Antibacterial Agents I

Question 1

Selective Toxicity

Answer 1

The chemotherapeutic agent should inhibit microbial growth or destroy the microbe without causing harmful effects in the host.
(Selective Toxicity = the basis for successful, effective chemotherapy)

Question 2

Cell Wall Synthesis Inhibitors

Answer 2

Cell Wall Synthesis: cephalosporins, penicillins, and vancomycin

Question 3

DNA Gyrase Inhibitors

Answer 3

DNA gyrase: fluoroquinolones (Cipro)

Interferes with nucleic acid metabolism

Question 4

DNA Dependent RNA Polymerase Inhibitors

Answer 4

DNA dependent RNA polymerase: Rifampin

Interferes with nucleic acid metabolism

Question 5

Protein Synthesis Inhibitors (50S)

Answer 5

Protein Synthesis Inhibitors (50S): macrolides (erythromycin), chloramphenicol, clindamycin

Question 6

Protein Synthesis Inhibitors (30S)

Answer 6

Protein Synthesis Inhibitors (30S): tetracyclines (doxy) and aminoglycosides (genta and streptomycin)

Question 7

Cell Membrane Agents

Answer 7

Cell Membrane Agents: polymyxins
Alteration of cell membrane integrity

Can cause neurotoxicity and nephrotoxicity, but have been brought back because of bacterial resistance

Question 8

Anti-Metabolite Drugs

Answer 8

blockade of specific metabolic steps
Examples: sulfonamides & trimethoprim

Sulfonamides: blocks dihydropteroate synthase
Trimethoprim: blocks dihydrofolate reductase

Anti-metabolite drugs – look like biochemical compounds that microbe is using, but have affinity for enzymes and processes and compete for them and slow down bacterial growth
Do not kill them, but slow down growth

Question 9

Bacteriocidal vs. Bacteriostatic

Answer 9

Cidal: killing and is irreversible action
Static: slow growth and is reversible

Protein synthesis inhibitors bind reversible and slow growth down, but aminoglycosides bind irreversibly and produce cidal effect

Question 10

Bacteriostatic

Answer 10

Concentrations that inhibit growth are much lower than those that kill
Examples: macrolides, sulfonamides & tetracyclines

Question 11

Bactericidal

Answer 11

Little difference between concentration that inhibits growth and that which kills

used for difficult or hard to eliminate pathogens like meningitis or in immunocompromised host; bacterial endocarditis also should use this

Examples: penicillins, cephalosporins, aminoglycosides & fluoroquinolones

Question 12

Bactericidal Examples

Answer 12

Aminoglycosides
Cephalosporins
Penicillins
Metronidazole
Polymyxins
Fluroquinolones
Rifampin
Vancomycin

Question 13

Bacteriostatic Examples

Answer 13

Chloramphenicol
Clindamycin
Macrolides
Sulfonamides
Tetracyclins
Trimethoprim

Question 14

Synergism vs. Antagonism Examples

Answer 14

Antagonism - penicillin G + a tetracycline

Synergism -
penicillin G + gentamicin (or streptomycin)
trimethoprim + sulfamethoxazole
amoxicillin + clavulanic acid

Question 15

Enterococcal Endocarditis Tx

Answer 15

Penicillin + Aminoglycoside Synergy

An example of a disease that is treated most effectively with two antibiotics is enterococcal endocarditis. The recommended treatment is with a penicillin (penicillin G or ampicillin) and an aminoglycoside (gentamicin or streptomycin).

Question 16

Decreased Drug Entry or Accumulation

Answer 16

Decreased drug entry or accumulation

Loss of membrane permeability (due to alteration in porin number or structure in gram negative bacteria), OR decreased entry due to an altered transport system
decreased drug accumulation due to an efflux pump

Examples: resistance to aminoglycosides, macrolides, penicillins/cephalosporins & tetracyclines

Question 17

Change in Affinity of Binding Sites

Answer 17

Change in the affinity of intracellular binding sites

Examples:
altered ribosomal binding sites for macrolides
altered PBPs for penicillins
altered target enzyme, DNA gyrase, for fluoroquinolones

Question 18

Alternative Metabolic Pathways

Answer 18

Development of alternate metabolic pathways

Example: increased production of PABA by bacteria to overcome inhibition by sulfonamides