Epidemiology, Mechanisms of Resistance and Treatment Algorithm for Infections Due to Carbapenem-Resistant Gram-Negative Bacteria: An Expert Panel Opinion

Abstract

Antimicrobial resistance represents a serious threat for global health, causing an unacceptable burden in terms of morbidity, mortality and healthcare costs. In particular, in 2017, carbapenem-resistant organisms were listed by the WHO among the group of pathogens for which novel treatment strategies are urgently needed. Fortunately, several drugs and combinations have been introduced in recent years to treat multi-drug-resistant (MDR) bacteria. However, a correct use of these molecules is needed to preserve their efficacy. In the present paper, we will provide an overview on the epidemiology and mechanisms of resistance of the most common MDR Gram-negative bacteria, proposing a treatment algorithm for the management of infections due to carbapenem-resistant bacteria based on the most recent clinical evidence.

Outcome of patients with Carbapenem-Resistant Acinetobacter baumannii infections treated with cefiderocol: a multicenter observational study

“…The emergence of AMR is limiting the use of the traditional drugs active against A.baumannii infections, including colistin [6]. The recent development of novel agents, including cefiderocol, is a promising resource against CRAB infections, but data on its efficacy in this setting is limited and contrasting.…”

“…Due to its difficult-to-treat resistance phenotype and the increased mortality rate compared with carbapenem-susceptible A. baumannii infections [5,6], the preferred treatment for carbapenem-resistant A. baumannii (CRAB) infections is still controversial [7]. The recent development of novel agents such as cefiderocol, a siderophore cephalosporin with a large spectrum of resistance towards most betalactamases, could expand the armamentarium against CRAB infections.…”

Emerging infections in vulnerable hosts: Stenotrophomonas maltophilia and Elizabethkingia anophelis

“…S. maltophilia and E. anophelis are both considered MDROs because of their intrinsic resistance to multiple classes of antibiotics, including penicillin, cephalosporins, macrolides, aminoglycosides, FQs, and carbapenems [81,82]. The molecular mechanisms of antimicrobial resistance in S. maltophilia include chromosomal ß-lactamases ( bla L1 and/or bla L2 ), class 1 intergrons and ISCR elements, multiple efflux pumps, Sm qnr , antibiotic-modifying enzymes, phosphoglucomutase, mutations of topoisomerase and gyrase genes, and a reduction in outer membrane permeability [83,84–86]. For E. anophelis , several antimicrobial resistance genes, including bla B , bla GOB , bla CME , Sul2 , erm(F) , GyrA , Tet(X) , and catB, were identified in genomic analysis and were associated with ß-lactam, trimethoprim/sulfamethoxazole, macrolide, quinolone, and chloramphenicol resistance [87–90,91 ▪ ,92].…”

Carriage of multidrug-resistant carbapenemase-producing gram-negative bacteria in patients admitted to NHS Greater Glasgow and Clyde hospitals: Implications for treatment

“…Over the last decade, CPO have spread throughout the world and are now endemic in healthcare facilities in numerous countries. 1,2 CPO are being frequently encountered in hospitals and pose a significant challenge in clinical practice due to their resistance to many or all antibiotics in clinical use. Clinical outcome studies into infections caused by CPO have shown mortality rates to be as high as 40%.…”