Download Gram Positive Infections

Gram Positive Pyogenic Cocci
(Streptococcus, staphylococcus,
Pneumococcus)
Yewande Dayo
Student Pharmacist
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Objectives
Upon completion of this section, students should be able
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Describe characteristics of different gram-positive bacteria
Differentiate between different bacteria based on unique
features and characteristics
Describe pathogenic characteristics of different gram-positive
bacteria
Identify infections caused by different gram-positive bacteria
General Characteristics of Staphyloccoci
They grow characteristically in irregular groups like clusters of
grapes.
They are facultative anaerobic, nonmotile, non-spore forming,
and catalase test positive.
Common inhabitant of the skin and mucous membranes
Lack flagella
May have capsules
31 species
3 major pathogens in this genus: S. aureus, S. epidermidis, and S.
saprophyticus.
S. aureus is the only coagulase-positive species.
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Staphylococcal Infections
There are three clinically relevant members of the
staphyloccocal bacteria species
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S. aureus
S. epidermidis
S. saprophyticus
Unique Characteristics of S. aureus
• It is -hemolytic on blood agar
plates.
• Its cell wall has a unique
protein A.
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Sources and Routes of Infection
Carriage
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nasal carriage: 35% of normal adult
skin carriage: 10-20% of normal person
Air-borne dissemination
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from droplet of respiratory tract
from desquamated skin scales
Disseminated by contact
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Virulence factors of S. aureus
Enzymes:
 Coagulase – coagulates plasma and blood; produced by
97% of human isolates; diagnostic
 Hyaluronidase – digests connective tissue
 Staphylokinase – digests blood clots
 DNase – digests DNA
 Lipases – digest oils; enhances colonization on skin
 Penicillinase – inactivates penicillin
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Virulence factors of S. aureus
Toxins:
 Hemolysins (α, β, γ, δ) – lyse red blood cells
 Leukocidin – lyses neutrophils and macrophages
 Enterotoxin – induce gastrointestinal distress
 Exfoliative toxin – separates the epidermis from the
dermis
 Toxic shock syndrome toxin (TSST) - induces fever,
vomiting, shock, systemic organ damage
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Local (Skin) Pathologic Effect
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Folliculitis, acne, stye, paronychia
Furuncle, carbuncle
Bullous impetigo
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Disseminated Pathologic Effect
Bacteremia: Osteomyelitis,
endocarditis, arthritis,
cerebral, pulmonary and
renal abscess.
 Toxemia:
1. Scalded skin syndrome.
2. Staphylococcal toxic
shock syndrome
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Toxemia
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Staphylococcal scalded skin syndrome
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Bullous Impetigo
Ritter's disease
Staphylococcal Toxic Shock Syndrome
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Menstrual TSS (TSST 1)
Non-menstrual TSS (TSST-1, enterotoxins)
Treatment: aggressive fluid replacement with saline and
intravenous administration of oxacillin or nafcillin, 8-10 g/day.
Coagulase-negative staphylococci (CONS)
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They are opportunistic or nosocomial pathogens.
Infections by CONS are always associated predisposing
factors such as immunosuppression, surgery, and
indwelling devices.
S. epidermidis is the organism most frequently associated
with CONS endocarditis, wound infections, and urinary
tract infections in elderly hospitalized men.
S. saprophyticus is an agent for the primary urinary tract
infection in women.
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Identification of Staphylococcus in Samples
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Frequently isolated from pus, tissue exudates, sputum,
urine, and blood
Cultivation, catalase, biochemical testing, coagulase
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Comparison between S. aureus and S.
epidermidis
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Coagulase assay
Hemolysis
Growth on mannitol salt plate
Treatment for Staphylococcal Diseases
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Simple drainage of abscess usually suffices for superficial
lesion.
Deep-infections require intensive prolonged
chemotherapy.
Most clinical isolates are penicillin resistant.
In acute and serious staphylococcal infection,
cephalosporin or vancomycin are usually used in therapy.
Systemic infections require intensive lengthy therapy.
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Emergening Problems of S. aureus infections
(Antibiotic Resistant S. aureus)
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Penicillin-resistant S. aureus (PRSA). Resistance is due to
the production of plasmid encoded -lactamase.
Penicillinase-resistant -lactam cephalosporin was used.
