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Infections caused by anaerobes L11 Flashcards

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1
Q

what is an anaerobe

A

any organism that does not require oxygen for growth OR required reduced oxygen tension and fails to grow on solid media in 10% CO2 (an equivalent of 20% molecular oxygen)

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2
Q

what is aerotolerance

A

tolerate 2-8 % oxygen

degree to which superoxide dismutase expressed

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3
Q

what are the anaerobes that generally cause human infection

A

aerotolerant (ie tolerate 2-8 % oxygen) and can survive sustained periods- but the do not replicate- in an oxygenated atmosphere

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4
Q

what is a feature most anaerobes do not posess

A

catalase

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5
Q

what do the anaerobes that cause human disease often have

A

superoxide dismutase (catalyses partitioning of O2 radical into their molecular O2 or H2O2) and in general the degree to which this enzyme is expressed dictates the aerotolerance of the organism

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6
Q

how are bacteria currently classified

A

This is the scheme that divides the medically important anaerobes by genus. In decreasing frequency we distinguish: 1. GRAM-ve RODS; 2. GRAM+ve COCCI; 3. GRAM+ve spore forming BACILLI (Clostridia) and non sporing bacilli 4. GRAM-ve COCCI (mailny Veillonella spp)

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7
Q

what is the cause of most anaerobic infections

A 
endogenous microbial flora
Normal flora (Skin, Upper airways, genito-urinary tract and gastro-intestinal)
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8
Q

what is the endogenous role in normal flora

A

providing colonisation resistance
Serve nutritional function
Exert effect on host immunity

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9
Q

how do endogenous strains of normal flora gain access to normally sterile sites

A

breach to anatomical barrier

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10
Q

what do ANA infections indicate

A

ANA infections are usually endogenous indicating that they originate from the hosts’s own flora

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11
Q

what is exogenous acquisition

A

relates to either contamination of wound by objects contaminated
ingestion of food containing (C. botulinum and C. perfringens)
colonisation of GIT with spores and toxin production inside host
person to person spread

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12
Q

what are clinical syndromes examples -main clinical features of anaerobic infection

A

Abscess formation/empyema
> Foul-smelling pus or discharge (eg surgical wound)
> Gas formation in tissues
Necrotising fasciitis (myofasciitis/gas gangrene)
Sepsis syndromes
Toxin-mediated disease

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13
Q

what are clostridia

A

Large Gram-positive spore-bearing bacilli

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14
Q

what feature varies in clostridia

A

Vary considerably in O2 tolerance

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15
Q

what are clostridia important for

A

Most are environmental saprophytes important in putrefaction

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16
Q

what does clostridia produce

A

exotoxins

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17
Q

what are exotoxins

A

Biologically active proteins
Antigenic in nature
Neutralised with specific antisera
Detection can be diagnostic

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18
Q

how many types of Clostridium perfringens are there

A

5

A-E

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19
Q

what does Clostridium perfringens make

A

potent toxins
α toxin = lecithinase = phospholipase C
Egg yolk medium

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20
Q

how is clostridium perfringens differentiated on agar

A

Double zone β haemolysis
Where u get precipitate there is no antitoxin
diagnostic way to see if its perfringens

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21
Q

what is Clostridium perfringens like

A

Non motile, freq non spore forming

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22
Q

what does Clostridium perfringens cause

A

gas gangreene (myonecrosis)
it is life threatening
need surgery and antibiotics

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23
Q

how does Clostridium perfringens cause food poisoning

A

enterotoxin production during sporulation

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24
Q

what is Clostridium tetani

A

Straight slender ‘drumstick’ terminal spore (spore at the terminal end)
neurotoxin

