Clostridium perfringens Clostridium tetani

Clostridium botulinum Clostridium difficile

Clostridium septicum

ANAEROBIC, SPORE-FORMINGGRAM-POSITIVE BACILLI

Clostridium perfringens

Causes two distinct diseases:

Gas gangrene

Food poisoning

Clostridium perfringens

Pathogenesis

Present in soil, water and sewage, and as a normal resident of the gastrointestinal tract

Spore formation enables the organism to survive in the environment

Clostridium perfringens

Clostridium perfringens

Pathogenesis

Alpha toxin: A phospholipase C (lecithinase) lyses erythrocytes, platelets, leukocytes and

endothelial cellsincreased vascular permeabilitymassive hemolysis and bleedingtissue destructionhepatic toxicitymyocardial dysfunction

Clostridium perfringens

phosphatidylcholine

Clostridium perfringens

Pathogenesis

Beta toxin necrotic lesions in necrotizing enteritis

Epsilon toxin increases vascular permeability

Iota toxin ADP ribosylating lethal toxin, necrotic activity, increases vascular permeability

Enterotoxin released during spore formation in the small intestine, disrupts ion transport

Clostridium perfringens

Zone of complete hemolysis caused by theta toxin

Wider zone of partial hemolysis caused by alpha toxin

Clostridium perfringens

Transmission

Exogenous exposure (soil, food, trauma, surgery) is more common than endogenous spread

Vegetative cells are part of the normal flora of the colon and vagina

Clostridium perfringens

Clinical syndromes

Myonecrosis (gas gangrene)Life-threatening diseaseMuscle necrosis, shock, renal failureDeath frequently within 2 days of onsetGas generated by the metabolic activity of the rapidly dividing bacteria

Clostridium perfringens

Clinical syndromes

Cellulitis: Necrosis of the skin layer (subcutaneous gas)

Fasciitis: Infection of the fascia, suppuration, gas

Food poisoning: Abdominal cramps and watery diarrhea

Necrotizing enteritis: Bloody diarrhea, shock and peritonitis

Clostridium perfringens

Clostridialcellulitis followingcompound fractureof the tibia

Clostridium perfringens

Treatment and control

Rapid treatment is essentialsurgical debridement high-dose penicillin G therapy

Proper wound care and use of prophylactic antibiotics can prevent infections

Clostridium tetani

Causes tetanus (lockjaw) Small, motile, spore-forming bacillus

Frequently stains negative

Terminal spores give the appearance of a drumstick

Clostridium tetani

Gram stain withterminal spores

Clostridium tetani

PathogenesisTetanospasmin

Synthesized as an A-B toxin

B chain binds to a receptor on neuronal membranes

Clostridium tetani

PathogenesisTetanospasmin

“A” chain (zinc endopeptidase)Localizes in vesicles in presynaptic

nerve terminals of inhibitory synapses

Causes the excitatory synaptic activity to be unregulated

Leads to spastic paralysis

Clostridium tetani

Pathogenesis

TetanolysinOxygen-labile hemolysinInhibited by serum cholesterol

Spore formation

Clostridium tetani

Transmission

In fertile soil and the GI tract of many animals and humans

> 1 million cases worldwide (mortality rate 20-50%)Half the deaths occurring in neonatesAssociated with minor trauma

skin break with contaminated splinter or nail Germination of spores favored by necrotic tissue

and poor blood supply

Clostridium tetani

Clinical syndromes

Generalized tetanus (trismus or lockjaw) risus sardonicus: "smile" due to sustained

contraction of the facial musclesDrooling, sweating, persistent back spasmsCardiac arrythmias, fluctuations in blood

pressure, hyperthermia, dehydration High mortality rate

Clostridium tetani

Clostridium tetani

Risus sardonicuscaused bysustained spasmsof the massetermuscles

Clinical syndromes

Localized tetanus: Involvement of muscles in area of primary injury. Prognosis favorable

Cephalic tetanus: Cranial nerves. Very poor prognosis

Neonatal tetanus: Via umbilical stump. Very poor prognosis when mothers are not immune

Clostridium tetani

Treatment and control

Debridement of the primary woundMetronidazole or penicillin GHuman tetanus immunoglobulinVaccination with tetanus toxoid

Three doses of tetanus toxoid and a booster every 10 years

Clostridium tetani

Pathogenesis

Botulinum toxinSimilar to tetanus toxin, but inhibits

cholinergic synaptic transmissionBinary toxin

Two components that combine to disrupt vascular permeability

Spore formation

Clostridium botulinum

Clostridium botulinum

Transmission and clinical syndromes

Foodborne botulismHome-canned foodsWeakness and dizziness 1-2 days laterBlurred vision, dry mouth due to

anticholinergic effect of the toxinConstipation and abdominal pain

Clostridium botulinum

Transmission and clinical syndromes

Progressive diseaseWeakening of peripheral muscles (flaccid

paralysis)Respiratory paralysisComplete recovery months to years

(regeneration of paralyzed nerve endings)

Clostridium botulinum

Transmission and clinical syndromes

Infant botulismIngestion of spores in food (contaminated

honey)Colonization of the GI tractInitial symptoms: constipation, weak cry,

failure to thrive

Clostridium botulinum

Transmission and clinical syndromes

Wound botulismDue to infection of woundsGI symptoms less severeOther symptoms identical to foodborne

disease

Clostridium botulinum

Treatment and control

Ventilatory supportLavageMetronidazole or penicillin therapyBotulinum antitoxin against toxins A, B and EPreventing spore germination by maintaining foods

in acid pH and at 4oCNo honey for children younger than 1 year

Clostridium botulinum

Antibiotic-associated gastrointestinal diseases

Can cause life-threatening pseudomembranous colitis

In soil, water and sewage

Clostridium difficile

Pathogenesis

Antibiotics (clindamycin and ampicillin) can alter the normal enteric flora and enable the overgrowth of relatively resistant C. difficile

Disease develops if the organism develops in the colon and produces toxins

Clostridium difficile

Pathogenesis

Enterotoxin (toxin A)

Causes hypersecretion of fluid (watery diarrhea) and hemorrhagic necrosis

Clostridium difficile

Pathogenesis

Cytotoxin (toxin B)ADP-ribosylates the GTP-binding protein

RhoInduces depolymerization of actinCauses damage to the colonic mucosa,

leading to pseudomembrane formation

Clostridium difficile

Pathogenesis

Adhesin factorMediates binding to human colonic cells

HyaluronidaseHydrolytic activity

SporesSurvival for months in a hospital environment

Clostridium difficile

Clinical syndromes

Diarrhea, associated with pseudomembranes (yellow-white plaques) on the colonic mucosa

Found in the GI tract of about 3% of the general population and up to 30% of hospitalized patients

The most common nosocomial cause of diarrhea

Clostridium difficile

Clostridium difficile

Antibioticassociated colitis

Plaques of fibrin,mucus andinflammatory cells

Antibioticassociated colitis

Plaque

Intact intestinalepithelium

Clostridium difficile

Treatment and control

Discontinuation of the implicated antibiotic

Therapy with metronidazole or vancomycin

Resistant spores can be a major source of nosocomial outbreaks

Clostridium difficile

Treatment and control

In patients with occult colon cancer, acute leukemia and diabetes

It can spread into tissues and proliferate, causing death within a few days of initial symptoms

Clostridium septicum