4):289-96, 2007
10. Iwatsuki K et al: Staphylococcal cutaneous infections:
invasion, evasion and aggression. J Dermatol Sci.
42(3):203-14, 2006
11. Ladhani S: Understanding the mechanism of action of
the exfoliative toxins of Staphylococcus aureus. FEMS
Immunol Med Microbiol. 39(2):181-9, 2003
12. Lichtenberg, F: Pathology of Infectious Diseases. New York:
Raven Press, 1991
13. Hurwitz RM et al: Cutaneous pathology of the toxic shock
syndrome. Am J Dermatopathol. 7(6):563-78, 1985
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
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21
STAPHYLOCOCCUS SPECIES INFECTIONS
p
p
Gross and Microscopic Features
(Left) This gross photograph
of lethal staphylococcal
neumonia demonstrates
a bronchopleural fistula
. (Courtesy Franz von
Lichtenberg Collection of
Infectious Disease Pathology,
BWH.) (Right) Staphylococcal
bronchopneumonia
demonstrates focal mucosal
erosion . (Courtesy Franz
von Lichtenberg Collection of
Infectious Disease Pathology,
BWH.)
(Left) This is an additional
section of staphylococcal
bronchopneumonia
demonstrating focal mucosal
erosion (early stage).
(Courtesy Franz von
Lichtenberg Collection
of Infectious Disease
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
Pathology, BWH.) (Right)
This section of staphylococcal
bronchopneumonia
demonstrates fibrinopurulent
exudate lining the
artially necrotic alveolar
walls. (Courtesy Franz von
Lichtenberg Collection of
Infectious Disease Pathology,
BWH.)
(Left) Staphylococcal
colonies are easily
visualized by Gram stain in
bronchopneumonia (and can
also be seen as basophilic
clusters on H&E). (Courtesy
Franz von Lichtenberg
Collection of Infectious
Disease Pathology, BWH.)
(Right) This image depicts
bacterial mini emboli of the
bladder from a case of S.
aureus sepsis. (Courtesy Franz
von Lichtenberg Collection of
Infectious Disease Pathology,
BWH.)
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2
22
STAPHYLOCOCCUS SPECIES INFECTIONS
Gross and Microscopic Features
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
(Left) S. aureus sepsis can
also cause miliary abscesses
(here in the myocardium).
Note the colony of
bacteria surrounded
by abscess formation
. (Courtesy Franz von
Lichtenberg Collection
of Infectious Disease
Pathology, BWH.) (Right)
This gross photograph
depicts large vegetations
in staphylococcal
endocarditis. (Courtesy
Franz von Lichtenberg
Collection of Infectious
Disease Pathology, BWH.)
(Left) This gross photograph
illustrates large, "shaggy"
aortic valve vegetations
in staphylococcal
endocarditis. (Courtesy
Franz von Lichtenberg
Collection of Infectious
Disease Pathology, BWH.)
(Right) Septic emboli
from Staphylococcal
endocarditis can cause
mycotic aneurysms of
distant vessels (here the
hepatic artery). (Courtesy
Franz von Lichtenberg
Collection of Infectious
Disease Pathology, BWH.)
(Left) Septic emboli from
staphylococcal endocarditis
can cause infected infarcts
of distant organs (here,
the brain). (Courtesy
Franz von Lichtenberg
Collection of Infectious
Disease Pathology, BWH.)
(Right) Septic emboli from
staphylococcal endocarditis
can cause infected infarcts of
distant organs (here, the
lung). (Courtesy Franz von
Lichtenberg Collection of
Infectious Disease Pathology,
BWH.)
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23
STREPTOCOCCUS AND ENTEROCOCCUS SPECIES INFECTIONS
These lungs from a patient who died of S. pneumoniae
pneumonia demonstrate the heavy mixed inflammatory
exudates of red hepatization .
TERMINOLOGY
Abbreviations
Group B streptococci (GBS)
Definitions
Greek: "Streptos" (twisted chain) + "kokkus" (grain)
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
Greek: "Entero" (intestine) + "kokkus" (grain)
ETIOLOGY/PATHOGENESIS
Environmental Exposure
Streptococcal species reside upon human or animal
oropharyngeal, urogenital, and gastrointestinal
mucous membranes
Spread is generally through direct contact or droplet
exposure
Enterococci reside within human or animal
gastrointestinal tract, though they are able to persist in
harsh environmental conditions
Infectious Agents
Clinically relevant Streptococcal species can be
practically split between -hemolytic and -hemolytic
groups
-hemolytic include: Streptococcus pyogenes
(group A), Streptococcus agalactiae (group B), and
Streptococcus dysgalactiae (group C or G)
-hemolytic include: Streptococcus pneumoniae,
Streptococcus mitis group, Streptococcus anginosus
group, Streptococcus salivarius group, Streptococcus
mutans group, and Streptococcus bovis (gallolyticus)
group
Clinically important species of enterococci (formerly
known as group D streptococci) are Enterococcus
faecium and Enterococcus faecalis
II
Numerous gram-positive cocci in pairs and chains
are visible in the lungs of this patient who died from S.
pneumoniae pneumonia.
CLINICAL ISSUES
Epidemiology
S. pyogenes infection (as acute pharyngitis) is usually
found in patients 5-15 years old
S. agalactiae is most often a cause of disease in
neonates born to colonized women (10-30% of
urogenital and gastrointestinal tracts of healthy adults)
S. pneumoniae colonizes nasopharynges of 30-70% of
young children and only 5% of adults
S. mitis, S. anginosus, S. salivarius, and S. mutans groups
(collectively called viridans streptococci) are most
heavily concentrated in oral cavity, but also found as
commensals in gastrointestinal tract, on skin, and in
female genital tract
S. bovis group members are often found in alimentary
tracts of ruminants
Invasive disease is associated with colorectal
malignancy
Enterococcal species colonize large intestine, which is
thought to be prerequisite for invasive disease
Treatment
Surgical approaches
Necrotizing fasciitis requires surgical debridement
Endocarditis may require surgical repair of
damaged valves
Drugs
-hemolytic streptococci: Penicillin
Resistance to penicillin among the -hemolytic
streptococci makes extended-spectrum
cephalosporins, macrolides, fluoroquinolones, &/or
vancomycin more effective choices
Enterococci: Vancomycin resistance is a serious issue
for E. faecium
E. faecalis has a number of options guided by
susceptibility testing
2
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STREPTOCOCCUS AND ENTEROCOCCUS SPECIES INFECTIONS
Etiology
Streptococcal species reside upon human or animal
oropharyngeal, urogenital, and gastrointestinal
mucous membranes
Clinically relevant streptococci include S. pyogenes
(group A), S. agalactiae (group B), S. dysgalactiae
(group C or G), S. pneumoniae, S. mitis group, S.
