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ID Week 3 > ICL 2.6 & 2.7: Bacillus & Clostridum > Flashcards

ICL 2.6 & 2.7: Bacillus & Clostridum Flashcards

1
Q

what’s the microbiology of bacillaceae family?

A

cocci and bacillus

they span a wide range of aerobic and anaerobic metabolic requirements

gram (+) and (-)

clearly there’s alot of variety so the reason that they’re lumped together is because they can make endospores!!

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2
Q

how toxic are bacillaceae family bacteria?

A

highly toxic

noninvasive

tons of damage from icrobial products

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3
Q

what are the two clinically important genera of bacillaceae?

A
  1. bacillus

2. clostridium

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4
Q

what is the microbiology of the bacillus genus?

A

bacillaceae family

gram (+) spore forming bacillus

strict aerobic and facultative anaerobic spore-former

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5
Q

what is the microbiology of the clostridium genus?

A

bacillaceae family

gram (+) spore forming bacillus

strict anaerobe spore-former

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6
Q

what does facultative anaerobe mean?

A

facultative anaerobes means they will go anaerobic because it’s more efficienct but if they run out of oxygen they can become anaerobic

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7
Q

what are the major species and respective diseases caused by the bacillaceae family?

A
  1. bacillus anthracis –> anthrax
  2. bacillus cereus –> food poisoning and eye infection
  3. clostridium botulinum –> botulism
  4. clostridium tetani –> tetanus
  5. clostridium perfringens –> gas gangrene and gastrointestinal toxicity (common)
  6. clostridium difficile –> gastrointestinal infections (more common)
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8
Q

which bacillaceae family bacteria has an FDA vaccine?

A

clostridium tetani

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9
Q

what are the general characteristics of the bacillaceae family?

A
  1. organisms are ubiquitous in soil
  2. can grow very rapidly in tissues under appropriate conditions
  3. produce a wide variety of extremely potent toxins
  4. can produce endospores
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10
Q

where are bacillaceae found?

A

in the soil everywhere

also since they can produce endospores, it means they can survive for long periods of time and resist extreme conditions

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11
Q

how are endospores formed?

A

endospores are dormant cells and they’re formed by vegetative cells in response to environmental signals that indicate a limiting factor for vegetative growth

they’re a dormant, tough, and non-reproductive structure produced by some bacteria

  1. DNA is replicated and condenses
  2. spore septum forms
  3. dehydration & formation of coat layers
  4. vegetative cell disintegrates and spore released

although cryptobiotic, they retain viability indefinitely

under appropriate conditions they germinate to form a vegetative cell

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12
Q

what are the parts of an endospore?

A
  1. spore core
  2. cortex
  3. coat
  4. exposporium
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13
Q

what does the endospore core contain?

A
  1. genome
  2. minimal set of proteins
  3. large amounts of Ca+2
  4. dipicolinic acid
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14
Q

what is the endospore coat?

A

part of the endosome

the coat consists mainly of highly crosslinked proteins

it acts to exclude toxic matter

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15
Q

what is the exosporium?

A

it’s part of the endospore but it’s only present in some endospores

it’s present in bacillus anthracis

it’s made of polysaccharides, lipid structures and proteins

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16
Q

what is the endospore cortex?

A

it’s part of the endospore

it resembled peptidoglycan and is different from vegetative cells

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17
Q

how long do spores survive in the environment?

A

endospores are the most durable cells produced in nature

millions of years old!

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18
Q

how do we inactivate spores?

A

incineration will kill everything (>500 C)

also autoclave/pressure cooker will kill all forms of life including endospores

boiling doesn’t kill endospores

intermittent boiling does kill endospores though

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19
Q

what are binary toxins?

A

there are two discrete proteins that have to be combined to elicit toxicity in bacillaceae family

many bacterial binary toxins initially engage cells as an intact “A-B” structure composed of single- or multiple-chain proteins

the “B” oligomers are generated only after proteolysis of “B” precursor molecules

the B complex then acts as a docking platform that helps translocates the enzymatic “A” component(s) into the cytosol via acidified endosomes

once A component is inside the cytosol it can inhibit normal cell functions through different mechanisms

so B component gives you specificity and tells you which cells it can bind do and then the A component is the toxic part that once it’s inside the cytosol will kill cells

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20
Q

how does the A component of a binary toxin inhibit normal cell functions?

A

binary toxins are produced by the bacillaceae family

A components from this binary family can inhibit normal cell functions by one or more of the following mechanisms:

  1. mono-ADP-ribosylation of G-actin –> cytoskeletal disarray and cell death
  2. proteolysis of mitogen-activated protein kinase kinases (MAPKK), which inhibits cell signaling (particularly in immune cells)
  3. increasing intracellular levels of cyclic AMP (cAMP) that result in edema and immunosuppression
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21
Q

how is anthrax toxin different from most A-B binary toxins in the bacillaceae family?

A

the A and B moieties interact only after being secreted from the bacteria

the toxin has two A moieties (EF and LF) that enter the cell via a single B moiety – so the toxin is actually 3 parts!

