Alternative approaches to optimizing antimicrobial pharmacodynamics in critically ill patients

Critical illness results in a constellation of physiologic changes that subsequently impact antibiotic pharmacokinetic and pharmacodynamic parameters. These changes can result in poorly treated infections that in turn lead to longer intensive care unit (ICU) and hospital stays, prolonged use of mechanical ventilation, and higher mortality rates. Research has expanded our understanding of antibiotic pharmacodynamics among ICU patients, and some investigators and clinicians have questioned traditional antibiotic dosing schemes among this population. Alternative dosing strategies to optimize antibiotic pharmacodynamics of aminoglycosides, beta-lactams, fluoroquinolones, and vancomycin have been explored. Appropriate duration of exposure to beta-lactam antibiotics has been recognized as an important parameter associated with successful treatment outcomes. To maximize this exposure, continuous infusions over a 24-hour period have resulted in higher clinical response rates and improved surrogate markers of infection. Equally as promising is the alternative of extending the infusion time to increase exposure while maintaining the same daily beta-lactam dose and frequency. Data from clinical trials have suggested that the area under the concentration-time curve to minimum inhibitory concentration ratio for aminoglycosides, fluoroquinolones, and vancomycin is a better correlate for successful treatment outcomes. Optimizing antibiotic pharmacodynamics by changing dosage methods should be considered in ICU patients to improve treatment response and success.