Comparison of European Committee on Antimicrobial Susceptibility Testing (EUCAST) and CLSI screening parameters for the detection of extended-spectrum β-lactamase production in clinical Enterobacteriaceae isolates

Objectives To compare the performance of European Committee on Antimicrobial Susceptibility Testing (EUCAST) and CLSI breakpoints following their revision in 2010, for the detection of extended-spectrum β-lactamase (ESBL) production in Enterobacteriaceae. Methods 236 well-characterized clinical isolates (including 118 ESBL producers) were investigated by antibiotic disc testing with cefpodoxime, ceftriaxone, cefepime, cefotaxime EUCAST (5 μg/disc), ceftazidime EUCAST (10 μg/disc), cefotaxime CLSI (30 μg/disc) and ceftazidime CLSI (30 μg/disc) with the Kirby-Bauer method. Additionally, synergy phenomena were recorded between amoxicillin/clavulanic acid discs (20/10 μg/disc) and cefepime (30 μg/disc), EUCAST cefotaxime (5 μg/disc), EUCAST ceftazidime (10 μg/disc), CLSI cefotaxime (30 μg/disc) and CLSI ceftazidime [30 μg/disc; disc approximation method (DAM)]. Results Overall sensitivity of the cefotaxime EUCAST non-susceptible breakpoint equalled sensitivity of the cefotaxime CLSI ESBL screening breakpoint (99.2%). With the ceftazidime EUCAST non-susceptible breakpoint, 27/118 ESBL-producing isolates were not detected, whereas the ceftazidime CLSI ESBL screening breakpoint missed 41/118 ESBL-producing isolates. For cefpodoxime the resistant EUCAST breakpoint showed higher sensitivity for ESBL detection compared with the CLSI ESBL screening breakpoint/disc content (100% versus 98.3%, respectively). Sensitivities of ceftazidime and cefotaxime DAM with CLSI or EUCAST disc contents were comparable (sensitivities ranging from 84.7% to 89.8%). DAM with cefepime displayed the highest overall sensitivity (96.6%). In AmpC-producing isolates, synergy of amoxicillin/clavulanic acid with cefepime showed sensitivity and specificity for ESBL detection of 100% and 97.4%, respectively. Conclusions EUCAST non-susceptible breakpoints for ceftazidime and cefpodoxime detect more ESBL-producing Enterobacteriaceae isolates compared with corresponding CLSI ESBL screening breakpoints. Implementation of the cefepime DAM can facilitate ESBL screening, especially in strains producing an AmpC β-lactamase since the test shows high sensitivity and specificit

Additional file 1: of Therapeutic potential of antiviral drugs targeting chemorefractory colorectal adenocarcinoma cells overexpressing endogenous retroviral elements

HERV-3 protein downregulation. (DOCX 157 kb

Neuropilin 1 Directly Interacts with Fer Kinase to Mediate Semaphorin 3A-induced Death of Cortical Neurons*

Neuropilins (NRPs) are receptors for the major chemorepulsive axonal guidance cue semaphorins (Sema). The interaction of Sema3A/NRP1 during development leads to the collapse of growth cones. Here we show that Sema3A also induces death of cultured cortical neurons through NRP1. A specific NRP1 inhibitory peptide ameliorated Sema3A-evoked cortical axonal retraction and neuronal death. Moreover, Sema3A was also involved in cerebral ischemia-induced neuronal death. Expression levels of Sema3A and NRP1, but not NRP2, were significantly increased early during brain reperfusion following transient focal cerebral ischemia. NRP1 inhibitory peptide delivered to the ischemic brain was potently neuroprotective and prevented the loss of motor functions in mice. The integrity of the injected NRP1 inhibitory peptide into the brain remained unchanged, and the intact peptide permeated the ischemic hemisphere of the brain as determined using MALDI-MS-based imaging. Mechanistically, NRP1-mediated axonal collapse and neuronal death is through direct and selective interaction with the cytoplasmic tyrosine kinase Fer. Fer RNA interference effectively attenuated Sema3A-induced neurite retraction and neuronal death in cortical neurons. More importantly, down-regulation of Fer expression using Fer-specific RNA interference attenuated cerebral ischemia-induced brain damage. Together, these studies revealed a previously unknown function of NRP1 in signaling Sema3A-evoked neuronal death through Fer in cortical neurons