sheet micro # ?? - Hala Al-ansari

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sheet micro # ?? - Hala Al-ansari

Post by Shadi Jarrar on 15/11/2010, 3:43 am

بسم الله الرحمن الرحيم

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بسم الله الرحمن الرحيم

Before we start, you should know that the “ Clostridia” handout is included within the sheet.( from clinical syndromes of clostridia perfringens to the end)
In this lecture we’ll continue talking about Clostridia :
 clinical syndromes caused by clostridia perfringens.
 Clostridium tetani
 Clostridium botulinum
 Clostridium difficle
 Clostridium sordelli
 Clostridium septicum
THEN , we’ll move to new subject:
 Anaerobic Non Spore-forming
Gram-Positive Bacilli : Actinomyces

Clinical syndromes (of Clostridium perfringens):
 Myonecrosis (Gas gangrene):

 the most important disease caused by Clostridiuom perfringens.
 results from Initial trauma to host tissue damages muscle and impairs blood supply.
 this is a good environment for the growth of clostridia because it results in lack of oxygenation which causes the oxidation-reduction potential to decrease and allows the growth of anaerobic clostridia, and as they grow they destroy muscles and produce gas as a consequence of anaerobic fermentation of muscles.
So they ferment carbohydrate and produce gas, and that’s why the name “Gas Gangrene” , because of the necrotic type of damage that results.
 Infected muscle becomes discolored (purple mottling) and edematous and produces a foul-smelling exudate.
[ the characteristic feature of anaerobic infection is foul-smelling, as a result of accumulation of gas]
even in the oral cavity , if we have abscess or infection in the root of the tooth, you can smell the puss,
if it is foul-smelling  anaerobic infection, because aerobic infections are not associated with foul smell.
 Gas bubbles are generated as a result of anaerobic fermentation.
 capillary permeability increases , which leads to the accumulation of fluid which increased venous return,eventually resulting in increased edema,and blockage of tissue drainage.
 Septicemia although rare, may occur in the late stages of the disease.
 Severe shock with massive hemolysis and renal failure is usually the ultimate cause of death.
There are:
 enterotoxin.
 FOUR major toxins: destroy WBCs, RBCs,etc..
 SEVEN minor toxins: destroy different parts of connective tissue.
So as a result hemolysis developes ,because many of these toxins are hemolytic, or they destroy cells.

 It is primarily caused by C. perfringens but C. septicum and C. novyii may cause it, But when a case of gas gangrene is diagnosed, it’s usually associated with C. perfringens.
 In rare occasions,it may be due to with C. septicum or C. novyii.

 gas gangrene disease illustrates the full virulence potential of histotoxic clostridia.
 the Onset is characterized by severe/ intense pain, generally 1 week after introduction by trauma or surgery,

 Most commonly associated with contamination with spores, because of the abundance of the organism in nature, like in car accidents or other types of trauma, it introduces spores into tissues where it will grow.

 In case of contaminated abdominal surgery, that’s associated with contamination by normal flora of the GI tract, and these organisms are present normally in the GI tract.
 The introduction of the organisms from the GI tract into tissue like skin or abdominal cavity can result in infection and development of gas gangrene.

 The progression from the time of onset through extensive muscle necrosis, shock, renal failure, and death is rapid, frequently occurring in less than 2 days.
So within 24-48 hours, patient dies of severe toxemia, as a result of the rapid progression of lesion.
So this is characteristic of myonecrosis  the rapid progression of the illness to severe necrosi and shock with organ failure take place with less than 2 days characteristic
 Macroscopic examination of muscle reveals devitalized necrotic tissue with the presence of gas. (bubbles cans be seen in the infected tissue.)
 Extensive bleeding and hemolysis are characteristic.( because of the toxins)
NOW, the picture in the handout shows an example of myonecrosis in legs.
The only treatment of this case to stop the infection is to amputate above the knee, otherwise the disease will progress.
 Progressive surgical debridement is required in any case.
but for example,you can’t amputate the abdomen, there should be an aggressive surgical debridement of the dead tisse ( devitalized connective tissue). Otherwise, the organism will still spread,so here conservative treatment leads to death, because it doesn’t stop the pollution of the organism,and as a conqequence it leads to toxemia,and death.

