Management of carbapenem-resistant Enterobacteriaceae infections

Abstract

Background: Carbapenem resistance is defined as in vitro non-susceptibility to any carbapenem and/or documented production of a carbapenemase. This feature has rapidly spread worldwide among clinical isolates of Enterobacteriaceae, mostly Klebsiella spp., and is associated with diverse molecular mechanisms. Carbapenem resistance is often associated with resistance to all traditional b-lactams and other classes of antibiotics, denoting a typical example of an extensively drug-resistant phenotype. Objectives: To summarize and interpret in a balanced manner the most clinically relevant data in terms of carbapenem-resistant Enterobacteriaceae (CRE) infection management. Sources: Data were extracted by PubMed and clinicaltrials.gov search and manual scrutiny among references of analysed articles. Content: Features of newer and older, rediscovered antimicrobial options for CRE are described. Observational studies and randomized clinical trials (RCT) of CRE treatment are summarized, with a specific focus on the effects of monotherapy compared with combination treatment. Implications: The available evidence on the current management of CRE mostly comes from observational, non-comparative, retrospective, small studies, with a high risk of selection bias. Very little evidence comes from RCT. Conflicting results of RCT and observational studies call for caution before combination therapies are deemed superior to monotherapy. Data on newer agents have spurred enthusiasm but remain limited as concerns severe CRE infections. A balanced approach should guide the clinician in the choice of old or new drugs, and of monotherapies or combination regimens. Efforts should be made to perform adequately sized clinical trials answering well-defined research questions.

The Current Burden of Carbapenemases: Review of Significant Properties and Dissemination among Gram-Negative Bacteria

“…Carbapenems proved especially useful since ESBL producers are also resistant to other antibiotic classes including aminoglycosides, tetracyclines, and fluoroquinolones [71]. Unfortunately, this has led to the emergence of carbapenem-resistant Enterobacteriaceae (CRE), defined as bacteria belonging to the Enterobacteriaceae family that have the ability to survive and grow in the presence of clinically relevant concentrations of carbapenems [182]. From a therapeutic perspective, CRE represent a threat as only a few antibiotics retain activity against them.…”

Epidemiology and risk factors of rectal colonization of carbapenemase-producing Enterobacteriaceae among high-risk patients from ICU and HSCT wards in a university hospital

“…Carbapenem-resistant Enterobacteriaceae (CRE) has become a serious public health threat worldwide [1,2]. CRE infections have been increasing rapidly and posing serious challenges to the clinical management [3], thus, timely and efficient diagnosis, strict and evidence-based infection control measures, and prompt and effective therapy are of paramount importance.…”

Antimicrobial resistance trends among important clinical pathogens reported from the ARINCQ surveillance of bacterial resistance, 2012-2018: multi-center retrospective surveillance study in Chongqing

“…The emergence of CRE raises a global health-care threat. CRE infections are related to high mortality because therapeutic options are very limited [15,16,17,18]. As to the isolation rates of carbapenem-resistant Enterobateriaceae, that of CRKPN was much higher than that of CRECO according to Figure 2.…”