MultiRapid ATB NP test for detecting concomitantly susceptibility and resistance of last resort novel antibiotics available to treat multidrug-resistant Enterobacterales infections

Background: Among the recently developed Antibacterial therapeutics against Gram-negatives, there are the β-lactam-β-lactamase inhibitor combinations ceftazidime-avibactam (CZA), meropenem-vaborbactam (MEV), and imipenem-relebatam (IPR), and there is the siderophore cephalosporin cefiderocol (FDC). This study is aimed to develop a rapid test, namely the MultiRapid ATB NP test, for rapid identification of susceptibility/resistance to CZA, MEV, IPR, and FDC for Enterobacterales.in a single test for rapid clinical decision making.

Methods: The MultiRapid ATB NP test is based on the detection of glucose metabolization occurring after Bacterial growth in the presence of defined concentrations of CZA, MEV, IPR, and FDC. Followed by visual detection of color change of the pH indicator red phenol (red to yellow) generated by the acidification of the medium upon Bacterial growth. It is performed in 96-well microplates. The Multi Rapid ATB NP test was evaluated with 78 Enterobacterales isolates, and its performances compared to the reference method broth microdilution.

Results: The MultiRapid ATB NP test displayed 97.0% (97.0%, CI 92.6 - 98.8%) of sensitivity, 97.7% (97.7%, CI 94.3 - 99.1%) of specificity, and 97.4% (97.4%, CI 95.0% - 98.7%) of accuracy. The results were obtained after 3 h of incubation at 35°C ± 2°C, representing at least a 15 h gain-of-time compared with currently used antimicrobial susceptibility testing methods.

Conclusion: The MultiRapid ATB NP test was capable of providing accurate results for a concomitant detection of susceptibility/resistance to CZA, MEV, IPR, and FDC in Enterobacterales, independent from its resistance mechanism. It may be suitable for implementation in any microbiology routine laboratory.

Enterobacterales; MultiRapid ATB NP test; carbapenem resistance; novel antibiotics.