 Soft tissue Infections (Cellulitis, fasciitis)

 can be caused by Clostridia, specially clostridia perfengens.
 Differs from myonecrosis by the lack of muscle involvement ,so muscle is spared,but it shares the same fatal outcome.
 cellulitis is as fatal as myconecrosis.
 Surgical intervention is generally unsuccessful,because of the rapidity with which the organisms spread.
 In cellulitis, the infecting organisms invade only tissue that is already dead, the infection does not spread to healthy undamaged tissue.
 No systemic toxemia.

 Food poisoning
 it’s a GI tract illness caused by clostridium perfengens.
 Abdominal cramps and watery diarrhea in 5-24 hours but no fever, nausea or vomiting.
 Disease is due to ingestion of meat products contaminated with enterotoxin producing type ( A ) C. perfrengens. (self limited in 24 hours).
 disease is due to readymade enterotoxin,usually in contaminated meat dishes, like: shawerma, clostridium perfengens is the most common cause.
Spores are present in meat when people who deals with the meat contaminate it, and these spores will germinate on food.
The cooking of shawerma will not sufficiently destroy the organism spores, but the spores germinate from spore form to vegetate form,during this process they produce the toxin.
So the food is contaminated with toxins, and ingestion of readymade toxins results in this case.
 Enteritis Necroticans
 also called “ necrotizing enterocollitis” , “pg-bel” .
 it’s a GI tract illness caused by clostridium perfengens.
 Acute necrotizing process in the small intestine that is characterized by abdominal pain, bloody diarrhea, shock, and peritonitis.
 Beta toxin is responsible for it.
So dhiarrhea here is different from enterotoxin associated dhiarrhea.

 Bacteremia
- More than half of cases represent transient bacteremia, or more likely contamination and therefore are insignificant.
NOTE: Bacteremia can be  transient
permenant or continuous
And can also be  symptomatic
 asymptomatic

o Early, rapid initiation of surgical treatment, with aggressive surgical debridement and high dose penicillin therapy.
o Mortality is 40-100%.

Clostridium tetani
 the most famous of all clostridia, because it’s associated with tetanus.
 tetanus is a classical disease commonly caused by these organisms, but with the introduction of vaccines ,the incidence of this disease has dropped significantly.
 as an organism, Clostridia tetani is motile because of the presence of flagella around the organism from all sides (peritrichous flagella) and they have terminal spores.
 It causes tetanus by virtue of producing a potent, heat labile, neurotoxin (tetanospasmin) that is produced during the stationary phase of growth and released when cell lysis occurs.
 it also produce another toxin that lysis the RBCs. ( “hemolysin” , “tetanolysin”)
 tetanospasmin is responsible for the clinical manifestations associated with infections caused by clostridium tetani.
 the organism itself is not invasive.
 in many cases, it’s difficult to make an early diagnosis because of the lack of the initial infection,
Example, someone who stepped on a nail and forgot about it,then after 2 months, he develops tetanus.
It’s also very difficult to find at the point of entry of the organism, any inflammatory response or any infection.
So  it’s the presence of organisms that set there, starting the production of the toxin, make this producing while dying actually.
So  tetanus is produced during the maximum stationary phase of growth,and when decline phase they start to release the toxin they produced during the maximum stationary phase.
Remember the bacterial growth curve :

 The toxin is composed of two chains,one is responsible for binding,and the other is responsible for the biological function of the toxin,
 light and heavy (A and B), and it is cleaved into the subunits by protease when it is released from the cell.
 The two chains are held together by an S-S bond.
 The heavy chain binds to gangliosides (GT1) on neuronal membranes.
 The light chain is then internalized and moves from the peripheral nerve terminals to the CNS by retrograde axonal transport.
So, the retrograde axonal transport is responsible for the introduction of the toxin.
 It is released from the postsynaptic dendrites, crosses the synaptic cleft, and is localized within vesicles in the presynaptic nerve terminals, where they block the release of mediators, that’s why they cause severe convulsions or spasm.
Toxin Effect:
o 130 ug (microgram) is lethal for humans.
o It enters through neuromuscular junction of α motor neurons and it involves three components of the nervous system.
1. Central motor control
2. Neuromuscular junction (defective release of Acetylcholine)
3. Autonomic function

o Once it gains access to inhibitory neurons it blocks the release of the neurotransmitters glycine and gamma- aminobutyric acid
o This permits simultaneous spasms of both agonist and antagonist muscles producing muscle rigidity and convulsions  this is the net effect of the toxin.
o C. tetani also produces an oxygen labile hemolysin (tetanolysin).

