S1B5 - Bacillus Flashcards
Which of the following is the greatest risk factor for developing Clostridium difficile colitis?
A) Prolonged use of clindamycin
B) Prolonged use of metronidazole
C) Ingestion of Clostridium difficile spores
D) History of ulcerative colitis
Prolonged use of clindamycin
Answer Explanation
C. difficile is considered an iatrogenic infection. The greatest risk factor is prolonged use of antibiotics. Clindamycin, second/third generation cephalosporins, and ampicillin/amoxicillin are the most commonly implicated antibiotics. However, any antibiotic can predispose to C. diff colitis, even metronidazole, which is used to treat C. diff infections. Patients become colonized when they ingest C. diff spores, but this does not automatically result in C. diff colitis.
Inhalational anthrax causes which of the following clinical entities?
A) Pulmonary hemorrhage
B) Cutaneous pustules
C) Empyema
D) Otitis media
E) Splenic infarction
Pulmonary hemorrhage
Answer Explanation
Inhalation anthrax begins when anthrax spores are ingested by macrophages and carried to mediastinal lymph nodes. There, the bacteria elaborate exotoxins that cause pulmonary hemorrhage. Bacteremia can also result, with more systemic shock developing soon after. Cutaneous pustules are a feature of cutaneous anthrax. Pneumonia is not a feature of inhalational anthrax, nor is splenic infarction. In theory, hemorrhagic pleural effusions can become superinfected and lead to empyema, but patients usually die of systemic shock before bacterial superinfection occurs.
What characteristic of Clostridium spp. accounts for its ability to survive unfavorable conditions?
Clostridium spp. form spores that can survive boiling at normal pressure.
What disease(s) are caused by Bacillus anthracis?
Bacillus anthracis causes cutaneous anthrax, inhalation (pulmonary) anthrax, and alimentary (oral and gastrointestinal) anthrax.
What is the molecular mechanism of Clostridium botulinum toxin? What type of toxin is it?
C. botulinum secretes botulinum, a protease that cleaves fusion proteins, blocking acetylcholine (ACh) release at neuromuscular junctions and causing a descending flaccid paralysis.
Compare the progression of paralysis seen in Clostridium botulinum with that seen in Guillain-Barre syndrome.
The symmetric descending paralysis of C. botulinum infection should be contrasted with the symmetric ascending paralysis in Guillain-Barre syndrome.
A 36-year-old woman has a persistent Clostridium difficile toxin positive test despite 3 weeks of treatment with oral metronidazole. What is the next best treatment modality?
A) Initiate oral vancomycin
B) Continue oral metronidalole
C) Initiate intravenous vancomycin
D) Initiate intravenous metronidazole
Initiate oral vancomycin
Answer Explanation
The mainstays of C. diff treatment are metronidazole and oral vancomycin. Metronidazole can be given either PO or IV, with no evidence to show that one route is better than the other. Vancomycin should be given PO as it is not absorbed systemically and reaches the colon. In this patient, since metronidazole has failed, switching to or adding on oral vancomycin is the next best treatment modality.
What diseases does Clostridium botulinum cause?
Clostridium botulinum causes adult and infant botulism.
How is Bacillus anthracis infection prevented?
Anthrax outbreak in endemic regions can be prevented by controlling the disease in animals through vaccination. Widespread decontamination of the soil is not feasible.
What two exotoxins does C. perfringens produce?
C. perfringens produces two exotoxins, an alpha toxin and an enterotoxin.
Is B. cereus motile or non-motile? This is in contrast to what related organism?
B. cereus is a motile organism, in contrast to the non-motile organism Bacillus anthracis.
How should recent exposure to Bacillus anthracis be managed?
Early or prophylactic antibiotic treatment after exposure is crucial for good prognosis.
What symptoms do the heat-labile enterotoxin of B. cereus cause?
The heat-labile enterotoxin is formed from the ingestion of spores that germinate in the small intestine and is responsible for the diarrheal syndrome. This toxin functions to increase cAMP, activating the CFTR channel leading to secretion of chloride ions.
What is the characteristic appearance of Clostridium tetani on gram stain?
C. tetani can have a tennis racket or drumstick appearance on gram stain.
An otherwise healthy, 37-year-old leather tanner presents with a 2-day history of a lesion on his left hand. It started as a 2 cm papule but ruptured this morning. The lesion is non-tender, with a raised, regular edge. He complains of left axilla tenderness as well. What is the likely diagnosis?
A) Lymphocutaneous tularemia
B) Ascending lympghangitis
C) Cutaneous andthrax
D) Staphylococcal abscess
E) Bubonic plague
Cutaneous anthrax
Answer Explanation
Nontender, papular lesions that rupture into ulcers, associated with painful lymphadenopathy in patients with exposure to animals are hallmarks of cutaneous anthrax. A black eschar classically forms 7 days after rupture.
Bubonic plague doesn’t result in ulcers but rather in painful lymphadenopathy of the groin/axilla.
In tularemia, the papules are tender, ulcerate, and produce yellow exudate. In addition there is usually a history of exposure to rodents such as rabbits or squirrels.
Staphylococcal abscesses are very tender and does match the presentation described in the vignette.
Ascending lymphangitis can occur with many localized infections, but more typically with local abscesses.
What is the pathway of lethal factor (LF) in Bacillus anthracis anthrax toxin?
Lethal factor (LF), upon entering the cell, inactivates the MAP kinase pathway, leading to rapid cell death.
What are the symptoms of botulinum intoxication?
The symptoms of botulinum infection include
- Flaccid paralysis (floppy baby syndrome)
- Dry mouth
- Blurry vision (classic signs of ACh blockade)
- Death from respiratory failure
What is the morphology and gram staining of Clostridium spp.? Aerobic or anaerobic?
Clostridium spp. are a family of gram-positive bacilli and obligate anaerobes.
What bacteria is most likely found on these sheep agar plates?
Bacillus anthracis
On sheep blood agar plates:
- Non-motile, non-hemolytic, irregularly round
- Spike-like projections at colony edges (Medusa-head colony)
- firmly adherent colonies on agar
What is the mechanism and its effects of the alpha toxin produced by C. perfringens?
Alpha toxin is a lecithinase, an enzyme that cleaves lecithin (a key component of cell membranes that includes phosphatidylcholine) that can be directly inoculated into tissue in the event of trauma to the skin or muscle.
What is the treatment protocol for C. perfringens infections?
Treatment includes excision of necrotic tissue, allowing for exposure of anaerobic spaces to oxygen, along with antibiotic regimen of penicillin with clindamycin or tetracycline.
A 60-year-old patient develops toxin-mediated diarrhea after taking a 2-week course of clindamycin. The organism is confirmed to be from an anaerobic, gram-positive rod. Sterilization of equipment used in the care of this patient will require which of the following?
A) Boiling in water for 2 hours
B) Exposure to 121C steam in a closed container for 15 minutes
C) Submersion in 95% ethanol for 1 hour
D) Boiling in water for 1 hour
Exposure to 121C steam in a closed container for 15 minutes
Answer Explanation
The organism in question is C. difficile. Clostridia species all form spores that are highly resistant to environmental stresses. Normal atmospheric pressure boiling doesn’t kill the spores, nor does ethanol (which is why you can’t use alcohol-based hand cleansers after coming in contact with a patient with a C. difficile infection). Autoclaving will kill the spores (pressurized steam exposure).
What risk factors predispose to Clostridium difficile superinfection?
Disease often arises from nosocomial infection through fecal-oral transmission. A common risk factor includes antibiotics use (e.g. fluoroquinolones, ampicillin, clindamycin) that alter intestinal flora, allowing C. difficile to flourish. C. difficile is the most common cause of nosocomial diarrhea.
What diseases does B. cereus cause?
B. cereus causes food-borne illnesses, such as food poisoning, with associated gastrointestinal symptoms.
What two toxins does C. difficile produce?
C. difficile produces two exotoxins, toxin A (enterotoxin) and B cytotoxin.
How are C. perfringens infections diagnosed?