Methicillin-resistant S. aureus (MRSA). Some of these
strains further develop resistance to cephalosporin due
to expression of unusual chromosomal encoded PBP
which is peptidoglycan transpeptidase and has a lowaffinity for -lactam antibiotics.
Vancomycin-resistant S. aureus (VRSA).
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Prevention of Staphylococcal
Infections
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Universal precautions by healthcare providers to prevent
nosocomial infections
Hygiene and cleansing
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General Characteristics of Streptococci
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Gram-positive spherical/ovoid cocci arranged in long
chains; commonly in pairs
Non-spore-forming, nonmotile
Can form capsules and slime layers
Facultative anaerobes
Do not form catalase, but have a peroxidase system
Most parasitic forms are fastidious and require enriched
media.
Small, nonpigmented colonies
Sensitive to drying, heat and disinfectants
25 species
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Streptococci
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Lancefield classification system based on cell wall Ag – 17
groups (A,B,C,….)
Another classification system is based on hemolysis
reactions.
β-hemolysis – A,B,C,G and some D strains
α-hemolysis – S. pneumoniae and others collectively
called viridans
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Human Streptococcal Pathogens
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S. pyogenes
S. agalactiae
Viridans streptococci
S. pneumoniae
Enterococcus faecalis
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β-hemolytic S. pyogenes
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Most serious streptococcal pathogen
Strict parasite
Inhabits throat, naso-pharynx, occasionally skin
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Virulence Factors of β-hemolytic
S. pyogenes
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Produces surface antigens:
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C-carbohydrates – protect against lysozyme
Fimbriae - adherence
M-protein – contributes to resistance to phagocytosis
Hyaluronic acid capsule – provokes no immune response
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Virulence Factors of β-hemolytic
S. pyogenes
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Extracellular toxins:
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streptolysins – hemolysins; streptolysin O (SLO) and
streptolysin S (SLS) – both cause cell and tissue injury
pyogenic toxin (erythrogenic) – induces fever and typical red
rash
superantigens – strong monocyte and lymphocyte stimulants;
cause the release of tissue necrotic factor
Virulence Factors of b-hemolytic
S. pyogenes
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Extracellular enzymes
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streptokinase – digests fibrin clots
hyaluronidase – breaks down connective tissue
DNase – hydrolyzes DNA
Epidemiology and Pathogenesis
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Humans only reservoir
Inapparent carriers
Transmission – contact, droplets, food, fomites
Portal of entry generally skin or pharynx
Children predominant group affected for cutaneous and
throat infections
Systemic infections and progressive sequelae possible if
untreated
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Scope of Clinical Disease
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Skin infections
Impetigo (pyoderma) – superficial lesions that break and
form highly contagious crust; often occurs in epidemics in
school children; also associated with insect bites, poor
hygiene, and crowded living conditions
Erysipelas – pathogen enters through a break in the skin
and eventually spreads to the dermis and subcutaneous
tissues; can remain superficial or become systemic
Throat infections
Streptococcal pharyngitis – strep throat
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Scope of Clinical Disease
Systemic infections
 Scarlet fever
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strain of S. pyogenes carrying a prophage that codes for
pyrogenic toxin; can lead to sequelae
Septicemia
Pneumonia
Streptococcal toxic shock syndrome
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Long-Term Complications of Group A
Infections
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Rheumatic fever
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Follows overt or subclinical pharyngitis in children; carditis with
extensive valve damage possible, arthritis, chorea, fever
Acute glomerulonephritis
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Nephritis, increased blood pressure, occasionally heart failure;
can become chronic leading to kidney failure
Group B: Streptococcus agalactiae
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Regularly resides in human vagina, pharynx and large
intestine
Can be transferred to infant during delivery and cause
severe infection
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most prevalent cause of neonatal pneumonia, sepsis, and
meningitis
15,000 infections and 5,000 deaths in US
Pregnant women should be screened and treated.
Wound and skin infections and endocarditis in debilitated
people
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Group D Enterococci and Groups C and G
Streptococci
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Group D:
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Enterococcus faecalis, E. faecium, E. durans
normal colonists of human large intestine
cause opportunistic urinary, wound, and skin infections,
particularly in debilitated persons
Groups C and G:
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common animal flora, frequently isolated from upper
respiratory; pharyngitis, glomerulonephritis, bacteremia
Identification
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Cultivation and diagnosis ensure proper treatment to
prevent possible complications.
