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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Optimizing use of quinolones in the critically ill
Jenny C Yang1, Brian T Tsuji, Alan Forrest
1SUNY-Buffalo School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY 14206, USA.
Seminars in Respiratory and Critical Care Medicine
|December 21, 2007
Summary
Fluoroquinolones (FQs) are potent antimicrobials effective against severe infections. Optimizing FQ dosing in critically ill patients requires individualizing treatment based on pathogen susceptibility and patient factors to prevent resistance.
Area of Science:
- Pharmacology
- Infectious Diseases
- Critical Care Medicine
Background:
- Fluoroquinolones (FQs) are broad-spectrum, bactericidal antimicrobials frequently used for severe nosocomial infections.
- FQ efficacy relies on inhibiting DNA gyrase and topoisomerase IV, with resistance emerging through mutations, efflux pumps, and plasmids.
- Optimal antimicrobial effect is linked to the ratio of the area under the free-drug concentration-time curve to the minimum inhibitory concentration (AUC:MIC).
Purpose of the Study:
- To review the pharmacokinetic/pharmacodynamic (PK/PD) principles of fluoroquinolone optimization in critically ill patients.
- To discuss factors influencing FQ dosing, including patient-specific variables and pathogen characteristics.
- To highlight the importance of individualized dosing strategies to maximize efficacy and minimize resistance.
Main Methods:
- Review of existing literature on fluoroquinolone pharmacokinetics and pharmacodynamics.
- Analysis of factors affecting FQ drug exposure and activity in various patient populations.
- Discussion of resistance mechanisms and strategies for prevention.
Main Results:
- Fluoroquinolone dosage adjustments are generally not required for hepatic insufficiency, fluid accumulation, or burn patients.
- Renal function significantly impacts FQ pharmacokinetics, necessitating dose adjustments.
- The AUC:MIC ratio is a key determinant of FQ efficacy and resistance prevention.
Conclusions:
- Optimizing fluoroquinolone therapy in critically ill patients is complex and requires individualized approaches.
- Consideration of pathogen minimum inhibitory concentration (MIC), FQ PK/PD profile, and patient's pathophysiological state is crucial.
- Tailored dosing strategies are essential for maximizing treatment success and combating antimicrobial resistance.
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