anginosus group, S. salivarius group, S. mutans group,
S. bovis (gallolyticus) group
Enterococci reside within human or animal
gastrointestinal tract, though they are able to persist
in harsh environmental conditions
Clinically important species of enterococci (formerly
known as group D streptococci) are Enterococcus
faecium and E. faecalis
Presentation of Streptococcal Species
S. pyogenes, group A streptococci
Streptococcal pharyngitis ("Strep throat")
Presents with sore throat, malaise, high fever, and
headache (often gastrointestinal symptoms in
pediatric patients)
Complications: Scarlet fever, suppurative
complications (e.g., abscess, meningitis,
pneumoniae), and nonsuppurative complications
(rheumatic fever and poststreptococcal
glomerulonephritis)
Erysipelas: Infection of dermis with lymphatic
involvement
Raised lesions, a clear border between involved
and uninvolved skin, and strong red color
Often involves face or lower extremities
Those with a compromised barrier are most at risk
Streptococcal cellulitis: Infection involving skin and
subcutaneous tissues
Usually in skin compromised by trauma or
wounds
Unlike erysipelas, lesions are neither raised nor
well demarcated
Necrotizing fasciitis: Infection of subcutaneous
tissue and fascia, which results in rapidly spreading
tissue necrosis
Diagnosis can be challenging, especially in early
stages, and may rely on deep tissue biopsy
S. pneumoniae
Pneumonia
Responsible for ~ 25% of community-acquired
pneumonia in United States
Presents acutely with cough, fatigue, shortness
of breath, dyspnea, fever/sweats/chills, purulent
sputum, and pleuritic chest pain
Meningitis
Most common cause of bacterial meningitis in
adults
Also a common cause of otitis media and sinusitis
S. agalactiae (group B streptococci)
Bacteremia
Key Facts
Clinical Issues
Streptococci
Enterococci
Viridans streptococci
Presentation of Enterococcal Disease
Bacteremia
Endocarditis (particularly E. faecalis)
Streptococcal pharyngitis ("Strep throat")
Skin and soft tissue infections (SSTI)
Infective endocarditis
Pneumonia
Meningitis
Infection of endometrium, placenta, cesarean
section wounds
Infections in newborn
Bacteremia
Endocarditis (particularly E. faecalis)
Presents with fever, chills and change in mental
status
Endometrium, placenta, infection of cesarean
section wounds
Complications can include pelvic abscess, septic
shock, or septic thrombophlebitis
Infections in newborns
Bacteremia, meningitis, and pneumonia
Can be early onset (within 6 days of life) or late
onset (between 7 and 89 days of life)
Late-onset cases are often (~ 50%) associated with
preterm birth
Bacteremia
Most likely to be clinically significant in context
of chemotherapy-induced neutropenia
Infective endocarditis
20% of infectious endocarditis
Splenomegaly, Osler nodes, splinter hemorrhages,
and a murmur may be present
Other manifestations: Meningitis, pneumonia, and
endophthalmitis (particularly with compounded
injections for macular degeneration)
Milleri group of viridans streptococci (S. anginosus,
Streptococcus intermedius, and Streptococcus
constellatus)
Abscess formation of head and neck, central
nervous system, and abdominal cavity
S. bovis group of viridans streptococci (S. gallolyticus,
Streptococcus pasteurianus, and Streptococcus
infantarius)
Infective endocarditis (11-17% of infective
endocarditis cases)
Strong association with colorectal malignancy and
hepatobiliary disease
Typically subacute with "B" symptoms, fevers, and
murmurs
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
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STREPTOCOCCUS AND ENTEROCOCCUS SPECIES INFECTIONS
Also urinary tract infections (usually in catheterized
patients), meningitis (uncommon), skin and soft tissue
infections, and abdominal and pelvic infections (often
as part of polymicrobial infection)
A common agent of a wide spectrum of neonatal
disease (due to presence in vagina)
MICROBIOLOGY
Morphological/Biochemical
Streptococci
Facultatively anaerobic gram-positive cocci that are
arranged in pairs and chains and produce neither
catalase nor coagulase
Enterococci
Characteristically able to hydrolyze esculin in
presence of bile
Culture
Cultured on 5% sheep’s blood agar
Microbiological Identification
Discriminated by colony characteristics (color, size,
hemolysis) along with biochemical reactions
Vitek platform can differentiate many species with its
gram-positive card
Several smaller scale identification strips can
differentiate among streptococci, e.g., API strep strip
(BioMrieux) and the RapID strep strip (Remel)
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
MACROSCOPIC FEATURES
General Features
Endocarditis (viridans streptococci, S. bovis group,
enterococci)
Vegetation may be seen on heart valves
Size may range from thin veneer to bulky and
obstructing
Meningitis
Exudate may be seen coating surfaces of
leptomeninges
Acute inflammatory infiltrate in CSF along with
gram-positive cocci or diplococci
Can be complicated by abscess underneath capsule
of palatine tonsil
Pneumonia (commonly S. pyogenes and S. pneumoniae)
S. pyogenes: Marked edema, hemorrhage, abscess,
and empyema
Necrotic macrophages and numerous bacteria may
be seen
S. pneumoniae: Less acute, nonnecrotizing
Early phase: "Red hepatization," marked by
extensive edema, hemorrhage, and acute
inflammation
Late phase: "Gray hepatization," marked by
macrophage infiltrate
Skin and soft tissue (commonly S. pyogenes)
Erysipelas: Acute inflammation, edema, and
occasionally subepidermal bullae
Cellulitis: Inflammation in dermis and subcutaneous
tissue, fat necrosis
Necrotizing fascitis: Acute inflammation and
necrosis along fascial planes, often more extensive
than apparent from clinical exam
CNS
Meningitis (commonly S. pneumoniae and S.
