صفحه 1:
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Lecture Power Pont tp arp
Talaro
Chapter 19
The Gram-Positive
Bacilli of Medical
Importance
صفحه 2:
Medically Important Gram-
Positive Bacilli
Three general groups:
1. Endospore-formers
Bacillus, Clostridium
2. Non-endospore-formers
Listeria, Erysipelothrix
3. Irregular shaped and staining
properties
Corynebacterium, Proprionibacterium,
Mycobacterium, Actinomyces, Nocardia
2
صفحه 3:
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Endospore-forniors [Now-Eadospore-tormers
i
ام Regular shape and Irregular shape and
Conran saining properties staining properties
1
Listeria.
مروت
Non-acidfast Acid-fast Filamentous,
branching cells
Corynebacterton ‘Mycabacteriwn Actinomyces
Propionibacterium Necardia
صفحه 4:
Spore-forming Bacilli
Genus Bacillus
Genus Clostridium
صفحه 5:
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General Characteristics of
the Genus Bacillus
¢ Gram-positive, endospore-forming, motile rods
٠ Mostly saprobic
¢ Aerobic and catalase positive
¢ Versatile in degrading complex
macromolecules
٠ Source of antibiotics
¢ Primary habitat is soil
* 2 species of medical importance:
- Bacillus anthracis
- Bacillus cereus
صفحه 6:
Bacillus anthracis
۰ Large, block-shaped rods
* Central spores that develop under all
conditions except in the living body
* Virulence factors - polypeptide
capsule and exotoxins
* 3 types of anthrax:
- cutaneous - spores enter through skin,
black sore- eschar; least dangerous
- pulmonary -inhalation of spores
- gastrointestinal - ingested spores
صفحه 7:
Control and Treatment
* Treated with penicillin, tetracycline,
or ciprofloxacin
¢ Vaccines
- live spores and toxoid to protect
livestock
- purified toxoid; for high risk occupations
and military personnel; toxoid 6X over
1.5 years; annual boosters
صفحه 8:
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صفحه 9:
Bacillus cereus
* Common airborne and dustborne; usual
methods of disinfection and antisepsis
are ineffective
* Grows in foods, spores survive cooking
and reheating
* Ingestion of toxin-containing food
causes nausea, vomiting, abdominal
cramps and diarrhea; 24 hour duration
* No treatment
* Increasingly reported in
immunosuppressed
صفحه 10:
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The Genus Clostridium
* Gram-positive, spore-forming rods
¢ Anaerobic and catalase negative
* 120 species
* Oval or spherical spores produced only
under anaerobic conditions
¢ Synthesize organic acids, alcohols, and
exotoxins
* Cause wound infections, tissue infections,
and food intoxications
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Gas Gangrene
* Clostridium perfringens most frequent
clostridia involved in soft tissue and
wound infections - myonecrosis
¢ Spores found in soil, human skin,
intestine, and vagina
* Predisposing factors - surgical
incisions, compound fractures,
diabetic ulcers, septic abortions,
puncture wounds, gunshot wounds
صفحه 13:
Virulence Factors
¢ Virulence factors
- toxins -
*alpha toxin - causes RBC rupture,
edema and tissue destruction
- collagenase
- hyaluronidase
- DNase
صفحه 14:
Pathology
* Not highly invasive; requires damaged
and dead tissue and anaerobic
conditions
* Conditions stimulate spore germination,
vegetative growth and release of
exotoxins, and other virulence factors.
¢ Fermentation of muscle carbohydrates
results in the formation of gas and
further destruction of tissue.
14
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صفحه 16:
Treatment and Prevention
* Immediate cleansing of dirty wounds,
deep wounds, decubitus ulcers,
compound fractures, and infected
incisions
* Debridement of disease tissue
* Large doses of cephalosporin or penicillin
* Hyperbaric oxygen therapy
* No vaccines available
صفحه 17:
Clostridium difficile-
Associated Disease (CDAD)
Normal resident of colon, in low numbers
Causes antibiotic-associated colitis
- relatively non-invasive; treatment with broad-
spectrum antibiotics kills the other bacteria,
allowing C. difficile to overgrow
Produces enterotoxins that damage
intestines
Major cause of diarrhea in hospitals
Increasingly more common in community
acquired diarrhea
17
صفحه 18:
Treatment and Prevention
¢ Mild uncomplicated cases respond to
fluid and electrolyte replacement and
withdrawal of antimicrobials.
