B6.088 Gangrene Flashcards
gram + organisms on this test
staph strep pyogenes clostridium actinomyces Propionibacterium
gram - organisms on this test
bacteroides
fusobacterium
prevotella
porphyromonas
how are strep species serotyped
surface carbohydrate antigens
B hemolytic strep
Group A: s.pyogenes
Group B: s.agalactiae
resp tract infections associated with GAS
strep throat
pharyngitis
skin infections associated with GAS
impetigo
erysipelas/ cellulitis (dermis)
necrotizing faciitis (subQ tissue)
systemic infections associated with GAS
bacteremia
rheumatic fever
acute glomerulonephritis
streptococcal TSS
impetigo (strep)
usually occurs in young kids (2-5)
honey colored crusty lesions
“crusty, weeping”
erysipelas
raised, bright red plaques with sharply defined borders
coalescing bullae
time frame of TSS and necrotizing fasciitis
within less than 24 hours of infection
time frame of acute glomerulonephritis after GAS infection
2-3 weeks after initial infection
adhesins on GAS
M protein: >160 serotypes
protein F: binds fibronectin
lipoteichoic acid
capsule of GAS
hyaluronic acid
prevents immune system attack
streptolysin O
pore forming toxin
lyses target cells
hyaluronidase
spreads through tissues and breaks down hyaluronic acid
sometimes mutated/inactivated
streptococcus pyrogenic exotoxins (Spe)
superantigen
can cause scarlet fever and TSS
streptokinases
activate plasminogen to dissolve clots
drugs of choice for GAS infections
all isolates susceptible to penicillin (no beta lactamase)
strep throat: amoxicillin
cellulitis: penicillin, ceftriaxone
TSS: penicillin + clindamycin
function of clindamycin in GAS infection
suppresses toxin production
why might you see recurrent disease from GAS
re-infection from an asymptomatic family member
colonization with different bacteria that produce beta-lactamase
describe the staph species
gram + cocci clusters non motile, non spore forming facultative anaerobes catalase + oxidase - major component of normal skin and nares flora
infections associated with staph
80% of skin and soft tissue infections ortho infections endocarditis nosocomial blood infections septic shock
ESKAPE organisms
have antibiotic resistance enterococcus staph aureus klebsiella actinobacter pseudomonas enterobacter
how do you acquire MRSA from MSSA
within 2 yrs of methicillin use
associated with increased mortality
VISA
vancomycin intermediate: thickened cell wall
VRSA
vancomycin resistant
resistance plasmid from enterococci
adherence factors of staph aureus
protein A - binds the Fc region of Abs
fibronectin binding proteins
collagen binding proteins
virulence factors of staph aureus that aren’t adherence factors
4 cytolysins leukocidins phenol-soluble modulins 12 enterotoxins (superantigens) secreted enzymes: proteases, nucleases, hyaluronidase, coagulase
skin infections associated with staph aureus
95% of all staph infections are skin infections
cellulitis, impetigo, folliculitis, abscess
cellulitis
warm, red, swollen soft tissue that is tender to the tough
impetigo (staph)
classically, erythematous papules and pustules with yellow “honey” crusting
typically on face
large bullae suggest staph
furuncle / abscess
associated with a hair follicle
infection occurring in deep tissues at base of hair follicle resulting in collection of pus
tender to palpation
may or may not spontaneously drain purulent material
staph aureus»_space;> GAS
cause of scalded skin syndrome
diffuse exfoliation
exfoliative dermatitis caused by toxin producing strains: exfoliative toxins ETA and ETB
toxins absorbed by bloodstream
symptoms of SSS
localized tender erythema, systemic spread, fever, blisters
usually involves children < 5
mortality and scarring are rare
cause of TSS
superantigen carried by 20% of staph aureus isolates
symptoms of TSS
sudden fever followed by headache, sore throat, diffuse red rash, skin desquamation
shock within 48 h
epidemiology of TSS
6,000 cases/ year in US
5% fatality w ttx
65% fatality w/o ttx
TSST-1 toxin
released into blood
binds TCR and MHC2 simultaneously
nonspecifically activated 10-20% of T cells
cytokine storm (IFNy, IL-2)
capillary leakage > hypotension > shock > death
C3b defense against staph
activated by staph cell wall fragments
opsonizes bacteria and enhances phagocytosis
neutrophil defense against staph
engulf the bacteria
intracellular killing by O2 radicals
predispositions to staph infections?
