Comparison of the in vitro activities of ceftazidime/avibactam with other drugs used to treat carbapenem-resistant Enterobacteriaceae

Background & Objective:: Our goal was to compare the in vitro activities of ceftazidime/avibactam (CZA) to those observed in response to other drugs used to treat carbapenem-resistant Enterobacteriaceae (CRE). Methods:: Bacterial isolates collected from intensive care unit patients with hospital-acquired infections were identified using the VITEK 2TMCompact 15. Susceptibility testing for Escherichia coli and Klebsiella spp. was performed using Kirby- Bauer disk diffusion and the VITEK2 system. Minimum inhibitory concentration (MIC) E-test strips were used to examine susceptibility to fosfomycin, colistin, and CZA. Detection of carbapenemase in isolates of Enterobacteriaceae was performed using the modified carbapenem inactivation method (mCIM) and multiplex polymerase chain reaction. Results:: A full 62.5% of the Enterobacteriaceae isolates were CRE. The sensitivity and specificity of mCIM were 98.3% and 100%, respectively, with positive predictive and negative predictive values and accuracy at 100%, 97.3%, and 98.96%, respectively. The most prevalent of the carbapenemase genes was blaKPC which was detected in 46.7% of all isolates and in 83.3% of those identified as Klebsiella pneumoniae. CRE were most sensitive to colistin (96.7%), CZA (80%) and tigecycline (71.7%) (p<0.001). The MIC50 for CZA (≤0.016 μg/mL) was the lowest of all the drugs evaluated, followed by colistin (1 μg/mL) and tigecycline (2 μg/mL). All metallo-ß-lactamase-negative isolates were sensitive to CZA. Conclusions:: mCIM is sensitive, specific, inexpensive and easy to perform; as such, it an ideal method for identification of carbapenem-resistant strains. Our results suggest that CZA may be a good choice for treating infections with CRE if therapeutic options are limited.