What is the most simple and high throughput in vitro method to characterise antibiotics/antifungals as time- vs concentration dependent? Is there any "general" cut off?
Optimum dosage of antibiotic concentration -https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&cad=rja&uact=8&ved=2ahUKEwibmtO10vr3AhWGSmwGHcotCswQFnoECAsQAw&url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F19667545%2F&usg=AOvVaw1G4KlDiMBlQxLUlExiJ4FW
Time-Dependent Killing:
For certain classes of antibiotics, the major killing effect against an organism is produced by either the time or the concentration of the drug at the binding site. In fact, of these two factors of bacterial killing, the killing process may be so minimal that it can be ignored in the prediction of a clinical response. For instance, certain antibiotics, like beta-lactams (penicillins, cephalosporins, carbapenems, monobactams), clindamycin, macrolides (erythromycin, clarithromycin), oxazolidinones (linezolid), can be effective because of the extensive amount of time the antibiotic binds to the microorganism. The inhibitory effect can be effective because their concentration exceeds the MIC for the microorganism. Hence, these antibiotics are referred to as time-dependent antibiotics. For time-dependent drugs, the pharmacodynamic parameter can be simplified to the time that serum concentrations remain above the MIC during the dosing interval (t>MIC)
Concentration-Dependent Killing:
Other classes of antibiotics, such as aminoglycosides and quinolones, have high concentrations at the binding site which eradicates the microorganism and, hence, these drugs are considered to have a different kind of bacterial killing, named concentration-dependent killing. For concentration-dependent agents, the pharmacodynamic parameter can be simplified as a peak/MIC ratio
Please find details in the link:
Pharmacodynamics of Antimicrobial Agents: Time-Dependent vs. Concentration-Dependent Killing (antimicrobe.org)
I'm aware of 2 methods that can be used to ascertain the pharmacodynamic driver (i.e., "time above MIC" versus "area under the curve over MIC") of an antibiotic. The two methods both employ dose fractionation, in which the dose of the antibiotic is delivered all at once, divided into two evenly spaced doses, or into 3 evenly-spaced doses, etc. This can be done in vivo using an animal infection model (typically with mice) or in vitro using the hollow fiber system.
Neither of these methods is simple or high-throughput, unfortunately.