Antimicrobial Resistance Flashcards

1
Q

Bactericidal

A

directly kills susceptible bacteria

host responses NOT needed

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2
Q

Bacteriostatic

A

inhibits bacterial growth and relies on host defences (immune system) to clear the bacteria

won’t use for certain infections since it doesn’t directly kill

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3
Q

Narrow spectrum antibiotics

A

active against a small group of bacteria

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4
Q

Broad spectrum antibiotics

A

active against a much wider variety of bacteria

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5
Q

Resistance

A

when an organism no longer responds to a therapy OR is associated with failure in vivo

no longer has clinical impact

patient will not improve

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6
Q

Sensitive/Susceptible

A

when an organism responds to an antimicrobial and has activity in vivo

patient will get better when using this antibiotic

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7
Q

Antimicrobial Targets (4)

A

interferes with:

1) bacterial cell membrane

2) nucleic acid
-DNA –> RNA –> protein

3) protein synthesis
-RNA –> protein

4) potential for organism to obtain things they need to grow - folate synthesis

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8
Q

Bacterial cell membrane synthesis antibiotic mechanism

A

beta-lactam antibiotics

beta-lactam ring is the central component of all beta-lactam antibiotics

inhibits synthesis of bacterial cell membrane synthesis

transpeptidase enzyme crosslinks the
peptidoglycans NAG and NAM

beta-lactam antibiotics
bind to transpeptidase enzyme complex and blocks this reaction

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9
Q

Beta-lactam antibiotics (many)

A

Active in both gram positive AND gram negatives

penicillins (Group A strep, Group B strep, syphillis)

amoxicillin (common in peds)

cephalosporins

minocyclines

carbapenems

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10
Q

Penicillins

A

narrowest

penicillinG

penicillinV

cloxacillin

amoxicillin

peperacillin

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11
Q

Cephalosporins

A

1st gen - broader
-ampicillin

2nd gen - broader
-cefazolin

3rd gen - very broad
-ceftazidime
-ceftriaxone
-cefixime

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12
Q

Carbapenems

A

BROADEST

multi drug resistant organisms, last resort

Ertapenem

Meropenem

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13
Q

Glycopeptides

A

non Beta-Lactam

cell wall active agents

bacteriocidal

vancomycin, teicoplanin

act on the cell wall of GRAM POSITIVE organisms
-C. difficile
-MRSA

stops the extension of the peptidoglycan unit of the bacterial cell wall

interferes with D-Ala, D-Ala binding

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14
Q

Protein synthesis inhibitors

A

binds parts of the ribosomes (make proteins from nucleic acids)

antibiotics bind the 30S and 50S subunits of ribosomes to stop protein synthesis

tetracyclines - 30S
e.g. doxycycline

macrolides - 50S
-e.g. azithromycin

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15
Q

Nucleic acid inhibitors

A

fluoroquinolones

bind to nuclear enzymes (topoisomerase an gyrase) inhibiting DNA replication

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16
Q

fluoroquinolones

A

excellent drugs with a broad spectrum of activity

good tissue penetration

used to used for UTIs, stopped, can use again

CAP

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17
Q

Metabolic Inhibitors

A

prevent acquisition or generation of things like folate

Trimethoprim/Sulfamethoxazole (Septra, Bactrim)
-inhibitors of the active form of folic acid (tetrahydrofolic acid)

Trimethoprim - structural analogue of DHF (dihydrofolic acid) and competitive inhibitor of dihydrofolate reductase

Sulfamethoxazole - Structural analogue of PABA and competitively inhibits synthesis of DHF

18
Q

Intrinsic resistance

A

bug is already always resistance to the antibiotic

like how skin is waterproof

19
Q

Inducible resistance

A

acquired

has to get it from somewhere

from other bacteria, the environment, or sub-optimal exposure (not finishing dose as prescribed, taking when not needed, skipping doses*** - like a punching bag making the bug stronger)

20
Q

Antibiotic Susceptibility Testing

A

done in vitro (in glass)

interpretations:
S = susceptible/sensitive (organism doesn’t grow)
I = intermediate
R = resistant (organisms grows, don’t use)

several methods are done to test the sensitivity of the organism to antibiotics

21
Q

Resistance Detection

A

Antibiotic disc

Zone of inhibition (in mm)

Bigger the zone=more susceptible

Use guidelines to interpret the zone of inhibition as S, I or R

22
Q

Micro-Broth Dilution

A

different concentrations of antibiotics from L of the plate to the R

suspension of bacteria added to the plate and incubated

last well before growth is seen is the Minimum Inhibitory Concentration (MIC)

bacteria makes liquid go cloudy (turbidity)

23
Q

Bacterial Resistance Types (2)

A

1) inherited

2) acquired - another bug that’s shared DNA with bug to give it phenotype that’s resistant

24
Q

What bacterial characteristic contributes to bacterial resistance?