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22
Q

how does the anthrax toxin work?

A
  1. B component = protective antigen (PA) binds to a receptor and is cleaved by protease
  2. cleavage product (PA63) self-associates to form the heptameric prepore

under the influence of low pH the prepore converts to a pore and EF and LF are translocated to the cytosol

  1. then up to 3 molecules of edema factor (EF) and/or lethal factor (LF) bind to the prepore = A components
  2. then the complex is endocytosed and trafficked to an acidic intracellular compartment
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23
Q

what does EF do?

A

it’s one of the A components of the anthrax toxin

EF catalyzes formation of cAMP which:

  1. leads to edema
  2. inhibits phagocyte function
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24
Q

what does LF do?

A

it’s one of the A components of the anthrax toxin

LF proteolytically inactivates MAPKK’s which:

  1. leads to death of host cell
  2. believed suppress host innate immune cells
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25
Q

what would the clinical presentation of an anthrax infection be?

A

black necrotic lesion on her left cheek and periorbital edema

was fine till 15 days before when we noticed a small, painless, pruritic papule on her face that quickly enlarged & developed central vesicle

the vesicle burst, leaving a painless necrotic ulcer with a black, depressed eschar

extensive edema of the eyelids developed and progressed over a period of 7 days

at presentation, she was afebrile with no lymphadenopathy

patient was from a northern Iranian village where exposure to contaminated soil and livestock products is common

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26
Q

how would you treat anthrax infection?

A

IV penicillin G was administered

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27
Q

is B. anthracis anaerobic or aerobic?

A

facultative anaerobe

prefers oxygen but in a bind can go anaerobic

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28
Q

what does B. anthracis look like?

A

cells have characteristic squared ends

may grow singly or paired in clinical samples

grow in chains in culture

endospores are ellipsoidal shaped and located centrally in the sporangium –> they’re produced under limiting conditions so they’re not usually seen in clinical specimens

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29
Q

what does the capsule of b. anthracis made of?

A

polypeptides!

most capsules are usually polysaccharides = carbohydrates that make the bug look boring so that the immune system ignores it

but with B. anthracis it’s a polypeptide capsule!!

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30
Q

who usually gets anthrax infections?

A

anthrax is primarily a disease of herbivores = cattle and sheep

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31
Q

how can anthrax be transmitted?

A
  1. inoculation/cutaneous
  2. ingestion
  3. inhalation
  4. injection
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32
Q

how can anthrax be transmitted cutaneously?

A

95% of human cases are cutaneous!

spores are introduced through exposed skin
from contaminated soil or infected animal products

it starts with the development of a painless papule at the inoculation site that progresses to an ulcer surrounded by vesicles, and eventually a necrotic eschar*

mortality rate in untreated patients is < 20% (bad if goes systemic)

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33
Q

how can anthrax be transmitted by ingestion?

A

most common in livestock (rare, but deadly in humans)

symptoms correlate with the site of infection = lymphadenopathy and sepsis

Mortality is believed to be 25-60%; may be higher in untreated patients

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34
Q

how can anthrax be transmitted by inhalation?

A

this is the most virulent form!

aka Wool-sorters’ disease

spores are inhaled into the lungs where they infect lung APC’ and travels to lymphatics (not true pneumonia*!)

alveolar macrophages ingest and migrate to mediastinal lymph node, where germinate & grow

bacteria eventually escape macrophages and lymphatics to enter the circulation (septicemia)

this causes edema, sepsis and rapid death; almost all patients progress to shock and death within 36-72h of initial symptoms

untreated patients have 85-97% mortality while treated have 75% mortality

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35
Q

what is the hallmark of an inhalation anthrax infection?

A

enlargement of mediastinal lymph node

CXR shows widened mediastinum

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36
Q

how big is the infectious dose of B. anthracis?

A

super low…

the LD50 for humans was estimated to be 8000-40,000 spores = 1 breath

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37
Q

what is the function of the anthrax capsule? what are its characteristics?

A

there’s a unique polypeptide capsule made of nontoxic poly D-glutamic acid

it protects bacteria against:

  1. antibacterial serum components
  2. phagocytosis
  3. phagocyte killing mechanisms
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38
Q

what are the anthrax toxins?

A
  1. PA = protective antigen
  2. EF = edema factor
  3. LF = lethal factor

you need all 3 toxins to get edema, necrosis, and lethality seen in anthrax

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39
Q

how do you diagnose anthrax infection?

A
  1. microscopic examination of papules, ulcers, blood or CSF
    - presence of characteristic lesions
    - large gram (+) bacilli without endospores (after culture, can see chain growth and endospores)
    - confirm presence of polypeptide capsule
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40
Q

can anthrax be grown in the lab?

A

yup

it’s readily grown on most nonselective laboratory medium

no hemolysis

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41
Q

how do you treat anthrax infections?

A

antibiotic therapy should be initiated as soon as possible after exposure

  1. ciprofloxacin
  2. doxycycline
  3. amoxicillin

Anthrasil is used to treat inhalational anthrax in combination with the above antibiotics

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42
Q

are there anthrax vaccines?

