Beta-lactams

What is the mechanism of action of B-lactam/

inhibit penicillin-binding proteins that catalyze the cross-linking of bacterial cell walls

What are the action of B-lactam?

Bactericidal

Target of Beta-Lactam MOA

Bacterial cell wall synthesis.

Beta-lactams are most effective against which type of bacteria?

Only growing & metabolically active bacteria

Urine

A significant portion of beta lactam antibiotics is excreted unchanged in the

B-lactamases

bacterial enzymes that inactivate B-lactam ATB through hydrolysis of the B-lactam ring

Penicillinase

B-lactamases specific for penicillin

Cephalosporinase

b-lactamases specific for cephalosporins

Penicillin

first antibiotic introduced in medicine

drug of choice for the initial treatment of infections in horses and cattle

poor oral absorption

PCN is poorly absorbed in this route 

Probenecid

it was used to prolong the half-life of PCN through competitive inhibition of renal tubular secretion of PCNs

Natural PCN

Aminopenicillin

Antistaphylococcal PCN

Beta-lactamase resistant

Extended-spectrum PCN

Types of Penicillin

Natural PCNs

extracted and purified from mold cultures

with narrow spectrum of activity (Some G+ and selected G-)

Penicillin G

Degraded by stomach acid

Metabolized to PABA and can inactivate sulfonamides

Penicillin V

more stable in stomach (can be orally administered)

What structural feature distinguishes aminopenicillins from natural penicillins?

an added amino group

Amoxicillin, ampicillin

examples of aminopenicillins

B-lactamase inhibitors

It is combined with aminopenicillins to overcome resistance and increase the spectrum

Beta-lactamase inhibitors

a class of drugs with little antibacterial effect but can inhibit beta-lactamase enzyme

Why are anti-staphylococcal penicillins effective against Staphylococcus species?

Because they are resistant to β-lactamase, the enzyme Staph produces to destroy penicillin.

What is the main type of bacteria these drugs target?

gram positive bacteria, especially staphylococcus

Name three anti-staphylococcal penicliins commonly used

Oxacillin, cloxacillin, dicloxacillin

name two synthetic anti-staphylococcal penicillins

methicillin and nafcillin

Anti-pseudomonal PCNs

Also known as extended spectrum PCNs

have the most activity against G-aerobic and anaerobic bacteria of all the PCNs

Piperacillin, Ticarcillin, Carbenicillin

examples of anti-pseudomonal PCNs

reptiles

it is slow clearance in this species which permits infrequent dosing intervals (once every 3-5 days)

birds

High renal clearance and metabolic rate in this species which requires frequent dosing in birds

dysbiosis

PCNs can cause this imbalance in the gut microbiota due to reduction in beneficial bacteria and an overgrowth of abnormal flora