Antibiotic Agents Targeting Bacterial Cell Wall Synthesis

Question 1

Penicillins (drug example, mech of action. no details of side effects, unless mechanistic basis for side effects)

Answer 1

Drug examples: Penicillin, monobactam, cephalosporin, carbapenem. All have 4 membered Beta-lactam ring core.
Mechanism: For example, penicillin looks like the D-ala-D-ala ending of th eAA chain in the peptidoglycan, croslinked via transpeptidase. It’s a mimic. During crosslinking, serine of transpeptidase attackes penicillin instead of peptide of bacterial AA, linking to the bacteria. this link is perminant, ending peptidoglycan uses, so no more peptido glycan crosslinking.
Drug notes: bacterialcidal during peptido glycan production in GROWING CELLS ONLY
Downfall: in face of serine beta-lactamase (has classes A, C, D) of bacteia, the lactmase hydrolyzes the beta-lactam ring of penicillin . Carries whater to free irtself from it after. Hydrolyzed their whole facmily

Question 2

b-lactamase inhibitors/

Answer 2

Examples: Claculanic acid, tazobactam (only works on class A).
Action: Extends the lifespan of beta lactam antiobiotics, that you you would initially add (Penicillin + beta lactamase inhibitor)
Mechanism: covalent (permanantly) binds to beta-lactamases, so water cannot hydrolyze them off.

Question 3

Avibactam

Answer 3

Most current beta-lactamase inhibitor. Works on beta-lactamase inhibitor classes A, C, some D (Broader spectrum). No beta-lactam core

Question 4

Penicillin G

Answer 4

beta-lactam antibiotic. Downfall: b-lactamase susceptible. Also acid labile (will hydrolyze in your stomach)
Suitable for Gram(+),
Gram(-) cocci and non beta-lactamase-producing anaerobes.

Question 5

anti-staphylococcal penicillins

Answer 5

Examples: oxacillin (no Cl),
cloxacillin (one Cl),
dicloxacillin (two Cl)
Benefits: Acid stable (won’t get wrecked in stomach).
beta-lactamase resistant.
Suitable for b-lactamase producing strains of staph, as well as penicillin-susceptible strains of streptococci and pneumonococci.
Downfall: Not suitable for enterococci, anaerobic bacteria, and Gram(-)
cocci and rods.

Question 6

extended-spectrum penicillins

Answer 6

Example: Amoxicillin
Benefits: Greater activity against Gram(-) because of their ability to penetrate outer membrane. Suitable for UTIs, sinusitis, otitis,
lower respiratory tract infections.
Downfall: Inactivated by lactamases. Thus,
available in combination with beta-lactamase
inhibitors (eg. amoxicillin + clavulanate = Augmentin).

Question 7

Cephalosporins
cefazolin:
cefuroxime axetil:
ceftazidime:
cefepime:
Cephalosporins:

Answer 7

Broader spectrum due to rise in beta-lactamases
cefazolin: Gen 1, gram +, no CNS penetrartion
cefuroxime axetil: Gen 2, heterogenous, increaed gram - coverage
ceftazidime: Gen 3, even more gram - coverage, but less gram + coverage, some could be used without beta lactamase inhibitor, some crossed BBB, NO LONGER CROSS REACTiON WITH PENICILLIN ALLERGY
cefepime: Gen 4, strongest against beta-lactamase, true broad spectrum drug (effective against both gram + and -), penetrates CNS. Renal issues = can’t eliminate any of gens 1-4 (becomes toxic).
Cephalosporins: Gen 5. Great against gram -. BEST CHOICE AGAINST MRSA (methecillin resistant staph aureus)
Ceftaroline: Specifically high affinity for unique transpeptidase in MRSA

Question 8

Monobactams

Answer 8

Example: Aztreonam
Mech: Acts a beta-lactam class antibiotic. Monocyclic core, active against gram -, NO transpeptidase binding in gram + or anaerobes, no penicillin cross reactivity,

Question 9

Carbapenems

Answer 9

Example: Imipenem
Beta-lactam class drug, broad spectrum (gram - and +), use for mixed infections,, best against serine beta-lactamases, add Cilastatin to it in order to inhibit renal dehydropeptidases in kidneys and increases its halflife in the body, attacks CNS, not good with penicillins.

Question 10

Vancomycin

Answer 10

Non- beta-lactam cell wall synthesis inhibitor. Too thick to go through hydrophillic pore, so it can’t work against gram neg, only gram +.
Mech: binds directly to peptide cross linker, sequesters it, preventing BOTH transppetidases and trasnglycosylases from getting to it.
Downfall: Bacgteria switch from D-ala-D-ala to D-ala-D-lactate, breaking H bond that renders vancomysin useless
Action: Works against gram opos, and methicillin reisstant.
Issue: use for 7-10 days IV…reserve for hospital use
Newer drugs (-vancin, which are semisynthetic) are one shot injections that last for 10 days

Question 11

Daptomycin

Answer 11

Gram +, forms pores in cell membrane, letting K+ escape and killing bacteria. prevents toxins within the bacteria from escapoing to the body.

Question 12

Polymyxins (perforators)

Answer 12

ONLY WORKS FOR GRAM NEG, as it only binds to outter protein outside gram negs. Upon binding, both inside and outside layers are wrecked, causing bacterial death. Use as topical ointment…in neosporin.

Question 13

Fosomycin

Answer 13

Blocks MurA. Invloved in first commited step in convereting NAG to NAM in peptidoglycan formation in bacteria. binding is covalent. Works in both gram + and - bacteria. Snergistic. This dru causes Tb, is resistant to Tb.

Question 14

Bacitracin

Answer 14

Gram pos only. Removed on of the phosphates in lipid carrier that carries peptidoglycan outside of the cell. Toxic,m so use topically.

Question 15

D-cycloserine

Answer 15

Binds racemase enzyme that converts L-Ala to D-ALa in peptidoglycan production. Also binds ligase whihc joins D-ala and D-ala together. Drug is used only for Tb. Too many side effects. Makes you sick.