* Severe infections treated with oral
vancomycin or metronidazole and
replacement cultures
۰ Increased precautions to prevent
spread
صفحه 19:
Tetanus
* Clostridium tetani
* Common resident of soil and GI tracts
of animals
* Causes tetanus or lockjaw, a
neuromuscular disease
* Most commonly among geriatric
patients and IV drug abusers; neonates
in developing countries
صفحه 20:
Pathology
* Spores usually enter through accidental
puncture wounds, burns, umbilical stumps,
frostbite, and crushed body parts.
٠ Anaerobic environment is ideal for
vegetative cells to grow and release toxin.
¢ Tetanospasmin - neurotoxin causes
paralysis by binding to motor nerve endings;
blocking the release of neurotransmitter for
muscular contraction inhibition; muscles
contract uncontrollably
* Death most often due to paralysis of
respiratory muscles
20
صفحه 21:
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21
صفحه 22:
۱ Prevention
¢ Treatment aimed at deterring degree of
toxemia and infection and maintaining
homeostasis
¢ Antitoxin therapy with human tetanus
immune globulin; inactivates circulating
toxin but does not counteract that which is
already bound
* Control infection with penicillin or
tetracycline; and muscle relaxants
* Vaccine available; booster needed every 10
years
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صفحه 23:
Clostridial Food Poisoning
٠ Clostridium botulinum - rare but
severe intoxication usually from
home canned food
٠ Clostridium perfringens - mild
intestinal illness; second most
common form of food poisoning
worldwide
صفحه 24:
Botulinum Food Poisoning
٠ Botulism - intoxication associated
with inadequate food preservation
* Clostridium botulinum - spore-
forming anaerobe; commonly
inhabits soil and water
صفحه 25:
Pathogenesis
Spores are present on food when gathered
and processed.
If reliable temperature and pressure are not
achieved air will be evacuated but spores
will remain.
Anaerobic conditions favor spore
germination and vegetative growth.
Potent toxin, botulin, is released.
Toxin is carried to neuromuscular junctions
and blocks the release of acetylcholine,
necessary for muscle contraction to occur.
Double or blurred vision, difficulty
swallowing, neuromuscular symptoms
صفحه 26:
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صفحه 27:
Infant and Wound
Botulism
Infant botulism - caused by
ingested spores that germinate
and release toxin; flaccid
paralysis
Wound botulism - spores enter
wound and cause food poisoning
symptoms
صفحه 28:
۱
* Determine presence of toxin in food,
intestinal contents or feces
¢ Administer antitoxin; cardiac and
respiratory support
¢ Infectious botulism treated with
penicillin
¢ Practice proper methods of
preserving and handling canned
foods; addition of preservatives.
صفحه 29:
Clostridial Gastroenteritis
* Clostrium perfringens
* Spores contaminate food that has not
been cooked thoroughly enough to
destroy spores.
* Spores germinate and multiply
(especially if unrefrigerated).
* When consumed, toxin is produced in
the intestine; acts on epithelial cells,
acute abdominal pain, diarrhea, and
nausea
* Rapid recovery
صفحه 30:
Gram-Positive Regular Non-
Spore-Forming Bacilli
Medically important:
° Listeria monocytogenes
٠ Erysipelothrix rhusiopathiae
صفحه 31:
Listeria monocytogenes
* Non-spore-forming Gram-positive
* Ranging from coccobacilli to long filaments
¢ 1-4 flagella
* No capsules
۰ Resistant to cold, heat, salt, pH extremes
and bile
* Virulence attributed to ability to replicate
in the cytoplasm of cells after inducing
phagocytosis; avoids humoral immune
system
صفحه 32:
2
8
صفحه 33:
Epidemiology and
Pathology
¢ Primary reservoir is soil and water;
animal intestines
* Can contaminate foods and grow during
refrigeration
* Listeriosis - most cases associated with
dairy products, poultry, and meat
* Often mild or subclinical in normal adults
* Immunocompromised patients, fetuses
and neonates; affects brain and meninges
- 20% death rate
33
صفحه 34:
Diagnosis and Control
* Culture requires lengthy cold
enrichment process.
