Carbapenemase-producing Enterobacterales infections: recent advances in diagnosis and treatment

Abstract

Increasing carbapenem resistance in Enterobacterales poses a threat to public health. In recent decades, this increase in carbapenem resistance has been caused by the global dissemination of carbapenemase-producing Enterobacterales (CPE). Carbapenemases are members of the β-lactamases that are divided into classes A, B and D based on their molecular structures. Although certain traditionally used antibiotics, such as amikacin, polymyxins, tigecycline and fosfomycin, may remain effective against some CPE, their clinical use is limited owing to adverse effects, including renal toxicity, tissue penetration or the requirement for combination treatment. Recently, several novel agents have been approved for clinical use, such as ceftazidime/avibactam, ceftolozane/tazobactam, cefiderocol, eravacycline, omadacycline, meropenem/vaborbactam, imipenem/cilastatin/relebactam and plazomicin. However, the spectrum of antimicrobial activities and efficacies of novel agents vary depending on the mechanisms associated with carbapenem resistance in Enterobacterales. Therefore, it is of utmost importance to enable accurate and rapid diagnosis of CPE infection, including the determination of their antimicrobial resistance mechanisms. Here, recent advances in methods for the identification of CPE have been reviewed, including phenotypic methods (carbapenemase inactivation methods), biochemical methods [Carbapenemase Nordmann-Poirel (Carba NP) test and modified Carba NP test], immunochromatographic methods, proteomic methods [matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS)] and molecular-based methods [nucleic acid amplification technologies, hybridisation techniques (microarray) and whole-genome sequencing]. Both precise diagnosis and adequate treatment are important to combat the emerging CPE crisis.