Anaerobic Model

strict anaerobes

-lack the cytochrome systems for metabolism of O2
-lack the ability to detoxify reactive oxygen species
-require a low oxidation reduction potential to function

most anaerobic infections of humans are caused by

moderately obligate anaerobes

facultative anaerobes

favor anaerobic conditions over aerobic conditions when present at an infection they use up available O2 and then change to anaerobic metabolism

aerotolerant anaerobes

exclusively use anaerobic type of metabolism but are insensitive to the presence of O2

anaerobes in the colon

secrete products that are important for human health like vit K and bile
anaerobes outnumber aerobes 1000:1
Bacteriodes spp. and Fusobacterium are predominant

normal vaginal flora

Prevotella
Bacteroides
Fusobacterium
Clostridium spp.

normal oral flora

Prevotella
Porphymonas spp.
Bacteroides
Fusobacterium
Actinomyces spp.

infections caused by anaerobes

often polymicrobial
usually arise when there is a disruption in the mucosa and resident flora contaminate the usually sterile site

hallmark of contamination of sterile site by anaerobic gram-negative bacteria

abscess formation

anaerobic infection is suspected when

- putrid discharge
- gram stain shows polymicrobial flora
- infection is adjacent to a mucosal surface commonly colonized w/ anaerobic flora
- aerobic cultures are negative
- gas is present in tissues
- patient has failed to respond to a course of antibiotics

Bacteroides spp.

-gram negative slender ods or coccobacilli
- resistant to bile and hydrolyze esculin
- normal inhabitants of human colon and other sites
- major player in infection is B. fragilis

B. fragilis

virulence factors:
- polysaccharide capsule is the major virulence factor
- endotoxin (LPS) possesses little biological activity
-organism produces other enzymes and toxins (neuraminidase, protease, pili, hemagglutinins)
most commonly isolated organism in intra-abdominal infections
drug resistance is common

Porphyromonas spp.

gram-negative bacilli
pigmented colonies on blood agar
part of normal oral flora
typically involved in oral and dental infections

Prevotella spp.

gram-negative slender bacilli or coccobacilli
pigmented colonies on blood agar
part of normal oral and vaginal flora
typically involved in oral dental and URT infections

Fusobacterium spp.

pleomorphic gram-negative rods that can appear needle-like
part of normal flora of mouth, colon and other sites
frequently isolated from mixed infections

Peptostreptococcus spp.

gram-positive cocci of variable size
part of normal flora of skin and mucous membranes
frequently found in mixed infections due to normal flora

Actinomyces spp.

gram-positive branching rods that tend to form branches or filaments
non-acid fast
some are oxygen-tolerant
slow growing
soil organisms
part of normal flora in gingival crevices and female genital tract
cause of actinomycosis

actinomycosis

caused by Actinomyces spp.
chronic granulamatous inflammation leading to abscess formation, suppuration and sinus drainage

diagnosis of anaerobic infections

in many cases isolation and ID is not necessary particularly when a mixed infection is suspected
if bacteremia is suspected culture can be very helpful
specimen collection and transport is critical to successful culture of anaerobes

treatment of anaerobic infections

- surgical drainage
- antimicrobial therapy
- Bacteroides spp. Prevotella spp. Porphyromonas spp. and Fusobacterium spp. utilize B-Lactamase production as a mechanism for resistance.

Clostridium spp.

gram-positive
spore forming
bacilli
organisms are anaerobic
spores are aerotolerant

Clostridum botulinum
encounter

Botulism
spores are found in soil or marine sediments and contaminate meats, veggies, and fish
Heat resistant spores can survive food processing and canning when the temp is not high enough
inside the can b/c conditions are anaerobic the spores will germinate and release toxins
toxins are so potent even a nibble of contaminated food can cause lethal disease

Clostridum botulinum
damage

-produces 8 neurotoxins. Human cases are associated mostly with types A and B and sometimes E
-Botulism is caused by ingestion of a preformed neurotoxin; neurotransmission at peripheral cholinergic synapses is blocked by release of acetylcholine

botulism
clinical disease

onset occurs 12-36 hours post ingestion
characterized by flaccid paralysis of muscle
-cranial nerves are affected first causing blurred and double vision
-difficulty swallowing is an early sign
-paralysis descends and striated muscles weaken then respiratory muscles weaken
-illness may last for weeks

infant botulism

-toxin is not found in food but produced in infant's intestinal tract; organism colonized the large intestine where it produces toxin
-onset is slower and occurs in infants between 3-20 weeks of age
-disease produces a generalized hyptonic (floppy) state and infant's cry becomes feeble and suck reflexes weaken
-favorable outcome in majority of cases even w/ supportive care alone

Botulism treatment

-antitoxin is available for types A, B, and E and should be administered asap. antitoxin is acquired from horses and there has been a high association w/ hypersensitivity
-supportive care is the most important aspect of treatment
-illness may last for many weeks and some muscles may be paralyzed for months or permanently
-even w/ care mortality is 25%

