Clostridium

Question 1

Name the most clinically relevant spp of Clostridium

Answer 1

C difficile

C perfringens

C tetani

C botulinum

C sordelii

C septicum

Question 2

How do you get C tetani introduced into the body?

Answer 2

Through puncture wounds (from dirty nails/needles/barbed wire)

Contaminated surgical procedures (**infected umbilical stump after unsterile delivery**)

Question 3

Disease caused by C tetani is mediated by the germination of spores, resulting in release of ___

Answer 3

tetanospasmin (tetanus toxin)

Question 4

Tetanus toxin consists of two subunits, the __ subunit which binds motor neurons and facilitates retrograde transport to the spinal cord/brain stem, and the __ subunit which has proteolytic activity and cleaves GABA and Glycine (thereby inhibiting these inhibitory signals)

Answer 4

Tetanus toxin consists of two subunits, the B subunit which binds motor neurons and facilitates retrograde transport to the spinal cord/brain stem, and the A subunit which has proteolytic activity and cleaves GABA and Glycine (thereby inhibiting these inhibitory signals)

**in the Sketchy video: this is the scissors that are being pulled up by the monkey are the toxin with its proteolytic activity, and the people wearing GG suites - inhibition of gaba and glycine**

Question 5

The action of the tetanus toxin leads to ___ (spastic/flaccid) paralysis

Answer 5

The action of the tetanus toxin leads to spastic paralysis

Question 6

2 distinguishing features of tetanus are ___ and ___ (aka eveil smile)

The disease can also present with an arched back - contractions of back muscles - in a condition known as ___

Answer 6

2 distinguishing features of tetanus are lockjaw and risus sardonicus (aka evil smile)

The disease can also present with an arched back - contractions of back muscles - in a condition known as opisthotonos

Question 7

Other forms of tetanus include: ___ which is localized to the spore inoculation site, cephalic tetanus and __ tetanus

Answer 7

Localized

Cephalic (Cranial nerve involvement: dysphagia, dysphonia, risus sardonicus)

Neonatal: (Trismus, inability to nurse, rigidity, apnea)

Question 8

How do you Dx tetanus?

Answer 8

Mainly from H and P

(culture only useful if bacteria are cultured from the wound. the toxn don’t got no detectable antibodies)

Question 9

How do you treat tetanus?

Answer 9

Clean or debride wound

Intramuscular tetanus immunoglobulin (antitoxin)

Tetanus vaccine at a different site

Maintain airway, treat hemodynamic instability, administer sedatives, muscle relaxants

Rx drug: Metronidazole (preferred) or penicillin

Question 10

Unlike tetanus, the botulinim toxin targets the ___ at the NMJ >> affects peripheral voluntary and autonomic cholinergic receptors >> results in ___ (spastic/flaccid)

Answer 10

Unlike tetanus, the botulinim toxin targets the ACh receptors at the NMJ >> affects peripheral voluntary and autonomic cholinergic receptors >> results in flaccid paralysis

Question 11

What kind of toxin (heat labile or otherwise) is C botulinim toxin?

Answer 11

Botulinum toxin is heat labile, but resistant to degradation by enzymes of GI tract

Question 12

There are generally 4 catgories of Botulism. Name them.

Answer 12

Foodborne botulism

Infant botulism

Wound botulism

Inhalational botulism

Question 13

___ botulism results from ingestion of pre-formed toxin from improper canning/preservation

Answer 13

Foodborne

**note that the toxin is already in the improperly canned food**

Question 14

Infants can also get foodborne botulism by ingesting ___. This typically occurs following exposure to ___. Signs include poor feeding , hypotonia, drooling and ptosis

Answer 14

Infants can also get foodborne botulism by ingesting spores. This typically occurs following exposure to wild honey or other home-canned foods. Signs include poor feeding , hypotonia, drooling and ptosis

Question 15

Wound botulism results from ___

What are the implications of black tar heroin use in wound botulism?

Answer 15

Wound botulism results from contamination of wound or otherdead tissue by spores

Black tar heroin: basically heroin mixed with come extra stuff to preserve it during transport from wherever. When the heroin is prepared, the cooking doesn’t kill the C botulinum spores which can germinate later. Skin popping creates an anaerobic env for the spores to grow and produce toxin resulting in manifestation of disease

Question 16

Inhalation botulism can result from __

Answer 16

Aerosolized Botulinum toxin

Question 17

The main clinical features of botulinum toxin involve cranial neuropathies with ___ progressing to ___

Answer 17

Cranial neuropathies >> symmetric, descending paralysis >> respiratory failure

Question 18

How would you Dx C botulinum infection?