A

yes

it’s derived from sterile culture supernatant from an attenuated non-capsule strain

therefore, the vaccine does not contain live or dead organisms

only recomended for high risk people or after exposure

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43
Q

FLASHCARD: microbiology, pathology, epidemiology, clinical symptoms, diagnosis and treatment of bacillus anthracis

A

MICROBIOLOGY: Gram + rods, facultative anaerobe, spore-forming, polypeptide capsule, non-motile

PATHOLOGY: Grow in local tissue, and either travel inside macrophages to tissues/organs or disseminate into bloodstream to cause sepsis. Disease is caused by binary toxin that suppresses immune system (lethal factor) and elicits edema (edema factor). Capsule allows persistence in macrophages and tissues.

EPIDEMIOLOGY: Free-living or persist as endospores for extremely long periods. Found in soils or associated with animal skin and other products. Can acquire by skin cuts, ingestion, or inhalation (most severe). High risk are veterinarians, farmers, handlers of animal products. Also a Tier 1 select agent, due to high mortality via aerosol exposure.

CLINICAL: In skin, forms pimple, then pustule, then necrotic lesion (eschar) with extreme edema. If remains localized, no severe effects if treated. If disseminate from cutaneous or inhaled, are taken up by macrophages, then migrate to lymphatics (e.g. mediastinal widening in lungs) and into bloodstream; not pneumonia. Develop bacteremia, sepsis, and even meningitis, all which can rapidly progress from fever and myalgia to death within 24-48 hours.

DIAGNOSIS: Highly infectious, so handle with BSL3 technique. Easily cultured on most media from abscess, CSF, or blood. String-of-pearl appearance if producing capsule. May see endospore in Gram stain, but not dependable.

TREATMENT: If treat before symptoms, then readily cured. Treatment after severe symptoms has 40-90% mortality rate, so treat quickly based on epidemiology. Treat cutaneous as outpatient. Can use ciprofloxacin (quinolone), doxycycline, or amoxicillin

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44
Q

is bacillus cereus aerobic or anaerobic?

A

ubiquitous motile spore-former that can grow aerobic or anaerobic

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45
Q

where is bacillus cereus found?

A

spores are everywhere, but cause different diseases depending on environment

Grows well under a range of environmental conditions

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46
Q

what 2 types of common food-borne intoxications does B. cereus cause?

A
  1. short-incubation or emetic-toxin form

2. long-incubation or diarrheal form

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47
Q

what is the short incubation form of B. cereus?

A

aka emetic-toxin form

caused by a plasmid-encoded preformed heat-stable enterotoxin (cereulide; 5 kD)

characterized by nausea, vomiting and abdominal cramps

Often associated with rice, milk, or pasta contaminated with B. cereus

it resembles Staphylococcus aureus food poisoning in its symptoms and incubation period (1 to 6 hours)

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48
Q

what is the long incubation form of B. cereus?

A

aka diarrheal form

mediated by a heat-labile enterotoxin (50 kD) produced by vegetative cells after spores germinate in small intestine

manifested primarily by abdominal cramps and diarrhea

resembles food poisoning caused by Clostridium perfringens

incubation period of 8 to 16 hours

Toxin stimulates the adenylate cyclase-cAMP cycle in intestinal epithelium

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49
Q

how long do B. cereus infections last?

A

B. cereus causes two types of common food-borne intoxications

in either type of food-borne intoxications, illness usually lasts <24 hours after onset and antibiotics are not useful (or prescribed)

so it’s self limiting and your normal flora will take care of it so you don’t give antibiotics you just ride it out

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50
Q

when is the only case that you should be worried about a B. cereus infection?

A

when it causes a food-borne illness it’s self limiting and goes away on its own without antibiotics

but it can cause ocular infection following either trauma to eye or endogenous seeding from distant site

it’s one of the most destructive organisms to infect the eye and you can get complete loss of sight within 48 hours!!!

so in this case you have to administer antibiotics really quickly

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51
Q

which toxins are implicated in B. cereus eye infections?

A
  1. necrotic toxin

heat-labile enterotoxin

  1. cereolysin

hemolysin

  1. phospholipase C

lecithinase that attacks phospholipids in retinal tissue

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52
Q

what other bacillaceae bacteria can cause eye infections other than B. cereus?

A

bacillus thuringiensis

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53
Q

deletion of which virulence factor by itself would have the largest effect on development of anthrax pathology?

A

PA = protective antigen

without PA, the other toxins can’t get into the cell to do damage

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54
Q

what are the clinical presentations of clostridium botulinum?

A

6-month-old male who presented with a 3-day history of increasing hypotonia and a 1-day history of dehydration

decreased suck while breast-feeding

generalized weakness with decreased movement and difficulty sitting up

trouble with gurgling in the back of his throat, very poor head control, and increased floppiness

4 weeks constipation

increasing respiratory difficulty

55
Q

what is the microbiology of clostridium botulinum?

A

fastidious anaerobic bacteria = picky, don’t want oxygen

56
Q

where is clostridium botulinum found?