 The organism is not invasive and remains confined to the necrotic tissue where the vegetative cells elaborate the lethal toxin.
 Tetanus is either generalized or local.
 the generalized is usually Descending, whereas the Localized is Ascending, and that is related to the amount of toxin produced.

 In generalized (descending) tetanus,the amount of toxin is High,so it is not possible to absorb all of the toxin by local nerve endings, therefore, it passes into the blood stream (blood and lymph) with subsequent absorption by motor nerves.
 that’s why the convulsions and muscle spasm starts from the upper part of the body,the muscles of the face,( masseter muscles),so the first symptom is usually trismus (lock jaw( (عدم القدرة على تحريك الفك) with muscle spasms descending from the neck to the trunk and limbs.
 As the disease progresses, the spasm increases in severity becoming very painful and exhausting.
 Spasm is initiated by environmental stimuli (light flash, footstep sound).
So the patient who suffers from tetanus is kept in a dark room with the lights off to keep him relaxed,but if u turn the light on , or he hears footsteps, this can initiate spasmatic attack of tetanus.
 In Localized tetanus (ascending), all amount of toxin is absorbed, toxins travel along the neural route causing a disease confined to the extremities,and causing troubles to the spinal cord.

Clinical Syndromes:
 Variable incubation (few days to weeks to months); the length is directly related to the distance of the primary wound infection from the central nervous system.
Which means, it depend on the site that has the toxin producing organism,and the CNS.
That’s why in the extremeties  incubation period is long.(several weeks)
But if it is in the face  incubation period is several days. ( known as “ cephalic tetanus” )
So, the closer to the CNS, the shorter the incubation period.
 The initial symptom is cramping and twitching of muscles around the wound  this is characteristic of tetanus.
 Spasm with head and hands are bent backward and the body bowed forward is common  this is characteristic of tetanus.
 Complications include fractures( because of severe spasm), muscle ruptures, hematomas and organ failure.

 Generalized tetanus is the most common form seen.
 Involvement of the masseter muscles (trismus or lock-Jaw) is the presenting sign in the majority of patients.
 The sardonic smile characteristic of sustained trismus is known as "risus Sardonicus" السحنة السردونية
So the patient looks like he’s smiling,but he’s not, and this expression is due to muscle spasm.
 Other early signs include drooling, sweating, irritability and persistent back spasms.
 More severe disease is seen with involvement of the autonomic nervous system with cardiac arrhythmias, fluctuation in blood pressure, profound sweating, and dehydration.
 A variant of localized tetanus is cephalic tetanus in which the primary site of infection is the head (very poor prognosis).

 Neonatal tetanus
-In newborns , in 2 cases, if :
1) susceptible mothers.
mothers who don’t have immunity,and that’s why the prevention of neonatal tetanus is to vaccinate the mother, because antibodoies that are produced will pass through the placenta to the fetus,and if the fetus is exposed to the organism, he has immunity, antibodied that protect him through the neonatal period ( 6 months) ,then he’ll be immunized after 2 months of age he’ll be given the vaccine,and he’ll develop his own immunity. But, if the mother is not immuned,the new born will also be susceptible.

2) the umbilical stump is contaminated.
Contamination of the umbilical cord takes place because of the use of contaminated items to cut the cord. ( when the mother has her baby in the dessert, or far places, the knife used will be contaminated with organisms from the animals)
 average mortality rate : 90%  highly fatal ,whereas 40% for adults.

a. Proper care of wounds ( e.g. surgical care).
b. Anti toxin : should be given intrawound (antibodies given inside the wound).
c. Vaccination (Toxoid)
Treatment :
if the individual develops the disease , the only treatment is antitoxin, there’s no need to treat the organism, because there’s no organism by that time, it’s only intoxication.
 No immunity following infection.
 That’s why individuals can be reinfected, and the vaccine for infection, but toxin antibodies can’t be produced if he survive, they can resist the toxin but not the infection,the infection takes place because there’s no immunity to the infection.
Now the pictures:
In the first picture you can see a neonate with spasm, head backward, hand forward.
In the second picture, you can see a newborn with what we call “risus Sardonicus”, due to severe spasm in masseter muscles.
In the third picture you see the typical spasm, the back and head backwar, and hand forward.
So tetanus is a disease that should be prevented not treated, it’s highly fatal and communities can’t afford to treat patients after they are diseased with it.
That’s why tetanus toxoid is one of the components of the immunization program in all countries, including Jordan . ( the EPI: Extended Program of immunization) .
 Tetanus is what we know as "الكزاز" , and when someone for example step on a needle, he is given tetanus toxoid, and this provides him with the vaccine before the toxin is made, because the incubation period is long, so you protects him.
And that’s why we need proper care of wounds, if it’s treated properly there would be no infection , but if the person is injured and didn’t pay attention to it ( specially young kids , they don’t seek medical care, so they might develop the disease).

