Gram (+)

Bacterial
Infection

Benito K. Lim Hong III

 Objectives
1. To know the various diseases caused
by Gram (+) Bacteria limited to
Robbins Pathologic Basis of
Diseases & common in the local
settings:
1. Staphylococcal Infection
2. Streptococcal Infection
3. Diphtheria
4. Listeriosis
5. Nocardia
 Objectives

2. To know the gross appearance of the

common disease cause by Gram (+)
organisms as well as histopathologic
appearance of only commonly
biopsied lesion limited to Robbins
Pathologic Basis of Disease
 Objectives

3. To know the mechanism of action of

the Gram (+) infectious agents as to
how they cause diseases to humans
limited to Robbins Pathologic Basis
of Disease
 Clinical Case

A 23 year old female came in to your

clinic complaining of a mass in the left
axilla. V/S: BP=120/80, HR=60bpm,
RR=20cpm, T=36.5ºC. On Physical
Examination, the mass was described
to be tender, movable, well-
circumscribed, erythematous.
Staphylococcal Infection
Etiologic Agents:
1. Staphylococcus aureus
2. Staphylococcus epidermidis
3. Staphylococcus saphrophyticus
Pyogenic
Non-motile
Gram (+) cocci in clusters
Staphylococcus sp.
Staphylococcal Infection
1. Myriad of skin infections
2. Osteomyelitis
3. Pneumonia
4. Endocarditis
5. Food Poisoning
6. Toxic Shock Syndrome
7. Prosthetic Cardiac Valve Infection
8. Urinary Tract Infection
Staphylococcal Infection
Virulence Factors:
1. Surface protein involved in
adherence to host cells
2. Enzymes that degrade host
proteins
3. Exotoxin – toxins that lyze host
cells & cause Scalded Skin
Syndrome
4. Endotoxin & Toxic Shock Syndrome
Toxin - produce shock
Staphylococcal Infection
Virulence Factors:
5. Clumping Factor, Fibronectin,
Vitronectin – binds to host cells
endothelium
6. Polysaccharide Capsule – resist
host cell phagocytosis
7. Lipase – degrades lipids on skin
surface to produce skin abscesses
Staphylococcal Infection
Virulence Factors:
8. Protein A – binds Fc portion of
immunoglobulin
9. Plasmids – confers antibiotics
resistance
10.Alpha-Toxin (α-Toxin) – pore-
forming proteins that intercalates
into the plasma membrane of host
cells & depolarizes them
Staphylococcal Infection
Virulence Factors:
11.Beta-Toxin (β-Toxin) -
sphingomyelinase
12.Delta-Toxin (δ-Toxin) – Detergent-
like peptide
13.Gamma-Toxin (γ-Toxin) – lyse RBC
14.Leukocidin – lyse Phagocytic Cells
Staphylococcal Infection
 Virulence Factors:
15.Exfoliative Toxins – serine proteases
that split the skin by cleaving the
protein desmoglein 1, which is part of
the desmosomes that hold epidermal
cells tightly together superficial
epidermis to split away from deeper
skin vulnerable to skin infections.
Staphylococcal Infection
 Virulence Factors:
16.Superantigens – bind to conserve
portion of MHC molecules & to
relatively conserved portions of TCR
β-cells stimulates up to 20% of T-
lymphocytes massive T-
lymphocytes proliferation & cytokines
release capillary leaks & shock
Staphylococcal Infection

Morphology:
Whether the lesion is located in the
skin, lungs, bones, or heart valves,
Staphylococcus aureus cause
pyogenic inflammation, which is
remarkable for its local
destructiveness
Staphylococcal Infection
Morphology:
1. Impetigo - a contagious skin
disorder, caused by streptococci,
staphylococci, or a combination
of organisms and marked by
vesicles or bullae that become
pustular, rupture, and form yellow
crusts; also called impetigo
contagiosa or impetigo vulgaris.
Impetigo
Staphylococcal Infection
Morphology:
2. Furuncle – focal suppurative
inflammation of the skin &
subcutaneous tissue, either solitary,
multiple, or recurrent in successive
crops. Most frequent in moist, hairy
areas. Beginning in a single hair
follicle a growing & deepening
hair abscess that eventually “comes
to the head” by thinning & rupturing
the overlying skin.
Furuncle
Staphylococcal Infection
Morphology:
3. Carbuncle – is associated with
deeper suppuration that spread
laterally beneath the deep
subcutaneous fascias & burrows
superficially to erupt in multiple
adjacent sinuses. Typically appear
beneath the skin of the upper back
& posterior neck where fascial
planes favor their spread.
Cabuncle
Staphylococcal Infection

