Lecture 3: Cell Wall Synthesis- Inhibiting Antibacterial Agents

What is the mechanism of action for penicillins?

Inhibit cell wall synthesis by irreversibly binding PBPs and blocking peptidoglycan cross-linking.

Why are penicillins bactericidal?

They cause irreversible damage to the cell wall, leading to osmotic lysis and bacterial death.

What is the major resistance mechanism to penicillins?

Bacterial beta-lactamases that cleave the beta-lactam ring and inactivate the drug.

What is the major side effect of penicillins?

Mild anaphylaxis; also endotoxin release and bleeding disorders in some cases.

How do penicillins relate to MIC and time-dependent killing?

Efficacy depends on maintaining plasma concentrations above MIC for 50-100% of the dosing interval.

Why do penicillins have low volume of distribution?

They are ionized in plasma, but Vd increases in inflamed tissues due to barrier permeability.

How do sustained-release penicillins help maintain MIC?

Formulations like procaine or benzathine slowly release drug to prolong plasma levels above MIC.

What are issues with sustained-release penicillins?

Procaine can cause CNS excitement in horses and is banned in racehorses; not safe for small exotics.

Name penicillin potentiators and their function.

Clavulanate, sulbactam, tazobactam — inhibit beta-lactamases and protect the antibiotic.

Give examples of six penicillin groups.

Penicillin G, amoxicillin, ticarcillin, cloxacillin, amoxicillin-clavulanate, hetacillin.

What are unique traits of each penicillin group?

Penicillin G: Gm(+); Amoxicillin: extended spectrum; Ticarcillin: anti-Pseudomonas; Cloxacillin: anti-Staph; Potentiated: beta-lactamase resistant; Hetacillin: mastitis.

Clinical use of penicillins in companion animals?

Amoxicillin-clavulanate for pyoderma, URIs, wounds, abscesses.

Clinical use of penicillins in food animals?

Ampicillin for BRD and mastitis; cloxacillin for mastitis.

Why are penicillins more effective against Gm(+) bacteria?

Gm(+) bacteria have a thick, exposed peptidoglycan layer; Gm(-) have outer membrane barriers.

Do penicillins have post-antibiotic effects?

No — they kill slowly and require continuous exposure above MIC; PAE is irrelevant for Gm(-).

Which penicillin is best for Pseudomonas infection?

Ticarcillin — MIC < breakpoint and longest time over MIC.

What is the mechanism of action for cephalosporins, carbapenems, and monobactams?

Inhibit cell wall synthesis by binding PBPs and blocking peptidoglycan cross-linking.

Are beta-lactams bacteriostatic or bactericidal?

Bactericidal.

What is the major resistance mechanism for cephalosporins?

Cephalosporinases — beta-lactamases that degrade the drug.

Are there potentiators for cephalosporins?

Yes, e.g., avibactam, but no veterinary-approved combinations.

Describe pharmacokinetics of cephalosporins.

Time-dependent killers; higher Vd than penicillins; renally eliminated.

Which cephalosporins have sustained-release formulations?

Cefovecin and ceftiofur.

What is flip-flop kinetics of cefovecin?

Absorption from injection site is slower than elimination, prolonging drug action.

Spectrum of 1st gen cephalosporins?

Mostly Gm(+).

Spectrum of 2nd gen cephalosporins?

Gm(+) and Gm(-).

Spectrum of 3rd gen cephalosporins?

Broad — Gm(+) and Gm(-).

Spectrum of 4th gen cephalosporins?

Mostly Gm(-), including Pseudomonas and Proteus.

Spectrum of 5th gen cephalosporins?

MRSA — best BBB penetration.

Which cephalosporin is most useful clinically?

Cephalexin — effective, inexpensive, widely used.

Why prefer cefpodoxime over cephalexin?

Once-daily dosing and lower resistance risk due to 3rd-gen classification.

Describe three formulations of ceftiofur.

CFA: single dose, no milk withdrawal, behind ear; RTU: daily SC, no milk withdrawal; Naxcel: reconstituted, IV in horses, milk withdrawal.

Should you give cefovecin to a healthy goat?

No — not approved in goats and inappropriate for prophylactic use in food animals.

Spectrum of carbapenems?

Very broad — Gm(+), Gm(-), aerobes, anaerobes.

Spectrum of monobactams?

Only Gm(-) aerobes.

Spectrum of bacitracin?

Only Gm(+) aerobes.

What is the mechanism of action for bacitracin?

Inhibits early step of cell wall synthesis by binding pyrophosphate.

Is bacitracin absorbed orally?

No — used topically or enterically.

Is bacitracin nephrotoxic?

Yes — not used systemically.

What are bacitracin's clinical uses?

Feed additive in poultry and swine for growth promotion and dysentery.

What is the mechanism of action for glycopeptides?

Inhibit first step of peptidoglycan synthesis by binding PTDG precursors.

Spectrum of glycopeptides?

Only Gm(+) aerobes, especially MRSA.

Resistance mechanism for glycopeptides?

Point mutations in PTDG precursor; resistance gene often co-located with tylosin resistance gene.

Why is vancomycin use restricted?

Last-line drug for MRSA; must be reserved for life-threatening infections in dogs; banned in food animals.

Side effects of vancomycin?

Tissue irritant, must be given slow IV; causes vomiting and nephrotoxicity.

What is avoparcin?

A glycopeptide formerly used in poultry feed; now banned due to resistance concerns.