Determination of alternative ceftolozane/tazobactam dosing regimens for patients with infections due to Pseudomonas aeruginosa with MIC values between 4 and 32 mg/L

Abstract

Background

Optimization of the antibiotics for patients with infections due to MDR Pseudomonas aeruginosa (MDR-PA) often requires consideration of alternate dose and infusion times that can be influenced by renal function.

Objectives

We sought to identify ceftolozane/tazobactam dosing schemes that optimized the probability of target attainment (PTA) against infections due to MDR-PA with ceftolozane/tazobactam MICs between 4 and 32 mg/L across different categories of renal function.

Methods

A prior validated ceftolozane/tazobactam population pharmacokinetic model was used for Monte Carlo simulation of 128 alternate permutations of dose, infusion time and renal function in 5000 cases/permutation. Four ceftolozane/tazobactam doses (250/125 mg to 2/1 g) every 8 h with infusion durations of 1–7 h and as continuous infusions were simulated. The model simulated ceftolozane/tazobactam clearance as a function of creatinine clearance (CL_CR) within four categories of estimated renal function: 15–29, 30–50, 51–120 and 121–180 mL/min. The PTA was benchmarked on 40% free ceftolozane/tazobactam concentration time above the MIC.

Results

The 512 alternate scenarios identified the current ceftolozane/tazobactam dose of 1/0.5 g to be optimal for MICs ≤32 mg/L (CL_CR 15–50 mL/min), ≤16 mg/L (CL_CR 51–120 mL/min) and ≤8 mg/L (CL_CR 121–180 mL/min). Extended infusion of 4–5 h had a higher PTA than shorter and continuous infusions in simulations of augmented renal clearance across infections with MICs of 4–32 mg/L.

Conclusions

Extended infusion ceftolozane/tazobactam regimens should be investigated as a potential dosing solution to improve the PTA against infections due to MDR-PA with higher ceftolozane/tazobactam MICs.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2jRdwJr
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