BackgroundCoagulase-negative staphylococci, mainly Staphylococcus epidermidis, are the most frequent cause of late-onset sepsis (LOS) in the neonatal intensive care unit (NICU) setting. However, recent reports indicate that methicillin-resistant, vancomycin-heteroresistant Staphylococcus capitis could emerge as a significant pathogen in the NICU. We investigated the prevalence, clonality and vancomycin susceptibility of S. capitis isolated from the blood of NICU infants and compared these data to adult patients.Methodology/Principal FindingsWe conducted a retrospective laboratory-based survey of positive blood cultures in NICU infants ≥3 days of age (n = 527) and in adult ICU patients ≥18 years of age (n = 1473) who were hospitalized from 2004 to 2009 in two hospital centers in Lyon, France. S. capitis was the most frequent pathogen in NICU infants, ahead of S. epidermidis (39.1% vs. 23.5% of positive blood cultures, respectively). Conversely, S. capitis was rarely found in adult ICU patients (1.0%) compared to S. epidermidis (15.3%). S. capitis bloodstream isolates were more frequently resistant to methicillin when collected from NICU infants than from adult patients (95.6% vs. 53.3%, respectively). Furthermore, we collected and characterized 53 S. capitis bloodstream isolates from NICU infants and adult patients from six distant cities. All methicillin-resistant S. capitis isolates from NICU infants were clonally related as determined by pulsed-field gel electrophoresis. These isolates harbored a type V-related staphylococcal chromosomal cassette mec element, and constantly showed either vancomycin resistance (37.5%) or heteroresistance (62.5%). Conversely, the isolates that were collected outside of the NICU were genetically diverse and displayed much lower rates of vancomycin resistance and heteroresistance (7.7% and 23.1%, respectively).Conclusions/SignificanceA clonal population of methicillin-resistant S. capitis strains has spread into several French NICUs. These isolates exhibit reduced susceptibility to vancomycin, which is the most widely used antimicrobial agent in the NICU setting.

Amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) are devastating neurodegenerative diseases involving the progressive degeneration of neurons. No cure is available for patients diagnosed with these diseases. A prominent feature of both ALS and PD is the accumulation of protein inclusions in the cytoplasm of degenerating neurons; however, the particular proteins constituting these inclusions vary: the RNA-binding proteins TDP-43 and FUS are most notable in ALS, while α-synuclein aggregates into Lewy bodies in PD. In both diseases, genetic causes fail to explain the occurrence of a large proportion of cases, and thus, both are considered mostly sporadic. Despite mounting evidence for a possible role of epigenetics in the occurrence and progression of ALS and PD, epigenetic mechanisms in the context of these diseases remain mostly unexplored. Here we comprehensively delineate histone post-translational modification (PTM) profiles in ALS and PD yeast proteinopathy models. Remarkably, we find distinct changes in histone modification profiles for each. We detect the most striking changes in the context of FUS aggregation: changes in several histone marks support a global decrease in gene transcription. We also detect more modest changes in histone modifications in cells overexpressing TDP-43 or α-synuclein. Our results highlight a great need for the inclusion of epigenetic mechanisms in the study of neurodegeneration. We hope our work will pave the way for the discovery of more effective therapies to treat patients suffering from ALS, PD, and other neurodegenerative diseases.

Lower respiratory tract infections are important causes of morbidity and mortality. The global increase in antimicrobial resistance necessitates rapid diagnostic assays. The BioFire FilmArray Pneumonia plus (FAPP) panel is an FDA approved multiplex polymerase chain reaction assay that detects the most important etiological agents of pneumonia, and associated antibiotic resistance genes, in approximately one hour. This study assessed the diagnostic performance of this assay by comparing it to conventional culture methods in the analysis of 59 lower respiratory tract specimens. The sensitivity and specificity of the FAPP panel for bacterial detection were 92.0% (95% CI, 80.8% - 97.8%) and 93.8% (95% CI, 91.1% - 95.3%) respectively. For detecting antibiotic resistance, the positive- and negative percent agreement were 100% (95% CI, 81.5% - 100.0%) and 98.5% (95% CI, 216 96.7% - 99.4%) respectively. The FAPP panel was found to be highly accurate in evaluating tracheal aspirate specimens from hospitalised patients.

Sepsis and septic shock are key contributors to mortality in critically ill patients and thus prompt recognition and management thereof is central to achieving improved patient outcomes. Early initiation of appropriate antimicrobial therapy constitutes a crucial component of the management strategy and thus early identification of the causative pathogen is essential in informing antimicrobial therapeutic choices. The BioFire FilmArray blood culture identification (BCID) panel is a US Food and Drug Administration (FDA) approved rapid, multiplex polymerase chain reaction assay for use on positive blood cultures. This study evaluated its clinical utility in the intensive care unit (ICU) setting, in terms of amendment of empiric antimicrobial therapy in critically ill patients with sepsis. The assay proved useful in this setting as final results were made available to clinicians significantly earlier than with conventional culture methods. This, in turn, allowed for modification of empirical antimicrobial therapy to more appropriate agents in 32% of patients. Additionally, the use of the BioFire FilmArray BCID panel permitted the prompt implementation of additional infection prevention and control practices in a sizeable proportion (14%) of patients in the study who were harbouring multidrug resistant pathogens. These findings support the use of the BioFire FilmArray BCID panel as a valuable adjunct to conventional culture methods for the diagnosis and subsequent management of critically ill patients with sepsis.