Clostridium botulinum
 the 3rd classical infection by anaerobic clostridia.
 The etiological agent of botulism(الانسمام الوشيقي) it’s usually associated with anaerobic production of the toxin in canned food, and ingestion of the toxin ( not the organism) .

Botulinum is endotoxication in most cases.
 Four groups I-IV.
 Seven antigenically distinct toxins (A-G) have been described with human disease associated with types A, B and E.
 Toxin is composed of two subunits , one is responsible for binding, and the other is responsible for the biological function of the toxin,
 A (neurotoxin) and B the nontoxic subunit which protects the neurotoxin from inactivation by stomach acids.

 Effect of the toxin : Botulism is very specific for cholinergic nerves.
 The toxin blocks neurotransmission at peripheral cholinergic synapses by preventing release of acetylcholine  resulting in flaccid paralysis.
Tetanus  spasm convulsions
Botulism  flaccid paralysis.
Opposite effect .
 Three forms of botulism have been identified, classical (or food borne), infant, and wound botulism.
 the classical botulism : Toxin binds to neuromuscular junctions of parasympathetic nerves.
 Cranial nerves are affected first followed by motor nerves.
* Problems in eyesight, hearing and speech.
* Double or blurred vision, dilated pupils.( because of paralysis of the muscles controlling the eye movement).
* slurred speech, decreased salivation and
* difficulty in swallowing.
Patients usually die from respiratory failure, resulting from paralysis of all muscle.

Clinical Syndromes
 Food-borne Botulism:

 1-4 days ( incubation period) after consumption of contaminated food the patient develops weakness and dizziness.
 The initial signs of botulism include blurred vision with fixed dilated pupils, dry mouth (anticholinergic effect), constipation and abdominal pain.
 Bilateral descending weakness of the peripheral muscles develops in progressive disease (flaccid paralysis) with death most commonly attributed to respiratory paralysis.
 Complete recovery in patients who survive this initial period frequently requires many months to years until the affected nerve endings regrow.
 Mortality has been reduced to 10% (was 70%) with better supportive care.
In the past, patients usually died from respiratory failure, now there is artificial respiration, this is how they survive.

 Infant Botulism

 it is different from other types of botulism in that the organism is ingested ( NOT the toxin), and then starts to make the toxin inside the body.
 usually associated with Consumption of contaminated honey.
That’s why Honey is contraindicated for children , you shouldn’t feed children under the age of 1 year honey , although it’s very rich.
Honey is commonly contaminated with clostridium perfringens or clostridium botulinum, ( by bees,they only transport these organisms), and it’s kept within the honey or their spores,and contaminate it.

 In contrast to the food-borne variant, it is caused by the in vivo production of neurotoxin by C. botulinum colonizing the gastrointestinal tract of young infants (1-6 months).

 It has low mortality (1-2%).

 Wound Botulism

 It is rare resulting from contaminated wounds.
 Identical in clinical picture to the food-borne but less prominent gastrointestinal symptoms.

