MOA

Question 1

Aminoglycoside (AG) Examples

Answer 1

gentamycin

tobramycin

amikacin

streptomycin

plazomycin (new)

Question 2

AG MOA (General)

Answer 2

multifactorial: inhibition of protein synthesis

Aminoglycosides irreversibly bind to the 30S ribosomal subunit (some to 50S subunits), which results in a disruption in the initiation of protein synthesis, a measurable decrease in protein synthesis, and misreading of messenger RNA.

Question 3

AG MOA for gram negative bacteria

Answer 3

1. For Gram-negative bacteria, the aminoglycosides must first bind to and diffuse through the outer membrane through porin proteins.
2. Once in the periplasmic space, the aminoglycosides must then be transported across the cytoplasmic (inner) membrane  a process that is dependent upon a membrane potential, is energy-dependent, requires oxygen (why they are not useful against anaerobes), and is rate-limiting.
3. Following transport across the cytoplasmic membrane, the aminoglycosides bind to polysomes and inhibit the synthesis of proteins, which disrupts the structure of the cytoplasmic membrane.

Question 4

AGs: Bactericidal or bacteriostatic

Answer 4

bactericidal in a concentration-dependent manner

but

bacteriostatic against enterococcus

Question 5

Cephalosporin Examples

Answer 5

1st: cefazolin, cephalexin
2nd: cefuroxime, cefotetan, cefprozil, cefoxitin
3rd: ceftriaxone, cefoperazone, ceftazidime, cefpodoxime
4th: cefepime

4th?: ceftaroline

Question 6

Cephalosporin MOA (General)

Answer 6

Interfere with cell wall synthesis by binding to and inhibiting enzymes, called penicillin-binding proteins (PBPs i.e. responsible for peptidoglycan cross-linking)

Inhibition of PBPs by beta-lactam antibiotics leads to inhibition of the final transpeptidation step of peptidoglycan synthesis –> exposing a less osmotically-stable cell wall that leads to decreased bacterial growth, bacterial cell lysis, and death.

Question 7

Cephalosporin: Bactericidal or bacteriostatic

Answer 7

bactericidal in a time-dependent manner

Question 8

FQ Examples

Answer 8

Ciprofloxacin, levofloxacin, moxifloxacin, delafloxacin

Question 9

FQ MOA (General)

Answer 9

Unique mechanism of action that includes inhibition of DNA synthesis by binding to and inhibiting bacterial topoisomerases (enzymes needed for maintaining cellular DNA in an appropriate state of supercoiling in both the replicating and nonreplicating regions of the bacterial chromosome)

Question 10

FQ MOA (Specific)

Answer 10

Inhibition of DNA gyrase prevents the relaxation of positively supercoiled DNA that is required for normal transcription and replication.

FQs form a stable complex with DNA and DNA gyrase, which blocks the replicating fork leading to a sudden and lethal cessation of DNA replication (For many Gram-negative bacteria, DNA gyrase is the primary target of the FQs)

Inhibition of topoisomerase IV interferes with the separation of replicated chromosomal DNA into respective daughter cells during cell division that are the product of DNA replication, causing a cessation in DNA replication (For many Gram-positive bacteria (S. aureus), topoisomerase IV is the primary target of the FQs)

Question 11

FQ: Bactericidal or bacteriostatic

Answer 11

concentration-dependent bactericidal activity

Question 12

Macrolide Examples

Answer 12

Erythromycin, azithromycin, clarithromycin

Question 13

Macrolide MOA

Answer 13

Macrolide antibiotics interfere with microbial protein synthesis (translocation steps) at the ribosomal level. The macrolides reversibly bind to the 50S ribosomal subunit to induce dissociation of peptidyl transfer RNA from the ribosome during the elongation phase so that protein synthesis is suppressed and bacterial growth is inhibited.

Question 14

Macrolide: Bactericidal or bacteriostatic

Answer 14

Bacteriostatic activity

HOWEVER

They may display bactericidal activity when present at high concentrations against very susceptible organisms (Streptococcus pneumoniae, Streptococcus pyogenes)

Question 15

Tetracycline Examples

Answer 15

tetracycline, doxycycline, minocycline

Question 16

Tetracycline and tetracycline analogs MOA

Answer 16

Inhibit bacterial protein synthesis by reversibly binding to the 30S ribosome, blocking binding of amino-acyl tRNA to the acceptor (A) site on the mRNA-ribosomal complex.

This prevents the addition of amino acid residues to the elongating peptide chain and inhibits protein synthesis

Question 17

Tetracyclines: Bactericidal or bacteriostatic

Answer 17

bacteriostatic in action

BUT

May be bactericidal in high concentrations or against highly susceptible organisms

Question 18

TMP and SMX Examples

Answer 18

TMP = Trimethoprim

SMX = Sulfamethoxazole

Question 19

TMP and SMX MOA (Both General)

Answer 19

Produce sequential blockade of microbial folic acid synthesis

Question 20

SMX MOA

Answer 20

A sulfonamide that competitively inhibits the incorporation of p-aminobenzoic acid (PABA) into folic acid by inhibiting dihydropteroate synthetase, which inhibits the formation of dihydrofolic acid

Question 21

TMP MOA

Answer 21

Competitively inhibits the activity of bacterial dihydrofolate reductase to prevent the reduction of dihydrofolate to tetrahydrofolate

Question 22

SMX + TMP: Bactericidal or bacteriostatic

Answer 22

Together, these two agents produce sequential inhibition of the synthesis of folate, which is necessary for microbial production of DNA, producing a synergistic bactericidal effect against many Gram-positive and Gram-negative aerobic bacteria that may not be present with each agent alone

