Performance evaluation of the Streck ARM-D Kit, β-Lactamase for molecular detection of acquired β-lactamase genes.

Objectives: Despite clinical relevance, commercially available molecular tools for accurate β-lactamase detection are limited. In this study, we evaluated the performance of the ARM-D Kit, β-Lactamase, a commercially available multiplex PCR assay designed to detect nine β-lactamase genes, including the five major plasmid-mediated carbapenemases, ESBL and AmpC genes circulating in the United States.

Methods: A diverse collection of 113 Gram-negative isolates, including 42 with multiple β-lactamases genes, was selected from the U.

Analytical evaluation of the cobas® 6800 system for the detection and quantification of BK Virus (BKV) and Epstein Barr Virus (EBV) at a US solid organ and hematopoietic stem cell transplant center.

The cobas® EBV and BKV assays are the first FDA-approved, quantitative assays for monitoring posttransplant reactivation of these viruses. In this study, we assessed performance of the fully-automated cobas® assays, compared with Diasorin Molecular ASR, our laboratory developed test, and demonstrated a strong interassay correlation for BK and EBV monitoring.

Carbapenemase production among less-common Enterobacterales genera: 10 US sites, 2018.

Background: Historically, United States' carbapenem-resistant Enterobacterales (CRE) surveillance and mechanism testing focused on three genera: , , and (EsKE); however, other genera can harbour mobile carbapenemases associated with CRE spread.

Objectives: From January through May 2018, we conducted a 10 state evaluation to assess the contribution of less common genera (LCG) to carbapenemase-producing (CP) CRE.

Methods: State public health laboratories (SPHLs) requested participating clinical laboratories submit all Enterobacterales from all specimen sources during the surveillance period that were resistant to any carbapenem (Morganellaceae required resistance to doripenem, ertapenem, or meropenem) or were CP based on phenotypic or genotypic testing at the clinical laboratory.

Public Health Response to an Avian Influenza A(H7N8) Virus Outbreak in Commercial Turkey Flocks - Indiana, 2016.

In January 2016, highly pathogenic avian influenza (HPAI) A(H7N8) virus and low pathogenicity avian influenza (LPAI) A(H7N8) virus were detected in commercial turkey flocks in Dubois County, Indiana. The Indiana State Department of Health (ISDH) and the Dubois County Health Department (DCHD) coordinated the public health response to this outbreak, which was the first detection of HPAI A(H7N8) in any species (1). This response was the first to fully implement unpublished public health monitoring procedures for HPAI responders that were developed by the U.

A large HCV transmission network enabled a fast-growing HIV outbreak in rural Indiana, 2015.

Background: A high prevalence (92.3%) of hepatitis C virus (HCV) co-infection among HIV patients identified during a large HIV outbreak associated with injection of oxymorphone in Indiana prompted genetic analysis of HCV strains.

Methods: Molecular epidemiological analysis of HCV-positive samples included genotyping, sampling intra-host HVR1 variants by next-generation sequencing (NGS) and constructing transmission networks using Global Hepatitis Outbreak and Surveillance Technology (GHOST).

Detailed Transmission Network Analysis of a Large Opiate-Driven Outbreak of HIV Infection in the United States.

In January 2015, an outbreak of undiagnosed human immunodeficiency virus (HIV) infections among persons who inject drugs (PWID) was recognized in rural Indiana. By September 2016, 205 persons in this community of approximately 4400 had received a diagnosis of HIV infection. We report results of new approaches to analyzing epidemiologic and laboratory data to understand transmission during this outbreak.

HIV Infection Linked to Injection Use of Oxymorphone in Indiana, 2014-2015.

Background: In January 2015, a total of 11 new diagnoses of human immunodeficiency virus (HIV) infection were reported in a small community in Indiana. We investigated the extent and cause of the outbreak and implemented control measures.

