Cell Wall/Membrane Acting Agents

What is the primary target of β-lactam antibiotics?

β-lactam antibiotics target penicillin-binding proteins (PBPs), specifically transpeptidases involved in peptidoglycan synthesis.

How do β-lactam antibiotics inhibit PBPs?

β-lactam antibiotics mimic the D-ala-D-ala structure of peptidoglycan and irreversibly bind to PBPs, inhibiting their enzymatic activity.

What is the result of β-lactam inhibition of PBPs?

Inhibition prevents cross-linking of peptidoglycan chains, leading to weakened bacterial cell walls and cell lysis.

Why are β-lactam antibiotics highly reactive?

The reactivity is due to the ring strain in the β-lactam ring and the lack of resonance stabilization in the amide bond.

What happens to the terminal D-alanine during transpeptidase inhibition by β-lactam antibiotics?

The terminal D-alanine is released during the formation of a covalent bond between the β-lactam antibiotic and the PBP.

What is target alteration as a mechanism of resistance to β-lactam antibiotics?

Bacteria acquire PBPs with reduced affinity for β-lactam antibiotics, such as PBP2a in MRSA.

How does reduced permeability contribute to β-lactam resistance in Gram-negative bacteria?

The outer membrane limits antibiotic entry, and variations in porin channels reduce drug uptake.

What role do efflux pumps play in β-lactam resistance?

Efflux pumps actively remove β-lactam antibiotics from bacterial cells before they can act.

How do β-lactamases confer resistance to β-lactam antibiotics?

β-lactamases hydrolyze the β-lactam ring, inactivating the antibiotic.

What are extended-spectrum β-lactamases (ESBLs)?

ESBLs are enzymes that can hydrolyze extended-spectrum β-lactams, including penicillins, cephalosporins, and monobactams.

What is the primary mechanism of β-lactamase inhibitors?

β-lactamase inhibitors irreversibly bind to the active site of β-lactamase enzymes, preventing them from hydrolyzing β-lactam antibiotics.

How do β-lactamase inhibitors mimic substrates?

They structurally resemble β-lactam antibiotics, allowing them to acylate the β-lactamase enzyme and inactivate it.

What is an example of a β-lactamase inhibitor's role in combination therapy?

Clavulanic acid is combined with amoxicillin to protect it from enzymatic degradation by β-lactamases.

Why are β-lactamase inhibitors not effective on their own?

They do not possess significant antibacterial activity and rely on the β-lactam antibiotic for bacterial cell wall inhibition.

What types of β-lactamases are inhibited by clavulanic acid?

Clavulanic acid inhibits most serine β-lactamases, including those in classes A, C, and D.

What types of hypersensitivity reactions can penicillin cause?

Penicillin can cause immediate IgE-mediated reactions (Type I), antibody-mediated cytotoxic reactions (Type II), immune complex-mediated reactions (Type III), and delayed T-cell-mediated reactions.

What is a common severe reaction associated with penicillin allergy?

Severe T-cell-mediated reactions, such as Stevens-Johnson syndrome (SJS), can occur in some patients.

How can penicillin allergy impact antibiotic selection?

Reported penicillin allergy can lead to the use of broader-spectrum antibiotics, increasing risks of antimicrobial resistance and Clostridium difficile infection.

What diagnostic steps can confirm a penicillin allergy?

Penicillin skin testing and direct amoxicillin challenges are used to confirm or rule out penicillin allergy in patients with a history of allergic reactions.

What is a unique feature of Gram-positive cell walls?

They have a thick peptidoglycan layer with teichoic acid embedded in the wall.

What is a defining feature of Gram-negative cell walls?

They have an outer membrane containing lipopolysaccharides (LPS) and a thin peptidoglycan layer.

Where is β-lactamase located in Gram-negative bacteria?

β-lactamase is located in the periplasmic space between the outer membrane and the plasma membrane.

What is the role of porin channels in Gram-negative bacteria?

Porin channels allow the passage of small molecules through the outer membrane.

Peptidoglycan contains D-amino acids to protect it from _______ by host peptidases.

hydrolysis

What causes penicillin allergy?

Penicillin covalently binds to plasma proteins, forming antigenic conjugates that trigger an immune response.