* Rapid diagnostic tests using ELISA
available
¢ Ampicillin and
trimethoprimsulfamethoxazole
٠ Prevention - pasteurization and
cooking
صفحه 35:
Erysipelothrix
rhusiopathiae
¢ Gram-positive rod widely distributed in
animals and the environment
* Primary reservoir - tonsils of healthy
pigs
* Enters through skin abrasion, multiples
to produce erysipeloid, dark red lesions
* Penicillin or erythromycin
* Vaccine for pigs
صفحه 36:
Gram-Positive Irregular Non-
Spore-Forming Bacilli
Medically important genera:
* Corynebacterium
° Proprionibacterium
° Mycobacterium
¢ Actinomyces
° Nocardia
صفحه 37:
* Pleomorphic; stain unevenly
° 20 genera; Corynebacterium,
Mycobacterium, and Nocardia
greatest clinical significance
° All produce catalase, possess
mycolic acids, and a unique
peptidoglycan.
صفحه 38:
Corynbacterium
diptheriae
¢ Gram-positive irregular bacilli
¢ Virulence factors assist in
attachment and growth.
- diphtherotoxin - exotoxin
* 2 part toxin - part B binds and induces
endocytosis; part A arrests protein
synthesis
صفحه 39:
Granules
39
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Pleomorphism Palisades arrangement
‘© Gorge WicerViusls United
صفحه 40:
Epidemiology and
Pathology
¢ Reservoir of healthy carriers;
potential for diphtheria is always
present
* Most cases occur in non-immunized
children living in crowded, unsanitary
conditions.
¢ Acquired via respiratory droplets
from carriers or actively infected
individuals
صفحه 41:
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صفحه 42:
Epidemiology and
Pathology
2 stages of disease:
1. Local infection -upper respiratory tract
inflammation
- sore throat, nausea, vomiting, swollen lymph
nodes;
pseudomembrane formation can cause
asphyxiation
2. Diptherotoxin production and toxemia
- target organs primarily heart and nerves
42
صفحه 43:
Diagnostic Methods
¢ Pseudomembrane and swelling
indicative
¢ Stains
* Conditions, history
* Serological assay
صفحه 44:
320 اداع ادع ۱
¢ Antitoxin
¢ Penicillin or erythromycin
* Prevented by toxoid vaccine series
and boosters
صفحه 45:
Genus Proprionibacterium
¢ Propionibacterium acnes most
common
¢ Gram-positive rods
¢ Aerotolerant or anaerobic
¢ Nontoxigenic
* Common resident of sebaceous glands
* Causes acne
صفحه 46:
Mycobacteria: Acid-Fast
Bacilli
¢ Mycobacterium tuberculosis
° M. leprae
¢ M. avium complex
° M. fortuitum
¢ M. marinum
¢ M. scrofulaceum
¢ M. paratuberculosis
صفحه 47:
Genus Mycobacterium
¢ Gram-positive irregular bacilli
* Acid-fast staining
* Strict aerobes
* Produce catalase
¢ Possess mycolic acids and a unique type
of peptidoglycan
¢ Do not form capsules, flagella or spores
* Grow slowly
صفحه 48:
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صفحه 49:
Mycobacterium
tuberculosis
¢ Tubercle bacillus
¢ Produces no exotoxins or enzymes
that contribute to infectiousness
* Virulence factors - contain
complex waxes and cord factor
that prevent destruction by
lysosomes or macrophages
صفحه 50:
50
Epidemiology of
Tuberculosis
Predisposing factors include: inadequate
nutrition, debilitation of the immune system,
poor access to medical care, lung damage,
and genetics.
Estimate 1/3™ of world population and 15
million in U.S. carry tubercle bacillus;
highest rate in U.S. occurring in recent
immigrants
Bacillus very resistant; transmitted by
airborne respiratory droplets
صفحه 51:
Course of Infection and
Disease
* Only 5% infected people develop
clinical disease
* Untreated, the disease progresses
slowly; majority of TB cases
contained in lungs
* Clinical tuberculosis divided into:
- primary tuberculosis
- secondary tuberculosis (reactivation or
reinfection)
- disseminated tuberculosis
صفحه 52:
Primary TB
¢ Infectious dose 10 cells
* Phagocytosed by alveolar macrophages
and multiply intracellularly
¢ After 3-4 weeks immune system attacks,
forming tubercles, granulomas
consisting of a central core containing
bacilli surrounded by WBCs - tubercle
٠ 11 center of tubercle breaks down into
necrotic caseous lesions, they
gradually heal by calcification.
