Anaerobes

Question 1

2 categories of anaerobes

Answer 1

• spore forming: rod, gram +: clostridium
• nonspore-forming: gm +rod -> propionibacterium, bifidobacterium, lactobacillus, eubacterium, actinomyces

nonspore-forming gm - rod –> bacteroides, fusobacterium, camplyobacter

nonspore-forming gm + cocci -> peptococcus, peptostreptococcus

nonspore forming gm - cocci -> veillonella

Question 2

Clostridium species

Answer 2

• clostridia are opportunistic pathogens, but they are responsible for some of the deadliest diseases including gas gangrene, tetanus and botulism. Less life threatening diseases include pseudomembranous colitis (c. difficile) and food poisoning.
• cause disease primarily through the production of numerous exotoxins

Question 3

Subtypes of clostridium species

Answer 3

perfringens, tetani, botulinum, difficile

Question 4

Pathogenesis of C. Tetani?

Answer 4

1. entry through wound (rusty nail)
2. spread of toxin
3. disease: rigid paralysis ex: lockjaw, cardiac failure, respiratory failure
4. no exit

Question 5

Where is C. tetani found?

Answer 5

worldwide, ubiquitous in the soil, it is occasionally found in intestinal flora of humans and animals

Question 6

What does C. tetani cause

Answer 6

tetanus or lockjaw. When spores are introduced into wounds by contaminated soil or foreign objects such as nails or glass splinters (no inhibition of ACh (in constant contraction –> tetany)

Question 7

Morphology of C. tetani, culture, biochem. activities, resistance, and classification

Answer 7

Morphology: long and slender, flagella no capsule, terminal located round spore (drum stick appearance)

Culture: obligate anaerobic, gram +, swarming occurs on blood agar, faint hemolysis

Biochem activities: doesn’t ferment any carbohydrate and proteins

resistance: tolerate boiling for 60 min. Live for several years in the soil.

classification and antigenic types: C. tetani is only species, no serotypes

Question 8

Pathogenicity of C. tetani

Answer 8

• produces 2 exotoxins: tetanolysin, and tetanospasmin (type of neurotoxin, toxicity strong) - taken up at neuromuscular junction
• Actions of tetanospasmin are complex and involve 3 components of the nervous system: central motor control, autonomic fxn, and neuromusc. junction.
• retrograde transport to CNS
• delitescence (latency): few days to several weeks
• the 2 animal species most susceptible to toxemia are horses and humans

Question 9

Tetanospasmin (exotoxin of c. tetani)

Answer 9

disseminates systemically

• binds to ganglioside receptors, inhibitory neurons in CNS
• glycine: neurotransmitter
• spastic paralysis
• severe muscle contractions and spasms
• can be fatal

Question 10

signs and sxs of tetanus

Answer 10

• initial sx: cramping and twitching of muscles around a wound, pt usually has no fever but sweats profusely and begins to experience pain, especially in area of the wound and around the neck and jaw muscles (trismus -> lock jaw)
• portions of the body may become extremely rigid, and opisthotonos (a spasm in which the head and heels are bent backward and body bowed forward) is common
• complications: fractures, bowel impaction, intramuscular hematoma, muscle ruptures, and pulmonary, renal, and cardiac problems

Question 11

generalized disease of C. tetani clinical manifestations

Answer 11

involvement of bulbar and paraspinal muscles (truisms, rises sardonicus (creepy smile), difficulty swallowing, irritability, opisthotonos), involvement of autonomic nervous system (sweating, hyperthermia, cardiac arrhythmias, fluctuations in BP

Question 12

cephalic disease of C. tetani clinical manifestations

Answer 12

• primary infection in head, particularly in the ear, isolated or combined involvement of CNs, particularly the 7th, very poor prognosis

Question 13

Localized disease of C. tetani clinical manifestations

Answer 13

involvement of muscles in area of primary injury, infection may precede generalized disease, favorable prognosis

