Implications of Augmented Renal Clearance on Drug Dosing in Critically Ill Patients: A Focus on Antibiotics

Abstract

Augmented renal clearance (ARC) has been reported in approximately 30-65% of patients in the intensive care unit (ICU) despite the presence of a normal serum creatinine concentration. In certain ICU patient populations (e.g., patients with sepsis or trauma), the incidence increases to roughly 50-85%. Risk factors for ARC include the following: age younger than 50-55 years, male sex, higher diastolic blood pressure, fewer comorbidities, and a lower Acute Physiology and Chronic Health Evaluation II (APACHE II) or modified Sequential Organ Failure Assessment (SOFA) score at ICU admission. In addition, patient populations with the highest reported incidence of ARC include those with major trauma, sepsis, traumatic brain injury, subarachnoid hemorrhage, and central nervous system infection. Due to the high incidence of ARC in patients with a normal serum creatinine concentration, clinicians should consider screening ICU patients deemed high risk by using the ARC scoring system or the identification and assessment algorithm provided in this review. In addition, an 8-hour continuous urine collection should be considered to assess a measured creatinine clearance for evaluating the necessity of medication dosage adjustments. There is a clear association between ARC and subtherapeutic antibiotic concentrations as well as literature suggesting worse clinical outcomes; thus, the risk of underdosing antibiotics in a patient with ARC could increase the risk of treatment failure. This review examines strategies to overcome ARC and summarizes current pharmacokinetic and pharmacodynamic literature in patients with ARC in an effort to provide dosing guidance for this patient population.

Safety, Tolerability, and Pharmacokinetics of 3 g of Ceftolozane/Tazobactam in Healthy Adults: A Randomized, Placebo‐Controlled, Multiple‐Dose Study

“…6 Higher doses of β-lactam antibacterials may be needed for difficult-to-treat infections such as nosocomial pneumonia: the increased prevalence of pathogens with relatively high minimum inhibitory concentration values may warrant higher-dose regimens to improve clinical outcomes and prevent emergence of resistance. [9][10][11] Higher doses may be especially useful in critically ill patients to (1) account for the much greater variability of plasma pharmacokinetics in this population [12][13][14][15] and (2) to rapidly achieve adequate free drug concentrations at the infection site. 10,16,17 Population pharmacokinetic modeling suggests that a 3-g q8h dose of ceftolozane/tazobactam is necessary to achieve >90% probability of target attainment in the treatment of nosocomial pneumonia due to moderate (50%) penetration of the drug into lung tissue and to adequately cover pathogens with ceftolozane/tazobactam minimum inhibitory concentrations of 8 μg/mL (ie, intermediate susceptible strains of P. aeruginosa according to current United States FDA-approved breakpoints).…”

What the non‐nephrologist needs to know about dialysis

“…As such, when possible, drug levels should be followed and doses adjusted accordingly. Significant potential exists for both over and under‐dosing medications, in particular antibiotics such as cefepime . Moreover, data are largely nonexistent regarding the quantity of medication removed by convection typical of lower volume isolated ultrafiltration.…”

Analisi farmakozinetiko/farmakodinamikoa antimikrobianoen erabilera hobetzeko gaixo larrietan

“…Gaixo hauetan gastu kardiakoa areagotu egiten da, eta, ondorioz, giltzurrunetako odol-fluxua handitzen da eta hiperfiltrazio glomerularra eragiten da. Egun, 130 mL/min/1,73m 2 -ko filtrazio glomerularra duten pazienteak hartzen dira hiperfiltratzailetzat, gehienetan sepsia edota traumatismoren bat duten gizonezko gaixo gazteak izan ohi direnak [19].…”