Infections caused by naturally AmpC-producing Enterobacteriaceae: Can we use third-generation cephalosporins? A narrative review.

The burden of antibiotic-resistant infections among Gram-negative bacteria is increasing. Resistance to third-generation cephalosporins (3GCs) in Enterobacteriaceae is mainly conferred by the acquisition of ß-lactamases or by deregulation of natural genetically-encoded ß-lactamase enzymes. Enterobacteriaceae such as Enterobacter spp., Serratia marcescens, Citrobacter freundii, Providencia spp. and Morganella morganii (ESCPM group) possess chromosomally-encoded inducible AmpC ß-lactamases. AmpC can be overproduced as a response to ß-lactam antibiotic exposure or by constitutive dysfunction of the AmpC regulation system. This overproduction can lead to the inactivation of 3GCs. Based on small clinical studies, international guidelines and expert recommendations suggest that 3GCs should be avoided as definitive therapy for infections caused by ESCPM group organisms. In this narrative review, we discuss the published literature and evaluate the risk related to 3GC use in the case of documented ESCPM infection.

Prediction of methicillin-resistant Staphylococcus aureus bloodstream infection: do we need rapid diagnostic tests?

Staphylococcus aureus (SA) is the leading cause of bloodstream infection (BSI). The incidence of methicillin-resistant SA (MRSA) has decreased in France and Europe since one decade. Early and precise prediction of methicillin susceptibility is needed to improve probabilistic antibiotic therapy of MRSA-BSI. The aim of this study was to identify MRSA-BSI risk factors at admission and evaluate which patients need costly rapid diagnostic tests. A single-center retrospective descriptive study of all diagnosed SA-BSI was conducted in a French University Hospital between January 2015 and December 2016. All medical charts were reviewed. Univariate and multivariate analyses by a logistic regression model were performed on the data. We then build a prediction score of MRSA-BSI by assigning one point for each of the risk factor identified. During the study period, 151 SA-BSI were identified including 32 (21%) MRSA-BSI. In multivariate analysis, three factors were associated with MRSA-BSI: coming from long-term care facility, known previous MRSA colonization and/or infection, and chronic renal disease. Among our population, respectively, 5% and 100% had a MRSA-BSI when no or three risk factors were identified. Therefore, among the PCR performed, 43 (96%) could be avoided according to our clinical score. In our study, methicillin-susceptible SA and MRSA-BSI can be predictable by counting MRSA risk factors. This prediction rule could avoid the use of expensive rapid diagnostic tests. Prospective studies and prediction rules could help physicians to predict SA-BSI susceptibility to improve appropriate empiric therapy choice.

Mitochondrial fusion/fission dynamics in neurodegeneration and neuronal plasticity.

Mitochondria are dynamic organelles that continually move, fuse and divide. The dynamic balance of fusion and fission of mitochondria determines their morphology and allows their immediate adaptation to energetic needs, keeps mitochondria in good health by restoring or removing damaged organelles or precipitates cells in apoptosis in cases of severe defects. Mitochondrial fusion and fission are essential in mammals and their disturbances are associated with several diseases. However, while mitochondrial fusion/fission dynamics, and the proteins that control these processes, are ubiquitous, associated diseases are primarily neurological disorders. Accordingly, inactivation of the main actors of mitochondrial fusion/fission dynamics is associated with defects in neuronal development, plasticity and functioning, both ex vivo and in vivo. Here, we present the central actors of mitochondrial fusion and fission and review the role of mitochondrial dynamics in neuronal physiology and pathophysiology. Particular emphasis is placed on the three main actors of these processes i.e. DRP1,MFN1-2, and OPA1 as well as on GDAP1, a protein of the mitochondrial outer membrane preferentially expressed in neurons. This article is part of a Special Issue entitled: Mitochondria & Brain.