Protein binding of antimicrobials: methods for quantification and for investigation of its impact on bacterial killing.
Plasma protein binding of antimicrobial agents is considered to be a key characteristic of antibiotics as it affects both their pharmacokinetics and pharmacodynamics. However, up to the present, no standard methods for measuring protein binding or for quantification of the influence of protein binding on antimicrobial activity exist. This short-coming has previously led to conflicting results on antibacterial activity of highly protein-bound antibiotics. The present review, therefore, set out to summarize (1) methods for quantification of protein binding, (2) microbiological growth media used for determination of the impact of protein binding on antimicrobial activity of antibiotics, and (3) different pharmacodynamic in vitro studies that are used in this context. The advantages and disadvantages of a wide range of different approaches are discussed and compared. The urgent call for international standardization by microbiological societies and laboratories may be considered as a logical consequence of the presented data.
Beer
Jürgen
J
Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Wagner
Claudia Christina
CC
Zeitlinger
Markus
M
D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism*; D001826:Body Fluids; D002623:Chemistry Techniques, Analytical / Q000295:instrumentation / Q000379:methods*; D003470:Culture Media / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D006801:Humans; D008657:Metabolic Clearance Rate; D008826:Microbial Sensitivity Tests / Q000379:methods* / Q000592:standards; D011485:Protein Binding; D013997:Time Factors
D000900:Anti-Bacterial Agents; D001798:Blood Proteins; D003470:Culture Media