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Microbiology Lecture Slides > Antibiotic Agents Targeting Bacterial Cell Wall Synthesis > Flashcards

Antibiotic Agents Targeting Bacterial Cell Wall Synthesis Flashcards

1
Q

Clavulanic acid, tazobactam, and avibactam are all

A

b-lactamase inhibitors

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2
Q

Cefazolin (1stgen), cefuroxime axetil (2ndgen), ceftazidime (3rdgen), cefepime (4thgen), and ceftolozane (the latest) are all?

A

Cephalosporins

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3
Q

Ceftaroline is a

A

Cephalosporin for MRSA

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4
Q

Aztreonam is a

A

Monobactam

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5
Q

Imipenem is a

A

Carbapenem

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6
Q

Vancomycin, oritavancin, and dalbavancin are classified as

A

Glycopeptides

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7
Q

Daptomycin (pore former) and polymyxins (membrane disruptors) are examples of

A

Lipopeptides

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8
Q

Fosfomycin, bacitracin, and D-cycloserine are inhibitors of

A

Peptidoglycan precursors

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9
Q

Life-threatening infections require the immediate use of broad-spectrum agents or

A

Combination therapy

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10
Q

A microorganism is said to be resistant to a drug if therapeutic levels of the drug at a particular site cannot be

A

Safely or effectively achieved

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11
Q

Exposure to harmful agents such as antibiotics increases the selective pressure to maintain

A

Acquired resistance

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12
Q

Many drugs work selectively against Gram(+) bacteria. Fewer work selectively against Gram(-) bacteria. Drugs that work against both classes of bacteria are said to be

A

Broad spectrum

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13
Q

A drug whose selectivity is broadened by chemical modification is said to have an

A

Extended spectrum

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14
Q

The outer membrane of Gram(-) bacteria is relatively

A

Impermeable

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15
Q

Cell wall agents block proper assembly of the

A

Peptidoglycan layer

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16
Q

Join the sugars that make polysaccharide chains

A

Transglycolase enzymes

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17
Q

Join the sugar-linked peptides to x-link polysaccharide chains

A

Transpeptidase enzymes

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18
Q

Mimics D-Ala-D-Ala, the last two amino acids of the peptide-bridge precursor

A

Penicillin

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19
Q

Similar to transpeptidases. However, they use H2O to hydrolyze serine-lactam linkage

A

Serine B-lactamases

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20
Q

A distinct class that hydrolyze lactams by a different mechanism

A

Metallo B-lactamases

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21
Q

Possess no antibacterial activity. They are combined with blactam antibiotics to extend their half-lives

A

B-lactamase inhibitors

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22
Q

These inhibitors bind b-lactamases covalently and inactivate irreversibly

A

Beta-lctamase inhibitors

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23
Q

Initially, b-lactamases were encoded by chromosomal genes of some bacteria. Amplification of the genes led to increased

A

Activity

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24
Q

Later, lactamases were found on plasmids that could transfer from

A

Organism to organism

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25
Q

Most active against plasmid encoded b-lactamases in staphylococci, H. influenza, N. gonorrhoeae, salmonella, shigella, E. coli, K. pneumoniae

A

Clavulanic Acid

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26
Q

Least active against chromosomally-encoded b-lactamases in enterobacter, citrobacter, serratia, pseudomonas

A

Clavulanic acid

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27
Q

Serine β-lactamases come in which three classes

A

A, C, and D

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28
Q

Traditional B-lactamase inhibitors work primarily on

A

Class A enzymes

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29
Q

A broader spectrum β-lactamases inhibitor that works on class A and C enzymes, as well as some D enzymes.

