Antibiotic Drugs

Question 1

Antibiotics: Peptidoglycan synthesis

Answer 1

• Beta Lactams
• Vancomycin
• Bacitracin
• Fosfomycin
• D cycloserine

Question 2

Antibiotic: rnap rna synthesis

Answer 2

• rifampin

- fidaxomicin

Question 3

Antibiotic: Key metabolic reactions

Answer 3

• trimethoprim

- sulfamethoxazole

Question 4

Antibiotic: Cell membrane

Answer 4

• polymyxins

- daptomycin

Question 5

Antibiotic: dna replication and repair

Answer 5

• fluoroquinolones

- metronidazoles

Question 6

Antibiotic: Ribosomes and protein synthesis

Answer 6

• tetracyclines
• aminoglycosides
• macrolides
• oxazolidinones
• clindamycin
• chloramphenicol
• tigecycline

Question 7

Peptidoglycan biosynthesis

Answer 7

1. Syn MurNAc pentapeptide precursors (cyto)
2. Lipid linkage; trans disaccharide precursors across membrane
3. Polymerization catalyzed by PBPs and crosslinking (extracellular)

Question 8

Beta Lactams

Answer 8

• block peptidoglycan crosslinking via binding PBPs
• 4 families
  - Penicillin (penicillin, ampicillin, amoxicillin, methicillin, oxacillin, ticarcillin, piperacillin)
  - Cephalosporin (1st gen-cefazolin, cephalexin; 2nd gen-cefuroxime, cefoxitin; 3rd gen-cetriaxone, ceftazadime; 4th gen-cefepime) **4th gen is most broad spectrum
  - Monobactam (aztreonam)
  - Carbapenem (imipenem, meropenem, ertapenem, doripenem)

Question 9

Mechanisms of Resistance to Beta lactams (3)

Answer 9

• beta lactamASE production=inactivates beta lactam ring
  - encoded in plasmid or chromosome
  - primarily found in Gram NEGATIVE bacteria
• decreased permeability = prevents beta lactam antibiotics from accessing PBPs
• altered PBPs = prevent binding of beta lactam antibiotics
  - most common in Gram POSITIVE bacteria

Question 10

Overcoming Beta lactamase - use inhibitor

Answer 10

• beta lactamase inhibitors: clavulanic acid, sulbactam, tazobactam
• administer with beta lactam antibiotics

Question 11

Glycopeptides (vancomycin)

Answer 11

• peptidoglycan inhibitor
• bind D-Ala-D-Ala at end of peptide side chain in peptidoglycan precursor, thus PBPs can’t act
• effective on Gram POSITIVE not on gram negative
• **often used for beta lactam resistant infections (MRSA) or beta lactam hypersensitivity

Question 12

Cycloserine

Answer 12

• inhibits peptidoglycan crosslinking
• structure similar to D Alanine
• **used as second line antiTB therapy

Question 13

Bacitracin

Answer 13

• in the group that acts at peptidoglycan synthesis
• too toxic for systemic use; topical ointments (neosporin)
• binds to pyrophosphate on lipid carrier for peptidoglycan percursors and blocks recycling, thus peptidoglycan syn can’t continue
• Group A streptococci are 10x more sensitive than other bacteria

Question 14

Daptomycin

Answer 14

• lipid modified peptide
• bacteriocidal
• narrow spectrum, Gram POSITIVE bacteria
• bind/disrupt cyto memb

Question 15

Polymyxins

Answer 15

• lipopeptide
• narrow spectrum, Gram NEGATIVE bacteria
• adverse effects due to toxicity limits use
• binds to bacteria LPS in outer membrane

Question 16

Tetracyclines

Answer 16

• inhibits protein syn; targets 30s function
• bacteriostatic
• broad spectrum (overuse thus wide resistance)
• Resistance mechanisms: efflux pump, mutations of ribosome

Question 17

Tigecyclin

Answer 17

• bacteriostatic
• binds 30s and additional unique sites on ribosome
• no cross resistance with tetracyclines

Question 18

Aminoglycosides

Answer 18

• *bacteriocidal (ONLY DRUG that attacks at protein syn)
• bind 30s and cause misreading
• USED for hard to kill Gram NEGATIVE bacteria
• adverse effects = ototoxicity, nephrotoxicity

Question 19

Macrolides (erythromycin, azithromycin, clarithromycin)

Answer 19

• binds 50s unit, prevents elongation of protein
• bacteriostatic
• for Gram POSITVE bacteria
• useful for patients allergic to beta lactams
• resistance mechanisms (common): modification of rna like methylation; efflux pumps

Question 20

Clindamycin

Answer 20

• bacteriostatic
• for Gram NEGATIVE
• useful for community acquired MRSA (resistance to hospital acquired)
• for tx of infection by toxin prod. S. Aureus
• resistance mechanisms: methylation; cross resistance with macrolides

Question 21

Chloramphenicol

Answer 21

• bacteriostatic
• broad spectrum
• potential toxicity –> aplastic anemia
• resistance mechanism: add acetyl group to drug

Question 22

Linezolid

Answer 22

• binds 50s
• used for tx of complicated skin infection
• NOT effective with Gram NEGATIVE
• resistance mechanisms: point mutations in ribosomal components to prevent binding; no cross resistance

Question 23

Fluoroquinolones (ciprofloxacin, norfloxacin, moxifloxacin, levofloxacin)

Answer 23

• inhibitors of dna replication
• bacteriacidal
• broad spectrum
• resistance mechanisms: point mutation in bacterial dna prevent antibiotic binding; efflux pump

Question 24

Metronidazole

Answer 24

• inhibit dna replication
• tx anaerobic bacterial infection
• common tx for C. Diff.
• produces radical in anaerobic environment thus damages bacterial dna

Question 25

Rifampin

Answer 25

• bactericidal
• binds beta subunit of bacterial rna polymerase to inhibit activity thus prevents rna synthesis
• resistance mechanism: mutation in beta subunit

Question 26

Fidoxomicin

Answer 26

• bactericidal

- noncompetitive inhibitor of rna syn - binds rna polymerase

Question 27

Antimetabolites (sulfonamides, trimethoprim)

Answer 27

• need tetrahydrofolate to make dna; these antibiotics look like substrates in the pathway
• they are used in combination
• sulfonamides = metabolic analog of p amino benzoic acid
• trimethoprim = metabolic analog of dihydrofolate
• resistance mechanism: acquire another gene encoding dihydrofolate reduction

Question 28

Targets on the bacteria of an antibiotic

Answer 28

• peptidoglycan synthesis
• RNAP and RNA synthesis
• key metabolic reactions
• cell membrane
• DNA replication and repair
• ribosomes and protein synthesis