C3 hypercatabolism
neutropenia
reduced production of H2O2 and O2
lazy leukocyte
topical ttx of staph aureus
bacitracin
muprirocin
ttx of MSSA
1st gen cephs, amoxicillin- clavulanate, nafcillin/ oxacillin
ttx of MRSA
clindamycin Bactrim doxycycline linezolid vancomycin (only IV) daptomycin (only IV)
VISA/VRSA ttx
resistant to methicillin as well
linezolid, daptomycin, quinupristin / dalfopristin
lab diagnosis of staph aureus
catalase +
coagulase +
beta hemolytic
mannitol fermentation
aerotolerance of anaerobes
most are aerotolerant
tolerate brief exposure to variable levels of O2
-some have SOD and catalase
-some have a very active NADH oxidoreductase
why can anaerobes not grow in presence of high O2
high redox potential of tissues due to dissolved O2
oxidation of sulfide to disulfide > inactive bacterial enzymes
all e- used to reduce O2 > blocks biosynthesis
endogenous anaerobes (normal flora)
opportunists gram neg: bacteroides fusobacterium prevotella prophyromonas gram pos: actinomyces Propionibacterium mobiluncus lactobacillus
exogenous anaerobes
clostridium (G+)
spore forming
areas of body with high conc of anaerobic flora
gingival crevice
colon
1000:1
anaerobes: aerobes
additional sites where anaerobes can thrive
hypoxic tissues (wounds, diabetics)
dental plaque
tonsillar crypts
microenvironments where aerobes or facultative anaerobes deplete O2
predisposing conditions to anaerobic infections
breeches in mucocutaneous barrier displacement of normal flora compromised vascular supply trauma with tissue destruction antecedent infection
clues to an anaerobic infection
foul odor
lesion near mucosal surface
infections with tissue necrosis and abscess formation
presence of underlying disease: tissue necrosis, impaired blood supple
previous abx therapy
infection following a bite wound
“sulfur granules” exudating
virulence factors of anaerobes
anti-phagocytic capsule
tissue destructive enzymes
beta-lactamase production (can protect themselves and other species in mixed infections)
SOD production (aerotolerant anaerobes)
function of SOD production in anaerobes
protect bacteria from toxic O2 radicals as they move out of usual niche
identification challenges associated with anaerobes
air in sample
identification takes several days or longer
often derived from normal flora sample
where is bacteroides fragilis found
colon and female GU tract
what allows b. fragilis to be the most common anaerobe isolated from human infection
highly tolerant to O2 (produces SOD)
polysaccharide capsule
modified LPS has little/no endotoxin activity
how does one get infected w b.fragilis
often released from colon after trauma
- intra abdominal abscesses
- peritonitis
- bacteremia
- skin and soft tissue infections
how is b. fragilis identified/ diagnosed?
bile resistant (grows in 20% bile) catalase + indole -
antibiotic resistance of b. fragilis
conjugative plasmids, transposons encoding high level of antibiotic resistance
- penicillin resistant
- kanamycin +/ vancomyin + blood agar plates (KV BAP)
2nd most common anaerobic bacteria causing infections
prevotella
porphyromonas
prevotella and porphyromonas normal locations
normal flora of: oropharynx nose GIT GUT
characteristics of prevotella
saccharolytic sensitive to penicillin kanamycin resistant (grow on KV BAP)
characteristics of porphyromonas
asacchrolytic
no growth on KV BAP
sensitive to penicillin
clinical manifestations of fusobacterium
pleuropulmonary abscess
intra-abdominal abscess
systemic infection
lab diagnosis of fusobacterium
slender, spindle shaped Gram - with tapered ends Kanamycin sensitive (no growth on KV BAP)
treatment of gram neg anaerobes
metronidazole
carbapenem
B lactam + B lactamase inhibitor
why are gram neg anaerobes so difficult to control
endogenous origin
normal flora
polymicrobial infections
description of Propionibacterium (p. acnes)
gram + bacilli anaerobic non spore forming catalase + indole + diphtheroid (cube shaped)
infections with p.acnes
human acne
opportunistic infections
normal flora of p.acnes
oral
nasopharynx
skin
GIT
DOC for p.acnes
benzoyl peroxide
erythromycin
description of actinomyces
gram + bacilli
anaerobic
catalase -
indole -
infections with actinomyces
actinomycosis abscesses
- cervicofacial or “lumpy jaw” (50%)