A

commonly isolated in soil and water worldwide

animals can carry in GI tract

57
Q

how many types of clostridium botulinum are there?

A

seven toxigenic types of the organism exist (A-G)

each produces an immunologically distinct form of botulinum toxin

most strains produce a single toxin

A, B, E, F, and G are associated with human disease

Type A causes >60% of U.S. cases

58
Q

what type of toxin is the botulinum toxin?

A

A-B type toxin

it’s synthesized as a single chain (150 kDa) and cleaved to form the dichain molecule with a disulfide bridge

light chain/A component acts as a zinc endopeptidase and is the most potent known toxin in the world

the heavy chain provides cholinergic specificy and binding of the toxin to presynaptic receptors

it also promotes light chain translocation across the endosomal membrane

59
Q

what does the botulinum toxin do?

A

unlike anthrax toxin that can act on most cells, botulinum is more cell specific

it binds to receptors on surface of presynaptic nerves and is then endocytosed

the A chain is released and it enzymatically cleaves the polypeptides that are essential for release of the acetylcholine (ACh) stored near the presynaptic cleft

the resulting ACh blockade causes flaccid paralysis

disrupting neurotransmission at cholinergic junctions in the autonomic nervous system can also cause various forms of autonomic dysfunction

the most life-threatening potential is disruption of neurotransmission in diaphragm and intercostal muscles

60
Q

what are the steps in the botulinum toxin MOA?

A
  1. BoNT-A binds to receptor and is endocytosed
  2. light chain released into motor terminal
  3. light chain cleaves synaptobrevin, SNAP-25 and VAMP
  4. synaptic fusion complex doesn’t form

ACh release is blocked

61
Q

what are the different types of botulism poisoning?

A
  1. wound botulism
  2. infant botulism
  3. food-borne botulism
  4. ihalation botulism
  5. iatrogenic botulism
62
Q

what is wound botulism?

A

used to be very rare

it’s when the toxin produced by C. botulinum bacteria in an infected wound

recently seen most often among iv drug abusers

63
Q

what is infant botulism?

A

toxin produced when C. botulinum spores germinate in intestine

it differs from food-borne botulism in that the toxin is not ingested though

instead, what happens is that C. botulinum spores are swallowed by the infant, germinate and produce the toxin in the favorable environment of the baby’s large intestine

the spores are nearly everywhere in the environment, children and adults regularly ingest them, yet very rarely suffer ill effects

but infants’ “incompletely-developed intestinal flora” is believed to allow the bacteria to thrive and produce toxin

it usually happens around the time of weaning because you’re introducing spore-containing food before the normal flora is fully developed

this is the most common form of the disease, but very, very rare in adults

64
Q

what is food-borne botulism?

A

person ingests the toxin itself by eating contaminated food

it happens following ingestion of toxin produced in food by C. botulinum

it is the most avoidable form of botulism

65
Q

what is inhalation botulism?

A

Associated with bioterrorist release of purified toxin as aerosol

toxin is considered a select agent

66
Q

what is iatrogenic botulism?

A

occurs from accidental overdose of botulinum toxin

aka botox treatments!

67
Q

how old are kids usually that get infant botulism?

A

under 6 months

68
Q

what is the first sign that an infant has botulism?

A

constipation (even though it’s not always apparent)

recognizable signs are lethargy & poor feeding because paralysis begins to affect the baby’s gag reflex and swallowing ability

there’s also dilated pupils because they’re relaxed muscles

69
Q

which food is linked to infant botulism?

A

honey!!

honey is literally filled with spores so don’t give your babies honey before 1 year

70
Q

how do you treat infant botulism?

A

antibiotics are not recommended for infant cases!!

they don’t work and they may even lyse the bacteria, causing increased toxin release

instead, antitoxin can be effective if administered early

71
Q

what is the most frequent cause of food botulism?

A

most frequent source is home-canned foods

unkilled spores germinate, leading to growth and toxin production

canned food are anaerobic because canning removes all the oxygen so the spores are very happy! so if you didn’t boil the food long enough before canning then you’ll probably get botulism

72
Q

what is the incubation period of food botulism?

A

symptoms begin within 6 h to 2 weeks after eating toxin-containing food

but it’s usually between 12 and 36 hours

73
Q

what are the symptoms of food botulism?

A
  1. double vision
  2. blurred vision
  3. drooping eyelids
  4. slurred speech
  5. difficulty swallowing
  6. dry mouth
  7. muscle weakness that always descends through the body

first shoulders are affected, then upper arms, lower arms, thighs, calves, etc.

paralysis of breathing muscles can cause a person to stop breathing and die, unless assistance with breathing (mechanical ventilation) is provided

74
Q

how do you diagnose food botulism?

A

botulism should be considered when three or more of the “Dozen D’s” are present

dry mouth, diplopia, dialted pupils, droopy eyelids, droopy face, diminshed gag reflex, dysphagia, dysarthria, dysphonia, difficulty lifting head, descending paralysis, dyspnea

75
Q

how do you treat botulism?

