Julie Farrar, PharmD, BCCCP (she/her/hers)
Assistant Professor
University of Tennessee College of Pharmacy
Memphis, Tennessee
Disclosure information not submitted.
Scott Mueller, PharmD, BCCCP,FCCM
Associate Professor
University of Colorado Skaggs School of Pharmacy, United States
Disclosure information not submitted.
Victoria Stevens, PharmD
University of Colorado Skaggs School of Pharmacy
Aurora, Colorado
Disclosure information not submitted.
Tyree Kiser, PharmD, BCCCP, FCCM
Professor
University of Colorado Anschutz Medical Campus
Denver, CO
Disclosure information not submitted.
Sim Taleb
Student pharmacist
University of Colorado Skaggs School of Pharmacy, United States
Disclosure information not submitted.
Paul Reynolds, BCCCP, PharmD
Assistant Professor
University of Colorado Skaggs School of Pharmacy
Denver, CO, United States
Disclosure information not submitted.
Title: Correlation of Antimicrobial Fraction Unbound & CRRT Sieving Coefficient: A Systematic Review
Background: Fraction unbound is a surrogate for antimicrobial sieving coefficient (SC) to predict extracorporeal clearance in critically-ill patients on continuous renal replacement therapy (CRRT), but this is based largely on expert opinion.
Objective: Examine relationships between package insert-derived fraction unbound (Fu-P), study-specific fraction unbound (Fu-S), and SC in critically-ill patients receiving CRRT.
Methods: English-language studies containing patient-specific in-vivo pharmacokinetic parameters for antimicrobials in critically-ill patients requiring CRRT were included. The primary outcome included correlations between Fu-S, Fu-P, and SC. Secondary outcomes included correlations across protein binding quartiles, serum albumin, and predicted in-hospital mortality, and identification of predictors for SC through multivariable analysis.
Results: Eighty-nine studies including 32 antimicrobials were included. SC was moderately correlated to Fu-S (R2=0.55, p< 0.001) and Fu-P (R2=0.41, p< 0.001). SC was best correlated to Fu-S in first ( < 69%) and fourth ( >92%) quartiles of fraction unbound and above median albumin concentrations of 24.5g/L (R2=0.71, p=0.07). Conversely, correlation was weaker in patients with mortality estimates greater than the median of 55% (R2=0.06, p=0.84). SC and Fu-P were best correlated in the first quartile of antimicrobial fraction unbound (R2=0.66, p< 0.001). Increasing Fu-P, flow rate, membrane surface area, and serum albumin, and decreasing physiologic charge significantly predicted increasing SC.
Conclusions: Fu-S and Fu-P were both reasonably correlated to SC. Caution should be taken when using Fu-S to calculate extracorporeal clearance in antimicrobials with 69-92% protein binding or with >55% estimated in-hospital patient mortality. Fu-P may serve as a rudimentary surrogate for SC when Fu-S is unavailable.