Gram positive Bacilli Clostridium species

Spore Forming
Gram positive Bacilli Clostridium species

Clostridium Species
Clostridia are large anaerobic, gram-positive, motile rods..
Their natural habitat is the soil or the intestinal tract of animals and humans,
C. tetani Tetanus
C. perfringens. Gas gangrene
C. botulinum. Botulism`
C. dif?cile pseudomembranous colitis.

Morphology & Identification
Typical Organisms
Spores of clostridia are usually wider than the diameter of the rods in which they are formed. In the various species, the spore is placed centrally, subterminally, or terminally. Most species of clostridia are motile and possess peritrichous flagella.
 



Clostridia grow under anaerobic conditions; a few species are aerotolerant and will also grow in ambient air. It grow well on the blood-enriched media . Some clostridia produce large raised colonies (eg, C perfringens); others produce smaller colonies (eg, C tetani). Some clostridia form colonies that spread on the agar surface. Many clostridia produce a zone of hemolysis on blood agar. C perfringens characteristically produces a double zone of hemolysis around colonies

Clostridium tetani

Pathogenesis
Tetanus toxin (tetanospasmin) is an exotoxin produced by vegetative cells at the wound site. This polypeptide toxin is carried intra-axonally (retrograde) to the central nervous system, where it binds to ganglioside receptors and blocks release of inhibitory mediators (e.g., glycine) at spinal synapses.



Clinical Findings
Tetanus is characterized by
strong muscle spasms (spastic paralysis, tetany).
Specific clinical features include lockjaw (trismus) due to rigid contraction of the jaw muscles, which prevents the mouth from opening;
and exaggerated reflexes. Opisthotonos, a pronounced arching of the back due to spasm of the strong extensor muscles of the back, is often seen.
Respiratory failure ensues. A high mortality rate is associated with this disease.
spastic paralysis (strong muscle contractions) occurs, whereas in botulism, flaccid paralysis (weak or absent muscle contractions) occurs.


Diagnosis
The diagnosis rests on the clinical picture and a history of injury,
The primary differential diagnosis of tetanus is strychnine poisoning.
Anaerobic culture of tissues from contaminated wounds may yield C tetani,
Proof of isolation of C tetani must rest on production of toxin and its neutralization by specific antitoxin.
C. tetani produces a terminal spore, i.e., a spore at the end of the rod. This gives the organism the characteristic appearance of a "tennis racket."



Treatment
Tetanus immune globulin is used to neutralize the toxin. The role of antibiotics is uncertain. If antibiotics are used, either metronidazole or penicillin G can be given. An adequate airway must be maintained and respiratory support given. Benzodiazepines, e.g., diazepam (Valium), should be given to prevent spasms.

Prevention
Tetanus is prevented by immunization with tetanus toxoid (formaldehyde-treated toxin) in childhood and every 10 years thereafter. Tetanus toxoid is usually given to children in combination with diphtheria toxoid and the acellular pertussis vaccine (DTaP).
When trauma occurs, the wound should be cleaned and debrided and tetanus toxoid booster should be given. If the wound is grossly contaminated, tetanus immune globulin, as well as the toxoid booster, should be given and penicillin administered.

Clostridium botulinum
Disease: causes botulism.
Transmission
Spores, widespread in soil, contaminate vegetables and meats
Pathogenesis
Botulinum toxin is absorbed from the gut and carried via the blood to peripheral nerve synapses, where it blocks release of acetylcholine.

Clinical Findings
Descending weakness and paralysis, including diplopia, dysphagia, and respiratory muscle failure, are seen. No fever is present. Two special clinical forms occur: (1) wound botulism, in which spores contaminate a wound, germinate, and produce toxin at the site; and (2) infant botulism, in which the organisms grow in the gut and produce the toxin there...

Laboratory Diagnosis
The organism is usually not cultured. Botulinum toxin is demonstrable in uneaten food and the patient s serum by mouse protection tests. Mice are inoculated with a sample of the clinical specimen and will die unless protected by antitoxin.
Treatment
Trivalent antitoxin (types A, B, and E) is given, along with respiratory support.
 
Prevention
Proper sterilization of all canned foods is essential. Food must be adequately cooked to inactivate the toxin.

Clostridium perfringens
C. perfringens causes two distinct diseases, gas gangrene and food poisoning, depending on the route of entry into the body.
Disease: Gas Gangrene
Gas gangrene (myonecrosis, necrotizing fasciitis) is one of the two diseases caused by C. perfringens. Gas gangrene is also caused by other histotoxic clostridia such as Clostridium histolyticum, Clostridium septicum, Clostridium novyi, and Clostridium sordellii.
Transmission
Spores are located in the soil; vegetative cells are members of the normal flora of the colon and vagina. Gas gangrene is associated with war wounds, automobile and motorcycle accidents, and septic abortions (endometritis).