A

Avibactam

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30
Q

The inhibitor is coformulated with 3rd generation cephalosporin, ceftazidime

-Note: The inhibitor does not contain a β-lactam core

A

Avibactam

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31
Q

How many classes of penicillins are there, defined by core structure plus substituents

A

Common penicillins, anti-staphylococcal penicillins, and extended-spectrum penicillins

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32
Q

Acid labile. b-lactamase susceptible. Suitable for Gram(+), Gram(-) cocciand non blactamase-producing anaerobes

A

Common penicillins

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33
Q

Acid stable. b-lactamase resistant. Suitable for b-lactamase producing strains of staph, as well as penicillin-susceptible strains of streptococci and pneumonococci

A

Anti-staphylococcal penicillins

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34
Q

Not suitable for enterococci, anaerobic bacteria, and Gram(-) cocciand rods

A

Anti-staphylococcal penicillins

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35
Q

Acid stable. Greater activity against Gram(-) because of their ability to penetrate outer membrane. Suitable for UTIs, sinusitis, otitis, lower respiratory tract infections

A

Extended-spectrum penicillins

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36
Q

Extended-spectrum penicillins are inactivated by

A

Lactamases

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37
Q

Inactivated by lactamases. Thus, available in combination with b-lactamase inhibitors (eg. amoxicillin + clavulanate = Augmentin)

A

Extended-spectrum penicillins

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38
Q

Routes of administration-oral, IV and IM (if combined with anesthetic). When taken orally, ingest one hour before or after meal to avoid binding to food proteins

A

Penicillins

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39
Q

Penicillins are eliminated by

A

Rapid active secretion

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40
Q

80% of a dose of penicillin can be cleared in

A

3-4 hours after administration

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41
Q

Competitively inhibits penicillin secretion. Use it to increase steady state level and t1/2

A

Probenecid

42
Q

Side effects can include diarrhea, nausea, rash, urticaria, and/or superinfectionwith other microbes (e.g. candidiasis)

A

Penicillins

43
Q

If a patient is allergic to penicillin, we an substitute with

A

Cephalosporins

44
Q

Penicillin resistance can occur by upregulation of chromosomally-encoded

A

B-lactamases

45
Q

Penicillin resistance can also occur by acquisition of B-lactamaes by horizontal gene transfer from other

46
Q

Mutation of the primary penicillin binding proteins (transpeptidases) such that penicillin binding affinity is reduced

47
Q

Broader spectrum due to increased resistance to b-lactamases

A

Cephalosporins

48
Q

Not active against enterococci, L.monocytogenesor E. coliand Klebsiellastrains that express extended-spectrum b-lactamases

A

Cephalosporins

49
Q

1st generation cephalosporins are broad spectrum, but are better for

50
Q

Restricted to surgical prophylaxis. Does not penetrate CNS

51
Q

In general they extend the coverage of Gram(-) bacteria over 1st generation drugs

-Heterogeneous class with individual specificities

A

2nd generation cephalosporins

52
Q

Extend Gram(-) activity at the expense of Gram(+) activity

A

3rd generation cephalosporins

53
Q

Some cross blood-brain barrier. Effective against inducible blactamase-production but not constitutive b-lactamase-producing strains

A

3rd generation cephalosporins

54
Q

Cetftazidime+ β-lactamase inhibitor (avibactam)

55
Q

More resistant to chromosomal b-lactamases

A

4th generation cephalosporins

56
Q

Increased activity toward Gram(+) and Gram(-) species. True broad spectrum drug. Penetrates the CNS

A

4th generation cephalosporins

57
Q

Route of administration -Some oral, some IV

A

Cephalosporins

58
Q

Used for sinusitis, otitis and lower respiratory tract infections.

-Fourth generation appropriate for MRSA

A

Cephalosporins

59
Q

Cephalosporins may elicit

A

Hypersensitivity reactions

60
Q

A 5th generation cephalosporin for treatment of Gram(-) bacteria that have become resistant to other drugs, particularly pseudomonas infections

A

Ceftolozane

61
Q

Used for complicated UTIs, and in combination to with metronidazole for complicated intra-abdominal infections

A

Ceftolozane

62
Q

A β-lactamase inhibitor that extends half-life of the cephalosporin

A

Tazobactam

63
Q

Approved in 2010 for use against MRSA.

-Drug has high affinity toward the unique transpeptidase commonly encoded by MRSA

A

Ceftaroline

64
Q

Ceftaroline, like other later generation cephalosporins, works on both

A

Gram (+) and Gram (-) bacteria

65
Q

The most common side effects of ceftaroline are

A

Diarrhea, nusea, and rash

66
Q

Monocyclic core.

