Clostridia and Other Anaerobes Flashcards
1
Q
Clostridium genus
A
- Gram +
- bacilli
- anaerobic
- spores
- medically important produce toxins
- C. perfringens
- C. tetani
- ç.botulinum
- C. difficle
2
Q
Propionibacterium
A
- Gram +
- pleomorphic bacilli
- skin
- no spores
- anaerobe
3
Q
Eubacterium
A
- Gram +
- long slender bacilli
- colon
- no spores
- anaerobe
4
Q
Bacteroides genus
A
- Gram -
- bacilli
- anaerobe
- B. fragilis
-polysaccharide capsule
•oxygen toleran through production of superoxide dismutase
5
Q
Prevotella
A
- Gram -
- bacilli
- anaerobe
6
Q
Poryphromonas
A
- Gram -
- bacilli
- anaerobe
7
Q
Fusobacterium
A
- Gram -
- bacilli
- anaerobe
8
Q
Anaerobic Infections Epidemiology
A
Despite our constant immersion in air, anaerobes are able to colonize the many oxygendeficient or oxygen-free microenvironments of the body.
- Sites include the skin, the gingival crevices of the gums, and the lumina of the intestinal and urogenital tracts.
- Anaerobic infections are almost always endogenous with the infective agent(s) derived from the patient’s resident microbiota.
9
Q
Anaerobic Infections Pathogenesis
A
The anaerobic microbiota normally live in a harmless commensal relationship with the host. However, when displaced from their niche on mucosal surfaces into normally sterile tissues, these organisms may cause life-threatening infections.
- Result of trauma (gunshot, surgery), disease (diverticulosis), or isolated events (aspiration).
- Host factors like impaired blood supply increase the probability that the dislodged flora will produce an infection.
- Bacteroides fragilis, among the species in the colonic flora is the most frequent anaerobe isolated from intra-abdominal abscesses.
10
Q
Anaerobic Infections Site of Infection
A
The resident microbiota and site of infection may be at some distance.
- Aspiration pneumonia, lung abscess, and empyema involve anaerobes found in the oropharyngeal flora
- Brain abscess is most often caused by these same oropharyngeal anaerobes.
- In the case of contaminated open wounds, clostridia can come from the intestinal flora or from spores surviving in the environment.
11
Q
Anaerobic Infections Additional Virulence Factors
A
While gaining access to tissue sites provides the opportunity, additional virulence factors are invariably required for anaerobes to cause infection symptomatology.
- Classical virulence factors such as toxins and capsules are known only for the toxigenic clostridia and B. fragilis
- Ability to survive brief exposures to oxygenated environments can also be viewed as a virulence factor.
- Anaerobes found in human infections are far more likely to produce catalase and superoxide dismutase than other anaerobes
12
Q
[] alone or together with other facultative or obligate anaerobes, are responsible for the overwhelming majority of localized abscesses within the cranium, thorax, peritoneum, liver, and female genital tract.
A
Bacteroides, Fusobacterium, and peptostreptococci alone or together with other facultative or obligate anaerobes, are responsible for the overwhelming majority of localized abscesses within the cranium, thorax, peritoneum, liver, and female genital tract.
13
Q
Anaerobic Infection Diagnosis
A
The key to detection of anaerobes is a high quality specimen, preferably pus or fluid taken directly from the infected site.
- Specimens need to be protected from oxygen exposure.
- Gram-stained smear of clinical material is very helpful, even diagnostic.
- Isolation of the organisms requires the use of an anaerobic incubation atmosphere and special media protected from oxygen exposure.
- Anaerobic jar is sufficient for isolation of clinically significant anaerobes.
14
Q
Anaerobic Infection Treatment
A
- As with most abscesses, drainage of the purulent material is the primary treatment, along with appropriate chemotherapy.
- Anaerobic organisms derived from the oral flora are usually susceptible to penicillin.
- Penicillin resistant infections are most likely to respond to metronidazole, imipenem, azthreonam or a third-generation cephalosporin like ceftriaxone.
15
Q
C. perferingens Manifestations
A
Clostridium perfringens produces a wide range of wound and soft tissue infections many of which are not different from those caused by other opportunistic bacteria. The most dreaded of these, gas gangrene, starts as a wound infection but progresses to shock and death in a matter of hours. Another form of disease is food poisoning characterized by diarrhea without fever or vomiting.