Question 14

Neonatal disease of C. tetani clinical manifestations

Answer 14

generalized disease in neonates, infection typically originates from umbilical stump; very poor prognosis in infants whose mothers are nonimmune

Question 15

Epidemiology of Tetanus

Answer 15

• 1 mill. cases occur annually in the world -> mortality rate ranging from 20-50%, rare in most developed countries
• in developing countries, tetanus is still one of the ten leading causes of death, and neonatal tetanus accounts for 1/2 of these cases
• in less developed countries -> mortality: 85% neonatal tetanus and 50% non-neonatal tetanus
• in U.S. -> IV drug users victim to this
• in untx tetanus, fatality rate is 90% for newborn and 40% for adults

Question 16

Immunity to C. tetani

Answer 16

humoral immunity (antitoxin), there is little, if any, innate immunity and the disease doesn't produce immunity in the patient
- active immunity follows vaccination with tetanus toxoid

Question 17

Dx of tetanus

Answer 17

dx is primarily by clinical sxs, the wound may not be obvious

• C. tetani can be recovered from the wound in only about 1/3 of the cases
• it is imp. for the clinician to be aware that toxigenic strains of C. tetani can grow actively in the wound of an immunized person
• numerous syndromes, including rabies, and meningitis, have sxs similar to those of tetanus and must be considered in d. dx

Question 18

vaccination for tetanus

Answer 18

• infant: get DTap - (diphtheria, pertussis, tetanus)

- tetanus toxoid: antigenic, no exotoxic activity

Question 19

Control of tetanus

Answer 19

• offending organism must be removed by local debridement
• toxoid
• TAT (tetanus antitoxin; metronidazole (for more serious wounds
• AIDS patients may not respond to prophylactic injections for tetanus toxoid

Question 20

C. perfringens where does it come from and what does it cause?

Answer 20

• found in soil, fecal contamination
• causes gas gangrene: swelling of tissues, gas release from fermentation products (spores in anaerobic environment: release exotoxins)
• wound contamination

Question 21

Pathogenesis of C. perfringens

Answer 21

• tissue degrading enzymes: lecithinase (toxin), proteolytic enzymes, saccharolytic enzymes –> spongy, crackling noise made when palpated, gas is produced by enzymes and is a waste product from toxins
• destruction of blood vessels
• tissue necrosis
• anaerobic enviro created
• organism spreads

Question 22

What will happen in gas gangrene without tx

what is tx?

Answer 22

DEATH occurs within 2 days

• effective abx therapy
• debridement: get rid of necrotic tissue
• anti-toxin
• amputation & death is rare

Question 23

Symptoms of gas gangrene and severity

Answer 23

• life threatening disease w/ poor prognosis and often fatal outcome
• initial trauma to host tissue damages muscle and impairs blood supply -> lack of oxygenation
• initial sxs: fever & pain in infected tissue, more local tissue necrosis and systemic toxemia. Infected muscle is discolored (purple mottling) and edematous and produces a foul-smelling exudate; gas bubbles form from the products of anaerobic fermentation

Question 24

progression of gas gangrene

Answer 24

• as capillary permeability increases, the accumulation of fluid increases, and venous return eventually is curtailed
• as more tissue becomes involved, the clostridia multiply w/in the increasing area of dead tissue, releasing more toxins into the local tissue and the systemic circulation

Question 25

Biologic features of C. botulinum

Answer 25

- anaerobic - gram + - rod shaped - spore former - produces a protein neurotoxin - soil, sediments of lakes, ponds, decaying vegetation - intestinal tracts of birds, mammals, fish - found in honey, natural spores (don't give to infants less than 1 -> don't have immunity) - found in improperly canned foods

Question 26

Transmission of botulism

Answer 26

- spores that are heat resistant, canning, anaerobic environment - botulism: eating uncooked foods, spores - GI, duodenum, blood stream, neuromuscular synapses - Binds to peripheral nerve receptors and block ACh neurotransmitter, - inhibits nerve impulses - leads to flacci paralysis - death b/c of respiratory and cardiac failure

Question 27

Why would the botulinum toxin be considered for bioterrorism?