-Relatively resistant to b-lactamases

A

Monobactams

67
Q

Monobactams are active against

A

Gram (-) rods

68
Q

Monobactams have no activity against

A

Gram (+) rods

69
Q

The drug does not bind transpeptidases of Gram(+) or anerobic bacteria

A

Monobactams

70
Q

Broad spectrum antibiotics with good activity against many Gram(-) rods (including P aeruginosa), Gram(+) bacteria and anaerobes

A

Carbapenems

71
Q

Resistant against the actions of serine b-lactamases but not metallo b-lactamases

A

Carbapenems

72
Q

Inactivated by dehydropeptidases in renal tubules

73
Q

An inhibitor of renal dehydropeptidase increases t1/2

A

Cilastatin

74
Q

The carbapenems are well distributed, including penetration of CNS. All are cleared renally. Dose (by IV) must be adjusted in patients with

A

Renal insufficiency

75
Q

Carbapenems may show cross-reactivity in patients with

A

Penicillin allergies

76
Q

Glycopeptide isolated from soil bacterium.

-Active against Gram(+) bacteria, especially staphylococci

A

Vancomycin

77
Q

Bactericidal for actively growing cells

-Binds the cell wall rather than enzymes used to make it

A

Vancomycin

78
Q

Vancomycin binds tightly to D-Ala-D-Ala of nascent peptidoglycan pentapeptide. The binding interferes with

A

Transglycosylation and transpeptidation reactions

79
Q

Vancomycin resistance in enterococci arises from a switch in the peptidoglycan pentapeptide from D-Ala-D-Ala to

A

D-Ala-D-Lac

80
Q

Common indications: methicillin-resistant endocarditis or sepsis

A

Vancomycin

81
Q

A better choice than vancomycin if the strain is methicillin sensitive

A

Penicillin

82
Q

Routes of administration–usually IV, oral for enterocolitis and diarrhea caused by C. dificile

A

Vancomycin

83
Q

Often used with aminoglycosides or gentamicin for treatment of enterococcal and other infections

A

Vancomycin

84
Q

Semisynthetic lipoglycopeptide derivative of teicoplanin

-Effective for skin infections by MR gram-positive bacteria

A

Dalbavancin

85
Q

Semisynthetic glycopeptide derived from vancomycin

-Comparable efficacy to vancomycin

A

Oritavancin

86
Q

Cyclic lipopeptide isolated from soil bacteria

A

Daptomycin

87
Q

Forms pores in membrane that allow K+ loss without cell rupture. No release of toxins

A

Daptomycin

88
Q

Based on evolutionarily conserved antimicrobial host defense peptides mimetics.

-Thought to form pores, like daptomycin

A

Brilacidin

89
Q

Brilacidin has potent broad-spectrum activity against Gram-positive and Gram-negative bacteria, including

90
Q

A class of lipopeptides that bind outer membrane of Gram(-) bacteria

A

Polymyxins

91
Q

Polymyxins ultimately leads to the permeability of both the

A

Inner and outer membranes

92
Q

Binds a lipopolysaccharide molecule specific to outer membranes of Gram(-) bacteria. There is little activity against Gram(+) bacteria

A

Polymyxins

93
Q

Drug inhibits first committed step in cell wall synthesis: conversion of NAG-UDP to NAM-UDP

A

Fosfomycin

94
Q

The drug binds covalently to the active site cysteine of the MurA enzyme

A

Fosfomycin

95
Q

Naturally resistant to fosfomycin

A

MurA of TB

96
Q

Fosfomycin is used for uncomplicated

97
Q

Cyclic polypeptide active against Gram(+) organisms

-Inhibits lipid phosphatase that dephosphorylates lipid carrier of peptidoglycan subunits

A

Bacitracin

98
Q

Only used topically because too nephrotoxic

A

Bacitracin

99
Q

Drug competitively inhibits alanine racemase and D-alanine ligase

A

D-cycloserine

100
Q

Second line drug with serious side effects: Dose related CNS toxicity (headaches, tremors, convulsions, psychosis)

A

D-cycloserine

Microbiology Lecture Slides (24 decks)

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