A

primary therapy is supportive care with mechanically-assisted ventilation – required for 2-8 weeks for most patients and up to 7 month in some cases

antibiotic treatment has little/no effect if ingest toxin

for food-borne cases, may administer treatment to induce vomiting or bowel movement to clear remaining toxin

there is is an FDA-approved human-derived antitoxin for infant botulism

76
Q

how long does recovery from botulism infection take?

A

recovery of function after botulism requires regeneration of the nerve endings

can take months and often need therapy to improve speech, swallowing, etc.

77
Q

how do you diagnose botulism?

A

diagnosis is based on physical signs, history, & detection of toxin in stool/vomit

stool test may take days and is only confirmatory;

tests are only 60% effective

78
Q

how do you prevent botulism infections?

A

proper food handling is best prevention

taste and smell will not give away the presence of C. botulinum or the toxin

79
Q

what factors favor spore germination?

A
  1. neutral or lacking acidity (pH > 5.0);
  2. low O2
  3. high water content

so add vinegar or other acid when preserving food (final pH<4.6) to prevent toxin production!

persons should avoid eating beached marine mammal carcasses and boil raw or fermented Alaska Native dishes >10 minutes before eating to inactivate botulinum toxin.”

80
Q

which bacterial toxin is used as a medicine?

A

botulism!

hello, botox!

blocks release of ACh which would otherwise signal the muscle to contract

81
Q

what is the botulism toxin used for medicall nowdays?

A

Eye muscle disorders

Head and neck muscle disorders

Elbow, wrist, and finger muscle stiffness/spasticity

Lower and upper limb spasticity

Excessive sweating

Eyebrow furrows (frown lines), forehead lines

Overactive bladder

Migrane headaches

Botox had worldwide sales of $3.8 billion in 2017

82
Q

FLASHCARD: microbiology, pathology, epidemiology, clinical symptoms, diagnosis and treatment of clostridium botulinum

A

MICROBIOLOGY: Gram + rods, strict anaerobic, spore-forming

PATHOLOGY: All symptoms are due to the effects of a binary toxin (botulinum toxin; Botox) that block the ability of acetylcholine to be released across the nerve synapse. Loss of nerve signaling causes localized paralysis. Larger quantities extends to additional nerves, causing loss of any muscle-based motor function blocked by toxin activity, which can eventually inhibit breathing.

EPIDEMIOLOGY: Free-living (anaerobic) or persist as endospores for extremely long periods. Found in soils and harvested produce. Most often acquire by ingest toxin-containing food (adult botulism) or ingest bacteria/spores in food (infant botulism) that produce toxin in gut. High risk are infants starting food intake (weaning), and ingestion of canned or fermented foods that have not been heated to inactivate the toxin. Much less often, could be exposed to aerosol (Tier 1 select agent), overdose of Botox administration, or contaminated wound at allows anaerobic growth.

CLINICAL: If toxin ingested, then see descending paralysis (start at head and then down). For infant botulism, starts in intestine (constipation) then moves up skeletal musculature, swallowing, then breathing.

DIAGNOSIS: Mainly diagnose by clinical appearance ( e.g. loss of muscle function; flaccid) and epidemiology. Most life-threatening outcome is loss of breathing.

TREATMENT: Antibiotics should NOT be used (promote toxin release); focus is on neutralizing any remaining free toxin (administer anti-toxin) and supportive care to allow breathing. May take months to recover, as have to regenerate all of the “blocked” nerve synapses.

83
Q

what is the microbiology f clostridium tetani?

A

small motile bacillus

round terminal endospores (drumsticks, literally)

spores are really resistant to heat, etc

84
Q

are clostridium tetani aerobic or anaerobic?

A

fastidious anaerobic bacteria

very sensitive to oxygen – causes sporulation

85
Q

where is clostridium tetani found?

A

ubiquitous in soil and water

ubiquitous in soil and water

86
Q

what two major toxins does clostridium tetani produce?

A
  1. tetanolysin

2. tetanospasmin

87
Q

what is tetanolysin?

A

clostridium tetani toxin

it’s a oxygen-labile hemolysin

unknown clinical importance

88
Q

what is tetanospasmin?

A

clostridium tetani toxin

heat-labile neurotoxin

plasmid encoded

A-B toxin that is one of the most potent known toxins

89
Q

how does tetanospasmin work?

A

clostridium tetani toxin

spores enter body via wound and anaerobic conditions allow germination

the toxin is produced during stationary phase growth and is released when the cell is lysed

the toxin is cleaved into 2 chains = heavy B chain and light A chain

B chain binds to receptor on neuronal membrane and A chain is internalized into axon

90
Q

what does the A chain in tetanospasmin do?

A

tetanospasmin is a clostridium tetani toxin

A chain is a zinc endopeptidase that possesses toxic properties of tetanospasmin

it travels to CNS by retrograde axonal transport and becomes fixed to gangliosides at presynaptic inhibitory motor nerve endings

it selectively cleaves synaptobrevin II component of synaptic vesicles which prevents the release of glycine and GABA across the synaptic cleft

nervous impulses cannot be checked by normal inhibitory mechanisms

this is what produces the generalized muscular spasms characteristic of tetanus

91
Q

what’s the incubation period of tetanus?

