Development and validation of a method for quantitation of cefepime/avibactam in M-H broth: application to antibacterial activity using in vitro PK/PD Model

Bingqian Yan; You LI; Miaomei Tian; Bingqian Yan; Siwei Guo; You LI; Miaomei Tian; Bing XU; Rong Jiang; Xin LI; Siwei Guo; Bing XU; Rong Jiang; Xin LI

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Development and validation of a method for quantitation of cefepime/avibactam in M-H broth: application to antibacterial activity using in vitro PK/PD Model

Author: Bingqian YAN ¹ ; You LI ¹ ; Miaomei TIAN ¹ ; Bingqian YAN ² ; Siwei GUO ² ; You LI ² ; Miaomei TIAN ² ; Bing XU ² ; Rong JIANG ² ; Xin LI ² ; Siwei GUO ³ ; Bing XU ³ ; Rong JIANG ³ ; Xin LI ³
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1. Hunan University of Chinese Medicine
2. The Third Hospital of Changsha
3. Changsha Institute of Clinical Application of Antibiotics
Publication Type:Journal Article
Keywords: avibactam; cefepime; HPLC; in vitro dynamic PK/PD model; LC-MS/MS
From: Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(1):52-60
CountryChina
Language:Chinese
Abstract: AIM: To establish a method for quantitation of cefepime and avibactam in M-H broth, and applicated in the in vitro dynamic PK/PD model. METHODS: The cefepime was also determined using the high-performance liquid chromatography method (HPLC), the avibactam was also determined using the liquid chromatography-mass spectrometry (LC-MS/MS), an in vitro dynamic PK/PD model was established to study the PK/PD relationship of cefepime/avibactam against carbapenem resistant Klebsiella pneumoniae (CRKP). RESULTS: The linear ranges of cefepime and avibactam were good at (0.5-20) and (0.1-25) μg/mL (r=0.999), and the lower limit concentrations were 0.5 and 0.1 μg/mL. The extraction recoveries of cefepime and avibactam in M-H broth were 88.0%-101.7% and 90.9%-95.2%, the relative standard deviation of intra-day precision and inter-day precision were less than 5.2%. The concentration-time curves were well simulated by the PK/PD model. All observed concentrations in each experiment were in the range of 20% of the targeted values. For the CRKP of MIC=8 μg/mL and MIC=16 μg/mL, the colony decreased to 2.783Log10 CFU/mL and 1.325Log10 CFU/mL at the cefepime/avibactam 2.5 g q8 h administration after 24 h. CONCLUSION: The determination method of cefepime and avibactam in broth established in this study has high sensitivity and good stability. For the CRKP with MIC≤8 μg/mL,cefepime/avibactam showed that good anti-CRKP activity under routine administration in vitro dynamic PK/PD model.