Rapid detection of Ceftazidine/Avibactam sensitivity in carbapenem-resistant Enterobacteriaceae

Abstract

Abstract Currently, ceftazidime-avibactam (CZA) is the primary antibiotic for treating carbapenem-resistant Enterobacteriaceae (CRE) infections in KPC and OXA-48 families. However, due to rising CZA resistance, a fast, simple, and effective technique is needed to detect CRE sensitivity to CZA. The rapidCZA test proposed in this study only takes 4 hours to determine the CRE sensitivity to CZA. In the presence of sufficient CZA (low concentration: 8 mg/mL ceftazidime and 4 mg/mL avibactam, high concentration: 16 mg/mL ceftazidime and 4 mg/mL avibactam), glucose metabolism of CZA-resistant bacteria changes bromocresol purple from purple to yellow. After K-B testing of CZA, 83 of 241 CRE strains were resistant (< 21 mm), and 158 were susceptible to CZA (≥ 21 mm). Furthermore, eCIM testing revealed that all 83 CZA-resistant strains were NDM type, while 121 of the 158 CZA-sensitive strains were KPC type and 37 were non-enzyme producing. After the rapidCZA test, 83 CRE strains (NDM type) were resistant to CZA, and 158 CRE strains (including KPC and non-carbapenemase production) were sensitive. The sensitivity, specificity, and positive predictive values and negative predictive values of this test were all 100%. This assay is fast, accurate, and offers clinical feedback on CRE strains' CZA sensitivity in 4 hours.