Progress in pharmacological treatment of carbapenem-resistant gram-negative bacteria infections

Addressing the severe challenge posed by carbapenem-resistant gram-negative bacteria (CR-GNB), this review systematically evaluates individualized application strategies for novel antimicrobial agents from a clinical pharmacy perspective based on the high-level evidence and pharmacokinetic/pharmacodynamic (PK/PD) studies in recent years.Novel enzyme inhibitor preparations(such as ceftazidime-avibactam,aztreonam-avibactam,ceftolozane-tazobactam,imipenem/cilastatin-relebactam,and sulbactam-durlobactam)and cefiderocol have precisely filled the gaps of treatment of carbapenem-resistant Enterobacterales (CRE) producing Klebsiella pneumoniae carbapenemase (KPC) or metallo-"β" -lactamases, carbapenem-resistant Acinetobacter baumannii (CRAB),and difficult to treat resistance-Pseudomonas aeruginosa(DTR-AB).Furthermore,traditional drugs such as polymyxins and tetracyclines also retain certain clinical niches after the optimization of regimen. It is necessary to pursue the integrated strategy of"precise diagnosis,targeted drug selection, and dosage optimization" so as to maximize the clinical value. It is the key to implement the individualized drug administration based on PK/PD principles that is supported by enzyme profile matching and therapeutic drug monitoring (TDM) so as to improve the prognosis and curb the development of drug resistance.