Clostridium difficile

 It is associated with the use of wide spectrum antimicrobial agents.
 If the normal flora is destroyed , clostridium difficile overgrow produces an enterotoxin (toxin A) that is responsible for diarrhea and pseudomembranous colitis, and a cytotoxin (toxin B).
 The enterotoxin is chemotactic for neutrophils (infiltration with PMNs and hemorrhagic necrosis).
o ( PMNs: Poly Morphic Neutrophils)
 Spreads infection among hospitalized patients ,nurseries, senior citizen houses, and those who are given antibiotics for long period of time.
 It is a major nosocomial pathogen that causes a spectrum of intestinal diseases from un complicated antibiotic associated diarrhea to severe, possibly fatal, antibiotic associated colitis.
 It is associated with the use of wide spectrum antimicrobial agents.
 Many antibiotics have been associated with it including ampicillin, cephalosporins, clindamycin and amoxicillin, in addition to newer penicillin and antineoplastics (methotrexate).
 Clinical syndromes vary widely from mild diarrhea to severe abdominal pain, fever, and severe weakness.
 These syndrome usually appears after using the antibiotic for a week or so.
 Variable pathology

Clostridium sordelli
 Produces several exotoxins.
 It has been implicated in bone and joint infections, in pulmonary infections, in bacteremia and in fulminant endometritis.

Clostridium septicum
 Has been recovered from patients with malignancy most likely in the ileum or colon.
 Should be treated quickly.
This is a characteristic of cancer; if patient starts to suffer from infection with clostridium septicum, one should suspect that they have colon cancer.
Clostridium septicum  highly associated with colon cancer.


Anaerobic Non Spore-forming Gram-Positive Bacilli

 Pleomorphic, gram-positive bacteria with some tendency toward mycelial growth.
 Despite their name, which means "ray fungus" They typically form delicate filamentous forms or hyphae, similar to fungi but they are true bacteria.
 They are facultative anaerobes or strict anaerobes, not acid fast and are nonmotile.
[Look at the picture in hand out that shows their growth]

 The organisms have a low virulence potential and cause disease only when the normal mucosal barriers are disrupted by trauma, surgery or infection.
 They can only cause infection in immunocompromised patients,or if displaced from its site ( e.g. from the oral cavity to the chest ,or to the abdomen, or to the pelvis or to the brain ) thay can sauce disease.
 They are members of the human oral flora and are major components of the dental plaque.
 They also normally colonize upper respiratory tract, gastrointestinal tract, and female genital tract.
 They tend to produce chronic, slowly developing infections.

 Actinomycosis results when bacteria resident in the mouth are introduced into tissues by mechanisms that are not clear.

 Actinomycosis is almost always a mixed infection and disease is an endogenous infection. ( not acquired from environment or another person, it’s already present normally in the oral cavity, and because of defect in the immunity of individual, he start developing disease)
 It is a chronic disease characterized by the production of suppurative abscesses or granulomas that eventually develop draining sinuses.

 They establish chronic, suppurative infection that can spread unchecked through tissue planes, producing a multiorgan disease.
 Actinomycosis is charachterized by multiple abscesses connected by sinus tracts.
 These lesions discharge pus containing the organisms in firm yellowish granules called sulfur granules.
 Macroscopic colonies (sulfur granules), appear yellow or orange, are filamentous organisms bound together by calcium phosphate.

 The areas of suppuration are surrounded by fibrous granulomatous tissue giving the surface overlying it a hard or woody consistency.
 The disease is divided into three major clinical types; cervicofacial, thoracic and abdominal.
 The majority of cases are cervicofacial, usually along the angle of the jaw and neck (that’s why it’s called “ the lumpy jaw” ). Lung and abdominal disease are less common, and so pelvic disease.

 It may involve any organ subsequent to direct or indirect (hematogenous) spread.

 Cervicofacial
 Involves the face, neck, jaw or tongue.
 Follows injury or a dental manipulation.
 Begins with pain and firm swelling along the jaw which progresses slowly until draining sinuses are produced. ( with characteristic discharge, yellowish sulfur granules)
 Thoracic
 Results from aspiration of pieces of infectious material from the teeth.
 Involves the chest wall, the lungs or both.
 Symptoms of chronic pulmonary disease.
 Spread leads to brain abscess. (by spreading through blood vessels to the brain )

 Abdominal
 Often associated with abdominal surgery, accidental trauma or acute perforative gastrointestinal disease.
 Persistent purulent drainage.

Treatment :
Long-term antibiotic (penicillin) therapy combined with surgical drainage and excision of damage tissue.
( Actinomycosis is a chronic infection that should be treated with long administration of penicillin along with surgical drainage and excision of damage tissue )

Done by: Hala Al- Ansari .
Lecture date: 1-11-2010
Shadi Jarrar
مشرف عام

عدد المساهمات : 997
النشاط : 12
تاريخ التسجيل : 2009-08-28
العمر : 27
الموقع : Amman-Jordan

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