A

short replication times

25
Resistance Mechanisms
resistance genes can be: 1) on the bacterial chromosome (intrinsic) OR 2) on a motile gene element called a plasmid (circular strand of DNA) MOST IMPORTANT**** often have costs associated with them (fitness or metabolic) always on OR inducible lack of selective pressure will result in the loss of a particular resistance mechanism
26
Resistance mechanisms (4)
1) Efflux pump -drug gets in, bug pumps it out 2) Reduced permeability -bacteria cell wall change size of porins to not allow drug to enter -normally allow proteins to move in and out 3) Enzymatic inactivation -bacteria produces protein/enzyme eats up the antibiotic -“ases” - beta-lactamase (penicillin) 4) Altered binding site -antibiotic binds to something, can no longer bind to to what it needs to e.g. vancomycin binds to: d-ALA, d-ALA, d-ALA etc. -MRSA - vancomycin can no longer bind
27
Sharing of resistance mechanisms (3 ways)
1) Conjugation -most important and common** -bacteria build bridge between each other - can transfer material between each other -gene transfer and recombination in bacteria that requires direct cell to cell contact 2) Transformation -naked DNA is taken up by a bacterial cell and incorporated into the recipients genome -free DNA fragments or a DNA plasmid -cell must be a competent cell to take up DNA -bacteria are floating around and see DNA, take capsule from the DNA -acquires capsules from the environment -e.g. strep pneumo 3) Transduction -bacteria have viruses can attack them called bacteriophages -bacteriophages carry this - e.g. resistant mutation, bacteria will become resistant to antibiotic -gives the bacteria resistance -e.g. Salmonella
28
Plasmids
ones we worry about can share quite effectively circular double stranded DNA that can exist and replicate independent of chromosome not required for cell’s growth may integrate with the chromosome
29
If resistance mechanisms carry a cost, why would bacteria carry resistance mechanisms?
selective pressure e.g. use to use ciprofloxacin in the early 2000s for E. coli, top cause of UTIs -stop using cipro for UTIs in 2010s -now using it again -can cycle
30
Antibiotic Selective Pressure
over use of antibiotics are a major reason (e.g - using an antibiotic for a viral infection) not completing a prescription - allows partially treated organisms to develop or become resistant use of antibiotics in our animal feeds using a left over prescription from someone else or another time
31
Resistant organisms - Gram + examples
Methicillin Resistant Staphylococcus aureus (MRSA) Vancomycin Resistant Enterococcus (VRE) Clostridium difficile (CDI)
32
Resistant organisms - Gram - examples
ESBL’s - Extended spectrum Beta-lactamase producers -does not respond to cephalosporins -respond to carbapenems CRE/CPE - Carbapenem resistant Organisms
33
Staphylococcus aureus
most virulent - causes the most disease common colonizer of skin, the nose and the perineum pne of the most common causes of soft skin infections, bacteremia, endocarditis, pneumonia and wound infections (soft tissue=bad) Types: -MRSA - resistant (increased morbidity, mortality) -MSSA - sensitive
34
Mechanism of MRSA
S.aureus cell wall is made up of penicillin binding proteins (PBP) that are targets for beta-lactam drugs MRSA -changes affinity of binding site -reduces ability of beta-lactams to bind to MRSA
35
MRSA Hospital Screening Programs
screen ANYONE that has had any contact with a health care facility in the last year due to the increased risk of invasive infections and the limited therapeutic options swab nose and butt if colonized --> contact precautions prevent: HAND WASHING
36
Enterococcus spp.
2 types relatively harmless, normal residents of the GI tract that occasionally cause infections, but typically in patients that are already very sick vancomycin sensitive or resistant screening: butt swab if colonized --> contact precautions significant amount of intrinsic resistance so not very many therapeutic options for treatment modifies d-ALA-d-ALA so vancomycin can't bind prevent: ENVIRONMENTAL CLEANING
37
Clostridium difficile associated diarrhea
can be colonized without diarrhea treat 3 diarrheal episodes in 24 hour without explanation children under 2 can't get not part of normal flora normal flora does not allow C. diff to colonize GI tract disturbance to normal flora allows it to grow produces spores - very environmentally stable toxin mediated, symptoms, RFs prevent: ENVIRONMENTAL CLEANING
38
Treatment of C. difficile
risk factor is antibiotic use but also use antibiotics to treat vancomycin and metronidazole high chance of re-currence Fecal Microbial Therapy
39
Gram Negatives: Extended-spectrum beta-lactamases (ESBL)
produce beta-lactamase enzyme that break up the beta-lactam ring which inactivates antibiotics (penicillins, up to 3rd gen. cephalosporins) E.coli and/or K. pneumoniae can use carbapenems risk factors: -antibiotic use -travel -hosp. -carriage of ESBL in GI
40
Carbapenem Resistant Organism (CRO)
any gram NEGATIVE that lives in your GI tract that is resistant to a Carbapenem last line drug - serious, resistance infections super bug RF: -travel for medical tourism (India, Israel, Greece, US) -exposure to some with a CRE -use of antibiotics over time