A

3-21 days

average is about 8 days

in general, the further the injury site is from the CNS, the longer the incubation period

the shorter the incubation period the higher the chance of death

in neonatal tetanus, symptoms usually appear from 4 to 14 days after birth (7)

92
Q

what are the 3 forms of tetanus?

A
  1. localized tetanus
  2. cephalic tetanus
  3. generalized tetanus
93
Q

what is localized tetanus?

A

patients have persistent muscle contraction in the same area as the injury

uncommon and rarely fatal

94
Q

what is cephalic tetanus?

A

involvement of the cranial nerves, especially in the facial area

occasionally occurs with otitis media

uncommon but usually with poor outcome

95
Q

what is generalized tetanus?

A

disease usually presents with a descending pattern – first sign is trismus or lockjaw

this is followed by stiffness of the neck, difficulty in swallowing, rigidity of abdominal muscles, seizures

other symptoms include a temperature rise of 2°- 4°C above normal, headache, sweating, elevated blood pressure, and episodic rapid heart rate

spasms may occur frequently and last for several minutes

neonatal form is seen in infants born to nonimmunized mothers – initial infection of the umbilical cord that becomes generalized

96
Q

how long does recovery from generalized tetanus take?

A

may take months

toxin binding is irreversible so you have to regenerate new axonal terminals

97
Q

how do you diagnose tetanus?

A

diagnosis is entirely based on clinical presentation & immunization history

98
Q

how do you treat tetanus?

A
  1. treatment requires debridement of the primary wound
  2. supportive therapy and quiet environment help prevent spasms
  3. human tetanus immune globulin (TIG) or equine antitoxin must be administered early but it can only neutralize free toxin
  4. sedation and/or muscle relaxants to control spasms
  5. maintain airway
99
Q

how do you prevent tetanus?

A

prophylactic immunization is accomplished with tetanus toxoid

DTaP is given to infants as 4 doses at 2, 4, 6, and 15-18 months of age and you need boosters every 10 years

natural infection does not result in immunity!!!! toxin levels aren’t enough to induce immunity

100
Q

FLASHCARD: microbiology, pathology, epidemiology, clinical symptoms, diagnosis, and treatment of clostrium tetani

A

MICRIOBIOLOGY: Gram + rods, strict anaerobic, spore-forming

PATHOLOGY: If introduced into necrotic tissue (e.g. lacks oxygen, thus promote anaerobic growth), bacteria grow and release binary toxin (tetanus toxin; tetanospasmin). Released toxin binds to gangliosides at presynaptic junction and inhibits synaptic vesicle, which prevents release of glycine and GABA. Thus, nervous impulses cannot be efficiently stopped, resulting in generalized and severe muscle spasms.

EPIDEMIOLOGY; Free-living (anaerobic) or persist as endospores for extremely long periods. Found in soils or associated anaerobic environments (e.g. rusty nail). Can acquire by skin cuts through contaminated objects and/or exposure to soil.

CLINICAL: Symptoms begin days to weeks after wound-associated introduction of bacteria or spores. Usually a descending pattern. Trismus (lockjaw) is early symptom, followed by neck stiffness and difficulty swallowing. Fever, sweating, and elevated blood pressure. Spasms increase in severity and frequency as toxin spreads. Usually fatal unless treated.

DIAGNOSIS: Based on clinical symptoms, epidemiology (introduction of contaminated material into wound), and immunization history. Natural infection does not elicit immunity.

TREATMENT: Very effective vaccine (DTaP) given to infants as 4 doses, 5th as child, then booster every 10 years. Debride wound to remove anaerobic growth environment and allow antibiotics to diffuse into wound. Only provide anti-toxin if seriously wounded patient lacks immunization history. If immunized, then give booster without anti-toxin. If disease develops, need supportive therapy to allow breathing and may need to sedate to prevent spasms

101
Q

Tetanus vinngette

A

63-year-old alcoholic was taken to the emergency room of an outside hospital with obvious gangrene of both feet

stuporous

he had a seizure and was treated with phenytoin and barbiturates

opisthotonic posturing and to have developed increasing rigor, respiratory distress, and unresponsiveness

fever

trismus, neck was stiff and hyper-extended,

necrotic, blackened areas were present over both feet, and several draining ulcers were noted on the heels and toes

neurologically the patient responded to deep pain with a grimace

102
Q

clostridium perfringens vingette

A

severe left upper extremity pain

cellulitis of the left upper arm

arm was very tender to palpation and had decreased range of motion

no history or evidence of trauma to her arm, and no scratches or other lesions were apparent

no axillary or cervical lymphadenopathy

cellulitis progressed over the next 2 hours
with a new finding of crepitance in the upper left arm

gas in soft tissues

crazy high WBC with 90% neutrophils

biopsy showed Gram + rod organism that grew only under anaerobic

103
Q

what is the micriobiology of clostridium perfringens?

A

large gram (+) bacillus

anaerobic

nonmotile but spreads radily

endospores

104
Q

how many clostridium perfringens strains are there?