16
Q
C. perfringens Organism
A
- C. perfringens is a large, Gram-positive, nonmotile rod.
- Much gas may be produced in vivo in necrotic tissues; hence the term gas gangrene.
- In general, there are five major types of toxic C. perfringens, based on the ability to produce combinations of four different toxins: alpha, beta, epsilon and iota
- a-toxin, a phospholipase, hydrolyzes lecithin and sphingomyelin and thus disrupts host cell membranes
- In addition to the major toxins reported above, C. perfringens strains have been reported in the literature to produce up to 20 total toxins
17
Q
C. perfringens Epidemiology of Gas Gangrene
A
Gas gangrene can develop in severe traumatic open lesions particularly when there is muscle necrosis. Contamination with dirt or other foreign material, introduces C. perfringens spores.
18
Q
C. perfringens Pathogenesis of Gas Gangrene
A
- If the oxidation-reduction potential in a wound is sufficiently low, C. perfringens spores can germinate, and the organism can multiply rapidly.
- a-toxin, passes along the muscle bundles killing cells and producing additional necrosis
- Increased vascular permeability and shock cause severe systemic disease.
19
Q
C. perfringens and Gas Gangrene Treatment
A
Fermentation of muscle carbohydrate by C. perfringens produces gas in the subcutaneous tissues that can be felt when palpated (crepitation) and seen on radiographs.
- Excision of all devitalized tissue is of paramount importance
- Administration of massive doses of penicillin is an important adjunctive procedure.
- Hyperbaric oxygen chambers increase the tissue level of dissolved oxygen and have been shown to slow the spread of disease.
- The single most effective method for preventing gas gangrene is the surgical debridement or amputation of traumatic injuries as soon after wounding as possible.
20
Q
C. perfringens and Food Poisoning
A
- C. perfringens can cause food poisoning if large numbers of an enterotoxin-producing strain are ingested. This occurs when spores survive cooking and convert to the vegetative form and multiply when the food is kept warm for an extended time (hours) prior to serving.
- An incubation period of 8 to 24 hours is followed by nausea, abdominal pain, and diarrhea.
- Outbreaks usually involve meat dishes such as stews, soups, or gravy
- Spores may survive initial cooking depending on the method and duration of heating. If there is a significant delay (hours) before serving during which the food is not refrigerated, the spores can germinate, and vegetative forms multiply. Enterotoxin producers then cause infectious diarrhea.
21
Q
C. perfringens and Extreme Clostridial Enteritis
A
22
Q
C. botulinum
A
- Botulism is usually caused by the ingestion of botulinum toxin preformed in food contaminated with C. botulinum.
- It begins with cranial nerve palsies and evolves into descending symmetrical motor paralysis including respiratory muscles.
- There is no fever or other signs of infection.
- The time course depends on the toxin dose.
- Less often the toxin is produced endogenously in the intestinal tract or a wound.
23
Q
C. botulinum Organism
A
- First isolated in 1895 from foodborne outbreak
- Soil bacterium
- Spores survive boiling water (most heat-resistant pathogen)
- Heat labile and destroyed rapidly at 1000C.
- Enters through GI tract
- Resistant to the enzymes of the gastrointestinal tract.
- Enzymatically act at neuromuscular junctions by cleaving host SNARE proteins resulting in a block in release of the excitatory neurotransmitter acetylcholine. The result is motor neuron blockage and flaccid muscular paralysis.
24
Q
C. botulinum Epidemiology and Pathogenesis
A
•Disease typically follows ingestion of home-canned alkaline vegetables, such as green beans or mushrooms, that prior to consumption have not been heated at temperatures sufficient to kill C. botulinum spores. The organism multiples on storage, often with no change in food taste or odor, and elaborates its toxin. If the food is ingested without cooking, botulism will result.
25
C. botulinum Symptoms
* Foodborne botulism symptoms begin 18-36hrs after ingestion
* Blurred vision, weakness, breathing difficulty, paralysis
* After an incubation period of 18 to 96 hours, signs of paralysis develop, first involving the ocular, pharyngeal, laryngeal, and respiratory muscles.
