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PHRM 865 > Bacterial Resistance > Flashcards

Bacterial Resistance Flashcards

What makes our life a living hell with germs

1
Q

PBPs

A

Penicillin-Binding Proteins

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2
Q

Enzymes vital for cell wall synthesis, cell shape, and structural integrity

A

Transpeptidases
Carboxypeptidases
Endopeptidases

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3
Q

T/F: There is a correlation of PBPs between Gram(+) and (-) bacteria

A

False; differ from one bacterial species to another

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4
Q

Binding to PBPs 1A, 1B, 2, and 3 result in ________ effect

A

Bactericidal effect

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5
Q

Most important PBP

A

Transpeptidase

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6
Q

Transpeptidase function

A

Catalyzes the final cross-linking in the peptidoglycan structure

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7
Q

Two types of resistance

A

Intrinsic and Acquired

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8
Q

Intrinsic is ______ resistant to a given antibiotic

A

Always

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9
Q

What are the two ways a bacteria can have intrinsic resistance?

A

-Absence of target site
-Bacterial cell impermeability

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10
Q

Examples of intrinsic resistance:

A

-Cephalosporins vs Enterococci
-B-lactam vs mycoplasma

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11
Q

Acquired resistance means the bacteria is initially ______ but develops ________ due to some mechanism

A

Susceptible, resistance

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12
Q

Examples of acquired resistance:

A

-Stable derepression of AmpC
-Acquisition of KPC gene in GNRs

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12
Q

What are two mechanisms a bacteria can develop acquired resistance?

A

-Mutation in bacterial DNA (spontaneously vs selective pressure)
-Acquisition of new DNA (chromosomal or extrachromosomal [Plasmid])

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12
Q

In acquired resistance, plasmids are _______

A

Transferable between organisms

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12
Q

In acquired resistance, conjugation involves direct contact or mating. How often is this the case?

A

Most common form of acquired resistance

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12
Q

In acquired resistance, transposons _______

A

Move from plasmid to chromosome or vice versa

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13
Q

In acquired resistance, _______ can transfer DNA from organism to organism

A

Phages

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14
Q

Mechanisms of antibiotic resistance includes:

A

-Altered cell wall protein/decreased porin production (decreased permeability)
-Increase in efflux pump activity (less drug in cell)
-Plasmids
-Modified drug target (decreases binding)
-Increased drug-inactivating enzyme (drug is rendered useless faster)

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15
Q

Enzymatic inactivation: B-lactamase MOA

A

Drug inactivation by hydrolyzing B-lactam ring by splitting amide bond

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16
Q

Two classification systems of B-lactamase inactivation

A

-Ambler class: classified according to amino-acid structure (class A-D)
-Bush-Jacoby-Mederios: according to functional characteristics

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17
Q

Two types of enzymatic inactivation with B-lactamase

A

-Serine B-Lactamase: serine residue at active site
-Metallo-B-Lactamases (MBL): zinc residue at active site

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18
Q

Ambler Class A B-lactamase

A

-narrow-spectrum B-lactamases
-Extended-spectrum-B-lactamases (ESBL)
-Serine carbapenemases

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19
Q

Ambler Class B

A

Metallo-B-lactamases

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20
Q

Ambler Class C

A

Cephalosporinases

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21
Ambler Class D
OXA-type
22
Narrow-spectrum characteristics
Hydrolyze penicillin; produced primarily by Enterobacterales
23
Extended-spectrum Characteristics
Hydrolyze narrow and extended-spectrum-B-lactam antibiotics
24
What enzyme is important to keep in mind for ESBL?
CTX-M-15
25
Serine carbapenemases Characteristics
Hydrolyze Carbapenems
26
Which enzymes are important to remember for serine carbapenemase?
KPC-1, KPC-2, KPC-3
27
Metallo-B-lactamase characteristics
Hydrolyze carbapenems
28
What enzyme is important to keep in mind for MBL?
NDM-1
29
Cephalosporinase characteristics
Inducible
30
What enzyme is important to keep in mind for cephalosporinases?
Amp-C
31
OXA-type characteristics
Hydrolyze oxacillin, oxyimino B-lactams, and carbapenems
32
What enzyme is important to keep in mind for OXA-type?
OXA-48
33
ESBL treatment of choice:
Carbapenems -meropenem -imipenem -doripenem -ertapenem
34
Piperacillin/tazobactam an option for treatment in ESBL for what infection?
Urinary source only
35
CTX-M enzyme most common enzyme in the US. What bacteria is it most prevalent in?
-Escherichia coli -Klebsiella pneumoniae/oxytoca -Proteus mirabillis
36
What is used as a proxy for ESBL production?
Ceftriaxone (MIC≥2)
37
Trial for ESBL treatment?
Merino Trial
38
Carbapenem-resistant Enterobacterales (CRE) involves which enzyme?
Carbapenemase
39
CRE is resistant to:
Whole beta-lactam class
40
Klebsiella pneumonia carbapenemase (KPC) is mediated by what?
Plasmid
41
Most common variants of KPC
KPC-2 and KPC-3
42
KPC is found in
-K. pneumoniae -K. oxytoca -E. coli -E. cloacae -E. aerogenes -P. mirabillis
43
Treatment option for B-lactam KPC
-ceftazidime/avibactam -meropenem/vaborbactam -imipenem/ cilastatin/relebactam
44
Treatment option for Non-B-lactam KPC
-Plazomicin -Eravacycline -Omadacycline
45
MBL is resistant to all B-lactams except what?
-Monobactams (aztreonam)
46
MBL enzyme to keep in mind
New Delhi MBL (NDM)
47
MBL treatment options
LIMITED OPTIONS: -Cefiderocol -Aztreonam + ceftazidime/avibactam
48
OXA-type primarily found in
-Acinetobacter baumannii -Pseudomonas aeruginosa -Some Enterobacterales, such as Klebsiella pneumonia
49
OXA-type treatment options
EXTREMELY Limited -Cefiderocol -sulbactam/durlobactam
50
CRE is ________ to other antibiotic classes
cross resistant
51
Carbapenem resistance can be due to
-B-lactamase vs Non-B-lactamase causes (porin channels and efflux pumps)
52
T/F: CRE means carbapenemases are present
False
53
Different Mechanisms for AmpC
1.) Inducible via chromosomally encoded AmpC genes 2.) Non-inducible chromosomal resistance via mutations (rare) 3.) Plasmid-mediated resistance
54
AmpC mechanism occurs in?
-Hafnia alvei -Enterobacter cloacae -Citrobacter freundii -Klebsiella aerogenes -Yersinia enterocolitica (HECK-YES)
55
AmpC induction
-Gene for B-lactamase production is repressed--> inducer--> gene derepressed--> increased B-lactamase production -Genetic Mutation--> gene repressed--> B-lactamase production back to low level -Genetic mutation--> gene derepressed--> stable derepression --> high level beta-lactamase production continuously
56
High susceptibility to AmpC hydrolysis strong inducers
-Penicillin G -ampicillin, -1st generation cephalosporins (cefazolin) -Cefoxitin
57
High susceptibility to AmpC hydrolysis weak inducers
-2nd and 3rd generation cephalosporins *****ceftriaxone -Piperacillin/tazobactam -Aztreonam
58
Low susceptibility to AmpC hydrolysis strong inducers
Carbapenems -Imipenem -Meropenem -Ertapenem
59
Low susceptibility to AmpC hydrolysis weak inducers
Cefepime****
60

PHRM 865 (4 decks)

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