agalactiae [neonates])
Meningeal and parenchymal hemorrhage,
neutrophilic infiltrate, arteritis obliterans, infarct,
thrombosis, vasculitis, and abscess
Acute inflammatory infiltrate in CSF, along with
gram-positive cocci or diplococci
Progresses to mixed inflammatory infiltrate and
organization
Abscess (commonly S. anginosus group of viridans
streptococci)
Chorioamnionitis (commonly S. agalactiae)
Necrotizing
Organisms often present
DIFFERENTIAL DIAGNOSIS
Other Bacterial Infections
Gram-positive cocci: Most commonly Staphylococcus
species
Gram-positive or negative rods: Culture required for
definitive diagnosis
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26
MICROSCOPIC PATHOLOGY
Histologic Features
Endocarditis (commonly viridans streptococci,
enterococci)
Most often subacute and demonstrates low-level
leukocyte involvement
Vegetations composed of fibrin, platelets, cellular
debris, organisms, host leukocytes
Organisms are revealed by tissue Gram stain &/or
silver stain
Neoangiogenesis and fibroplasia may be features
Tonsillitis and peritonsillar abscess (commonly
Viridans streptococci, S. pyogenes)
Chronic tonsillitis can cause reactive lymphoid
hyperplasia and fibrosis
Viral Pneumonia
Lack of gram staining for bacteria viral cytopathic
effect
SELECTED REFERENCES
1. Arias CA et al: The rise of the Enterococcus: beyond
vancomycin resistance. Nat Rev Microbiol. 10(4):266-78,
2012
2. Mook-Kanamori BB et al: Pathogenesis and
pathophysiology of pneumococcal meningitis. Clin
Microbiol Rev. 24(3):557-91, 2011
3. Doern CD et al: It’s not easy being green: the viridans
group streptococci, with a focus on pediatric clinical
manifestations. J Clin Microbiol. 48(11):3829-35, 2010
STREPTOCOCCUS AND ENTEROCOCCUS SPECIES INFECTIONS
p
p
g
Radiologic and Microscopic Features
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
(Left) This medium-
ower image shows acute
neumonia with patchy
hemorrhage and dense
acute inflammation , the
histologic correlate of "red
hepatization" noted on gross
examination. (Right) This
MR from a patient with a
streptococcal brain abscess
demonstrates ring-enhancing
lesions .
(Left) This high-power
image from a streptococcal
brain abscess shows
sheets of neutrophils
among a background
of necrotic brain matter
and necroinflammatory
debris . (Right) This
brain biopsy from a patient
with streptococcal brain
abscess demonstrates
numerous gram-positive
cocci in pairs and chains .
Cultures grew Streptococcus
intermedius, a member
of the milleri group
streptococci.
(Left) In streptococcal
erysipelas, there is
intense, acute, exudative
inflammation of all skin
layers with edema ,
blunting the dermal papillae
, and lifting the corneal
layer . (Courtesy Franz
von Lichtenberg Collection
of Infectious Disease
Pathology, BWH.) (Right)
This section is from the lung
of a 20-year-old woman who
died of sepsis. Blood cultures
rew group C. streptococci.
Numerous clusters of cocci
are seen .
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GRAM-NEGATIVE ENTERIC ORGANISMS AND THEIR INFECTIONS
This gross photograph demonstrates confluent
pneumonia caused by E. coli and E. cloacae.