صفحه 53:
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صفحه 54:
Secondary TB
* If patient doesn’t recover from primary
tuberculosis, reactivation of bacilli can
occur.
* Tubercles expand and drain into the
bronchial tubes and upper respiratory tract.
* Gradually the patient experiences more
severe symptoms.
- violent coughing, greenish or bloody sputum,
fever, anorexia, weight loss, fatigue
* Untreated, 60% mortality rate
54
صفحه 55:
Extrapulmonary TB
* During secondary TB, bacilli
disseminate to regional lymph
nodes, kidneys, long bones, genital
tract, brain, and meninges.
¢ These complications are grave.
صفحه 56:
Diagnosis
1. In vivo or tuberculin testing
Mantoux test - local intradermal injection of
purified protein derivative (PPD); look for
red wheal to form in 48-72 hours-
induration; established guidelines to
indicate interpretation of result based on
size of wheal and specific population factors
2. X rays
3. Direct identification of acid-fast bacilli
in specimen
4. Cultural isolation and biochemical
testing
56
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صفحه 58:
Management and Prevention
of TB
° 6-24 months of at least 2 drugs
from a list of 11
* One pill regimen called Rifater
(isoniazid, rifampin, pyrazinamide)
* Vaccine based on attenuated
bacilli Calmet-Guerin strain of M.
bovis used in other countries
صفحه 59:
Mycobacterium leprae: The
Leprosy Bacillus
Hansen’s bacillus/Hansen’s Disease
Strict parasite - has not been grown on
artificial media or tissue culture
Slowest growing of all species
Multiplies within host cells in large
packets called globi
Causes leprosy, a chronic disease that
begins in the skin and mucous
membranes and progresses into nerves
صفحه 60:
Epidemiology and
Transmission of Leprosy
* Endemic regions throughout the world
* Spread through direct inoculation from
leprotics
* Not highly virulent; appears that health
and living conditions influence
susceptibility and the course of the
disease
* May be associated with specific genetic
marker
صفحه 61:
61
Course of Infection and
Disease
* Macrophages phagocytize the bacilli, but a
weakened macrophage or slow T cell
response may not kill bacillus.
* Incubation from 2-5 years; if untreated,
bacilli grow slowly in the skin macrophages
and Schwann cells of peripheral nerves
¢ 2 forms possible:
- tuberculoid - superficial infection without skin
disfigurement which damages nerves and
causes loss of pain perception
- lepromatous - a deeply nodular infection that
causes severe disfigurement of the face and
extremities
صفحه 62:
Diagnosing
* Combination of symptomology,
microscopic examination of lesions, and
patient history
* Numbness in hands and feet, loss of heat
and cold sensitivity, muscle weakness,
thickened earlobes, chronic stuffy nose
* Detection of acid-fast bacilli in skin lesions,
nasal discharges, and tissue samples
62
صفحه 63:
Treatment and Prevention
¢ Treatment by long-term combined
therapy
¢ Prevention requires constant
surveillance of high risk
populations.
¢ WHO sponsoring a trial vaccine
صفحه 64:
Infections by Non-
Tuberculosis Mycobacteria
(NTM)
¢ M. avium complex - third most common cause
of death in AIDS patients
۰ ۸ kansaii - pulmonary infections in adult
white males with emphysema or bronchitis
¢ M. marinum - water inhabitant; lesions
develop after scraping on swimming pool
concrete
° M. scrofulaceum - infects cervical lymph nodes
* M. paratuberculosis - raw cow’s milk;
recovered from 65% of individuals diagnosed
with Crohn’s disease
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صفحه 65:
Actinomycetes: Filamentous
Bacilli
Genera Actinomyces & Nocardia are
nonmotile filamentous bacteria related
to mycobacteria.
May cause chronic infection of skin and
soft tissues
Actinomyces israelii - responsible for
diseases of the oral cavity, thoracic or
intestines - actinomycoses
Nocardia brasiliensis causes pulmonary
disease similar to TB.