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Pcol2 > Understanding Beta-Lactam Antibiotics: Part 1 > Flashcards

Understanding Beta-Lactam Antibiotics: Part 1 Flashcards

1
Q

B-lactam are bactericidal by inhibiting _________________, leading to loss of cell wall integrity and __________

A

bacterial cell wall synthesis; cell lysis

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2
Q

T/F: B-lactams are used in both inpatient and outpatient settings

A

T

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3
Q

Most commonly used class of antibiotics in the US

A

B-lactam

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4
Q

Possible ADE of B-lactams include

A

hypersensitivity reactions, gastrointestinal effects

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5
Q

Penicillinase-sensitive PCNs

A

PCN-G, PCN-V

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6
Q

Penicillinase-resistant (Anti-staphylococcal PCNs)

A

Methicillin, dicloxacillin, oxacillin, nafcillin

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7
Q

Extended-spectrum PCNs

A

Amoxicillin (+/- clavulanate)
Ampicillin (+/- sulbactam)
Ticarcillin (+/- clavulanate)
Piperacillin (+/- tazobactam)

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8
Q

Monobactams

A

Aztreonam

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9
Q

Beta-lactams also function by inhibiting the synthesis of the _______________ layer.

A

peptidoglycan

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10
Q

critical in the cross-linking of peptidoglycan chains

A

transpeptidase enzymes

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11
Q

Located in the periplasmic space between the peptidoglycan layer and the plasma membrane

A

Penicillin binding proteins (PBPs)

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12
Q

functions of the cross-linked peptidoglycan layer:

A

Maintains bacterial shape and integrity
Prevents cell lysis from high osmotic pressure

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13
Q

Peptidoglycan layer are found in both ___________ and _____________

A

Both gram-positive and gram negative bacteria

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14
Q

there is a very thick outer peptidoglycan scaffolding in gram ___________,

A

postivies

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15
Q

have thin peptidoglycan layer between the outer membrane and plasma membranes

A

gram negatives

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16
Q

If the peptidoglycan layer is weakened or its synthesis inhibited, there is ______________

A

bactericidal effect

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17
Q

Impaired peptidoglycan synthesis leads to loss of bacterial shape and integrity, then _________ occurs, making cells unable to _________. This ultimately will result to ____________

A

cell lysis; replicate; cell death

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18
Q

act as structural analogs, specifically targeting the D-ala-D-ala structure, inhibiting transpeptidase activity called transpeptidation.

A

Beta-lactam antibiotics

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19
Q

Beta-lactam antibiotics act as structural analogs, specifically targeting the ___________ structure, inhibiting transpeptidase activity called transpeptidation.

A

D-ala-D-ala

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20
Q

Before PG cross-linking, PG chains feature _________ moieties connected to 5-amino-acid peptides (ordered __________)

A

NAM, A-G-L-A-A

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21
Q

During PG cross-linking, ___________ (a type of PBP) removes the terminal A and links the 2nd A to neighboring L, thus forming a connected _________ (“-“ between A and L)

A

transpeptidase; latticework

22
Q

After PG cross-linking, the resultant scaffold provides ______________ to the bacterial cell

A

structural integrity

23
Q

four major mechanisms of bacterial resistance to beta-lactams:
- _____________ entry of beta-lactam into the cell via ___________ mutations
- altered target, specifically, ____________ not allowing for beta-lactam binding to their target
- _______________, as represented by beta-lactamases
- _______________ or an antibiotic once in the cell via _____________, for example, those found in ________

A

-decreased; porin
-PBP mutations
-degradation
-Removal; efflux pumps; P. aeruginosa

24
Q

B lactamases have major mechanism in

A

gram-negative pathogens

25
Q

May be passed from bacterium to bacterium via horizontal transfer

A

Plasmid-mediated B-lactamases

26
Q

B lactamases can be _______ or _________-mediated ; but most are _________

A

plasmid- or chromosomally-mediated; plasmid-mediated

27
Q

may harbor repressed AmpC β-Lactamase genes in their chromosomes which may become induced or derepressed during treatment with beta-lactams

A

SPACE organisms

28
Q

may initially be suscpetible to beta-lactams but become resistant during beta-lactam therapy

A

SPACE organisms

29
Q

Main types of B-lactamases:

A

-Penicillinases
-“Extended-spectrum B-lactamases”
-Carbapenemases

30
Q

inactivate penicillins

A

Penicillinases

31
Q

inactivate most B-lactams except for carbapenems

A

“Extended-spectrum B-lactamases” (ESBLs)

32
Q

they include things like penicillinaces and cephalosporinases

A

“Extended-spectrum B-lactamases” (ESBLs)

33
Q

Most commonly produced by E. coli and Klebsiella spp.

A

“Extended-spectrum B-lactamases” (ESBLs)

34
Q

are the antibiotics of choice for ESBL highly resistant pathogens

A

Carbepenems

35
Q

example of carbapenemases

A

OXA, KPC, metallo-B-lactamases

36
Q

inactivate carbapenems

A

Carbapenemases

37
Q

are the last resort for multi drug-resistant gram negative infections, unfortunately gram negatives that produce carbepenemases have recently emerged and spread globally

A

carbepenems

38
Q

tx of gram _________ pathogens are extremely challenging as they are often multi drug resistant

A

negative

39
Q

generally resistant to all available beta-lactams and most other antibiotic classes, with the exception of poly mix-ins which is an old class of antibiotics

A

Carbapenem-Resistant Enterobacteriaceae (CRE)

40
Q

an old class of antibiotics previously pulled from the shelves due to its renal toxicity and neural toxicity

A

poly mix-ins

41
Q

Carbapenem-Resistant Enterobacteriaceae (CRE) are resistant to all available beta-lactams and most of antibiotic class except for

A

poly mix-ins

42
Q

Altered PBPs are more common in

A

gram-positive pathogens

43
Q

clinical example of PBPs

A

MRSA and the SCCmec genomic island.

44
Q

Altered PBPs include different enzymes such as

A

transpeptidases, carboxypeptidases and endopeptidases

45
Q

main target of beta-lactams

A

Transpeptidase

46
Q

T/F: Altered PBPs may be unique to a particular pathogen

A

T

47
Q

main altered PBP in methicillin-resistant S. aureus (MRSA)

A

PBP2a

48
Q

main altered PBP in penicillin-resistant S. pneumoniae

A

PBP2x

49
Q

has very high affinity for PBP2a, which accounts for its unique, potent activity vs. MRSA

A

ceftaroline

50
Q

Resistance mechanism of MRSA:
-__________________________ is a genomic island that contains the mecA gene
-mecA encodes PBP2a, whose active site does not bind B-lactams (except ______________)

A

Staphylococcal cassette chromosome mec (SCCmec); mecA; ceftaroline

51
Q

Resistant to all B-lactams (except ceftaroline) and variable susceptibility to rifamycins, tetracyclines, lincosamides, TMP-SMX

A

MRSA

52
Q

MRSA is reliably treated with __________, __________, ______________, although rare reports of resistance

A

glycosides, lipopeptides, and oxazolidinones

Pcol2 (20 decks)

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