Answer 18

Mainly from H and P

Culture useful if +ve and if you get the bug from implicated food

Toxin can be detected in serum, feces or food

Question 19

Botulism treatment includes __ or penicillin/metronidazole and ventilatory support

Answer 19

Botulism Rx:

Ventilatory support

Botulinum antitoxin

Metronidazole or penicillin

Question 20

Botulism can be prevented by ___

Answer 20

maintaining food at an acidic pH or at 4oC or colder (prevent germination of spores)

preformed toxin destroyed by heating to 80oC for 20 minutes

Question 21

___ is found in the soil and GI tract and produces a double zone of hemolysis on blood agar

Answer 21

C perfringens is found in the soil and GI tract and produces a double zone of hemolysis on blood agar

Question 22

Which bug is this?

Answer 22

C perfringens

Question 23

Food poisoning from C perfringens is mainly ass’d with ___

C perfringens infection results in soft tissue infections, including ___ (aka gas gangrene)

Other complications that can arise include ___ and bacteremia

Answer 23

Food poisoning from C perfringens is mainly ass’d with contaminated meat products

C perfringens infection results in soft tissue infections, including myonecrosis (aka gas gangrene - remember the gas coming out of the soldier’s crashed motorcycle)

Other complications that can arise include massive hemolysis (think about the tomatoes in sketchy) and bacteremia

Question 24

The diarrhea caused by C perfringens food poisoning is due to a __ and is __ (watery/bloody) and usually self limited

Answer 24

The diarrhea caused by C perfringens food poisoning is due to a heat labile enterotoxin (alpha toxin) and is watery and usually self limited

Question 25

The main manifestation of C perfringens infection besides food poisoning is ___. Patients may present with severe pain progressing to edema, pallor and may have hemorrhagic bullae or subcutaneous emphysema (aka gas)

Another Clostridium bug that can cause a similar infection is ___

Answer 25

The main manifestation of C perfringens infection besides food poisoning is C perfringens myonecrosis. Patients may present with severe pain progressing to edema, pallor and may have hemorrhagic bullae or subcutaneous emphysema (aka gas)

C septicum (note that this is spore mediated, not toxin mediated like perfringens)

Question 26

How do you Dx C perfringens infection?

Which bug would you think of if the culture has spores vs lacks spores?

How do you treat C perfringens infection?

Answer 26

Dx: microscopy. bugs observed but no RBCs or WBCs

+spores: C septicum

-spores: C perfringens

Rx: Penicillin + Clindamycin for toxin syntheis inhibition, surgical debridement

Question 27

___ is the most common cause of antibiotic ass’d diarrhea

Answer 27

C difficile

Question 28

Describe the steps leading to C diff infection

Answer 28

Disruption of normal gut flora (due to antibiotics mostly) >> colonization with C diff >> production of Toxins A and B >> pseudomembranous colitis

Question 29

The clinical manifestations of C diff infection include ___ diarrhea, and cramping abdominal pain. In its most severe form, C diff infection manifests with __, bowel perforation and even death

Answer 29

The clinical manifestations of C diff infection include profuse watery or green mucoid, foul smelling diarrhea, and cramping abdominal pain. In its most severe form, C diff infection manifests with toxic megacolon, bowel perforation and even death

Question 30

How do you Dx C diff?

Answer 30

PCR amplifiction of toxin genes

Culture, immunoassays + cytotoxicity assays

(2 step testing: PCR/antigen + toxin immunoassay)

Question 31

How do you classify severity of C diff infection based on WBCs and creatinine? (what’s mild/moderate vs severe vs fulminant)

Answer 31

Mild-Moderate:

WBC <15,000 cells/mm3

Creatinine <1.5x baseline

–

Severe:

WBC ≥15,000 cells/mm3

Cr > 1.5x baseline

–

Fulminant (infection plus not doing well at all):

Severe CDI PLUS

Hypotension or shock , ileus, megacolon, perforation

Question 32

Complete the table below for C diff treatment based on disease severity

Answer 32

Remember the Sketchy van and metro train

Question 33

How do you treat C diff recurrence?

Answer 33

1st time:

If metronidazole used first, use vanc for 10 days

If vanc used first, use it longer (prolonged taper) or switch to fidaxomicin

2nd time:

Vanc taper or fidaxomicin

Fecal transplant