* There may be extensive paralysis of voluntary muscles.
* The mortality rate is 10 to 20%.
26
C. botulinum Infants
* The organism is apparently introduced to infants on weaning or with dietary supplements, especially honey.
* C. botulinum multiplies in the infant’s colon producing small amounts of toxin which are absorbed.
* The infant shows constipation, poor muscle tone, lethargy, and feeding problems and may have paralysis similar to adult toxin ingestion botulism.
27
C. botulinum Diagnosis
The toxin can be detected in blood, intestinal contents or the suspected food but these tests are only available in reference laboratories.
28
C. botulinum Treatment
* Intensive supportive measures, particularly mechanical ventilation, are the single most important determinant of clinical outcome
* Large doses of horse C. botulinum antitoxin are useful in neutralizing free toxin.
29
C. botulinum Prevention
* Adequate pressure cooking or autoclaving in the canning process will kill spores.
* Heating food at 100°C for 10 min before eating will destroy the toxin.
30
C. tetani
* C. tetani spores exist in many soils. Traumatically injected spores germinate, multiply and produce tetanus toxin.
* The striking feature of tetanus is severe muscle spasm (or “lockjaw” when the jaw muscles are involved). This takes place with minimal or no inflammation at the primary site of infection, which may be unnoticed even though the outcome is fatal.
* This is because the disease is caused by in vivo production of a neurotoxin which acts centrally, not at the local site.
* Immunization with inactivated toxin can prevent disease, even after stepping on a rusty nail.
31
C. tetani Organism
* The most important product of C. tetani is its neurotoxic exotoxin, tetanospasmin, a large, extracellular enzymatic protein
* The toxin is heat labile, antigenic, readily neutralized by antitoxin, and rapidly destroyed at 65°C and by intestinal proteases.
* Treatment with formaldehyde yields a nontoxic product, toxoid, that retains the antigenicity of toxin.
32
C. tetani Epidemiology
* Spores of C. tetani may be introduced into wounds with contaminated soil or foreign bodies.
* The predisposing wounds are often quite small, for example, a puncture wound containing a splinter.
33
C. tetani Pathogenesis
The usual predisposing factor for tetanus is inoculation into an area of very low oxidationreduction potential in which tetanus spores can germinate.
* Tetanospasmin is elaborated at the site of infection and reaches the central nervous system mainly by ascending through the axonal transport system of the motor nerves.
* In the spinal cord, it acts at the level of the anterior horn cells by degrading proteins involved in inhibitory neurotransmitter (GABA) release (Note: contrast with botulinum toxin). The result is unopposed active firing of motor neurons.
* Thus, a rigid paralysis occurs via spasmodic contractions of both protagonist and antagonist muscles
34
C. tetani Manifestation
The incubation period of the disease is from 4 days to several weeks. The shorter incubation period is usually associated with wounds in areas supplied by the cranial motor nerves, probably because of a shorter distance for the toxin to migrate to the central nervous system.
* The masseter muscles are often the first to be affected, resulting in inability to open the mouth properly (trismus or lockjaw)
* In extreme cases, generalized convulsions produce opisthotonos, caused by massive contractions of the back muscles.
35
C. tetani Treatment
•Specific treatment involves neutralization of any unbound toxin with large doses of human tetanus immune globulin (HTIG), which is derived from the blood of volunteers hyperimmunized with toxoid.
36
C. tetani Prevention
•Routine active immunization with tetanus toxoid, combined with diphtheria toxoid and pertussis vaccine (DPaT) for primary immunization in childhood prevents disease if immunizations are kept current.
37
Clostridioides (formerly Clostridium) difficile
* Clostridioides (formerly Clostridium) difficile is occasionally present in the intestinal microbiota of healthy persons. Its selection by the use of antimicrobial agents’ results is the most common cause of diarrhea which develops in this setting.
* In C. difficile infection (CDI) the diarrhea ranges from a few days of intestinal fluid loss to a life-threatening pseudomembranous colitis (PMC). T
-The latter is associated with intense inflammation and the formation of a pseudomembrane on the mucosal surface, which is composed of inflammatory debris.