Morphology:
4. Hidradrenitis suppurativa –
chronic abscess formation of the
apocrine gland regions, most
frequently of the axilla.
Hidradenitis suppurativa
Staphylococcal Infection

Morphology:
5. Paronychia – chronic abscess
formation of the apocrine gland
regions, most frequently of the nail
beds.
Paronychia
Staphylococcal Infection

Morphology:
6. Felons - chronic abscess formation
of the apocrine gland regions, most
frequently of the palmar sides of the
fingertips.
Felon
Staphylococcal Infection
Morphology:
7. Staphylococcal Lung Infection –
have polymorphonuclear infiltrates
similar to pneumococcus but more
destructive of lung tissues. Usually
occurs in patient with predisposing
conditions such as influenza or
hematogenous spread of infected
thombi.
Staphylococcal Lung Infection
Staphylococcal Infection
Morphology:
8. Staphylococcal Scalded Skin
Syndrome or Ritter Disease –
exfoliative dermatitis most
frequently occurs in children with
staphylococcal infection of the
nasopharynx or skin caused by
Exfoliative A or B Toxin. Sunburn-
like rash that spread over the entire
body & forms fragile bullae that
leads to partial or total skin loss.
Staphylococcal Infection
Morphology:
8. Staphylococcal Scalded Skin
Syndrome or Ritter Disease – The
intraepithelial split in
Staphylococcal Scalded Skin
Syndrome is in the granulosa layer,
distinguishing it from Toxic
Epidermal Necrolysis, or Lyell’s
Disease, which is secondary to
drug sensitivity, & causes splitting
at the epidermal-dermal junction.
 Staphylococcal Infection
Staphylococcal Scalded Toxic Epidermal
Skin Syndrome Necrolysis
 Staphylococcal Infection
Staphylococcal Scalded Toxic Epidermal
Skin Syndrome Necrolysis
 Clinical Case

A 56 year old female was rushed to

the ER due to dyspnea. The patient
also had history of high grade fever
(T=39ºC) & productive cough of rusty
sputum. V/S: BP=120/80, HR=100
bpm, RR=20 cpm, T=39ºC. On
Physical Examination: (+) rales on
chest & lung auscultation
Streptococcal Infection
Etiologic Agents:
1. Streptococcus pneumoniae
2. Streptococcus pyogenes
3. Streptococcus agalactiae
4. Streptococcus viridans
5. Streptococcus mutans
6. Enterococci
Facultative or Obligate Anaerobic
Gram (+) cocci in pairs or chains
Streptococcus sp.
Streptococcal Infection
I. Streptococcus pyogenes
1. Pharyngitis
2. Scarlet Fever
3. Erysipelas
4. Impetigo
5. Rheumatic Fever
6. Toxic Shock Syndrome
7. Glomerulonephritis
Streptococcal Infection
II. Streptococcus agalactiae
1. Sepsis in Neonates
2. Meningitis in Neonates
3. Chorioamionitis in Pregnancy
III. Enterococci
1. Endocarditis
2. Urinary Tract Infection
Streptococcal Infection

IV. Streptococcus pneumoniae

1. Community-acquired Pneumonia
2. Meninigitis in Adults
V. Streptococcus viridans
Endocarditis
VI. Streptococcus mutans
 Dental caries
Streptococcal Infection

Virulence Factors:
1. Capsules – resists phagocytosis.
2. M-protein - surface protein that
prevents bacteria from being
phagocytosed, & a complement
C5a peptidase, which degrades
this chemotactic peptide.
Streptococcal Infection

Virulence Factors:
3. Pneumolysin – inserts on target
cell membranes & lyses them,
greatly increases tissue damage.
Also activates classical pathway
of complement, reducing
complement available for
opsonization of bacteria.
Streptococcal Infection
Virulence Factors:
4. Phage-coded Pyrogenic Exotoxin
– causes fever & rashes in scarlet
fever.
5. Streptococcus mutans produces
caries by metabolizing sucrose to
lactic acid (which causes
demineralization of tooth enamel)
& by secreting high-molecular-
weight glucans that promotes
aggregation of bacteria & plaque
formation.
Streptococcal Infection
Morphology:
Streptococcal infections are
characterized by diffuse interstitial
neutrophilic infiltrates with minimal
destruction of host tissues. The skin
lesions cause by streptococci
resembles those of staphylococci,
although with streptococci there is
less of a tendency to form discrete
abscesses
Streptococcal Infection

