Anaerobes

A. Organisms- The spore-forming anaerobic pathogens are in the genus Clostridium

Gram positive rods; form endospores; resistant to desiccation and heat

Ubiquitous in nature in soil and dead and decaying organic matter

Man encounters these saprophytes accidently

Don't have enzymes to detoxify toxic oxygen products:
superoxide dismutase, catalase, peroxidase

Physiology and Structure
-Gram-positive rods with prominent terminal spores (drumstick appearance)
-Strict anaerobe
Difficult to isolate from clinical specimens

Virulence
-Tetanospasmin is a heat labile 150 kD A-B neurotoxin, released during growth of vegetative cells;
Binds to gangliosides on neuronal membranes and interferes with normal inhibitory function

Epidemiology
Ubiquitous; spores found in most soils


Reservoir- large intestines of wild and domesticated animals and humans; spores commonly found in soil

Portal of entry- spores enter through skin puncture; the spores and vegetative cells do not disseminate from initial site of infection

Predisposing factors-
outgrowth of vegetative cells in anaerobic wounds with necrotic tissue and decreased blood supply

People with inadequate vaccine-induced immunity; disease does not induce immunity

Generalized tetanus: Generalized musculature spasms and involvement of the autonomic nervous system
Severe disease (e.g., cardiac arrhythmias, fluctuations in blood pressure, profound sweating, dehydration)

Localized tetanus: Musculature spasms restricted to localized area of primary infection

Neonatal tetanus: Neonatal infection primarily involving the umbilical stump; very high mortality

Sample- bacteriological dx of little value, base dx on clinical presentation Neither tetanus toxin nor antibodies are typically detected

Etiologic agent- Clostridium tetani anaerobic, Gram positive, motile, spore forming rod; spores are terminal (tennis racket appearance)

1. Prophylaxis- active immunization with tetanus toxoid

2. Elimination of predisposing factors- surgical debridement of necrotic tissue

3. Vaccination- first w/ DPaT; toxoid every 10 y oftener if at risk. DT toxoid vaccine is available.

4. Drug or antibody prophylaxis- antibiotic therapy plus passive immunization with human anti-tetanus immunoglobulin for unvaccinated cases

5. Treatment of symptoms- supportive for CNS effects

6. Immunity- solid long lasting (10 years) after vaccination or recovery from disease

Large, rectangular, gram-positive rods

Spores, rarely seen in clinical specimens or culture; located sub-terminal

Replicates rapidly, large, spreading colonies seen on first day of culture

Produces many toxins and hemolytic enzymes; blood cells not seen in Gram-stains

Subdivided into five types (A to E) on the basis of toxin production

Portal of entry-
route- gunshots, puncture wounds, skin and uterus

predisposing factors- same as for tetanus

Immunity- not important

Mode of dissemination-
direct from original focal infection;

don't invade bloodstream except in uterine gas gangrene

Virulence factors-
extracellular, necrotizing, hemolytic and lethal toxins

incubation period ca. 1 day; acute inflammatory response in anaerobic cellulitis; extensive edema and tissue destruction; CO2 and H2 produced (crepitation);
The damaged tissue must be removed to save the patient

Incidence- all ages infected because organisms are widespread in environment

Incidence of food poisoning and gas gangrene parallels sanitary conditions

Reservoir- large intestine and female genital tract of humans and nonhuman animals

Type A is responsible for most human infections
Disease follows exogenous or endogenous exposure

based mostly on clinical observations

Sample- necrotic tissue and blood

Direct examination of specimen-

Gram stain shows only Gram + rod-shaped Clostridia;

1. Prophylaxis- immediate wound surgical debridement; massive antibiotic therapy; treatment in hyperbaric chamber

2. Elimination of predisposing factors- sterile surgical instruments; prophylactic antibiotic sterilization prior to abdominal surgery

3. Drug or antibody prophylaxis- high dose antibiotic coverage; passive administration of polyvalent antitoxin may help

4. Immunity- not applicable to rapidly progressing potentially fatal disease

Portal of entry-
oral route in food borne

colonization of GI tract in infants (not highly acidic stomach)

wound infection is rare

Mode of dissemination
digestive enzyme-resistant toxin absorbed from the GI tract

enters bloodstream, homes in on neuromuscular junctions

binds to gangliosides in nerve membranes

Virulence factors- neurotoxins

Immunity- no innate immunity,

C. botulinum causes food-borne botulism in all age groups worldwide; incidence related to sanitation

Infant botulism in infants < 9 mo old

Food-borne disease is ubiquitous

Commonly isolated from soil; found on fresh vegetables and in silt in lakes and ponds

