Enterobacteriaceae Antimicrobial Agents and Resistance: Relationship with the Therapeutic Approach

The spread of multi-drug resistant (MDR) microorganisms, especially carbapenem-resistant (CR)- Enterobacteriaceae (CRE) or more correctly carbapenem producing Enterobacteriaceae (CPE), has become a major problem worldwide, with a high impact on both morbidity and mortality in humans, as well as in the livestock industry. The continuing emergence of infections caused by MDR Gram-negative bacteria such as K. pneumoniae and E. coli constitutes an important issue for establishing an appropriate medical therapy in patients with diseases deriving from these microorganisms, showing a high rate of mortality both in intensive care units (ICUs) and in non-ICU settings. The choice of the most appropriate treatment against MDR infections represents a real challenge, although combination therapy seems to be more beneficial than monotherapy against CRE; however, the best regimen including two or more drugs has not been found yet. In this challenging scenario, alternative antimicrobial agents have been proposed including associations such as tigecycline in combination with colistin or with gentamicin, as well as the combination of two or more carbapenems. Unfortunately, CRE have recently developed resistance to colistin, the antibiotic of last resort against these bacteria. Traditional antimicrobial susceptibility testing seems to be no longer informative for clinicians and additional synergy tests, as well as the determination of the current MICs when a CRE is found, have been progressively recommended mainly highlighting the role of the microbiology laboratory as a crucial tool for the best therapeutic approach. Hence it would be important to examine innovative combinations of antibiotics in order to suggest suitable treatments. Above all the availability of new drugs against CRE seems to be encouraging for clinicians facing critically ill patients with systemic infections.

The scope of the current Research Topic is to stimulate the in vitro study of new antibiotics singly and in association against MDR Enterobacteriaceae and to relate the results to the clinical outcome. The antibiotics recently approved by FDA (Food and Drug Administration), such as meropenem/vaborbactam, plazomicine, and ceftazidime/avibactam, result as being still rarely used in clinical practice especially in the US, despite their efficacy towards these microorganisms and even though the development of new antibiotics for CRE is considered the primary purpose. The association of ceftazidime/avibactam with ertapenem, fosfomycin, and tigecycline should be accurately evaluated. Moreover, it is strongly suggested to analyze the resistance mechanisms of the new antimicrobial agents with various resistance patterns isolated.
Potential topics to be treated in this article collection could be the following:

· In-vitro studies on the synergistic activity of different antimicrobial combinations against MDR microorganisms
· Therapeutic options in the setting of colistin-resistance and other antimicrobial agent resistances
· Detection of carbapenemase-producing Klebsiella as KPC, metallo-beta-lactamase, or oxacillinase in different geographical areas
· Unconventional therapies and new drugs for CRE infections
· New diagnostic methods for detection of MDR microorganisms
· Molecular analyses of mechanisms of carbapenem-resistance
· Activity of Ceftazidime-Avibactam alone and in combination with ertapenem, fosfomycin, and tigecycline

To this end, we welcome reviews and original articles for a better understanding of antibiotic resistance and suggestions for more effective treatments.