Understanding Beta-Lactam Antibiotics: Part 1

Question 1

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

Answer 1

bacterial cell wall synthesis; cell lysis

Question 2

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

Answer 2

T

Question 3

Most commonly used class of antibiotics in the US

Answer 3

B-lactam

Question 4

Possible ADE of B-lactams include

Answer 4

hypersensitivity reactions, gastrointestinal effects

Question 5

Penicillinase-sensitive PCNs

Answer 5

PCN-G, PCN-V

Question 6

Penicillinase-resistant (Anti-staphylococcal PCNs)

Answer 6

Methicillin, dicloxacillin, oxacillin, nafcillin

Question 7

Extended-spectrum PCNs

Answer 7

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

Question 8

Monobactams

Answer 8

Aztreonam

Question 9

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

Answer 9

peptidoglycan

Question 10

critical in the cross-linking of peptidoglycan chains

Answer 10

transpeptidase enzymes

Question 11

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

Answer 11

Penicillin binding proteins (PBPs)

Question 12

functions of the cross-linked peptidoglycan layer:

Answer 12

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

Question 13

Peptidoglycan layer are found in both ___________ and _____________

Answer 13

Both gram-positive and gram negative bacteria

Question 14

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

Answer 14

postivies

Question 15

have thin peptidoglycan layer between the outer membrane and plasma membranes

Answer 15

gram negatives

Question 16

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

Answer 16

bactericidal effect

Question 17

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

Answer 17

cell lysis; replicate; cell death

Question 18

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

Answer 18

Beta-lactam antibiotics

Question 19

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

Answer 19

D-ala-D-ala

Question 20

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

Answer 20

NAM, A-G-L-A-A

Question 21

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)

Answer 21

transpeptidase; latticework

Question 22

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

Answer 22

structural integrity

Question 23

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 ________

Answer 23

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

Question 24

B lactamases have major mechanism in

Answer 24

gram-negative pathogens

Question 25

May be passed from bacterium to bacterium via horizontal transfer

Answer 25

Plasmid-mediated B-lactamases

Question 26

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

Answer 26

plasmid- or chromosomally-mediated; plasmid-mediated

Question 27

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

Answer 27

SPACE organisms

Question 28

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

Answer 28

SPACE organisms

Question 29

Main types of B-lactamases:

Answer 29

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

Question 30

inactivate penicillins

Answer 30

Penicillinases

Question 31

inactivate most B-lactams except for carbapenems

Answer 31

“Extended-spectrum B-lactamases” (ESBLs)

Question 32

they include things like penicillinaces and cephalosporinases

Answer 32

“Extended-spectrum B-lactamases” (ESBLs)

Question 33

Most commonly produced by E. coli and Klebsiella spp.

Answer 33

“Extended-spectrum B-lactamases” (ESBLs)

Question 34

are the antibiotics of choice for ESBL highly resistant pathogens

Answer 34

Carbepenems

Question 35

example of carbapenemases

Answer 35

OXA, KPC, metallo-B-lactamases

Question 36

inactivate carbapenems

Answer 36

Carbapenemases

Question 37

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

Answer 37

carbepenems

Question 38

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

Answer 38

negative

Question 39

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

Answer 39

Carbapenem-Resistant Enterobacteriaceae (CRE)

Question 40

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

Answer 40

poly mix-ins

Question 41

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

Answer 41

poly mix-ins

Question 42

Altered PBPs are more common in

Answer 42

gram-positive pathogens

Question 43

clinical example of PBPs

Answer 43

MRSA and the SCCmec genomic island.

Question 44

Altered PBPs include different enzymes such as

Answer 44

transpeptidases, carboxypeptidases and endopeptidases

Question 45

main target of beta-lactams

Answer 45

Transpeptidase

Question 46

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

Answer 46

T

Question 47

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

Answer 47

PBP2a

Question 48

main altered PBP in penicillin-resistant S. pneumoniae

Answer 48

PBP2x

Question 49

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

Answer 49

ceftaroline

Question 50

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 ______________)

Answer 50

Staphylococcal cassette chromosome mec (SCCmec); mecA; ceftaroline

Question 51

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

Answer 51

MRSA

Question 52

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

Answer 52

glycosides, lipopeptides, and oxazolidinones