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OBJECTIVES: Recent research has helped define the complex pathways in sepsis, affording new opportunities for advancing diagnostics tests. Given significant advances in the field, a group of academic investigators from emergency medicine, intensive care, pathology, and pharmacology assembled to develop consensus around key gaps and potential future use for emerging rapid host response diagnostics assays in the emergency department (ED) setting. METHODS: A modified Delphi study was conducted that included 26 panelists (expert consensus panel) from multiple specialties. A smaller steering committee first defined a list of Delphi statements related to the need for and future potential use of a hypothetical sepsis diagnostic test in the ED. Likert scoring was used to assess panelists agreement or disagreement with statements. Two successive rounds of surveys were conducted and consensus for statements was operationally defined as achieving agreement or disagreement of 75% or greater. RESULTS: Significant gaps were identified related to current tools for assessing risk of sepsis in the ED. Strong consensus indicated the need for a test providing an indication of the severity of dysregulated host immune response, which would be helpful even if it did not identify the specific pathogen. Although there was a relatively high degree of uncertainty regarding which patients would most benefit from the test, the panel agreed that an ideal host response sepsis test should aim to be integrated into ED triage and thus should produce results in less than 30 minutes. The panel also agreed that such a test would be most valuable for improving sepsis outcomes and reducing rates of unnecessary antibiotic use. CONCLUSION: The expert consensus panel expressed strong consensus regarding gaps in sepsis diagnostics in the ED and the potential for new rapid host response tests to help fill these gaps. These finding provide a baseline framework for assessing key attributes of evolving host response diagnostic tests for sepsis in the ED.

IntroductionThis expert review outlines current and future point-of-care technologies for the diagnosis of the SARS-CoV-2 virus, which is responsible for causing coronavirus disease COVID-19 in the emergency department. COVID-19 first emerged in late 2019 and is responsible for a range of presentations from minor upper respiratory tract symptoms to severe pneumonia and multisystem organ failure. Among the technologies available include the gold standard of molecular point-of-care tests as well as antigen detection tests.Areas coveredWe discuss point-of-care molecular tests including multiplex, targeted, and single plex panels as well as various antigen testing methodologies in terms of availability and performance characteristics. In addition, we focus on current testing best practices and considerations for point-of-care testing in the emergency department based on a search of the literature available in PubMed to date and a review of FDA and CDC guidance.Expert opinionWhile there have been many advances in SARS-CoV-2 point-of-care testing, there remain challenges to implementation in the emergency department setting. A paradigm shift is needed to improve diagnosis and clinical outcomes.

Pharyngitis is an inflammatory condition of the pharynx and/or tonsils commonly seen in both children and adults. Viruses and bacteria represent the most common encountered etiologic agents—yeast/fungi and parasites are infrequently implicated. Some of these are predominantly observed in unique populations (eg, immunocompromised or unvaccinated individuals). This manuscript (part 3 of 3) summarizes the current state of biomarker diagnostic testing and highlights the expanding role they will likely play in the expedited diagnosis and management of patients with acute pharyngitis. Biomarkers, in conjunction with rapid antigen and/or nucleic acid amplification testing, will likely become the standard of care to accurately diagnose the etiologic agent(s) of pharyngitis. This novel testing paradigm has the potential to guide appropriate patient management and antibiotic stewardship by accurately determining if the cause of pharyngitis is due to a viral or bacterial etiology. [ABSTRACT FROM AUTHOR]

Pharyngitis is an inflammatory condition of the pharynx and/or tonsils commonly seen in both children and adults. Viruses and bacteria represent the most common encountered etiologic agents—yeast/fungi and parasites are infrequently implicated. Some of these are predominantly observed in unique populations (eg, immunocompromised or unvaccinated individuals). This article (part 1 of 3) summarizes the impact of acute pharyngitis on the health care system and reviews the etiologic agents of acute pharyngitis, including both emerging and reemerging pathogens that health care providers should consider when evaluating their patients. Finally, it sets the stage for parts 2 and 3, which discuss the current and evolving state of diagnostic testing for acute pharyngitis. [ABSTRACT FROM AUTHOR]

Pharyngitis is an inflammatory condition of the pharynx and/or tonsils commonly seen in both children and adults. Viruses and bacteria represent the most common encountered etiologic agents—yeast/fungi and parasites are infrequently implicated. Some of these are predominantly observed in unique populations (eg, immunocompromised or unvaccinated individuals). This manuscript (part 2 of 3) summarizes the current state of laboratory and point-of-care diagnostic testing and highlights the expanding role of nucleic acid amplification in the expedited diagnosis and management of patients with acute pharyngitis. It discusses preanalytical, analytical, and postanalytical variables that impact the performance of culture, rapid antigen, and nucleic acid amplification testing. Finally, it sets the stage for part 3, which discusses the emerging role of biomarkers in the management of individuals with acute pharyngitis. [ABSTRACT FROM AUTHOR]