Diagnosis can be made from x-ray or CT revealing gas dissecting into muscle (classic sign), tissue biopsy revealing gram-positive rods without spores (sporulates only under nutritionally-deficient conditions), and relatively little inflammation (WBCs lysed by alpha toxin).
How does neonatal tetanus commonly occur?
Spores can affect neonates through a cut umbilical cord, especially when the mother is not immunized.
What is the mechanism of tetanic paralysis?
A) Exotoxin inhibiting glycine release
B) Cytotoxin that destroys neurons
C) Neurotoxin inhibiting acetylcholine release
D) Alpha toxin with phospholipase C-like activity
E) Cytotoxin that disrupts the cytoskeleton by depolymerizing actin filaments of gastrointestinal mucosal cells
Exotoxin inhibiting glycine release
Answer Explanation
Glycine and GABA are inhibitory neurotransmitters. Clostridium tetani releases an exotoxin that inhibits glycine release, so muscles are continuously stimulated. This leads to a rigid paralysis. Acetylcholine release inhibition is the mechanism of botulism toxin, a phage-encoded exotoxin. Botulism exotoxin acts as a protease and cleaves releasing proteins, inhibiting neurotransmitter release.
Alpha toxin is a virulence factor for Clostridium perfringens, and functions as a lecithinase with phospholipase C-like activity.
Tetanus does not involve primary neuron destruction. Like botulism, the tetanus exotoxin acts as a protease, cleaving releasing proteins and inhibiting neurotransmitter release.
Enterocyte cytotoxin (exotoxin B) is a feature of Clostridium difficile that functions to disrupt the cytoskeleton by depolymerizing actin filaments of gastrointestinal mucosal cells
What is the treatment for botulism?
Treatment for botulism includes administering immunoglobulin that binds toxin that is not yet bound to nerve endings.
What is the clinical presentation of inhalation anthrax?
Inhalation anthrax presents with nonspecific myalgias, fever, chest pain, and cough due to hemorrhage of thoracic lymph nodes, hemorrhagic mediastinitis, and necrotizing pneumonia. This is followed by bacteremia and meningitis in a fatal fulminant phase.
What is the mechanism and its effects of exotoxin B produced by C. difficile?
Toxin B (cytotoxin) of C. difficile disrupts the cytoskeleton by depolymerizing actin filaments causing GI mucosal cell death and eventually pseudomembranous colitis.
What disease does Clostridium tetani cause?
Clostridium tetani causes excessive muscle contraction, also known as tetanus.
What can be taken as prophylaxis for Clostridium tetani infections?
Prophylaxis includes the DTaP vaccine and a Tdap (or Td) booster every 10 years.
What are 4 options for diagnosing C. difficile and what are the limitations of each?
Diagnosis can be made from several tests. They include:
- Stool culture is the most sensitive, but not as quick.
- Glutamate dehydrogenase enzyme immunoassay is highly sensitive, but positive tests must be confirmed with another test.
- Real-time PCR for C. difficile gene toxin.
- Enzyme immunoassay for detecting toxins A and B. Highly specific, but only moderately sensitive and negative tests must be rechecked with alternate exam.
An organism is cultured and reveals gram-positive bacilli in chains, what organism is high on your differential?
Diagnosis of B. anthracis is made with standard culture revealing gram-positive bacilli in chains.
What is the mechanism and its effects of enterotoxin A produced by C. difficile?
Toxin A (enterotoxin) of C. difficile attracts neutrophils, which release cytokines and cause mucosal inflammation and gastrointestinal fluid loss.
What is the morphology, gram staining, motility, and oxygen requirement of Bacillus anthracis?
Bacillus anthracis is an aerobic or facultatively anaerobic, sporulating, non-motile, gram-positive bacilli.
What is the role of protective antigen (PA) in Bacillus anthracis anthrax toxin?
Protective antigen (PA) becomes a channel in the mammalian plasma membrane, allowing translocation of edema factor (EF) or lethal factor (LF) into the cytosol.
What diseases does Clostridium difficile cause?
Clostridium difficile causes pseudomembrane colitis and diarrhea.
