Pharmacokinetic/pharmacodynamic modelling to evaluate the efficacy of various dosing regimens of ceftazidime/avibactam in patients with pneumonia caused by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae: a multicentre study in northern China

Abstract

ABSTRACT: Objectives: The objective of this study was to evaluate the efficacy of different dosing regimens of ceftazidime/avibactam (CZA) in patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) pulmonary infections. Methods: A total of 70 KPC-Kp strains were isolated from sputum and bronchoalveolar lavage samples of patients with pulmonary infections in three hospitals in northern China from April 2015 to October 2015. Monte Carlo simulation (MCS) was performed using population pharmacokinetic parameters of CZA combined with the minimum inhibitory concentration (MIC) distributions gained from antimicrobial susceptibility testing to predict the efficacy of different dosing regimens. Various CZA dosing regimens were modelled using MCS. Results: The in vitro study showed potent activity of CZA against KPC-Kp strains with MIC50/90 values of 1/2 mg/L, with a susceptibility rate of 95.7%. The values of cumulative fraction of response (CFR) for bactericidal (50%fT>5 × MIC) target were as follows: for patients with creatinine clearance (CLCr) >51 mL/min, the CFR was 96.01% for 2.5 g CZA every 12 h (q12h) and 97.14% for 2.5 g CZA every 8 h (q8h); and for patients with moderate renal impairment (CLCr >30 to ≤50 mL/min), the CFR was 95.75% for 1.25 g CZA q12h and 97.09% for 1.25 g CZA q8h. Conclusion: This study indicated that the recommended dose of CZA can provide adequate pharmacodynamic exposure for treating KPC-Kp pneumonia.

Keywords

• Ceftazidime/avibactam
• Pharmacokinetic/pharmacodynamic
• Monte Carlo simulation
• Klebsiella pneumoniae carbapenemase
• KPC
• KPC-producing K. pneumoniae