(Courtesy Franz von Lichtenberg Collection of Infectious
Disease Pathology, BWH.)
INFECTIOUS AGENTS: EPIDEMIOLOGY, CLINICAL PRESENTATION, AND PATHOGENESIS
Escherichia coli
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
Enterotoxigenic E. coli (ETEC)
Associated with "traveler’s diarrhea"
Spread via contaminated food and water
Disease is characterized by watery diarrhea, nausea,
and cramps (no fecal blood, mucus, or leukocytes)
Pathogenesis linked to heat-stable (ST) and heatlabile (LT) enterotoxins, which result in active
chloride export by host cell and resultant passive
sodium and water loss
Enteropathogenic E. coli (EPEC)
In developed world, mainly associated with
nosocomial diarrhea
Spread person-to-person
Disease may be more severe than that caused by
ETEC, and symptoms may include fever, vomiting,
weight loss, and malnutrition
Pathogenesis is mediated by a pathogenicity island
encoding machinery to inject a receptor into host
cells, allowing for binding and distortion of host cell
architecture (formation of actin "pedestals")
This process, "attaching and effacing," is hallmark
feature of this pathotype
Shiga toxin-producing and enterohemorrhagic E. coli
(STEC and EHEC)
Causes mostly food-borne disease, especially via
undercooked beef and produce
Can present with severe abdominal cramping and
bloody or watery diarrhea ( fever)
Hemorrhagic colitis and hemolytic-uremic
II
syndrome are serious complications
2
A lung with enteric pneumonia shows inflammation filling
air spaces and involving bronchioles and vessels .
(Courtesy Franz von Lichtenberg Collection of Infectious
Disease Pathology, BWH.)
Pathogenesis of STEC strains is mediated by Shiga
toxin, encoded on a temperate bacteriophage,
which is toxic to host cell ribosome
Stressors to bacterial cell (such as antibiotics) cause
induction of toxin and are therefore contraindicated
Once released, toxin can disseminate throughout
body
Targeting of endothelial cells in particular is
linked with creation of microvascular thrombi and
development of hemolytic uremic syndrome (HUS)
EHEC strains, like EPEC strains, additionally carry
virulence factors necessary for "attaching and
effacing" in addition to Shiga toxin
These strains appear to be associated with a more
severe course of disease
Enteroaggregative E. coli (EAEC)
A growing cause of diarrhea among many
groups, including children, travelers, and
immunocompromised patients
May be associated with both acute and chronic
diarrhea
Clinical course is marked by abdominal cramping,
hematochezia, and passage of mucus
Organism named for characteristic clumping
phenotype it displays upon adherence to tissue,
which is linked to plasmid-encoded aggregative
adherence fimbriae
Enteroinvasive E. coli (EIEC)
Very similar to strains of Shigella
Clinical spectrum ranges from watery diarrhea to
dysentery
Once taken up by a phagocytic cell, EIEC can escape
from the phagosome, replicate in the cytoplasm,
and employ host actin to spread from cell to cell
Shigella
Clinically important species include Shigella sonnei
(most common), Shigella dysenteriae, and Shigella
flexneri
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GRAM-NEGATIVE ENTERIC ORGANISMS AND THEIR INFECTIONS
Bacterial Infections: Bacterial Infections Requiring Culture/Ancillary Confirmation
Spread from person to person and is considered the
most infectious bacterial diarrhea (requires very small
dose)
Shigella (along with enteroinvasive E. coli) is causative
agent of bacillary dysentery
Symptoms include fever and an initial phase of
abdominal cramping and watery diarrhea followed
by frequent, smaller volume bowel movements
containing mucus &/or blood
A type III secretion system is used to induce uptake by
intestinal epithelium
Upon entry, Shigella move from cell to cell via
subversion of host cytoskeleton, though they
generally stay confined to mucosa
Enterobacter, Serratia, Citrobacter, Proteus,
Providencia, Morganella
Usually implicated as agents of a wide spectrum of
disease (UTI, bacteremia, pneumonia) in hospital
patients
Citrobacter has a propensity for causing meningitis
complicated by abscess in neonatal populations
Virulence factors include an inducible, chromosomal
-lactamase in Enterobacter, Serratia, Citrobacter, and
Morganella
Proteus species, particularly Proteus mirabilis, are a
noteworthy cause of urinary tract infections (UTI),
particularly in catheterized patients
Tend to be more severe than UTIs caused by E.
