Optimizing use of quinolones in the critically ill.
Fluoroquinolones (FQs) are broad spectrum, concentration dependent, bactericidal antimicrobials that have been commonly utilized to treat severe nosocomial infections. FQ activity is derived from their ability to inhibit DNA gyrase and topoisomerase IV; resistance has been shown to develop in target site mutations, alterations in efflux pump systems, and incorporation of plasmids. The probability of preventing emergence of resistance and achieving maximal rates of kill are best related to the ratio of free-drug in the area under the concentration-time curve (AUC) to minimum inhibitory concentration (AUC:MIC). Major dosage adjustments for FQs are not necessary in hepatic insufficiency, accumulation of extracellular fluids, and burn patients. Appropriate dosage adjustments in renal function should be taken into consideration. FQ optimization in the critically ill is a multifactorial process that should be individualized to each patient and should take into account the MIC of the pathogen, pharmacokinetic/pharmacodynamic profile of the FQ, and the patient's pathophysiological state.
Yang
Jenny C
JC
SUNY-Buffalo School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY 14206, USA.
Tsuji
Brian T
BT
Forrest
Alan
A
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016638:Critical Illness / Q000628:therapy; D003428:Cross Infection / Q000188:drug therapy*; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones