2. Academic Validation
  3. Multicenter Evaluation of an MIC-Based Aztreonam and Ceftazidime-Avibactam Broth Disk Elution Test

Multicenter Evaluation of an MIC-Based Aztreonam and Ceftazidime-Avibactam Broth Disk Elution Test

  • J Clin Microbiol. 2023 Apr 18;e0164722. doi: 10.1128/jcm.01647-22.
Harley Harris 1,  Lili Tao 2,  Emily B Jacobs 1,  Yehudit Bergman 1,  Ayomikun Adebayo 1,  Tsigedera Tekle 1,  Shawna Lewis 1,  Ashley Dahlquist 3,  Taylor C Abbey 3,  Eric Wenzler 3,  Romney Humphries 2,  Patricia J Simner 1
Affiliations

Affiliations

  • 1 Department of Pathology, Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • 2 Department of Pathology, Microbiology, and Immunology, Division of Laboratory Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • 3 College of Pharmacy, University of Illinois Chicago, Chicago, Illinois, USA.
PMID: 37070979 DOI: 10.1128/jcm.01647-22
Abstract

Due to limited therapeutic options, there is a clinical need to assess the in vitro activity of the combination of aztreonam (ATM) and ceftazidime-avibactam (CZA) to guide the therapeutic management of multidrug-resistant (MDR) Gram-negative organism infections. We set out to develop a practical MIC-based broth disk elution (BDE) method to determine the in vitro activity of the combination ATM-CZA using readily available supplies and compare it to reference broth microdilution (BMD). For the BDE method, a 30-μg ATM disk, a 30/20-μg CZA disk, both disks in combination, and no disks were added to 4 separate 5-mL cation-adjusted Mueller-Hinton broth (CA-MHB) tubes, using various manufacturers. Three testing sites performed both BDE and reference BMD testing of Bacterial isolates in parallel from a single 0.5 McFarland standard inoculum and after overnight incubation, assessed them for growth (not susceptible) or no growth (susceptible) at a final concentration of 6/6/4 μg/mL ATM-CZA. During the first phase, the precision and accuracy of the BDE were analyzed by testing 61 Enterobacterales isolates at all sites. This testing yielded 98.3% precision between sites, with 98.3% categorical agreement and 1.8% major errors (ME). During the second phase, at each site, we evaluated unique, clinical isolates of Metallo-β-lactamase (MBL)-producing Enterobacterales (n = 75), carbapenem-resistant Pseudomonas aeruginosa (n = 25), Stenotrophomonas maltophilia (n = 46), and Myroides sp. (n = 1). This testing resulted in 97.9% categorical agreement, with 2.4% ME. Different results were observed for different disk and CA-MHB manufacturers, requiring a supplemental ATM-CZA-not-susceptible quality control organism to ensure the accuracy of results. The BDE is a precise and effective methodology for determining susceptibility to the combination ATM-CZA.

Keywords

CLSI; antimicrobial susceptibility testing; aztreonam; broth disk elution; ceftazidime-avibactam; multicenter study.

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