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

Abstract

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 disease (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 relevance. Forty antimicrobial, 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.

Influence of Renal Replacement Modalities on Amikacin Population Pharmacokinetics in Critically Ill Patients on Continuous Renal Replacement Therapy

“…In the present study, using the recommended 30-ml/kg/h effluent rate for both modes (a 30-ml/kg/h ultrafiltrate flow rate for CVVH and a 15-ml/kg/h dialysate flow rate associated with a 15-ml/kg/h ultrafiltrate flow rate for CVVHDF) (29), similar blood flow rates, and similar membranes during the RRT sessions, we did not show any significant differences in amikacin clearance. It could be hypothesized that when the recommended high doses of the effluent rate for continuous RRT are applied, the difference between convection and/or diffusion might not be significant for antibiotic pharmacokinetics (30).…”

Pharmacokinetics of Tedizolid in Subjects with Renal or Hepatic Impairment

“…Because of the fast clearance of small-molecular-weight compounds during dialysis, additional dosing considerations come into play when hemodialysis support is necessary (11,18). Tedizolid exhibits high protein binding (ϳ80%) compared with the low (ϳ30%) protein binding of linezolid (33).…”

“…Many antibacterials necessitate adjustments to dose size, dose frequency, or both when patients with impaired renal or hepatic function are treated (10,11) because chronic kidney disease and serious liver disease cause complex changes to the metabolism and elimination of many antibacterials (10,11). These disorders are also associated with increased risk of serious infections, including those due to drug-resistant Gram-positive pathogens (10,12,13), and clinically significant adverse effects caused by antibacterial treatment itself (10,14,15).…”

Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management

“…Patients with creatinine clearance (CrCl) of 25-50 ml/min/1.73 m 2 should be given 10 mg/ kg q12h; those with CrCl 10-25 ml/min/1.73 m 2 , 10 mg/kg q24h; and those with CrCl < 10 ml/min/1.73 m 2 5 mg/kg q24h. Patients on thrice-weekly hemodialysis should be given 2.5-5.0 mg/kg q24h (given after dialysis on those days), while those on peritoneal dialysis should be treated with 10 mg/kg q24h [107]. Approximately 15 % (9-22 % in 1 study [108]) of drug is bound to serum proteins and therefore much of the drug can be removed by dialysis.…”