Associated with consumption of inappropriately stored, tainted fresh, smoked or improperly canned food


Relatively few cases of botulism in the United States

Foodborne botulism:
blurred vision, dry mouth, constipation, and abdominal pain
->bilateral descending weakness of the peripheral muscles with flaccid paralysis

Infant botulism: Initially nonspecific symptoms (e.g., constipation, weak cry, failure to thrive)
->flaccid paralysis and respiratory arrest
low stomach pH so organisms remain in intestines and grow in situ

Wound botulism: Same as foodborne disease
incubation period longer
fewer gastrointestinal symptoms

Sample- food and/or feces

Gram positive spore-forming bacillus on anaerobic media
isolation from feces important in infant botulism detection

Confusing normal flora
other normal flora clostridia in stool sample

Prophylaxis- destruction of spores in food products

Drug or antibody prophylaxis
treat with polyvalent antitoxin vs. A, B, E toxins plus supportive therapy

Physiology and Structure

Gram-positive, spore-forming rod

Strict anaerobe (vegetative cells are extremely oxygen sensitive)

Enterotoxin (toxin A):
Produces chemotaxis; induces cytokine production with hypersecretion of fluid; produces hemorrhagic necrosis

Cytotoxin (toxin B):
Induces depolymerization of actin with loss of cellular cytoskeleton

Adhesin factor:
binds to human colonic cells

Spore formation:
survive for months in hospital environment

Organism is ubiquitous; colonizes the intestines of (<5%) of healthy individuals

Exposure to antibiotics causes overgrowth of C. difficile -> endogenous infection

Disease
Similar to C. perfringens: enteric disease

Diagnosis

Confirmed by detecting the cytotoxin or enterotoxin in feces

Treatment, Prevention, and Control

Discontinue the implicated antibiotic

Treat with vancomycin in severe disease

All are normal flora
Fusobacterium nucleatum
-Oral, pulmonary
Bacteroides fragilis
-Intra-abdominal infections
Prevotella melaninogenicus
-Pelvic infections
Porphyromonas gingivalis
-Oral, Dental infections
Peptostreptococcus
-Intraabdominal, Soft tissue, bone
Actinomyces israeli
-Actinomycosis

inhabit oropharynx, GI tract and GU tract as normal flora; G – rods and G+ cocci

opportunistic infections from endogenous spread to normally sterile body sites

ubiquitous in humans of all ages

involved in > 50% of all abscesses, aspiration pneumonias etc.

Reservoir- GI tract, GU tract and oral cavity

Portal of entry-
mucosal surfaces/organs colonized with liberated endogenous organisms

Predisposing factors
ruptured appendix, diverticulum, gunshot, low oxygen tension

Mode of dissemination-
localized except for abscess -> bacteremia

Virulence factors-
pili on some bacteroides; LPS incites inflammation

Encapsulated bacteria resist phagocytosis and evade PMN’s by bactericidal mechanisms
Microcolonies release tissue destroying factors to form localized abscesses
Organisms from abscess may enter bloodstream and seed other sites
Symptoms/signs: fever, pain, nausea, diarrhea, cellulitis, gangrene, FOUL ODORS
No adaptive immune response is elicited by these normal flora organisms. Innate immunity does result in inflammation, cytokine release etc. but clearance is minimal.

Sample- pus or fluid obtained by aspiration

Direct examination of specimen- Gram - thin rods, usually mixed infections; many PMNs



Confusing normal flora- combine direct smear and clinical picture for dx

Key diagnostic tests- biochemical tests plus end product ID by gas chromatography;

Prophylaxis- antibiotic sterilization prior to abdominal surgery; immediate debridement and disinfection of wounds

Vaccination- not applicable

Treatment of choice for bacteria- clindamycin, metronidazole, often multidrug protocols required

Treatment of symptoms- surgical irrigation and drainage; prolonged high dose antibiotics

Actinomyces:
Actinomycosis

Propionibacterium:
Acne, lacrimal canliculitis, opportunistic infections

Mobiluncus:
Bacterial vaginosis, opportunistic infections