A

5 strain types based on toxins

type A is responsible for most human infections

105
Q

where is clostridium perfringens found?

A

intestinal tract

fecal contaminated water

106
Q

what are the major clostridium perfringens toxins?

A

α, β, ε and ι

α most important

107
Q

what is the α toxin in clostridium perfringens?

A

Lecithinase (Phospholipase C) that lyses host cells

increase vascular permeability and tissue destruction

heat labile, released in alkaline conditions of intestine and alter membrane permeability

108
Q

what is the β toxin in clostridium perfringens?

A

responsible for necrotic lesions in necrotic enteritis

109
Q

what is the ε toxin in clostridium perfringens?

A

protoxin cleaved to form permease = increase vascular permeability

110
Q

what is the ι toxin in clostridium perfringens?

A

has necrotic activity and increases vascular permeability

111
Q

what are the different diseases that clostridium perfringens can cause?

A
  1. food poisoning
  2. necrotic enteritis
  3. cellulitis
  4. clostridial myonecrosis (gas gangrene)
112
Q

what is clostridium perfringens food poisoning?

A

one of the most commonly reported food-borne illnesses in the U.S.

typically, dozens or even hundreds of person are affected

intense abdominal cramps & diarrhea

C. perfringens can survive high temperatures

enterotoxin-mediated (Type A)

113
Q

how long does C. perfringens food poisoning last?

A

disease presents within 8-24 hours after consuming infected foods

but usually over within 24 hours

114
Q

how do you treat C. perfringens food poisoning?

A

antibiotics are ineffective

just oral rehydration for supportive therapy

115
Q

what is C. perfringens nectrotic enteritis?

A

caused by ingesting large numbers of C. perfringens Type C

major disease in poultry

death caused by necrosis of the intestines (β toxin) and septicemia

associated with protein deprivation!! this leads to inadequate synthesis of proteases

116
Q

how do you treat C. perfringens nectrotic enteritis?

A

parenteral metronidazole

may require surgery to remove necrotic tissue

117
Q

what is C. perfringens cellulitis?

A

infection of skin/connective tissue that is already dead

it doesn’t spread to live tissue but it can spread along plane between muscle groups

it has a good prognosis!

you just remove dead tissue

118
Q

what is C. perfringens clostridial myonectrosis?

A

initial trauma to host tissue damages muscle and impairs blood supply

anaerobic conditions lead to bacterial growth and α toxin production

this leads to rapid onset of generalized fever, consfusion/malaise and intense pain in infected tissues

various exotoxins are liberated and degrade the surrounding tissue = purple mottling of skin, edema, foul-smelling exudate, gas bubbles form

as more tissue becomes involved, the clostridia multiply and digest/ferment the increasing area of dead tissue, generating more gas (largely N2 ) which releases more toxins into the local tissue and the systemic circulation….

it can lead to shock, renal failure, and death within 48h of initial onset

119
Q

how do you treat C. perfringens clostridial myonectrosis?

A

aka gas gangrene

  1. therapy must be initiated immediately –> radiographic imaging to identify gas in deep tissues; muscle does not bleed, no pus, no neutrophls – easy to culture from tissue

lab confirmation after treatment

  1. aggressive surgical debridement and high dose penicillin

prognosis is poor without appropriate treatment

120
Q

FLASHCARD: microbiology, pathology, epidemiology, clinical symptoms, diagnosis and treatment of clostridium perfringens

A

MICRIOBIOLOGY: Gram + rods, strict anaerobic, spore-forming, non-motile but spread rapidly in tissue

PATHOLOGY: Major disease symptoms are caused by range of toxins. Enterotoxins cause “long-incubation” food poisoning.  toxin causes necrotic enteritis. Infection of skin tissue only causes cellulitis, but if goes invasive will produce  and other toxins that cause massive tissue destruction.

EPIDEMIOLOGY: Found in soils or can be part of “normal” flora of intestine. Introduction can be exogenous from contaminated wound or endogenous due to leakage from intestine (e.g. surgery or rupture). Contaminated food can lead to limited GI growth and food poisoning. In some populations (immunosuppressed, New Guinea natives), ingestion leads to intestinal necrosis.

CLINICAL: Contaminated food leads to abdominal cramps & diarrhea 8-24h after ingestion. In some populations, ingestion causes necrosis of intestines and septicemia (necrotic enteritis; pig-bel). Localized skin infection causes redness and gas pockets (crepitance) with little pain. If invasive, anaerobic growth causes local tissue destruction, which further increases the anaerobic environment, allowing the infection to spread rapidly (myonecrosis; gas gangrene). Very painful, fever, tissue mottling, foul smelling exudate, and dead tissue. Can lead to shock and death within 48 hours.

DIAGNOSIS: Based on clinical symptoms and epidemiology (e.g. food-borne, contaminated wound).

TREATMENT: Food poisoning is self-limited (no antibiotics) unless develop necrotic enteritis. For all destructive disease, must rapidly debride the wound site to limit anaerobic growth and allow blood/drug delivery into wound. DOC: Penicillin and/or protein synthesis inhibitors (e.g. clindamycin).

