Determination of Disk Diffusion and MIC Quality Control Guidelines for High-Dose Cefepime-Tazobactam (WCK 4282), a Novel Antibacterial Combination Consisting of a β-Lactamase Inhibitor and a Fourth-Generation Cephalosporin

摘要

β-Lactam antibacterial agents are among the most commonly used antibiotics worldwide (1). At the same time, the increase in resistance to β-lactam antibacterial agents among Gram-positive and Gram-negative organisms during the past 2 decades is one of the most significant global threats to the efficacy of this class of antimicrobial agents (2, 3). Combining various β-lactam antimicrobial agents with β-lactamase inhibitors has been proven to be an effective therapy for Gram-negative and Gram-positive infections (1). High-dose cefepime-tazobactam (1:1; WCK 4282) is a new antibacterial combination, consisting of 2 g of tazobactam combined with 2 g of cefepime to be administered as an intravenous infusion over 90 min. Cefepime-tazobactam has recently been evaluated in in vitro testing and clinical studies (4; A. Bhatia, R. Chugh, M. Gupta, and P. Iwanowski, presented at 26th European Congress of Clinical Microbiology and Infectious Diseases [ECCMID], Amsterdam, Netherlands, 9 to 12 April, 2016; H. Khande, P. Joshi, S. Palwe, K. Umarkar, S. Takalkar, S. Bhagwat, and M. Patel, presented at 26th ECCMID, Amsterdam, Netherlands, 9 to 12 April, 2016; K. Umarkar, J. Satav, A. Uday, A. Kulkarni, H. Khande, S. Palwe, S. Takalkar, S. Bhagwat, and M. Patel, presented at 26th ECCMID, Amsterdam, Netherlands, 9 to 12 April, 2016). A CLSI M23-styled (tier 2) quality control (QC) study in the style of was performed to establish disk diffusion and broth microdilution QC ranges for several relevant bacterial reference control strains to assist clinical laboratories in monitoring the in vitro activity of this combination during clinical trial development and routine antimicrobial susceptibility testing (5–8). Data from these studies were presented at the 2016 ASM Microbe and ECCMID meetings (M. D. Huband, J. E Ross, R. K. Flamm, R. N. Jones, and H. S. Sader, presented at ASM Microbe, Boston, MA, 16 to 20 June, 2016; J. E Ross, M. D. Huband, R. K. Flamm, R. N. Jones, and H. S. Sader, presented at 26th ECCMID, Amsterdam, Netherlands, 9 to 12 April, 2016).