Bloodstream infection is a serious condition associated with significant morbidity and mortality. The outcome of these infections can be positively affected by the early implementation of effective antibiotic therapy based on the identification of the infecting organism and genetic markers associated with antibiotic resistance. In this study, we evaluated the microarray-based Verigene Gram-negative blood culture (BC-GN) assay in the identification of 8 genus or species targets and 6 genetic resistance determinants in positive blood culture broths. A total of 1,847 blood cultures containing Gram-negative organisms were tested using the BC-GN assay. This comprised 729 prospective fresh, 781 prospective or retrospective frozen, and 337 simulated cultures representing 7 types of aerobic culture media. The results were compared to those with standard bacterial culture and biochemical identification with nucleic acid sequence confirmation of the resistance determinants. Among monomicrobial cultures, the positive percent agreement (PPA) of the BC-GN assay with the reference method was as follows; Escherichia coli, 100%; Klebsiella pneumoniae, 92.9%; Klebsiella oxytoca, 95.5%; Enterobacter spp., 99.3%; Pseudomonas aeruginosa, 98.9%; Proteus spp., 100%; Acinetobacter spp., 98.4%; and Citrobacter spp., 100%. All organism identification targets demonstrated >99.5% negative percent agreement (NPA) with the reference method. Of note, 25/26 cultures containing K. pneumoniae that were reported as not detected by the BC-GN assay were subsequently identified as Klebsiella variicola. The PPA for identification of resistance determinants was as follows; blaCTX-M, 98.9%; blaKPC, 100%; blaNDM, 96.2%; blaOXA, 94.3%; blaVIM, 100%; and blaIMP, 100%. All resistance determinant targets demonstrated >99.9% NPA. Among polymicrobial specimens, the BC-GN assay correctly identified at least one organism in 95.4% of the broths and correctly identified all organisms present in 54.5% of the broths. The sample-to-result processing and automated reading of the detection microarray results enables results within 2 h of culture positivity.

Recently, we demonstrated that Salmonella enterica serovar Typhimurium can form biofilm on HEp-2 cells in a type 1 fimbria-dependent manner. Previous work on Salmonella exopolysaccharide (EPS) in biofilm indicated that the EPS composition can vary based upon the substratum on which the bacterial biofilm forms. We have investigated the role of genes important in the production of colanic acid and cellulose, common components of EPS. A mutation in the colanic acid biosynthetic gene, wcaM, was introduced into S. enterica serovar Typhimurimn strain B J2710 and was found to disrupt biofilm formation on HEp-2 cells and chicken intestinal tissue, although biofilm formation on a plastic surface was unaffected. Complementation of the wcaM mutant with the functional gene restored the biofiim phenotype observed in the parent strain. A mutation in the putative cellulose biosynthetic gene, yhjN, was found to disrupt biofilm formation on HEp-2 cells and chicken intestinal epithelium, as well as on a plastic surface. Our data indicate that Salmonella attachment to, and growth on, eukaryotic cells represent complex interactions that are facilitated by species of EPS.

Objectives: Aerococcus spp are Gram-positive cocci increasingly recognized as uropathogens. The Clinical and Laboratory Standards Institute recently published specific breakpoints for Aerococcus spp (M45, third edition); however, the standardized method used for antimicrobial susceptibility testing (AST) requires media not often maintained in clinical laboratories. The purpose of this study was to evaluate and compare alternative methods of AST for Aerococcus isolates.Methods: AST was performed on 134 clinical isolates using the Etest on three different types of agar, Vitek 2, and BD Phoenix. These results were compared with broth microdilution using the Sensititre STP6F.Results: Aerococcus exhibited low minimum inhibitory concentrations to benzylpenicillin, meropenem, linezolid, and vancomycin. Variable resistance was seen to levofloxacin, ceftriaxone, and tetracycline. Meropenem and vancomycin met all acceptance criteria with every alternative method tested. Benzylpenicillin and linezolid did not meet essential agreement on any AST method. Tetracycline met the majority of acceptance criteria with the exception of more than 3% very major error when using the Etest on chocolate agar, the Vitek 2, and BD Phoenix.Conclusions: Overall, the alternate AST method with the highest agreement with broth microdilution was the Etest on Mueller-Hinton agar with 5% sheep blood and may be an optimal alternative to broth microdilution. [ABSTRACT FROM AUTHOR]