How does sporulation play a role in Bacillus anthracis infections?
When exposed to harsh conditions, Bacillus anthracis forms spores. Spores can survive in dry soil and goat skin for many years. Grazing herbivores ingest spores on grass and acquire alimentary canal anthrax. Spores are excreted in feces. Humans can acquire spores via close contact with infected animal products. Once exposed to suitable conditions in humans or animals, the spores revert to metabolically active bacteria.
How is Bacillus anthracis transmitted?
Bacillus anthracis is transmitted via skin contact, inhalation, or ingestion of spores and often occurs in individuals exposed to infected herbivores, their skins, and carcasses.
What types of treatments are given for patients with food-poisoning from Bacillus cereus?
Patients infected with food poisoning from B. cereus are only treated supportively.
Which is a feature unique to Bacillus anthracis?
A) Polypeptide capsule
B) Facultative intracellular status
C) Polysacharide capsule
D) Exotoxin elaboration
E) Formation of spores
Polypeptide capsule
Answer Explanation
B. anthracis is the only bacteria with a polypeptide capsule, specifically a poly-D-glutamate capsule.
What two enterotoxins are produced by B. cereus?
B. cereus produces two types of enterotoxin, a heat-stable enterotoxin (similar to Staphylococcus enterotoxin) and a heat-labile enterotoxin (similar to Escherichia coli heat labile toxin).
What are 3 classic signs of tetanus?
The excessive muscle contraction (tetanus) causes rigid paralysis and often presents clinically as:
- Trismus (“lockjaw”) due to jaw muscle contraction.
- Risus sardonicus (“ironic smile of tetanus”) due to facial muscle contraction.
- Opisthotonos (pronounced arching of back) due to contraction of back extensor muscles.
What is the clinical presentation of alimentary tract anthrax?
Gastrointestinal tract anthrax presents with abdominal pain, dysentery, and necrotic ulcers of the oral and gastrointestinal tract.
Where are Bacillus anthracis spores naturally present?
Bacillus anthracis spores are present in dry soil and in the gastrointestinal tract of animals. Exposure to infected cows, goats, and other herbivores, and their carcasses, skins, furs, and other products can cause naturally-occurring anthrax infection.
What symptoms does the heat-stable enterotoxin of B. cereus cause?
The heat-stable enterotoxin is formed from the ingestion of preformed toxin cereulide, responsible for the emetic syndrome, usually presents as vomiting and nausea.
Which pathogenic bacteria have a protein capsule?
B. anthracis is the only bacteria with a protein capsule, specifically a protein (poly-D-glutamate) capsule.
What are the three components of anthrax toxin and how are they usually combined in the toxin?
Bacillus anthracis releases anthrax toxin, which consists of protective antigen (PA), plus either edema factor (EF) or lethal factor (LF). The combination of PA and EF is called edema toxin (ET). The combination of PA and LF is called lethal toxin (LT).
What is the treatment for individuals affected with tetanus?
Treatment includes anti-tetanospasmin immunoglobulin, along with adjunctive antimicrobial therapy with metronidazole. Muscle spams can be controlled with benzodiazepines or neuromuscular blockade.
What is the molecular mechanism of Clostridium tetani toxin? What type of toxin is it?
C. tetani contains tetanospasmin, a protease that cleaves the releasing protein synaptobrevin. Following retrograde transport up the axon and intercellular transfer, tetanospasmin ultimately impairs the ability of inhibitory Renshaw neurons to release the neurotransmitter glycine and GABA. Therefore, tetanospasmin inhibits the inhibitor causing net stimulation.
What is the mechanism and its effects of the enterotoxin produced by C. perfringens?
When ingested, heat-labile enterotoxin can cause food poisoning by inducing membrane instability (formation of pores) and binding to claudins (proteins involved in maintaining intercellular junctions) on the surface of enterocytes. This results in osmotic swelling and lysis, leading to cell death.
What is the clinical presentation of cutaneous anthrax?
Cutaneous anthrax, the most common form, presents with rapidly growing papule developing into a painless ulcerous vesicle with a black necrotic eschar, accompanied by edema of surrounding tissues.