coli, with a higher proportion developing into
pyelonephritis and causing bacteremia
Important virulence factors in P. mirabilis include
urease production and swarming motility
Salmonella
Clinically relevant strains are serotypes of Salmonella
enterica subsp enterica
Within these, there is a basic division between
Salmonella ser Typhi and nontyphoidal Salmonella,
including the serotypes Typhimurium, Enteritidis,
and Newport
S. ser Typhi
Humans are only known reservoir; bacteria can be
shed in stools of convalescent patients
Typhoid (enteric fever) is characteristically bimodal
with an initial period (1-2 weeks) of fever and
constipation with positive blood cultures followed
by a diarrheic phase with positive stool cultures
Complications include intestinal hemorrhage
and perforation, encephalitis, neuropsychiatric
symptoms
Most other nontyphoidal Salmonella serotypes cause
food-borne illness and are associated with animals
(poultry, beef, and dairy products) as well as fresh
produce
Also associated with certain pets, e.g., lizards,
turtles, frogs, and snakes
S. ser Enteriditis is associated with chicken eggs,
which get contaminated within chicken ovaries
before shell is deposited
Most common clinical manifestation of Salmonella
infection is gastroenteritis
This usually presents within a day or 2 after
eating contaminated food and presents as watery,
nonbloody diarrhea, fever, nausea, vomiting, and
abdominal cramping
Symptoms generally last 3-7 days, with fecal
carriage of organisms continuing for 4-5 weeks
Bacteremia occurs in up to 8% of patients
Other pertinent clinical issues include propensity
of Salmonella to infect vascular sites and to
develop other localized infections; patients with
HIV infection are particularly vulnerable
Salmonella are able to tightly bind to and invade
intestinal epithelium using an array of virulence
factors
Multiple types of fimbriae contribute to adhesion,
while a type III secretion system injects multiple
proteins into host cell to subvert host cytoskeleton
and modulate immune response
Actin rearrangements (induced by the proteins SipA
and SipC) results in "membrane ruffling," which is
characterized bacteria-mediated endocytosis and
allows for uptake of the bacteria into the host cell
Klebsiella
Clinically relevant species are Klebsiella pneumoniae,
Klebsiella oxytoca, and Klebsiella granulomatis
K. pneumoniae
Implicated in pneumonia, urinary tract infections,
and liver abscess in immunocompetent patients
Among hospital patients, K. pneumoniae is isolated
as a frequent cause of wound infection, sepsis,
and other manifestations
Pneumonia caused by K. pneumoniae is termed
Friedlander disease due to characteristic severity,
tendency to include abscess, location in upper
lobes, association with "currant jelly sputum"
and "bulging fissure" sign on radiographs, and
propensity for alcoholic patients
K. pneumoniae subsp rhinoscleromatis is agent of
rhinoscleroma
Chronic granulomatous infection of respiratory
tract (particularly nasal passages)
Most common in developing countries
Spread by contaminated droplets
K. oxytoca
Less frequently isolated than K. pneumoniae, but
responsible for a similar spectrum of disease in
hospitalized patients
K. granulomatis
Responsible for chronic genital ulcerative disease
(granuloma inguinale)
Spreads through contact with open sores
Best characterized virulence factor of Klebsiella is
polysaccharide capsule
Yersinia
Clinically relevant species: Yersinia enterocolitica
Food-borne pathogen with reports of diverse sources
(often pigs and pork products)
Clinical manifestations of Y. enterocolitica infection
include enterocolitis (most common), mesenteric
adenitis, and exudative pharyngitis
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