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25
what is the Clostridium tetani gram stain feature
readily loses gram stain
26
what oxygen level does Clostridium tetanineed
Obligate anaerobe
27
what is Clostridium tetani like
motile, swarms
28
where is Clostridium tetani
Cattle faeces, contaminated soil
29
what does Clostridium tetani cause
Prevents muscle relaxation leading to spasticity = tetanus
30
what is the clinical diagnosis of Clostridium tetani
3 laboratory tests Isolate organism Detect toxin in serum (Ref lab) Low/no ab levels supports diagnosis
31
how is suspected Clostridium tetani - tetanus clinically managed
Require ITU observation Wound cleaned Antimicrobials including metronidazole or penicillin Anti-tetanus antibody (TIG) Vaccination with tetanus toxoid on recovery important to prevent future episodes
32
what are tetanus prone wounds like
Puncture-type Contact with soil/manure Significant degree of devitalised tissue Any wound with delay >6 hours before surgery
33
how is Clostridium tetani - tetanus prevented
Active immunisation with toxoid introduced in UK 1961 (5 doses)
34
what is the tetanus neurotixin
Tetanospasmin
35
what are the symptoms of tetanus
Symptoms involve characteristic grin of the face, spastic posture of limbs and trunk
36
how does tetanus neurotoxin work
binds to the resynaptic membrane of neuromuscular junction, internalized and transported retro-axonally to the spinal cord spastic paralysis induced by the toxin is due to the blockade of neurotransmitter release from spinal inhibitory interneurons
37
what is Clostridium botulinum
Motile | sub-terminal spores
38
where is Clostridium botulinum
always present in nature - soil
39
what is Clostridium botulinum known for
most powerful toxin known
40
what does Clostridium botulinum cause
Descending FLACCID paralysis = Blocks acetylcholine release at neuromuscular synapses Blurred vision, difficulty swallowing, headaches and muscle weakness
41
what can Clostridium botulinum be used for
Relatively heat stable: bioweapon potential | Botox
42
what causes food-borne botulism
ingestion of preformed toxin in food that has been contaminated as a result of it being improperly canned or preserved
43
what causes wound botulism
wound becomes infected with botulinum spores which then germinate, reproduce and then produce toxins ie growth of the organism
44
what causes infant botulism
very rare. Ingestion of spores or organisms followed by colonisation and toxin production in gut. Usually only affects babies < 12 months old. After this, children develop a defence against the spores
45
how are botulism clinical syndromes treated
Involve ITU Polyvalent antitoxin to neutralise unfixed toxin Wound botulism- surgical debridement and antibiotics
46
how is a reference laboratory of botulism clinical syndrome done
mouse bioassay for toxin | Anaerobic culture of food/faeces
47
how is botulism clinical syndromes prevented
Prophylactic use of polyvalent antitoxin Vaccine (not widely used as concerns re effectiveness and adverse effects) Avoid home canning/adequate food preparation Do not feed honey to infants <12 months
48
how do the seven serotypes of botulinum neurotoxins work
act at the periphery by inducing a flaccid paralysis due to the inhibition of acetylcholine release at the neuromuscular junction
49
what do tetanus and botulinum toxins have in common
have specific protease activities act on proteins in neurones which control neurotransmitter activity proteins included SNARE proteins
50
what do SNARE proteins do
facilitate fusion of vesicles with membranes to a allow delivery of molecules like neurotransmitters to control nerve function
51
PWID
people who inject drugs
52
clostridia and PWID
PWID can cause tetanus
53
where is Clostridium difficile present
normal flora in 3-5% adults
54
how does Clostridium difficile infect
administration of broad-spectrum antibiotics in vulnerable patients (e.g. elderly) allows C. diff to grow and produce TOXINS
55
what is Clostridium difficile the leading cause of
nosocomial diarrhoea
56
what does Clostridium difficile make
``` Toxin mediated process Exotoxin A (enterotoxin) Exotoxin B (cytotoxin) ```
57
what does infection with Clostridium difficile lead to
morbidity and mortality mild to severe diarrhea toxic megacolon pseudomemranous colitis
58
how is Clostridium difficile treated
withholding antibiotics where possible and replacing them with fluids Fecal bacteriotherapy, also known as a stool transplant colectomy - section of infected bowel is removed
59
what are the screening methods that can be used to diagnose Clostridium difficile
ELISA | PCR
60
what is the problem with using plates to diagnose Clostridium difficile
is slow process and need to know ASAP if infected so not regularly used in diagnostic labs
61
what is the problem with using cell rounding assay
labour intensive so not ideal
62
how is cell rounding assay performed
Take some supernatant from patient put onto eukaryotic cells | Will stop to round up due to the toxin
63
what is usually done first to test for Clostridium difficile
quick test apply sample to plate will tell if is - antigen positive (present) - antigen and toxin(s) positive (present and making toxins) - negative for antigen and toxin(s) (not present)
64
why does C.difficile not cause problem when there are no antibiotics present
Normally in gut with no antibiotics have a mix of different types of bacteria These bacteria take primary bile salts will be digested into secondary bile acids Secondary bile acids are inhibitory to C. difficile germination can’t germinate any spores so wont cause problems
65
where are primary bile acids made
normally produced as part of the digestive system
66
what is key in the break down of primary bile acids to secondary
C. scindens
67
why does C.difficile cause a problem when antibiotics are ingested
Take antibiotics will kill off the C. scindens So no longer get transformation of primary bile acids to secondary Nothing blocking the C. difficile from forming spores
68
what does C. difficile produce
produces two large exotoxins – TcdA and TcdB
69
what do the toxins C. difficile produce do
have activity against gut epithelial cell bind to the cell surface and trigger intracellular signalling pathways that cause changes in the cell cytoskeleton can lead to cell death
70
what is the effect does death of cells lining the colon
can result in changes in fluid absorption and diarrhoea
71
how is C. difficile treated
prevention rather than using antibiotics isolate patient Antibiotic therapy: Metronidazole, Vancomycin, Fidaxomicin Some alternative treatment options fall into four main areas: prebiotics and probiotics; "faecal transplants" — where stools donated from a healthy donor are placed in the bowel in an attempt to restore the normal microbiota
72
what is metronidazole
inhibitor of DNA synthesis
73
what does metronidazole require, why is it only effective against anaerobic bacteria and anaerobic protozoa
At low Eh values reduced to a short-lived intermediate which causes DNA strand breakages Because of this requirement for a low Eh value, only active against anaerobic bacteria and anaerobic protozoa

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