Morphology:
1. Erysipelas – most common among
middle-aged persons in warm
climates & is caused by exotoxins in
superficial infections of
Streptococcus pyogenes.
Streptococcal Infection
Morphology:
1. Erysipelas – Characterized by
rapidly spreading erythematous
cutaneous swelling that may begin
on the face, or less frequently, on
the body or an extremity. The
rashes has a sharp, well-
demarcated, serpiginous borders &
may form “butterfly” distribution on
the face.
Erysipelas (Gross)
Streptococcal Infection

Morphology:
2. Pharyngitis – Major antecedent of
Poststreptococcal Glomeruloneph-
ritis, is marked by edema,
epiglottic swelling, & punctate
abscesses of the tonsillar cyrpts,
sometimes accompanied by
cervical lymphadenopathy.
Streptococcal Infection

Morphology:
2. Pharyngitis – With extension of the
pharyngeal infection, there may be
encroachment of the airways,
especially if there is peritonsillar or
retropharyngeal abscess formation
(Quinsy sorethroat).
Streptococcal Pharyngitis (Gross)
Streptococcal Infection
Morphology:
3. Scarlet Fever – associated with
tonsillitis caused by Strepto-
coccus pyogenes, is most
common between age 3 to 15
years. Manifested by a punctate
erythematous rashes that is most
abundant over the trunk & inner
aspect of the arms & legs.
Streptococcal Infection

Morphology:
3. Scarlet Fever – The face is also
involved, but usually a small area
about the mouth remains relatively
unaffected to produce a circumoral
pallor. The tongue has the
characteristic “strawberry tongue”.
Scarlet Fever (Gross)
Scarlet Fever (Gross)
 Clinical Case
A 7 year old girl was rushed to the ER
due to barking cough & dyspnea. The
patient also had history of high grade
fever (T=39ºC) & productive cough of
rusty sputum. V/S: BP=90/60,
HR=120 bpm, RR=30 cpm, T=39ºC.
On Physical Examination: (+) grayish,
white patch on the throat with (+)
lymphadenopathy on bilateral neck
 Diphtheria
Etiologic Agent:
Corynebacterium diphtheriae
Slender, gram (+) rod with clubbed
ends
Mode of transmission: Aerosols or
Skin shedding
Toxin responsible for pathogenesis:
Diphtheria Toxin (1 toxin)
Corynebacterium diphtheriae
 Diphtheria

Mechanism of action for

pathogenesis: single molecule of
Diphtheria Toxin can kill a cell by ADP
ribosylating, & thus inactivating, more
than a million of EF-2 molecules
blocking protein synthesis of host
cells.
 Diphtheria

Morphology:
A life-threatening syndrome that
includes formation of a tough
pharyngeal membrane & toxin-
mediated damage to the heart,
nerves, & other organs
 Diphtheria
Morphology:
Inhaled organisms proliferate at
site of attachment on the mucosa
of the nasopharynx, oropharynx,
larynx, or trachea but also satellite
lesions in the esophagus or lower
airways Release of exotoxins
Necrosis of epithelium,
accompanied by an outpouring of a
dense fibrosuppurative exudates
 Diphtheria
Morphology:
The coagulation of this exudates
on the ulcerated necrotic surface
creates a tough, dirty gray to black,
superficial membrane. Neutrophilic
infiltration in the underlying tissues
is intense & is accompanied by
marked vascular congestion,
interstitial edema, & fibrin
exudation
 Diphtheria
Morphology:
When the membrane sloughs off
its inflamed & vascularized bed,
bleeding & asphyxiation may occur.
With control of infection, the
membrane is coughed up or
removed by enzymatic digestion, &
the inflammatory reaction subsides.
 Diphtheria
Morphology:
When the membrane sloughs off
its inflamed & vascularized bed,
bleeding & asphyxiation may occur.
With control of infection, the
membrane is coughed up or
removed by enzymatic digestion, &
the inflammatory reaction subsides.
 Diphtheria