How is B. cereus transmitted?
B. cereus is transmitted through ingestion of spores in food. B. cereus can contaminate uncooked food (e.g. rice). Formation of the heat-stable emetic toxins from vegetative forms can survive brief heating such as stir frying.
What is the role of edema factor (EF) and by what cellular pathway does EF act in Bacillus anthracis anthrax toxin?
Edema factor (EF), upon entering the cell, becomes an adenylate cyclase that increases cellular cAMP, causing edema and disruption of innate immunity.
How is the motility of Clostridium perfringens different than other Clostridium spp.? What diseases does Clostridium perfringens cause?
Clostridium perfringens is the only non-motile Clostridium and causes
- Cellulitis
- Gas gangrene
- Food poisoning
Gram-positive anaerobes are isolated from a 43-year-old man who developed flaccid paralysis several hours after eating soup from a can. His symptoms started with diplopia and dysphagia, and progressed to his trunk and extremities. Which of the following is the likely source?
A) Laceration from can with Clostridium tetani inoculation
B) Ingestion of tetanolysin toxin
C) Ingestion of Clostridium botulinum spores
D) Ingestion of botulinum toxin
E) Ingestion of Clostridium tetani spores
Ingestion of botulism toxin
Answer Explanation
Flaccid paralysis from ingestion is suggestive of botulism. The isolation of gram-positive anaerobes further clinches the diagnosis. Adults develop paralysis after ingesting preformed toxin. Babies develop paralysis after ingesting spores (classic food is honey). C. tetani causes rigid paralysis (tetanus) via production of the tetanolysin toxin. Ingestion of C. tetani spores is not a typical cause of tetanus; inoculation of a wound is the classic history.
Widening of the mediastinum is a classical (but nonspecific) finding of what infectious disease?
Widening of the mediastinum is a classic finding of inhalation anthrax, due to the hemorrhagic mediastinitis. This is a nonspecific finding.
What is the major virulence factor of Bacillus anthracis besides the protein capsule and what are its components?
Bacillus anthracis releases anthrax toxin, which consists of protective antigen (PA), plus either edema factor (EF) or lethal factor (LF). The combination of PA and EF is called edema toxin (ET). The combination of PA and LF is called lethal toxin (LT).
A mother feeds her infant honey. The infant develops a flaccid paralysis but the mother is fine despite ingesting much larger quantities of the same honey. What accounts for this difference?
C. botulinum spores are unable to germinate in adults’ mature intestinal tract. Adult botulism occurs only when adults ingest preformed toxin (foodborne botulinism). Infant botulinism occurs when babies ingest spores, often found in honey, that germinate and subsequently elaborate toxin.
What is the clinical presentation of each of the three forms of Bacillus anthracis infection?
Clinical presentation depends on the route of exposure. Patients typically present with
- Necrotic pustules in cutaneous anthrax
- Flu-like symptoms that rapidly progress to fever, pulmonary hemorrhage, mediastinitis, and shock in inhalation anthrax
- Dysentery in gastrointestinal (alimentary) tract anthrax.
What are the possible treatment options for Clostridium difficile infections (4)?
Treatment of C. difficile infection can include
- Oral metronidazole
- Oral vancomycin (not absorbed systemically, usually given IV for serious systemic infections)
- Fidaxomicin for recurrent cases
- Fecal microbiota transplant
What is the morphology and gram staining of Bacillus cereus? What is its status with regard to oxygen needs and spore-forming capacity?
Bacillus cereus is an aerobic spore-forming gram-positive bacilli.
Why are diagnostic tests not usually performed on suspected Bacillus cereus infections?
Laboratory testing is usually not performed on individuals with suspected B. cereus infection because it is self-limiting.
What is the name of a recombinant human antibody that treats inhalation anthrax by binding to the PA component of Bacillus anthracis?
Raxibacumab, a recombinant human antibody that binds to the PA component of B. anthracis, can be used in the treatment of inhalation anthrax following exposure in combination with appropriate antimicrobial therapy.
