Antibiotic resistance Flashcards
what are the most prescribed class of antibiotics in the world?
β-lactams
When was resistance to penicillin reported?
Resistance to penicillin G was reported three years before the drug was approved for prescription use
Macrolides structure
They consist of a macrocyclic lactone ring (typically >12 carbon atoms), substituted with deoxy sugars
How are macrolides similar to penicillin?
They are derived from natural products. Macrolides are often the ‘first choice’ antibiotic for patients who can’t tolerate penicillin
What type of activity does macrolides have?
Macrolides exhibit broad spectrum activity against many gram-positive bacteria.
Erythromycin
The most well-known macrolide, initially isolated in 1952. However, many semi-synthetic molecules have been developed that differ through their substitution pattern of the lactone ring system.
How do macrolides work?
Macrolides work in a different way to the β-lactams in that they inhibit the synthesis of bacterial proteins. It is thought that macrolides bind to a ribosomal unit involved with adding amino acids to tRNA.
bacteriostatic v bactericidal.
Bacteriostatic = restricts growth of bacteria
Bactericidal = causes bacterial cell death
macrolides are bacteriostatic, whereas β-lactams are bactericidal.
Daptomycin
This is one of the most recent antibiotics to be developed. It is a lipopeptide antibiotic used in the treatment of gram-positive bacteria. Crucially, cases of daptomycin resistance are incredibly rare and it is often used in treating multi-drug resistant infections
Daptomycin MOA
its precise mechanism of action is not known, it is generally thought to disrupt multiple cell membrane functions, leading to cell death.
Dosing regimens
They are often driven by PK parameters only.
how antibiotic resistance plays into Dosing regimens?
PD is extremely important and can be used to design dosing regimens that counteract or prevent resistance.
Pharmacokinetics (PK)
The study of how an organism affects a drug
Pharmacodynamics (PD)
The study of how a drug affects an organism
Minimum inhibitory concentration (MIC)
The lowest concentration of an antibiotic that completely inhibits the growth of a microorganism in vitro. Whilst the MIC is a good indicator of the potency of an antibiotic, it indicates nothing about the time course of antimicrobial activity.
PD properties are all crucial factors in determining the correct dosing of antibiotics such as…
time-dependence, concentration-dependence, and the persistent suppression of bacterial growth following antibiotic exposure
How can the dosing regimen change? For daptomycin?
The ideal dosing regime would be to maximise the concentration (higher the concentration the faster the bacteria cells are killed). Therefore, the peak MIC is an important predictor of antibiotic efficacy.
How can the dosing regimen change? For β-lactams and macrolides?
For β-lactams and macrolides the opposite of daptomycin is true. The ideal dosing regimen for these antibiotics would be to maximize their duration of exposure. The T>MIC is the parameter that best correlates with efficacy. β-lactams can be thought of as “time-dependent killers”. Their effect is directly proportional to the amount of time the concentration of the antibiotic at the site of infection is above the MIC of the organism.
Why has the number of new antibiotics developed has been steadily dropping in recent years?
New antibiotics are often used as a last resort, which means they sell in low amounts
Antibiotics must be tested against a variety of infectious diseases
Antibiotics must prove that they are significantly different from highly effective drug already on the market.
