The objective of our 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.
Seventy KPC-Kp strains were isolated from sputum and bronchoalveolar lavage (BAL) samples of patients with pulmonary infections in three hospitals in northern China. We performed Monte Carlo simulations (MCS) using population pharmacokinetic (PPK) parameters of CZA combined with the minimum inhibitory concentration (MIC) distributions gained from susceptibility tests to predict the efficacy of different dosing regimens. Various CZA dosing regimens were modeled using MCS.
Our in vitro study showed potent activity of CZA against KPC-Kp strains with MIC values of 1/2 mg/L and a susceptibility rate of 97.1%. The cumulative fraction of response (CFR) for bactericidal (50%fT>5 × MIC) target are below. For patients with creatinine clearance (CL) > 51 ml/min, CFRs were 96.01% for 2.5 g CZA twice daily, 97.14% for 2.5 g CZA three times daily. Similarly, for patients with moderate renal impairment (CL > 30 to ≤ 50 ml/min), CFRs were 95.75% for 1.25 g CZA twice daily, 97.09% for 1.25 g CZA three times daily.
Our study indicated that the recommended dose of CZA can provide adequate pharmacodynamic (PD) exposure for treating KPC-Kp pneumonia.

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