121
Q

clostridium difficile-associated diarrhea vingette

A

80-year-old female

post-operatively, she began a 7-day course of oral cephalexin

10 days post-operatively, she presented with a 3-day history of diarrhea

multiple watery, loose stools without blood, crampy abdominal pain, and vomiting

temperature of 38.2°C, pulse rate of 90/min, respiratory rate of 20/min, and blood pressure of 116/53 mm Hg

WBC was normal, but a large number (53%) of immature polymorphonuclear cells were seen

enzyme immunoassay (ETA) that was positive for the presence of a bacterial toxin in the stool

122
Q

where do you usually get C. difficile infections?

A

common hospital infection following antibiotic treatment

bacteria produce heat-resistant endospores that are exceedingly difficult to kill

very resistant to detergents and cleaning agents

the only thing that destroys them is bleach or hydrogen peroxide

123
Q

which antibiotics can treat C. difficile?

A

vacomycin and metronidazole

but we think that there is a new, hypervirulent strain of C. difficile was circulating

124
Q

what causes clostridium difficile infections?

A

c. difficile is part of the normal intestinal flora of healthy and hospitalized individuals

but during an extended antibiotic course, can proliferate to large numbers in colon

ampicillin, amoxicillin, cephalosporins, clindamycin, and fluoroquinolones are the antibiotics that are most frequently associated with eliciting CDAD

125
Q

what toxins does C. difficile produce?

A
  1. toxin A

2. toxin B

126
Q

what does toxin B from C. difficile do?

A
  1. Cause actin depolymerization
  2. Destruction of cytoskeleton
  3. Release of inflammatory cytokines
  4. Recruitment of neutrophils
127
Q

what are the risk factors for C. difficile?

A
  1. old age
  2. recent hospitalization
  3. recent course of antibiotics
  4. recent invasive procedure or intestinal procedure
128
Q

how do you diagnose C. difficile infection?

A
  1. patient should be at risk and display clinically significant diarrhea
    ex. loose stool frequency of 3 or higher daily for at least 1-2 days; maybe also fever, cramping, abdominal discomfort, leukocytosis
  2. must have a positive test that is clinically relevant to CDAD

**identification of C. difficile in stool is not sufficient for CDAD diagnosis!! it’s often present in colons of asymptomatic patients

129
Q

which tests can you run to test for C. difficile?

A
  1. anaerobic culture of stool grow out C. difficile that display cytotoxic activity
  2. PCR of stool is positive for the toxin B gene
  3. enzyme immunoassay of stool is positive for toxin B and/or toxin A
  4. stool is positive for glutamate dehydrogenase
  5. colonoscopic findings of pseudomembranous colitis
130
Q

how do you treat C. difficile infections?

A

in many cases, symptoms resolve 1-14 days after the offending antibiotic is discontinued so C. difficile-specific antibiotic treatment isn’t needed

supportive therapy is often needed to replace fluid loss

if you need to though, Vancomycin and metronidazole are the antibiotics of choice to treat serious disease

131
Q

what is pseudomembranous colitis?

A

leukocytic infiltration into lamina propria that form patches on mucosa

related to C. difficile infections

132
Q

how do you kill C. difficile?

A

bleach

hand sanitizer does not kill C. difficile and handwashing may be insufficient

133
Q

FLASHCARD: microbiology, pathology, epidemiology, clinical symptoms, diagnosis and treatment of clostridium difficile

A

MICROBIOLOGY: Gram + rods, strict anaerobic, spore-forming

PATHOLOGY: Disruption of normal gut flora promotes outgrowth of C. difficile in intestine and production of binary toxins (TcdA & TcdB) that inactivate GTPases. Toxins cause cytoskeletal change, disrupt tight junctions, and elicit inflammatory mediators that attract neutrophils. These neutrophils infiltrate into lamina propria, cause elaboration of fibrin and mucus patches on mucosa (pseudomembranous colitis; PC). Can also lead to toxic megacolon.

EPIDEMIOLOGY: Free-living or persist as endospores for extremely long periods. Endospores are commonly found in hospital or supportive care environment (nosocomial infection). Easily acquired by ingestion, and can be part of normal flora for many. Antibiotic administration kills much of normal gut flora, allowing C. difficile and their endospores to grow and produce toxins in gut. Most commonly seen in elderly, recently hospitalized, and undergoing extended antibiotic treatment. However, the newer, more virulent strains can be community acquired by healthy adults.

CLINICAL: Patients develop diarrhea (≥3 loose stools/day) that can persist indefinitely. May get fever, nausea, and abdominal pain. Develop PC, and potentially perforation of colon and sepsis.

DIAGNOSIS: Initially based on clinical symptoms and epidemiology (elderly, hospitalization, antibiotic usage). PCR test shows presence of toxin gene, but do not know if toxin expressed. ELISA shows presence of toxin in stool, but not as sensitive as PCR.

TREATMENT: Stop providing antibiotics that caused flora disruption; often get restoration of healthy flora. Vancomycin, metronidazole, fidaxomicin is DOC. Fecal transplant can provide good results

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