Rapid diagnostic tests based on monoclonal antibodies
that react with C-carbohydrates
Culture using bacitracin disc test, CAMP test
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Treatment and Prevention
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Groups A and B are treated with penicillin.
Sensitivity testing needed for enterococci
No vaccines available
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α-Hemolytic Streptococci:
Viridans Group
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Large complex group
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Streptococcus mutans, S. oralis, S. salivarus,
S. sanguis, S. milleri, S. mitis
Most numerous and widespread residents of the gums
and teeth, oral cavity and also found in nasopharynx,
genital tract, skin
Not very invasive; dental or surgical procedures facilitate
entrance
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Viridans Group
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Bacteremia, meningitis, abdominal infection, tooth
abscesses
Most serious infection – subacute endocarditis – bloodborne bacteria settle and grow on heart
lining or valves
Persons with preexisting heart disease are at high risk.
Colonization of heart by forming biofilms
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Viridans Group
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S. mutans produce slime layers that adhere to teeth, basis
for plaque.
Involved in dental caries
Persons with preexisting heart conditions should receive
prophylactic antibiotics before surgery or dental
procedures.
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Streptococcus pneumoniae: The
Pneumococcus
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Causes 60-70% of all bacterial pneumonias
Small, lancet-shaped cells arranged in pairs and short
chains
Culture requires blood or chocolate agar.
Growth improved by 5-10% CO2
Lack catalase and peroxidases
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cultures die in O2
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S. pneumoniae
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All pathogenic strains form large capsules – major
virulence factor.
Specific soluble substance (SSS) varies among types.
84 capsular types have been identified
Causes pneumonia and otitis media
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Epidemiology and Pathology
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5-50% of all people carry it as normal flora in the
nasopharynx; infections are usually endogenous.
Very delicate, does not survive long outside of its habitat
Young children, elderly, immune compromised, those with
other lung diseases or viral infections, persons living in
close quarters are predisposed to pneumonia
Pneumonia occurs when cells are aspirated into the lungs
of susceptible individuals.
Pneumococci multiply and induce an overwhelming
inflammatory response.
Gains access to middle ear by way of eustachian tube
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Cultivation and Diagnosis
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Gram stain of specimen – presumptive identification
α -hemolytic; optochin sensitivity
Quellung test or capsular swelling reaction
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Treatment and Prevention
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Traditionally treated with penicillin G or V
Increased drug resistance
Two vaccines available for high risk individuals:
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capsular antigen vaccine for older adults and other high risk
individuals-effective 5 years
conjugate vaccine for children 2 to 23 months
The Genus Clostridium
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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
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Clostridium perfringens most frequent clostridia involved
in soft tissue and wound infections
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myonecrosis
Spores found in soil, human skin, intestine, and vagina
Predisposing factors – surgical incisions, compound
fractures, diabetic ulcers, septic abortions, puncture
wounds, gunshot wounds
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Virulence Factors
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Virulence factors
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toxins –
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α-toxin – causes RBC rupture, edema and tissue destruction
collagenase
hyaluronidase
DNase
Pathology
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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.
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Treatment and Prevention
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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
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Clostridium difficile-Associated Disease
(CDAD)
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Normal resident of colon, in low numbers
Causes antibiotic-associated colitis
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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
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Treatment and Prevention
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Mild uncomplicated cases respond to fluid and electrolyte
replacement and withdrawal of antimicrobials.
Severe infections treated with oral vancomycin or
metronidazole and replacement cultures
Increased precautions to prevent spread
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Tetanus
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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
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Pathology
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Spores usually enter through accidental puncture wounds,
burns, umbilical stumps, frostbite, and crushed body parts.
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
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Treatment and Prevention
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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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Clostridial Food Poisoning
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Clostridium botulinum
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Rare but severe intoxication usually from home canned food
Clostridium perfringens
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Mild intestinal illness; second most common form of food
poisoning worldwide
Botulinum Food Poisoning
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Botulism
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Intoxication associated with inadequate food preservation
Clostridium botulinum
Spore-forming anaerobe; commonly inhabits soil and water
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Pathogenesis
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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
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Infant and Wound Botulism
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Infant botulism
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Caused by ingested spores that germinate and release toxin;
flaccid paralysis
Wound botulism
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Spores enter wound and cause food poisoning symptoms
Treatment and Prevention
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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.
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Clostridial Gastroenteritis
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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
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