Morphology:
Although the bacterial invasion
remains localized, general
hyperplasia of the spleen & lymph
nodes ensues owing to the
absorption of soluble exotoxin into
the blood.
 Diphtheria
Morphology:
The exotoxin may cause fatty
myocardial change with isolated
myofiber necrosis, polyneuritis with
degeneration of myelin sheaths &
axis cylinders & (less commonly)
fatty change & focal necroses of
parenchymal cells in the liver,
kidneys & adrenals.
Diphtheria (Gross)
Diphtheria Pseudomembrane
(Histopathology)
 Clinical Case
A 3 day old girl neonate was noted to
have yellowish discoloration on her
entire skin, irritability, & had tonic
clonic seizure. V/S: BP=90/60,
HR=175 bpm, RR=30 cpm, T=39ºC.
On Physical Examination: (+)
jaundice, (+) bulging fontanelles, (+)
Brudzinski Sign.
 Listeriosis

Etiologic Agent:
Listeria monocytogenes
Gram (+) rod
Motile
Facultative intracellular bacterium
Listeria monocytogenes
 Listeriosis

Susceptible patients:
1. Pregnant women & their neonates
2. Elderlies
3. Immunosuppressed persons (Ex:
Transplant recipients, AIDS
patient)
 Listeriosis
1. Food-borne infections
2. Amnionitis
3. Abortion
4. Stillbirth
5. Neonatal Sepsis
6. Granulomatosis Infantiseptica
7. Exudative Meningitis
 Listeriosis

Virulence Factors:
1. Internalins – leucine-rich protein
on the surface of the organism
which bind to E-cadherin on
host epithelial cells & induce
internalization of the bacterium.
 Listeriosis
Virulence Factors:
2. Listeriolysin O & 2
Phospholipases– pore-forming
protein which help the bacteria
escape from the membrane-
bound phagolysosomes inside
the cell.
 Listeriosis
Virulence Factors:
3. ACTA – a bacterial surface
protein which binds to host cell
cytoskeletal proteins & induces
actin polymerization, which
propels the bacteria into
adjacent uninfected host cells.
 Listeriosis

Protective Factors from Host Cell

to protect this organism from
spreading to nearby cells:
Interferon-γ (IFN-γ) produced by
Natural Killer Cells (NK Cells) &
T-cells
 Listeriosis
Morphology:
In acute human infection, the
organism evokes an exudative
pattern of inflammation with
numerous neutrophils
indistinguishable from that of
meningitis caused by other
pyogenic bacteria.
The finding of Gram (+), mostly
intracellular, bacilli in the CSF is
virtually diagnostics.
 Listeriosis
Morphology:
Focal abscesses alternate with
grayish or yellow nodules
representing necrotic amorphous
basophilic tissue debris can occur in
any organs.
In infection of longer duration,
macrophages appear in large
numbers to dispose of the necrotic
remnants, but true epithelioid cells
granulomas are rare.
 Listeriosis
Morphology:
Infants born live with Listeria
monocytogenes sepsis often have a
papular red rash over the
extremities, & listerial abscesses
can be seen in the placenta.
A smear of the meconium will
disclose the Gram (+) organism.
 Clinical Case
A 36 year old male was noted to have
chronic cough for 2 months, night
sweats, weight lost, lethargy, &
confusion. V/S: BP=90/60, HR=120
bpm, RR=35 cpm, T=38.5ºC. On
Physical Examination: (+) raised,
erythematous, tender skin lesion on
his both upper & lower extremities,
(+) rales on both lung fields, not
oriented as to person & time.
 Nocardia
Etiologic Agents:
1. Nocardia asteroides
2. Nocardia braziliensis
Aerobic
Gram (+) bacteria that grows in
distinctive branched chains
In culture, it forms aerial structures
with terminal spores, resembling
hyphae
Nocardia sp.
 Nocardia
I. Nocardia asteroides
1. Respiratory infections
2. CNS infections
3. Skin infections
II. Nocardia braziliensis
 Skin infections
Nocardia skin infection
 Nocardia

 Susceptible patients:
 Defects in T cell-mediated
immunity:
1. Prolonged steroid use
2. HIV infection
3. Diabetes Mellitus
 Nocardia
 Morphology:
 Diagnosis: Identification of Gram
(+) organisms arranged in
branching filaments either using
Gram Stain or Modified Acid Fast
Stain (Fite-Faraco Stain) which
appear similar in morphology with
Gram Stain
 Nocardia

 Morphology:
 At any site of infection, Nocardia
elicit a suppurative response with
central liquefaction & surrounding
granulation & fibrosis.
Granulomas do not form.
Nocardia infection in the
lungs