IMPORTANCE Initial public health data show that Black race may be a risk factor for worse outcomes of coronavirus disease 2019 (COVID-19). OBJECTIVE To characterize the association of race with incidence and outcomes of COVID-19, while controlling for age, sex, socioeconomic status, and comorbidities. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study included 2595 consecutive adults tested for COVID-19 from March 12 to March 31, 2020, at Froedtert Health and Medical College of Wisconsin (Milwaukee), the largest academic system in Wisconsin, with 879 inpatient beds (of which 128 are intensive care unit beds). EXPOSURES Race (Black vs White, Native Hawaiian or Pacific Islander, Native American or Alaska Native, Asian, or unknown). MAIN OUTCOMES AND MEASURES Main outcomes included COVID-19 positivity, hospitalization, intensive care unit admission, mechanical ventilation, and death. Additional independent variables measured and tested included socioeconomic status, sex, and comorbidities. Reverse transcription polymerase chain reaction assay was used to test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RESULTS A total of 2595 patients were included. The mean (SD) age was 53.8 (17.5) years, 978 (37.7%) were men, and 785 (30.2%) were African American patients. Of the 369 patients (14.2%) who tested positive for COVID-19, 170 (46.1%) were men, 148 (40.1%) were aged 60 years or older, and 218 (59.1%) were African American individuals. Positive tests were associated with Black race
Ft is a facultative intracellular pathogen that infects many cell types, including neutrophils. In previous work, we demonstrated that the type B Ft strain LVS disrupts NADPH oxidase activity throughout human neutrophils, but how this is achieved is incompletely defined. Here, we used several type A and type B strains to demonstrate that Ft-mediated NADPH oxidase inhibition is more complex than appreciated previously. We confirm that phagosomes containing Ft opsonized with AS exclude flavocytochrome b(558) and extend previous results to show that soluble phox proteins were also affected, as indicated by diminished phosphorylation of p47(phox) and other PKC substrates. However, a different mechanism accounts for the ability of Ft to inhibit neutrophil activation by formyl peptides, Staphylococcus aureus, OpZ, and phorbol esters. In this case, enzyme targeting and assembly were normal, and impaired superoxide production was characterized by sustained membrane accumulation of dysfunctional NADPH oxidase complexes. A similar post-assembly inhibition mechanism also diminished the ability of anti-Ft IS to confer neutrophil activation and bacterial killing, consistent with the limited role for antibodies in host defense during tularemia. Studies of mutants that we generated in the type A Ft strain Schu S4 demonstrate that the regulatory factor fevR is essential for NADPH oxidase inhibition, whereas iglI and iglJ, candidate secretion system effectors, and the acid phosphatase acpA are not. As Ft uses multiple mechanisms to block neutrophil NADPH oxidase activity, our data strongly suggest that this is a central aspect of virulence.
SUMMARY In this review we examine the literature related to emerging technologies that will help to reshape the clinical microbiology laboratory. These topics include nucleic acid amplification tests such as isothermal and point-of-care molecular diagnostics, multiplexed panels for syndromic diagnosis, digital PCR, next-generation sequencing, and automation of molecular tests. We also review matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) and electrospray ionization (ESI) mass spectrometry methods and their role in identification of microorganisms. Lastly, we review the shift to liquid-based microbiology and the integration of partial and full laboratory automation that are beginning to impact the clinical microbiology laboratory.
The ability to provide timely identification of the causative agents of lower respiratory tract infections can promote better patient outcomes and support antimicrobial stewardship efforts. Current diagnostic testing options include culture, molecular testing, and antigen detection. These methods may require collection of various specimens, involve extensive sample treatment, and can suffer from low sensitivity and long turnaround times. This study assessed the performance of the BioFire FilmArray Pneumonia Panel (PN panel) and Pneumonia Plus Panel (PNplus panel), an FDA-cleared sample-to-answer assay that enables the detection of viruses, atypical bacteria, bacteria, and antimicrobial resistance marker genes from lower respiratory tract specimens (sputum and bronchoalveolar lavage [BAL] fluid). Semiquantitative results are also provided for the bacterial targets. This paper describes selected analytical and clinical studies that were conducted to evaluate performance of the panel for regulatory clearance. Prospectively collected respiratory specimens (846 BAL and 836 sputum specimens) evaluated with the PN panel were also tested by quantitative reference culture and molecular methods for comparison. The PN panel showed a sensitivity of 100% for 15/22 etiologic targets using BAL specimens and for 10/24 using sputum specimens. All other targets had sensitivities of ≥75% or were unable to be calculated due to low prevalence in the study population. Specificity for all targets was ≥87.2%, with many false-positive results compared to culture that were confirmed by alternative molecular methods. Appropriate adoption of this test could provide actionable diagnostic information that is anticipated to impact patient care and antimicrobial stewardship decisions.
bInfections attributable to vancomycin-resistant Enterococcus (VRE) strains have become increasingly prevalent over the past decade. Prompt identification of colonized patients combined with effective multifaceted infection control practices can reduce the transmission of VRE and aid in the prevention of hospital-acquired infections (HAIs). Increasingly, the clinical microbiology laboratory is being asked to support infection control efforts through the early identification of potential patient or environmental reservoirs. This review discusses the factors that contribute to the rise of VRE as an important health care-associated pathogen, the utility of laboratory screening and various infection control strategies, and the available laboratory methods to identify VRE in clinical specimens. Hospital-acquired infections (HAIs) are a serious threat for patient care and carry a significant cost to hospitals, since treatment of these infections is no longer reimbursable. In addition, regulations requiring hospitals to report HAIs creates further pressure to reduce incidence rates. Screening patients at admission for methicillin-resistant Staphylococcus aureus (MRSA) has been a successful approach in reducing MRSA HAIs in some health care systems and may be a successful strategy for controlling other health care-associated pathogens, including Clostridium difficile, carbapenem-resistant Enterobacteriaceae (CRE), and vancomycin-resistant Enterococcus (VRE) (1). However, there is debate about the optimal approach to screening and infection control, which may differ between pathogens of interest.Members of the genus Enterococcus are well-documented pathogens associated with various clinical manifestations, including bacteremia, infective endocarditis, intra-abdominal and pelvic infections, urinary tract infections, and, in rare cases, central nervous system infections (2-4). Infection with vancomycin-resistant Enterococcus is associated with an increased mortality rate, illustrated by a 2.5-fold increase in mortality for patients suffering from VRE bacteremia (5). Vancomycin resistance in Enterococcus spp. has been increasing in prevalence since it was first encountered in 1986 (6, 7). Currently, 30% of Enterococcus species isolates from the United States are vancomycin resistant, and infection with these organisms causes an estimated 1,300 deaths each year (8). The majority of VRE are associated with the species E. faecium (77%) and E. faecalis (9%), with the remaining 14% of isolates representing species less frequently implicated in serious infections, including E. gallinarum, E. casseliflavus, E. avium, and E. raffinosus (8).The optimal approach to reducing VRE infections is multifactorial, requiring antimicrobial stewardship to reduce the selection of VRE in colonized patients, appropriate infection control practices to reduce transmission, and reliable sensitive laboratory methods for the detection of VRE in a timely manner. ANTIMICROBIAL RESISTANCE MECHANISMS AND APPROACHES TO THERAPYUnderstanding the mechanism be...
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