AUTHOR=Zhang Jingjia , Li Gang , Zhang Ge , Kang Wei , Duan Simeng , Wang Tong , Li Jin , Huangfu Zhiru , Yang Qiwen , Xu Yingchun , Jia Wei , Sun Hongli 

TITLE=Performance Evaluation of the Gradient Diffusion Strip Method and Disk Diffusion Method for Ceftazidime–Avibactam Against Enterobacterales and Pseudomonas aeruginosa: A Dual-Center Study

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.710526

DOI=10.3389/fmicb.2021.710526

ISSN=1664-302X

ABSTRACT=<p><bold>Objectives:</bold> Ceftazidime–avibactam is a novel synthetic beta-lactam + beta-lactamase inhibitor combination. We evaluated the performance of the gradient diffusion strip method and the disk diffusion method for the determination of ceftazidime–avibactam against <italic>Enterobacterales</italic> and <italic>Pseudomonas aeruginosa.</italic></p><p><bold>Methods:</bold> Antimicrobial susceptibility testing of 302 clinical <italic>Enterobacterales</italic> and <italic>Pseudomonas aeruginosa</italic> isolates from two centers were conducted by broth microdilution (BMD), gradient diffusion strip method, and disk diffusion method for ceftazidime–avibactam. Using BMD as a gold standard, essential agreement (EA), categorical agreement (CA), major error (ME), and very major error (VME) were determined according to CLSI guidelines. CA and EA rate &gt; 90%, ME rate &lt; 3%, and VME rate &lt; 1.5% were considered as acceptable criteria. Polymerase chain reaction and Sanger sequencing were performed to determine the carbapenem resistance genes of all 302 isolates.</p><p><bold>Results:</bold> A total of 302 strains were enrolled, among which 182 strains were from center 1 and 120 strains were from center 2. A percentage of 18.21% (55/302) of the enrolled isolates were resistant to ceftazidime–avibactam. The CA rates of the gradient diffusion strip method for <italic>Enterobacterales</italic> and <italic>P. aeruginosa</italic> were 100% and 98.65% (73/74), respectively, and the EA rates were 97.37% (222/228) and 98.65% (73/74), respectively. The CA rates of the disk diffusion method for <italic>Enterobacterales</italic> and <italic>P. aeruginosa</italic> were 100% and 95.95% (71/74), respectively. No VMEs were found by using the gradient diffusion strip method, while the ME rate was 0.40% (1/247). No MEs were found by using the disk diffusion method, but the VME rate was 5.45% (3/55). Therefore, all the parameters of the gradient diffusion strip method were in line with acceptable criteria. For 31 <italic>bla</italic><sub><italic>KPC</italic></sub>, 33 <italic>bla</italic><sub><italic>NDM</italic></sub>, 7 <italic>bla</italic><sub><italic>IMP</italic></sub>, and 2 <italic>bla</italic><sub><italic>VIM</italic></sub> positive isolates, both CA and EA rates were 100%; no MEs or VMEs were detected by either method. For 15 carbapenemase-non-producing resistant isolates, the CA and EA rates of the gradient diffusion strips method were 100%. Whereas the CA rate of the disk diffusion method was 80.00% (12/15), the VME rate was 20.00% (3/15).</p><p><bold>Conclusion:</bold> The gradient diffusion strip method can meet the needs of clinical microbiological laboratories for testing the susceptibility of ceftazidime–avibactam drugs. However, the VME rate &gt; 1.5% (5.45%) by the disk diffusion method. By comparison, the performance of the gradient diffusion strip method was better than that of the disk diffusion method.</p>