Mustafa Sadek

Background The treatment options for infections caused by carbapenem-resistant Enterobacterales (CRE) are extremely scarce nowadays and the development of new antibiotics does not follow the exponential increase in the dissemination of carbapenem resistance determinants worldwide. Meropenem/vaborbactam was recently approved for clinical use and it has been indicated for treating several infections. Although relatively rare, meropenem/vaborbactam resistance has already been reported in Enterobacterales and its early detection could be a valuable tool for faster clinical decision-making. Objectives To develop a rapid test, namely the Rapid MEV NP, for the identification of meropenem/vaborbactam resistance in Enterobacterales. Methods The Rapid MEV NP test is based on detection of glucose metabolization occurring upon bacterial growth in the presence of meropenem/vaborbactam at a concentration of 16/8 mg/L. Bacterial growth is detectable by a colour change of phenol red (from red to yellow) subsequent of the acidification of the medium upon bacterial growth. A total of 75 Enterobacterales isolates were randomly selected for evaluating the performance of the Rapid MEV NP test. Results The test showed 97.2% sensitivity and 93.8% specificity when compared with the reference method. The results are obtained after 3 h of incubation at 35°C ± 2°C, which is a gain of time of at least 15 h (one day in practice) compared with currently used antimicrobial susceptibility testing including broth microdilution methods. Conclusions The Rapid MEV NP test, easy to perform and to interpret, showed remarkable performance while providing fast results, and is therefore suitable for implementation in routine clinical microbiology laboratories.

Background Cefiderocol is among the latest generation of commercialized antibiotics against a large variety of MDR Gram-negative bacteria including carbapenem-resistant Enterobacterales and non-fermenters such as Pseudomonas aeruginosa and Acinetobacter baumannii. Cefiderocol susceptibility testing, a key element for implementing rapidly a cefiderocol-based treatment, might be still challenging. Objectives To develop a rapid culture-based test, Rapid Cefiderocol NP test, for the identification of cefiderocol resistance among MDR Enterobacterales. Methods The Rapid Cefiderocol NP test is based on glucose metabolization when bacterial growth occurs and the detection of bacterial growth in the presence of cefiderocol at 64 mg/L using iron-depleted CAMHB. Bacterial growth is visually detectable by a red-to-yellow colour change of red phenol, a pH indicator. A total of 74 clinical enterobacterial isolates from various clinical sources and of worldwide origin, among which 42 isolates were cefiderocol resistant, were used to evaluate the test performance. Results The sensitivity and specificity of the test were found to be 98% and 91%, respectively, by comparison with the reference broth microdilution (BMD) method. All positive results were obtained within 3 h after incubation at 35°C ± 2°C, that is a gain of time of ca. 18 h (1 day) compared with currently used techniques for susceptibility testing (BMD method). Conclusions This novel test is rapid, highly sensitive, specific, easily interpretable, and easy to implement in routine microbiology laboratories. Such a test may rapidly and accurately provide the information needed for the implementation of adequate cefiderocol-based treatment.