Pathogenesis
Organisms grow in traumatized tissue (especially muscle) and produce a variety of toxins. The most important is alpha toxin (lecithinase), which damages cell membranes, including those of erythrocytes, resulting in hemolysis. Degradative enzymes produce gas in tissues.


Clinical Findings
Pain, edema, and cellulitis occur in the wound area.
Crepitation indicates the presence of gas in tissues.
Hemolysis and jaundice are common, as are blood-tinged exudates.
Shock and death can ensue. Mortality rates are high.
Laboratory Diagnosis
Smears of tissue and exudate samples show large gram-positive rods.
The organisms are cultured anaerobically and then identified by sugar fermentation reactions and organic acid production.
C. perfringens colonies exhibit a double zone of hemolysis on blood agar. Egg yolk agar is used to demonstrate the presence of the lecithinase.


Treatment
Penicillin G is the antibiotic of choice. Wounds should be debrided.
Prevention
Wounds should be cleansed and debrided. Penicillin may be given for prophylaxis. There is no vaccine.


Disease: Food Poisoning
Food poisoning is the second disease caused by C. perfringens.
Transmission
Spores are located in soil and can contaminate food. The heat-resistant spores survive cooking and germinate. The organisms grow to large numbers in reheated foods, especially meat dishes.
Pathogenesis
C. perfringens is a member of the normal flora in the colon but not in the small bowel, where the enterotoxin acts to cause diarrhea. The mode of action of the enterotoxin is the same as that of the enterotoxin of S. aureus; i.e., it acts as a superantigen.

Clinical Findings
The disease has an 8- to 16-hour incubation period and is characterized by watery diarrhea with cramps and little vomiting. It resolves in 24 hours.
Laboratory Diagnosis
This is not usually done. There is no assay for the toxin. Large numbers of the organisms can be isolated from uneaten food.
Treatment
Symptomatic treatment is given; no antimicrobial drugs are administered.
Prevention
There are no specific preventive measures. Food should be adequately cooked to kill the organism.


Clostridium difficile
Disease
C. difficile causes antibiotic-associated pseudomembranous colitis. C. difficile is the most common nosocomial cause of diarrhea.
Transmission
The organism is carried in the gastrointestinal tract in approximately 3% of the general population and up to 30% of hospitalized patients. Most people are not colonized, which explains why most people who take antibiotics do not get pseudomembranous colitis. It is transmitted by the fecal-oral route. The hands of hospital personnel are important intermediaries.


Pathogenesis
Antibiotics suppress drug-sensitive members of the normal flora, allowing C. difficile to multiply and produce exotoxins A and B. Clindamycin was the first antibiotic to be recognized as a cause of pseudomembranous colitis, but many antibiotics are known to cause this disease. At present, second- and third-generation cephalosporins are the most common causes because they are so frequently used. Ampicillin and fluoroquinolones are also commonly implicated. In addition to antibiotics, cancer chemotherapy also predisposes to pseudomembranous colitis. C. difficile rarely invades the intestinal mucosa.

Clinical Findings
C. difficile causes diarrhea associated with pseudomembranes (yellow-white plaques) on the colonic mucosa.. The diarrhea is usually not bloody, and neutrophils are found in the stool in about half of the cases. Fever and abdominal cramping often occur. The pseudomembranes are visualized by sigmoidoscopy. Toxic megacolon can occur, and surgical resection of the colon may be necessary. Pseudomembranous colitis can be distinguished from the transient diarrhea that occurs as a side effect of many oral antibiotics by testing for the presence of the toxin in the stool.

Laboratory Diagnosis
The presence of exotoxins in a filtrate of the patient s stool specimen is the basis of the laboratory diagnosis. There are two types of tests usually used to detect the exotoxins. One is an enzyme-linked immunosorbent assay (ELISA) using known antibody to the exotoxins. The ELISA tests are rapid but are less sensitive than the cytotoxicity test. In the cytotoxicity test, human cells in culture are exposed to the exotoxin in the stool filtrate and the death of the cells is observed. This test is more sensitive and specific but requires 24–48 hours incubation time. To distinguish between cytotoxicity caused by the exotoxins and cytotoxicity caused by a virus possibly present in the patient s stool,

Treatment
The causative antibiotic should be withdrawn. Oral metronidazole or vancomycin should be given and fluids replaced. Metronidazole is preferred because using vancomycin may select for vancomycin-resistant enterococci. In many patients, treatment does not eradicate the carrier state and repeated episodes of colitis can occur.
Prevention
There are no preventive vaccines or drugs. Antibiotics should be prescribed only when necessary