Epidemiology and Treatment of MDR Enterobacteriaceae

Abstract

The major progress in the history of medicine represented by the discovery of antibiotics is nowadays compromised by the universal spread of antibiotic resistance. World Health Organization (WHO) lists third-generation cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae and carbapenem-resistant K. pneumoniae in a group of seven bacteria of international concern, responsible for both healthcare-associated and community-acquired infections. Patients infected by these pathogens have limited therapeutic options, worse clinical outcomes, increased mortality rates, and a higher healthcare resources consumption. In infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, appropriate monotherapy is effective and carbapenems are the drugs of choice; however, β-lactams/β-lactamase inhibitors (BLBLIs) are regarded as an alternative mainly in patients without severe infections, with E. coli bacteremia with urinary source or with low minimum inhibitory concentrations (MICs). For infections caused by carbapenem-resistant Enterobacteriaceae (CRE), where the predicted mortality rate of patients is high, a combination antimicrobial treatment should be preferred. Many important variables in the treatment such as the role of high dosages and loading doses, the variable degrees of dosage reduction for impaired renal function, and the inclusion of carbapenems or tigecycline are a matter of debate. Despite the obscure vision provided by a notable number of meta-analyses, tigecycline is an effective and safe option for the treatment of MDR Enterobacteriaceae, as part of a combination regimen in case of infections caused by CRE, where a higher dosage (200 mg/daily) should be preferred. Colistin is the most active in vitro agent against CRE. Despite clinical data about the efficacy of fosfomycin against MDR Enterobacteriaceae are limited, this molecule represents an interesting option for the treatment of lower urinary tract and even systemic infections caused by difficult-to-treat Gram-negative pathogens. Based on in vitro studies, ceftolozane–tazobactam and ceftazidime–avibactam will represent very interesting new drugs for the treatment of ESBL-producing and CRE infections, respectively.