Methods: We identified an outbreak-related case as laboratory-confirmed HIV infection newly diagnosed after October 1, 2014, in a person who either resided in Scott County, Indiana, or was named by another case patient as a syringe-sharing or sexual partner.

Multicenter Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Study for Identification of Clinically Relevant Nocardia spp.

This multicenter study analyzed Nocardia spp., including extraction, spectral acquisition, Bruker matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) identification, and score interpretation, using three Nocardia libraries, the Bruker, National Institutes of Health (NIH), and The Ohio State University (OSU) libraries, and compared the results obtained by each center. A standardized study protocol, 150 Nocardia isolates, and NIH and OSU Nocardia MALDI-TOF MS libraries were distributed to three centers.

ChIP-seq and in vivo transcriptome analyses of the Aspergillus fumigatus SREBP SrbA reveals a new regulator of the fungal hypoxia response and virulence.

The Aspergillus fumigatus sterol regulatory element binding protein (SREBP) SrbA belongs to the basic Helix-Loop-Helix (bHLH) family of transcription factors and is crucial for antifungal drug resistance and virulence. The latter phenotype is especially striking, as loss of SrbA results in complete loss of virulence in murine models of invasive pulmonary aspergillosis (IPA). How fungal SREBPs mediate fungal virulence is unknown, though it has been suggested that lack of growth in hypoxic conditions accounts for the attenuated virulence.

Two C4-sterol methyl oxidases (Erg25) catalyse ergosterol intermediate demethylation and impact environmental stress adaptation in Aspergillus fumigatus.

The human pathogen Aspergillus fumigatus adapts to stress encountered in the mammalian host as part of its ability to cause disease. The transcription factor SrbA plays a significant role in this process by regulating genes involved in hypoxia and low-iron adaptation, antifungal drug responses and virulence. SrbA is a direct transcriptional regulator of genes encoding key enzymes in the ergosterol biosynthesis pathway, including erg25A and erg25B, and ΔsrbA accumulates C4-methyl sterols, suggesting a loss of Erg25 activity [C4-sterol methyl oxidase (SMO)].

Endoplasmic reticulum localized PerA is required for cell wall integrity, azole drug resistance, and virulence in Aspergillus fumigatus.

GPI-anchoring is a universal and critical post-translational protein modification in eukaryotes. In fungi, many cell wall proteins are GPI-anchored, and disruption of GPI-anchored proteins impairs cell wall integrity. After being synthesized and attached to target proteins, GPI anchors undergo modification on lipid moieties.

Hypoxia enhances innate immune activation to Aspergillus fumigatus through cell wall modulation.

Infection by the human fungal pathogen Aspergillus fumigatus induces hypoxic microenvironments within the lung that can alter the course of fungal pathogenesis. How hypoxic microenvironments shape the composition and immune activating potential of the fungal cell wall remains undefined. Herein we demonstrate that hypoxic conditions increase the hyphal cell wall thickness and alter its composition particularly by augmenting total and surface-exposed β-glucan content.

SREBP coordinates iron and ergosterol homeostasis to mediate triazole drug and hypoxia responses in the human fungal pathogen Aspergillus fumigatus.

Sterol regulatory element binding proteins (SREBPs) are a class of basic helix-loop-helix transcription factors that regulate diverse cellular responses in eukaryotes. Adding to the recognized importance of SREBPs in human health, SREBPs in the human fungal pathogens Cryptococcus neoformans and Aspergillus fumigatus are required for fungal virulence and susceptibility to triazole antifungal drugs. To date, the exact mechanism(s) behind the role of SREBP in these observed phenotypes is not clear.

SREBP-dependent triazole susceptibility in Aspergillus fumigatus is mediated through direct transcriptional regulation of erg11A (cyp51A).

As triazole antifungal drug resistance during invasive Aspergillus fumigatus infection has become more prevalent, the need to understand mechanisms of resistance in A. fumigatus has increased. The presence of two erg11 (cyp51) genes in Aspergillus spp.