Detection of ceftazidime/avibactam-resistant Enterobacteriaceae strains using a new rapid test
Ceftazidime/avibactam (CZA) is a relatively new antibiotic with very good efficacy against carbapenem-resistant Enterobacteriaceae. Unfortunately, strains resistant to this antimicrobial treatment are now beginning to emerge. The authors of the presented study developed and tested a new laboratory test for the rapid and accurate detection of these multidrug-resistant Enterobacteriaceae.
Carbapenem-resistant bacteria − and how to deal with them?
The spread of carbapenem-resistant Enterobacteriaceae is becoming a global problem and is associated with significant morbidity and mortality. The combination of CZA consists of the 3rd generation cephalosporin ceftazidime and the beta-lactamase inhibitor avibactam, and this antibiotic is approved for the treatment of complicated intra-abdominal infections, urogenital tract infections, and nosocomial pneumonia.
Several mutations leading to bacterial resistance to CZA have already been discovered (mainly KPC lactamase mutations in Klebsiella pneumoniae), and another problem is posed by bacterial enzymes of class B (NDM, VIM, IMP) or D, which can hydrolyze beta-lactam antibiotics and are simultaneously resistant to avibactam cleavage.
Several methods are available for detecting multidrug-resistant bacteria, but these rely on comprehensive microbiological testing and the results take at least 16 hours. The aim of the cited research was to find a rapid and accurate test that would allow prompt modification of antimicrobial therapy.
Research progress and results
The principle of the new test ResaCeftazidime-avibactam Enterobacterales NP is the color change of resazurin from blue to purple or pink in the presence of metabolically active, i.e., CZA-resistant microorganisms. No color change occurs in the presence of CZA-sensitive bacteria.
To examine the test's reliability, 178 Enterobacteriaceae isolates were used. Sensitivity to CZA was detected after a 4.5-hour incubation at 37 °C, and the detected sensitivity and specificity of the test were compared with the results of the standard laboratory microdilution method. Of all 178 Enterobacteriaceae isolates, 100 were identified as CZA-sensitive, while the remaining 78 isolates exhibited resistance to CZA (37 Escherichia coli isolates, 20 Klebsiella pneumoniae isolates, and 21 Enterobacter cloacae isolates). The most common determinant of resistance was the production of metallo-beta-lactamases (NDM-1, NDM-5, and IMP).
Overall concordance in the results of ResaCeftazidime-avibactam Enterobacterales NP and the reference test was recorded in 96% of cases, with the new test showing false resistance in 7% of cases and no false sensitivity. For E. coli, the concordance of the two tests was complete, i.e., 100%. For K. pneumoniae, 99% of tests were concordant, with false resistance recorded in 2%. For E. cloacae, 87% concordance was achieved, with false resistance occurring in 25% of cases, and no false sensitivity was recorded.
Discussion and conclusion
Microdilution methods for detecting bacterial sensitivity to antibiotics are currently the gold standard, but their use requires collaboration with a clinical laboratory and is relatively time-consuming. Another commonly used test – Etest – shows excellent correlation with the microdilution method but is costly and results are available only after 16 hours of incubation. By contrast, the new test ResaCeftazidime-avibactam Enterobacterales NP provides results in just 4.5 hours, with an accuracy of 96% for Enterobacteriaceae strains and no false CZA sensitivity cases.
A rapid, simple, and accurate detection of sensitivity or resistance in multidrug-resistant bacterial strains is a highly valuable tool for clinical practice, as it allows for swift adjustments and necessary changes in antimicrobial therapy. The test ResaCeftazidime-avibactam Enterobacterales NP can be successfully used to test CZA sensitivity in E. coli and K. pneumoniae. Its use and improved accuracy for other strains, including E. cloacae, will be the subject of further research.
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Sources:
1. Feng L., Zhao Y., Yao Z. Rapid ResaCeftazidime-Avibactam Enterobacterales NP Test: rapid detection of ceftazidime-avibactam susceptibility in Enterobacterales. J Clin Microbiol 2022 Sep 21; 60 (9): e0000422, doi: 10.1128/jcm.00004-22.
2. SPC Zavicefta. Available at: www.ema.europa.eu/en/documents/product-information/zavicefta-epar-product-information_cs.pdf
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