Katzung 12th ed - Chapter 43 - Antibiotics: Beta-lactams - Penicillins (1) Flashcards
Name three subgroups of Beta-lactams.
1) Penicillins
2) Cephalosporins
3) Carbapenems (e.g. meropenem)
What are the 3 subgroups of penicillins? Give examples for each group.
Natural penicillins (e.g. penicillin V, penicillin G, procaine penicillin) Antistaphylococcal penicillins (e.g. flucloxacillin, dicloxacillin) Extended spectrum penicillins (e.g. amoxicillin, ampicillin, ticarcillin, piperacillin)
Describe the cell wall of gram positive bacteria.
Single phospholipid bilayer, surrounded by a thick layer of peptidoglycan.
Explain the mechanism of action of beta-lactam antibiotics.
Penicillins bind to penicillin-binding protein and inhibit transpeptidation in peptidoglycan synthesis. This prevents the formation of cross-links in the cell wall that confer rigidity.
Which groups of bacteria are killed by natural penicillins?
Gram positive cocci, Gram negative cocci, some anaerobes.
Name four resistance mechanisms that bacteria have developed against the natural penicillins.
1 – Beta-lactamase
2 – Alteration of the penicillin-binding protein
3 – Impaired penetrance of penicillin through membrane
4 – Efflux
What makes MRSA resistant to natural penicillins?
Altered penicillin-binding protein binding sites.
What advice should you give to a patient for the administration of most oral penicillins?
With the exception of amoxicillin, most oral penicillins should be taken 1-2hrs before or after food, because absorption is impaired by food.
How are the natural penicillins excreted?
By the kidneys.
What is the half-life of natural penicillins? What if there is renal failure?
30 minutes. Can be up to 10 hours in renal failure.
Name some specific bacteria that can be killed with penicillin G.
Streptococci, Meningococci, some Enterococci, some Pneumococci, some Staphylococci, Treponema pallidum, Clostridium.
What is significant about the action of flucloxacillin?
It is a beta-lactam that is not destroyed by beta-lactamase, and is therefore effective against MRSA.
What are the routes of metabolism and excretion of flucloxacillin?
Hepatic metabolism. Renal excretion.
What dose of flucloxacillin should be given to patients with renal failure?
The same dose as that given to patients with no renal failure. There is no dose adjustment for renal failure.
What is the standard dose of natural penicillins and flucloxacillin?
10-50mg/kg/day in 3-4 doses orally or IV.
What is the rate of true anaphylactic reaction to penicillin?
0.05% of recipients. (1 in 2000)
What are the routes of metabolism and excretion for amoxicillin, ampicillin, piperacillin and ticarcillin (the extended-spectrum penicillins)?
Hepatic metabolism. Renal excretion.
What dose of the extended-spectrum penicillins should be given to patients with renal failure?
The same dose as that given to patients with no renal failure. There is no dose adjustment for renal failure.
What is an adverse effect of penicillin given in high doses to patients with renal failure?
Hypernatraemia and Seizures.
Name some bacteria that are covered by the extended-spectrum penicillins.
All of those covered by natural penicillins (streptococci, meningococci, pneumococci, staphylococci, treponema pallidum, clostridium), as well as:
Ampicillin – Shigella, Anaerobes, E.coli, Salmonella (as long as they don’t contain beta-lactamase)
Ticarcillin – Pseudomonas, Enterobacter
Piperacillin – Klebsiella
Name the three beta-lactamase inhibitors that resemble beta-lactam molecules.
Clavulanic acid, Tazobactam, Sulbactam. Note that these do NOT have antibacterial activity alone.
What is the major clinical use of carbapenems?
Infections due to resistant organisms, such as resistant strains of pneumococci and enterobacter. Carbapenems have the same mechanism of action as other beta-lactams, but in addition they are resistant to most beta-lactamases.
What is another name for penicillin V?
Phenoxymethylpenicillin.
Clavulanic acid is active against beta-lactamases from which bacteria?
Haemophilus, Neisseria, Salmonella, Shigella, E.coli, Klebsiella, Legionella, Bacteroides.
Clavulanic acid is NOT active against beta-lactamases from which bacteria?
Enterobacter, Citrobacter, Serratia, Pseudomonas.
Carbapenems: Describe their absorption in tissues.
Carbapenems penetrate body tissues and fluids well, including CSF.
Carbapenems: How are they cleared?
Renally cleared. Dose adjustment required in renal failure.
Carbapenems: Half-life?
1 hour
What is another name for benzylpenicillin?
Penicillin G
Are penicillins bacteriostatic or bacteriocidal?
Bacteriocidal