38
C. dificile Organism
* Most strains produce a pair of toxins, toxin A (TcdA) and toxin B (TcdB) with similar structure and mode of action. They act in the cytoplasm disrupting signal transduction proteins (G proteins) involving the cell’s actin cytoskeleton.
* This action disrupts intercellular tight junctions followed by altered membrane permeability and hypersecretion of fluids. Some strains produce only TcdB.
* A third toxin (C. difficile transferase or CDT) with ADP-ribosylating activity has recently been discovered.
39
C. dificile Epidemiology
* C. difficile spores can mediate person-to-person spread. This has led to outbreaks in closed environments like hospitals.
* CDI is now the most common cause of death by diarrhea in the developed countries.
40
C. dificile Pathogenesis
The use of broad-spectrum antimicrobial agents results in suppression of many members of the resident intestinal bacterial microbiota. Under these circumstances, C. difficile is poised to move from a minor position in the flora to a dominant disease-producing one.
* The inert C. difficile spores are not affected by antimicrobial agents.
* Germination of spores is stimulated by taurocholate, a bile salt.
* Vegetative C. difficile cells released by germination have reduced competition for nutrients because the intestinal microbiota has been suppressed by the antibiotics.
* Production of TcdA & TcdB causes diarrhea and destruction of intestinal epithelial cells.
* In pseudomembranous colitis (PMC) an overlying layer composed of fibrin, leukocytes, and necrotic colonic cells is formed
* Toxic megacolon is the most serious endpoint.
41
C. dificile and pseudomembranous colitis (PMC)
•The diarrhea may be mild and watery or bloody and accompanied by abdominal cramping, leukocytosis, and fever. It is estimated that C. difficile is responsible for 25% of all reported cases of antibiotic-associated diarrhea (AAD) and for the overwhelming majority of those with PMC. If toxic megacolon develops total colectomy may be carried out as a life-saving measure.
42
C. dificile Diagnosis
* Because TcdA and/or TcdB are now readily detected directly in stool by immunoassay or PCR (also nucleic acid amplification or NAA) methods, culture for C. difficile has been abandoned as a diagnostic tool.
* These tests are now widely available even in emergency rooms and urgent care centers. This is the only disease routinely diagnosed by direct detection of its toxin(s).
43
C. dificile Treatment and Prevention
* PMC is treated with oral antimicrobials known to be active against Gram positive anaerobes such as vancomycin. The poor absorption of vancomycin administered orally is an advantage in this case because C. difficile remains in the intestinal lumen and does not invade.
* Unfortunately, relapses are common due to survival of the inert spores.
* In cases of multiple relapses infusion of donor feces into the intestine (fecal transplant) has been done in an effort to restore the intestinal microbiota. Controlled trials have now demonstrated the effectiveness of this somewhat sensational treatment.
44
B. fragilis
B. fragilis in the intestinal flora has an opportunity to produce disease when displaced into deep tissue sites. Deep pain and tenderness anywhere below the diaphragm is the typical onset of B. fragilis infection. Depending on the extent and spread of the intra-abdominal abscess, fever and widespread findings of an acute abdomen may be added findings.
45
B. fragilis Organism
* The B. fragilis group includes the most common opportunistic pathogens of the genus Bacteroides.
* Slim, pale-staining Gram-negative rods
* Relatively tolerant to atmospheric oxygen.
* Most strains produce a polysaccharide capsule
46
B. fragilis Pathogenesis
•Although B. fragilis constitutes less than 10% of Bacteroides species in the colon, it predominates among Gram-negative infections in the abdominal cavity.
-This is due in part to its ability to survive exposure to oxygen by deployment of detoxifying enzymes like catalase and superoxide dismutase.
•In addition, its polysaccharide capsule confers resistance to phagocytosis, stimulates abscess formation, and may inhibit macrophage migration.
-These are properties not found in the polysaccharide capsules of bacteria like Streptococcus pneumoniae.
•Recently, some new strains of B. fragilis have been found: these produce an enterotoxin (Enterotoxigenic B. fragilis; ETBF) and have been shown to be associated with GI malignancies.
47
B. fragilis Treatment
* Bacteroides fragilis is almost always resistant to penicillin and many other beta-lactams due to production of beta-lactamases.
* Most strains are susceptible to clindamycin, metronidazole, imipenem, and ceftriaxone.