Question 23

Penicillin Examples (All)

Answer 23

Natural Penicillins: Aqueous Penicillin G, Benzathine Penicillin, Procaine Penicillin G, Penicillin VK

Penicillinase-Resistant Penicillins: Nafcillin, Oxacillin, Methicillin, Dicloxacillin

Aminopenicillins: Ampicillin, Amoxicillin

Carboxypenicillins: Ticarcillin

Ureidopenicillins: Piperacillin

β-Lactamase Inhibitor Combinations: Ampicillin-Sulbactam (Unasyn), Amoxicillin-Clavulanate (Augmentin), Ticarcillin-Clavulanate (Timentin), Piperacillin-Tazobactam (Zosyn)

Question 24

Beta-LACTAMS (Penicillins, Cephalosporins, Carbapenems, Monobactams) General MOA

Answer 24

ALL SAME: Inhibitors of cell wall synthesis

Question 25

Beta lactams MOA (Specific)

Answer 25

Penicillins interfere with bacterial cell wall synthesis by binding to and inhibiting enzymes, called penicillin-binding proteins (PBPs expressed during cell division)

Inhibition of PBPs by beta-lactam antibiotics leads to inhibition of the final transpeptidation step of peptidoglycan synthesis, exposing a less osmotically-stable cell membrane that leads to decreased bacterial growth, bacterial cell lysis, and death.

Question 26

Beta lactams: Bactericidal or bacteriostatic

Answer 26

bactericidal, except against Enterococcus spp. where they display bacteriostatic activity

Question 27

Glycopeptide Example

Answer 27

Vancomycin

Question 28

Streptogramin Example

Answer 28

Quinupristin-dalfopristin (Synercid®)

Question 29

Oxazolidinones Example

Answer 29

Linezolid (Zyvox®), Tedizolid (Sivextro™)

Question 30

Lipopeptides Example

Answer 30

Daptomycin (Cubicin®)

Question 31

Lipoglycopeptides Examples

Answer 31

Telavancin (Vibativ™), Dalbavancin (Dalvance™), Oritavancin (Orbactiv™)

Question 32

Vanc (glycopeptide) MOA

Answer 32

Inhibits the synthesis of the bacterial cell wall by blocking glycopeptide polymerization at a site different from that of the beta-lactams.

Vancomycin inhibits synthesis and assembly during the second stage of cell wall synthesis by firmly binding to the D-alanyl-D-alanine portion of cell wall precursors. Vancomycin prevents cross-linking and further elongation of peptidoglycan, which weakens the cell wall making it susceptible to lysis.

Question 33

Vanc: Bactericidal or bacteriostatic

Answer 33

slowly bactericidal in a time-dependent (?) manner, except against Enterococcus spp. where it displays bacteriostatic activity

Question 34

QUINUPRISTIN / DALFOPRISTIN (Synercid) MOA

Answer 34

Quinupristin and dalfopristin act individually on the 50S ribosomal subunit to inhibit early and late stages of bacterial protein synthesis

Question 35

QUINUPRISTIN / DALFOPRISTIN (Synercid): Bactericidal or bacteriostatic

Answer 35

each agent alone is bacteriostatic, but the combination produces an additive or synergistic effect (sometimes bactericidal)

Question 36

OXAZOLIDINONES MOA

Answer 36

Oxazolidinones bind to the 50S ribosomal subunit near the surface interface of the 30S subunit, producing inhibition of the 70S initiation complex for protein synthesis (ultimately, inhibits protein synthesis).

Unique: Cross-resistance with other protein synthesis inhibitors unlikely.

Question 37

OXAZOLIDINONES: Bactericidal or bacteriostatic

Answer 37

For the most part, oxazolidinones are bacteriostatic

Question 38

LIPOPEPTIDES MOA

Answer 38

Daptomycin binds to bacterial membranes and inserts its lipophilic tail into the cell wall to form a transmembrane channel –> leakage of cellular contents and rapid depolarization of the membrane potential leading to inhibition of protein, DNA, and RNA synthesis, resulting in bacterial cell death.

Question 39

LIPOPEPTIDES: Bactericidal or bacteriostatic

Answer 39

Daptomycin exhibits rapid, concentration-dependent bactericidal activity.

Question 40

LIPOGLYCOPEPTIDES MOA

Answer 40

All lipoglycopeptides interfere with the polymerization and cross-linking of peptidoglycan by binding to the D-Ala-D-Ala terminus. The lipid side chain anchors the drugs to the cell membrane and concentrates the drug at the site of action.

Oritavancin and telavancin (NOT dalbavancin) also appear to bind to bacterial membranes and insert their lipophilic tails into the cell wall to form a transmembrane channel (like daptomycin) –> causes leakage of cellular contents and rapid depolarization of the membrane potential leading to inhibition of protein, DNA, and RNA synthesis, resulting in bacterial cell death.

Question 41

Polymyxin Examples

Answer 41

polymyxin B and colistin

Question 42

Polymyxin MOA

Answer 42

Polymyxins are cationic detergents that bind to the anionic lipopolysaccharide molecules of the outer cell membrane of Gram-negative bacteria causing displacement of calcium and magnesium, which normally stabilizes the cell membrane. This action leads to changes in cell wall permeability, leakage of cellular contents, and subsequent cell death.

Question 43

Polymyxin: Bactericidal or bacteriostatic

Answer 43

concentration-dependent bactericidal activity