Infections Caused by Carbapenem-Resistant Enterobacterales: Epidemiology, Clinical Significance, and Possibilities for Antibiotic Therapy Optimization

Abstract

The resistance of Enterobacterales to carbapenems can be realized by different mechanisms, but the most common one is enzymatic, associated with the production of carbapenemases. Carbapenemases of enterobacteria are characterized by a wide variety;they are represented in three classes of beta-lactamases. The most well-known carbapenemases belong to classes A (KPC, GESenzymes), D (OXA-48), and B (metalloenzymes — NDM, VIM, IMP). Detailed clinical and microbiological characteristics of carbapenemases are given, as well as recommendations for their detection. Carbapenemases are widespread, and the paper discusses the geographical distribution of carbapenemases in different regions of the world; OXA-48 and NDM are the most widelydistributed enzymes in Russia. The clinical significance of carbapenemases and risk factors for these infections are discussed,including the following: 1) previous carbapenem therapy; 2) high levels of carbapenemases in the Department; 3) colonization of theintestine with carbapenemase-producing enterobacteria; 4) traveling to regions with a high prevalence of carbapenemases (4th and5th epidemiological levels). The possibilities of antibacterial therapy of infections caused by carbapenem-resistant enterobacteriaare discussed, the clinical and pharmacological characteristics of different antibiotics (ceftazidime/avibactam, aztreonam, carbapenems, polymyxins, tigecycline, fosfomycin), their effectiveness and treatment options are analyzed in detail. Current clinicaldata showing the effectiveness of ceftazidime/avibactam monotherapy for infections caused by carbapenemase producers OXA-48and KPC are presented. Practical issues of management of such patients are discussed. Algorithms for empirical and targeted therapy of infections caused by carbapenem-resistant enterobacteria are presented.