Antimicrobial Dosing Concepts and Recommendations for Critically III Adult Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis

Infectious diseases and impaired renal function often occur in critically ill patients, and delaying the start of appropriate empiric antimicrobial therapy or starting inappropriate therapy has been associated with poor outcomes. Our primary objective was to critically review and discuss the influence of chronic kidney discase (CKD) and acute kidney injury (AKI) on the clinical pharmacokinetic and pharmacodynamic properties of antimicrobial agents. The effect of continuous renal replacement therapies (CRRTs) and intermittent hemodialysis (IHD) on drug disposition in these two populations was also evaluated. Finally, proposed dosing strategies for selected antimicrobials in critically ill adult patients as well as those receiving CRRT or IHD have been compiled. We conducted a PUbMed search (January 1980-March 2008) to identify all English-language literature published in which dosing recommendations were proposed for antimicrobials commonly used in critically ill patients, including those receiving CRRT or IHD. All pertinent reviews, selected studies, and associated references were evaluated to ensure their relcvance. Forty anti microbial, antifungal, and antiviral agents commonly used in critically ill patients were included for review. Dosage recommendations were synthesized from the 42 reviewed articles and peer-reviewed, evidence-based clinical drug databases to generate initial guidance for the determination of antimicrobial dosing strategies for critically ill adults. Because of the evolving process of critical illness, whether in patients with AKI or in those with CKD, prospective adaptation of these initial dosing recommendations to meet the needs of' each individual patient will often rely on prospectively collected clinical and laboratory data.