Answer 27

- not an infection - resembles a chemical attack - 10 ng can kill a normal adult

Question 28

Clinical syndromes of botulism

Answer 28

- 18-36 hours - weakness, dizziness, dryness of the mouth - N/V - neuro features: blurred vision, inability to swallow, difficulty in speech, descending weakness of skeletal muscles, respiratory paralysis

Question 29

How can you get botulism?

Answer 29

- food poisoning: rare but fatal - comes from germination of spore - inadequately sterilized canned food -> from home - not an infection

Question 30

neonatal botulism (infection with C. botulinum)

Answer 30

- uncommon, the predominant form of botulism - colonization occurs - no normal flora to compete - unlike adult botulism - don't give babies honey until 1 yo

Question 31

Dx of botulism

Answer 31

- by clinical sxs alone - differentiation difficult - most direct and effective: serum or feces - most sensitive and widely used: mouse neutralization test 48 h - culturing of specimens 5-7 days

Question 32

Tx of botulism

Answer 32

- individuals known to have ingested food w/ botulism should be tx immediately w/ antiserum - abx therapy if infection - vaccination will not protect hosts from botulism, however passive immunization w/ ab is the tx of choice for cases of botulism - need supp. care: respiratory support

Question 33

Prevention of botulism

Answer 33

- proper food handling and preparation - spores surviving boling (100 degrees at 1 atm) 1 hr - toxin heat-labile, boiling or intense heating, inactivate the toxin - bulge, gas -> spoiled

Question 34

When does C. difficile occur?

Answer 34

after abx use - intestinal normal flora -> greatly decreased - colonization occurs - enterotoxin secreted - pseudomembranous colitis

Question 35

Pseudomembranous colitis?

Answer 35

results predominantly as consequence of elimination of normal intestinal flora through abx therapy - sxs include abdominal pain w/ watery diarrhea and leukocytosis - pseudomembranous consisting of fibrin, mucus, and leukocytes can be observed by colonoscopy - untx pseudomembranous colitis can be fatal in about 27-44%

Question 36

Therapy for pseudomembranous colitis?

Answer 36

1st: discontinue initial abx (usually clindamycin) 2nd: specific abx therapy (doc: vanco , resistance to flagyl increasing)

Question 37

Where will you see anaerobe infections?

Answer 37

throughout the body, in the muscle, cutaneous/sub-cutaneous necrosis - abscesses - deep: ex -> liver infections - wound will be foul smelling - also see dental and sinus infections

Question 38

Why is it so hard to ID anaerobic infections?

Answer 38

- air in sampling -> no growth b/c of O2 - ID takes several days at least -> limiting usefulness - often derived from normal flora: sample contamination can confuse

Question 39

Characteristics of anaerobic infections

Answer 39

1. most pathogenic anaerobes are usually commensals -> originate from our own flora 2. predisposing conditions: breeches in mucocutaneous barrier so normal flora gets displaced, compromised vascular supply, trauma with tissue destruction - antecedent infection

Question 40

Characteristics of anaerobic infections

Answer 40

complex flora: multiple species, less complex than normal flora, fecal flora: 400 diff species, species uniquely suited to cause infection predominate - synergistic mixture of aerobes and anaerobes: e. coli consumes O2 so anaerobes are allowed to grow and anaerobes promote the growth of other bacteria by being antiphagocytic and producing B-lactamases

Question 41

Clues to anaerobic infection

Answer 41

1. infections in continuity to mucosal surfaces 2. infections with tissue necrosis, and abscess formation 3. putrid odor 4. gas in tissues 5. polymicrobial flora 6. failure to grow in the lab

Question 42

Bacteroides fragilis

Answer 42

Major disease causing strict anaerobic after abdominal surgery, non-spore-former - prominent capsule: anti-phagocytic, abscess formation - endotoxin: low toxicity, structure different than other lipopolysaccharide