Antibiotic therapy Flashcards
beta-lactam drugs
How can antibiotics groups be divided and what is the rationale for this division
Antibiotics can be divided into two basics groups based on their patterns of activity:
- Concentration (dose)- dependent drugs
- Time-dependent drugs
What is the principle of action of concentration-dependent antibiotics? Give some examples
Optimal antibiotic activity is achieved with high peak drug concentrations, rather than depending on the interval between doses
Examples: fluoroquinolones, tetracyclines, metronidazole
Higher doses once daily tend to give optimal results while minimizing bactetrial resistance
What is the characteristic of time-dependent drugs? Give some examples
This group comprise the majority of antibacterail drugs
They achieve optimal antibacterial activity when plasma concentration are maintained at approwimately four times the minimum inhibitory concentration for greater than 50% of the time
Examples: beta-lactams, clindamycin, macrolides
Frequent administration of these drugs tend to give maximal antibiotic effects
Explain the difference between bacterisotatic and bactericidal drugs
This is an in vitro classification that divides drugs into those that can kill bacteria (bactericidal) versus those that inhibit growth but do not kill the organisms (bacteriostatic)
Bactericidal drugs may only be bacteriostatic if adequate tissue or plasma concentrations cannot be achieved (the opposite may also be true where the drug is concentrated)
What should be keep in mind when choosing a bacteriostatic drug
Bacteriostatic drugs rely on the host immune response to affect a cure
They are not a good choice for immunocompromised patients or when the infection is located in a site that is not easily accessed by the body’s immune defenses (e.g., the CNS, walled off abscesses)
What characterizes the beta-lactam drugs
Beta-lactam drugs are characterized chemically by the fact that they all contain a lactam ring
This group includes penicillins, cephalosporins, monobactams and carbapenems
How can you qualify the beta-lactam drugs
They are time-dependent, bactericidal drugs
What is the mechanism of action of beta-lactams
They act by blocking the enzymes (i.e., Penicillin Binding Proteins) required for cell wall synthesis (cross-linkage of peptidoglycan)
- Cells that cannot maintain their cell wall will become osmotically unstable, and eventually lyse and die
The difference of affinities that various beta-lactam drugs have for these enzymes partially explain thediffering drug spectrums
Explain why gram-positive bacteria are more sensitive to the beta-lactam action
Because gram-positive bacteria have a greater reliance on peptidoglycan for their wall integrity, beta-lactams are traditionally most effective against this class of microbes
Explain the mechanism of resistance to beta-lactam drugs
The beta-lactam ring can be damaged by beta-lactamase, preventing the binding of the antibiotic with the penicillin binding proteins
Beta-lactamase breaks a bond in the beta-lactam ring to disable the molecule
How is beta-lactam resistance acquired
The genes for the manufacture of the beta-lactamase (residing either in the bacterial genome or extrachromosomally in plasmids) can be passed horizontally and vertically amongst bacterial populations
Many pathologically important bacterial species have been shown to produce beta-lactamases (e.g., staphylococcus, bacillus, escheria)
Explain what is the specific mechanism of resistance for methicillin resistant staphylococcus (MRSA)
They have a modified penicillin binding protein in their cell wall with reduced affinity with the beta-lactam ring
What are the 3 classes of penicillins? Give examples
Natural penicillins:
- Penicillin G or benzyl-penicillin
Aminopenicillins:
- Ampicillin and amoxicillin
Extended-spectrum carboxypenicillins:
- Icarcillin
What are the specificities of Penicillin G
It is the naturally produced penicillin by the mold Penicillium
Penicillin G is degraded in the stomach, and as such can only be given parenterally
It is inactivated by beta-lactamases
It is ineffective against Gram-negative organisms
It remains the most effective of the penicillin group on many gram-positive and anaerobic organisms
What are the specificities of aminopenicillins
The addition of an amino group to penicillin allows this drug to penetrate the outer membrane of some gram-negative organisms (e.g., E. coli, Proteus and Salmonella), thus extending the antibacterial spectrum
They are absorbed from the GI tract (amoxicillin > ampicillin)
Amoxicillin is often paired with clavulanate to overcome beta-lactamase resistance
What are the specificities of extended-spectrum carboxypenicillins
They have increased activity against organisms such as Pseudomonas (as well as Proteus, Enterobacter)
They are destroyed by beta-lactamases so they are often paired with clavulanate
They are not well absorbed orally (given IV)
They are very expensive and used for multi-drug resistant infections
What is the influence of food on the bioavailability of orally administered penicillins
Food in the stomach can decrease the bioavailability of orally administered pencillins except for amoxicillin
What is the elimination route of penicillins and what is the medical conseuqence of it
All penicillins are eliminated via the kidney by glomerular filtration and active tubular excretion
Dose reduction in patients with renal insufficiency is not necessary because of low toxicity
IV injections of potassium-containing penicillins should be used with caution in oliguric patients because of the risk of hyperkalemia
Penicillins are widely distributed in the body except where
Brain
CSF
aqueous humor
What are the toxic effects of penicillins
The use of pneicillin and its derivatives are very safe and adverse effects are uncommon
Hypersensitivity reactions (urticaria, fever, joint pain, anaphylaxis) have been reported in cats but theyr are rare
Why clavulanic acid is paired to amoxicillin despite its very weak antibiotic activity
It is also a beta-lactam molecule and it binds strongly and irreversibly to beta-lactamase
It is rapidly absorbed rom the gut and has a wide tissue penetration except for the CNS
It is excreted unchanged in the urine
What are the principal characteristics of carbapenems
They are reserved for the treatment of severe, multi-drug resistant bacterial infections
They have a very broad spectrum of activity except for MRSA
They ahve a poor oral bioavailability
What are the characteristics of cephalosporins
They are beta-lactam antibiotics derived from a chemical (cephalosporin C) produced by the fungus Cephalosporium acremonium
They inhibit the cross-linking of peptidoglycan in the bacterial cell wall
Tehy are most effective against actively dividing bacteria
What is the difference between the third generation of cephalosporins and the 1st and 2nd ones
First generation cephalopsorins have good activity against gram-positive and anaerobes, have a wide distribution (except CNS) and are excreted unchanged in the urine
Third generation cephalosporins have greater activity against gram-negative bacteria and less active against gram-positive and anaerobic organisms than the first and second generation drugs
They have variable urine and biliarry excretion