- thoracic, abdominal, pelvic, CNS
distinguishing features of actinomyces infections
abscesses with sulfur granules
molar tooth colonies
treatment of actinomyces
surgical treatment + penicillin
etiology of bacterial vaginosis
displacement of normal flora (typically lactobacilli)
polymicrobial: gardnerella, mobiluncus
distinguishing features of mobiluncus
fishy odor of discharge + KOH
“clue cells” : coccobacilli adhering to epithelial cells
pH > 4.5
treatment of mobiluncus
metronidazole or clindamycin
features of lactobacilli
gram + bacillus
facultative to strict anaerobe
normal flora of lactobacilli
oral
GI
GU
infections associated with lactobacilli
transient bacteremia after gyn procedure or birth
endocarditis
septicemia in immunocompromised
DOC for lactobacilli
vanc resistance
penicillin + aminoglycoside
4 types of clostridium
clostridium botulinum (botulism) c. diff (pseudomembranous colitis) clostridium perfringens (gas gangrene) clostridium tetani (tetanus)
features of all clostridium
spore forming gram + bacilli anaerobes saprophytic (love dead organic matter) opportunists all produce highly degradative enzymes and/or extremely potent exotoxins
4 types of botulism
- classical / food bore
- infant
- wound
- undetermined
food borne / classical botulism
ingestion of improperly canned food
germinated spores in food (preformed toxin)
infant botulism
ingestions of spores from soil, dust, honey
in vivo production of toxin
wound botulism
contamination of traumatic wound with spores
in vivo production of toxin
lethal dose of botox
1-2 mg
structure of A-B exotoxins of botulism
released during growth and autolysis of bacteria
- heavy chain (B): targeting to axon terminal
- light chain (A): protease that cleaves SNAP-25 protein (required for ACh vesicle fusion w axon)
effect of A-B exotoxins
blocks fusion of vesicles and release of ACh
inhibit nerve pulses
botulism incubation
18-26 hours
systemic symptoms of botulism
weakness, dizziness, dry mouth, nausea, vomiting
neuro features of botulism
blurred vision inability to swallow difficulty in speech descending weakness (flaccid paralysis) respiratory paralysis
diagnosis of botulism
clinical symptoms only
ttx of botulism
antiserum -history of questionable food ingestion -toxin-receptor binding blocks Ab binding antibiotics: -only in case of infection prevention: -proper food handling
description of c. perfringens
large gram + bacilli occasional spores non motile encapsulated double zone of B hemolysis lecithinase activity (egg yolk)
a toxin of c. perfringens
lecithinase (phospholipase C)
- lyses a variety of cells
- cellulitis w gas formation
- fasciitis (suppurative myositis)
- myonecrosis (gas gangrene)
process of gas gangrene formation
- spores germinate > vegetative cells
- growth, fermentation of carbs > gas formation
- distention of tissue > interference with blood supply
- bacteria produce necrotizing toxin & hyaluronidase > spread
- tissue necrosis extends > increased bacterial growth
- hemolytic anemia > severe toxemia > death
treatment of c. perfringens fasciitis or myonecrosis
prompt and extensive debridement
penicillin + clindamycin
hyperbaric chamber
no effective antitoxin
description of clostridium tetani
ubiquitous
peritrichous flagella
terminal round spore (drum stick)
culture: swarming on blood agar, faint hemolysis
c. tetani toxins
bacterium is not invasive, but secretes toxins that spread
- tetanolysin
- tetanospasmin (neurotoxin)
function of tetanospasmin
A-B toxin
blocks release of inhibitory neurotransmitter GABA
pathogenesis of c. tetani
- contamination of dead tissue with spores
- germination into vegetative cells
- secretion of tetanospasmin
- transport of toxin to CNS via retrograde axonal transport or via blood
- binding of toxin to gangliosides in spinal cord or brainstem
- toxin mediated neuro disorders
clinical symptoms of c.tetani
4-5 day incubation no fever, but profuse sweating pain around wound, neck, jaw convulsive tonic contraction (at site of injury, jaw muscles) interference w respiration death
diagnosis of c.tetani
based on clinical symptoms
can grow in wound of immunized individuals
treatment of c.tetani
humoral immunity through antitoxin antibodies
no cell mediated immunity
immunization with tetanus toxoid
