Gram positive

Cocci

Staphylococci

Streptococci

Enterococci

Bacilli

Bacillus

Clostridia

Corynebacteria

Genus Clostridium

Learning objectives:

Describe the basic microbiological features of the

genus Clostridium

Describe clinical significance of the genus Clostridium

List the most clinically important Clostridium species

List the main clinical conditions caused by C.

perfringens, C. tetani, C. botulinum and C. difficile

and describe their major virulence factors

Learning objectives:

Describe the major differences between the

main clinical conditions caused by C.

perfringens, C. tetani, C. botulinum and C.

difficile and describe the laboratory methods

used in the diagnosis of each infection

Describe in general the management of the

main infections caused by genus Clostridium

Clostridium

> 200 species and sub-species

Thick, Gram-positive, sporing rod

Strict anaerobes

Soil is natural habitat

GIT

Exotoxins and enzymes

Medically important speciesC. perfringens

◦Anaerobic cellulitis and gas gangrene (clostridial myonecrosis)

C. tetani◦Tetanus

C. botulinum◦Botulism

C. difficile◦Pseudomembranous colitis

Diagnosis of clostridial infections

Identification of the pathogen

◦Gas gangrene

Identification of the pathogen +

toxins

◦Tetanus, botulism and colitis

Morphology and culturingLarge, Gram-positive rod

Flagellated (except C. perfringens)

Sporulated

Anaerobic atmosphere at 37°C

C. perfringens colonies are convex, smooth, and hemolytic

Colonies of motile clostridia have an irregular edge

Management Penicillin GAntitoxins are used in therapy of

tetanus and botulismHyperbaric O2 is used to treat

gas gangreneThe most important preventive

measure against tetanus is active vaccination with tetanus toxoid

Gas gangrene (clostridial myonecrosis)

Anaerobic cellulitis

Pathogen spectrumClostridium perfringens

C. novyi

C. septicum

C. histolyticum

Toxins and enzymesToxins:

◦Necrotizing, hemolytic, and/or lethal activity

Enzymes:◦Collagenases, proteinases, DNases,

lecithinases, and hyaluronidase

Pathogenesis and clinical pictureFrequently contaminate open

wounds

Types of infections:

◦Anaerobic cellulitis

◦Gas gangrene (clostridial myonecrosis)

Anaerobic cellulitis

Infection restricted to the fascial spaces that does not affect musculature

There is no toxemia

Gas gangrene (clostridial myonecrosis)

An aggressive infection of the muscles

Gas, myonecrosis and toxemia

Medical emergency

Laboratory diagnosisSpecimens

Direct examination

Anaerobic culture

Identification

Clostridium tetani

(Tetanus)

Tetanus (lockjaw)

Acute clostridial disease

Clinical manifestations caused by

strong neurotoxin

(tetanospasmin)

Pathogenesis and clinical picture

Pathogens invade tissues following injuries

Toxin produced

Increased muscle tone and spasms

Diagnosis

Toxin detection in wound material

The pathogen is difficult to culture

Treatment

Anti-toxin

Wound cleaning

Muscle relaxants

Clostridium botulinum

(botulism)

Botulism

Rare but serious paralytic illness

The toxin enters the human body in one of three ways:

◦Ingestion of spores (infant botulism)

◦Toxin ingested with food (adult botulism)

◦Infected wounds (wound botulism)

Clostridium botulinum toxin

Very strong neurotoxin

Heat-labile protein

Flaccid paralysis

Clinical picture of classic botulismParalysis especially in the nerves

of the headFrequent symptoms: seeing

double, difficulty swallowing and speaking, constipation, and dry mucosa

Mortality and cause of death

Mortality: 25–70%, depending on

the amount of toxin ingested

Death usually results from

respiratory paralysis

Diagnosis and treatment

Diagnosis:

◦Toxin detection

Therapy:

◦Anti-toxin

Clostridium difficile

(pseudomembranous colitis)

Clostridium difficileFecal flora of 1–4% of healthy

adults and in 30–50% of children during the first year of life

Pseudomembranous colitis:◦Clindamycin◦Aminopenicillins◦Cephalosporins

Antibiotic-associated colitis

Pathological mechanism

Based on formation of two toxins:

◦Toxin A is an enterotoxin

◦Toxin B is a cytotoxin

Laboratory diagnosis

Isolation of the pathogen

Cytotoxin detection in stool

filtrates by cytopathic effect

ELISA for toxins “A” and “B”

Treatment

Not always required

Indicated only in severe cases

Metronidazole is the drug of choice