Emerging ceftazidime-avibactam resistance against carbapenem resistant Escherichia coli and Klebsiella pneumoniae in Lebanon

Introduction: Ceftazidime-avibactam (CZA) has been introduced as a novel drug to essentially combat the rising trends of carbapenem resistant Enterobacteriaceae. In the absence of in vitro data about the activity of this drug against carbapenem resistant (CR) Escherichia coli and Klebsiella pneumoniae in Lebanon, this study was warranted.        Methodology: A total of 150 isolates, identified using the MALDI-TOF,  encompassing 50 CR E. coli, 60 CR K. pneumoniae, and 10 isolates each of extended-spectrum Beta-lactamases (ESBLs), and non-CR multidrug-resistant (MDR) of each species were analyzed.  The minimum inhibitory concentration (MIC) for CZA was determined by the E-test (Liofilchem, Roseto degli Abruzzi, Italy). In addition, the disk diffusion (DD) test was used to determine the activity of CZA and of the antimicrobials routinely used to test for such pathogens.   Results:  The CZA activity against the 50 CR E. coli showed an MIC50 ≥ 256 μg/mL, an MIC90 ≥ 256 μg/mL, and an MIC range of 0.023 to ≥ 256 μg/mL, reflecting a susceptibility of 40 %. As For the 60 CR K. pneumoniae isolates, the MIC50 was ≥ 256 μg/mL, MIC90 ≥ 256 μg/mL, and the MIC range was 0.094 to ≥ 256 μg/mL, reflecting a susceptibility of 35%. However, uniform CZA susceptibility (100%) was detected against ESBL and MDR isolates of both species, being comparable or higher to the routinely used antimicrobials.     Conclusion: Although CZA was recently introduced into this country, it was surprising to note this humble susceptibility of CZA against CR E. coli and CR K. pneumoniae. To explain such findings, it is worth pursuing investigations related to antimicrobial utilization in clinical practice and antimicrobial stewardship. Moreover, genotypic determination is needed to be revealed to help explain the observed phenotypic resistance   &nbsp