Pharmacodynamics Modeling To Optimize Dosage Regimens of Sulbactam

Abstract

The aim of this study was to reveal population pharmacokinetics and assess the efficacies of various dosage regimens of sulbactam in terms of the probability of target attainment with this agent over a range of MICs. Monte Carlo simulations were performed to determine the probability of attaining specific pharmacodynamic targets. The results indicated that a regimen consisting of a 4-h infusion of 3 g of sulbactam every 8 h would be an alternative treatment option for less-susceptible pathogens.

Population Pharmacokinetics and Pharmacodynamics Modeling To Optimize Dosage Regimens of Sulbactam in Critically Ill Patients with Severe Sepsis Caused by Acinetobacter baumannii

“…Our population PK studies of sulbactam were performed during the steady state on the 4th day of sulbactam administration, and the two-compartment model was the best model for describing the concentration-time profile of sulbactam, which was consistent with the results of previous population PK studies (11,19,20). The central V (V c ) and peripheral V (V p ) of sulbactam were 14.56 and 9.55 liters, respectively, which are greater than the values obtained from previous studies in patients with impaired renal function (11) and healthy volunteers (21). In addition, in the current population PK analysis, we found that the low hemoglobin value had a significant effect, resulting in an increased V c of sulbactam.…”

“…All enrolled patients had hypoalbuminemia, which may have been due to the decrease in protein synthesis from the liver, as well as increased capillary permeability and leakage into interstitial space in severe illness, leading to higher free-drug concentrations and tissue distribution. The CLs of sulbactam in the current study were 2.26 liters/h and 7.64 liters/h in patients aged Ͼ65 years and Յ65 years, respectively, which are lower than the values obtained from our previous study in healthy volunteers (21). Moreover, we found that the CL CR s of most recruited patients decreased during the PK studies on the 4th day of antibiotic therapy compared to their initial CL CR s at enrollment.…”

Ampicillin/sulbactam: Its potential use in treating infections in critically ill patients

“…Further to this, the manufacturer has recommended that the daily sulbactam dose does not exceed 4 g/day. More recently, a pharmacokinetic/pharmacodynamic (PK/PD) modelling study of sulbactam using PK data from healthy volunteers has advocated a regimen of 3 g of sulbactam every 8 h as a 4 h infusion as necessary to achieve optimal antibiotic exposures for less susceptible pathogens [51]. However, this study may not be confidently extrapolated to critically ill patients considering the PK variations common to these patients as well as the frequently higher MICs of bacterial pathogens.…”

Improving antimicrobial use in critically ill patients

“…Further to this, the manufacturer has recommended that the daily sulbactam dose does not exceed 4 g/day. More recently, a PK/pharmacodynamic (PK/PD) modelling study of sulbactam using PK data from healthy volunteers has advocated a regimen of 3 g of sulbactam every 8 h as a 4-h infusion as necessary to achieve optimal antibiotic exposures for less susceptible pathogens [181]. However, this study may not be confidently extrapolated to critically ill patients considering the PK variations common to these patients as well as the frequently higher MICs of bacterial pathogens.…”

“…AUC/MIC [160,161]. Emerging data suggests that fT >MIC may also be important for sulbactam [181,232] doses between 4g -12g/day may be required for critically ill patients [233]. The aim of this study is to describe the PKs of ampicillin/sulbactam in critically ill patients at risk of MDR-Ab infections.…”