Botulism prevention

-proper canning methods are key
-proper terminal heating will destroy toxins and kill spores
-most cases assoc. w/ home canning

wound botulism

- rare
-toxins produced at wound site are absorbed into the tissues and cause a neurological disease similar to food-borne botulism

clinical uses for botulism toxin

-cervical dystonia
-strabismus
-blepharospasm
-hemifacial spasm
-excessive underarm sweating
-temporarily improves appearance of moderate to severe frown lines between eyebrows

Clostridium tetani
encounter

-causes tetanus
- C. tetani is ubiquitous in GI tract of humans and animals and in soil
- most cases associated w/ traumatic wound
-neonatal tetanus occurs from contamination of umbilical cord at time of delivery

Clostridium tetani
damage

-major toxin, tetanospasmin, accounts for all symptoms (A-B toxin)
-transmitted through intraspinal transmission among involved motor neurons or through bloodstream to cranial nerve nuclei
-toxin inhibits neurotransmitter release and normal inhibitory input; excitatory transmitter continuously stimulates the motor neurons causign characteristic reflex spasms and spastic paralysis

Tetanus- clinical presentation

- begins w/ trismus (lockjaw)
- descends involving neck and back muscles, progressing to board-like rigidity of abdominal musculature and stiffness of extremitites
- generalized spasm characterized by tonic seizure
-death eventually caused by paralysis of chest muscles

Tetanus - treatment

-antitoxin is available but usually futile b/c toxin irreversibly binds to nerve cells
- penicillin G can be administered to eliminate the organisms that continue to produce toxin in the wound
- surgical debridement of the wound may help eliminate the environmental source of the organism

Tetanus - prevention

Immunization
- vaccine consists of tetanus toxoid, a formalin-inactivated form of the toxin that retains its antigenicity
-tetanus toxoid is the T part of DPT vaccine
-toxin produced during the disease is too small to generate sufficient antibody reaction for subsequent protection

Clostridium perfringens
encounter

tissue infections
- widespread in soil and commonly contaminate wounds
-about 30 species of clostridia cause local and systemic effects in wound infections
-damaged tissue has characteristics that create good conditions for growth and germination of spores

Clostridium perfringens
damage

-major pathogen is C. perfringens which produces 12 toxins
- a-toxin lecithinase damages cell membranes and causes gas gangrene
-muscle tissue is destroyed, no longer reacts to stimuli and grow black and gangrenous, necrosis progresses rapidly
-gram positive spore forming bacteria are readily detectable in gram-stained smears of tissue, pus or other material from wounds
-abundant gas is produced by organism and gas bubbles under skin can be palpated
-pt. develops fever, sweating, low bp, and decreased urinary output
-pts. die from shock and renal failure w/i a few days of onset

Lecithiniase

-toxin produced by C. perfingens
- damages cell membranes and causes cell death by hydrolyzing phosphatidylcholine and sphingomyelin

C. perfringens - tissue infection
treatment

- prompt and extensive surgical removal of the involved tissue
-penicillin cna be administered to control infection
-antitoxin produced in horses but is not effective
-hyperbaric oxygen is sometimes used

C. perfringens - tissue infection
prevention

-early and adequate cleansing of contaminated wounds and surgical debridement is important
-restoration of arterial blood supply to the affected area is the most effective means in preventing gangrene from developing in traumatic wounds

C. perfringens - food poisoning

-some strains produce a powerful endotoxin that when ingested causes diarrhea
-when large amounts of organisms are ingested and sporulate in the gut, enterotoxin is formed
-w/i 6-18 hours of ingestion the toxin causes hypersection of the jejunum and ileum w/ loss of fluids and electrolytes in an intense diarrhea w/o vomiting or fever
-illness is usually self-limited and lasts 1-2 days

Clostridium difficile
encounter

diarrheal disease
- most frequent cause of nosocomial diarrhea
-organism is shed into environment by ppl who are colonized or infected and can be found on hospital surfaces
-spores are transmitted via fecal-oral route
-colonized human GI tract after the normal intestinal flora have been disrupted by antimicrobial therapy
- antibiotics frequently implicated in predisposition to C. difficile are clindamycin, fluoroquinolones, cephalosporins, and penicillins

C. difficile
damage

-once in colon spores germinate into vegetative cells that produce toxins
-releases 2 toxins, toxin A (enterotoxin) and toxin B (cytotoxin) which inactivate regulatory pathways involved in cytoskeleton structure and signal transducion
- cytoskeleton disruption manifests w/ gross findings of shallow ulcerations on intestinal mucosal surface
-toxin A causes inflammation leading to intestinal fluid secretion and mucosal injury
-stool toxin level correlate w/ disease severity

C. difficile
symptoms

-cardinal clinical symptom is watery diarrhea
- C. difficile diarrhea w/ colitis : watery diarrhea w/ lower abdominal pain, cramping, low grade fever, and leukocytosis
-pseudomembranous colitis : in addition to typical C. difficile colitis sigmoidoscopic examination reveals presence of pseudomembranes (shallow ulcerations on intestinal mucosal surface that appear as yellow or off-white plaques)

C. difficile
diagnosis

-stool toxin assays detect presence of C. difficile toxins
- anaerobic culture is less frequently used but possible
- PCR: detection of genes for toxins

C. difficle
treatment and prevention

- antibiotics known to be assoc. w/ disease should not be used on susceptible populations
- hand-washing!!!