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The bioMérieux BIOFIRE Joint Infection (JI) Panel is a multiplex in vitro diagnostic test for the simultaneous and rapid (~1 h) detection of 39 potential pathogens and antimicrobial resistance (AMR) genes directly from synovial fluid (SF) samples. Thirty-one species or groups of microorganisms are included in the kit, as well as several AMR genes. This study, performed to evaluate the BIOFIRE JI Panel for regulatory clearance, provides data from a multicenter evaluation of 1,544 prospectively collected residual SF samples with performance compared to standard-of-care (SOC) culture for organisms or polymerase chain reaction (PCR) and sequencing for AMR genes. The BIOFIRE JI Panel demonstrated a sensitivity of 90.9% or greater for all but six organisms and a positive percent agreement (PPA) of 100% for all AMR genes. The BIOFIRE JI Panel demonstrated a specificity of 98.5% or greater for detection of all organisms and a negative percent agreement (NPA) of 95.7% or greater for all AMR genes. The BIOFIRE JI Panel provides an improvement over SOC culture, with a substantially shorter time to result for both organisms and AMR genes with excellent sensitivity/PPA and specificity/NPA, and is anticipated to provide timely and actionable diagnostic information for joint infections in a variety of clinical scenarios., Competing Interests: J.E. has received research funding from bioMérieux and has served as a consultant for bioMérieux. AL has received research funding from BioFire, Cepheid, and Luminex. J.M.B.L. has served as a consultant for bioMérieux and has also participated in other BioFire clinical studies. B.S. has received research funding from BioFire, Becton, Dickinson and Company, and DiaSorin.

The rapid pace of name changes of medically important fungi is creating challenges for clinical laboratories and clinicians involved in patient care. We describe two sources of name change which have different drivers, at the species versus the genus level. Some suggestions are made here to reduce the number of name changes. We urge taxonomists to provide diagnostic markers of taxonomic novelties. Given the instability of phylogenetic trees due to variable taxon sampling, we advocate to maintain genera at the largest possible size. Reporting of identified species in complexes or series should where possible comprise both the name of the overarching species and that of the molecular sibling, often cryptic species. Because the use of different names for the same species will be unavoidable for many years to come, an open access online database of the names of all medically important fungi, with proper nomenclatural designation and synonymy, is essential. We further recommend that while taxonomic discovery continues, the adaptation of new name changes by clinical laboratories and clinicians be reviewed routinely by a standing committee for validation and stability over time, with reference to an open access database, wherein reasons for changes are listed in a transparent way., Competing Interests: The authors declare no conflict of interest.

Background: The high clinical burden of Clostridioides difficile infections merits rapid and sensitive identification of affected individuals. However, effective diagnosis remains challenging. Current best practice guidelines recommend molecular and/or direct toxin detection-based screening for symptomatic individuals, but previous work has called into question the concordance and performance of extant clinical assays., Aim: To better correlate the genomic and phenotypic properties of clinical C. difficile isolates with laboratory testing outcomes in both C. difficile-infected patients and asymptomatic carriers., Methods: Whole-genome sequencing of clinical C. difficile isolates collected from an inpatient population at a single healthcare institution was performed, enabling examination of their molecular epidemiology and toxigenic gene content. Genomic findings were compared with clinical testing outcomes, identifying multiple diagnostic discrepancies., Findings: Toxigenic culture, considered a 'reference standard', provided perfect sensitivity and specificity in predicting toxigenic gene content, whereas reduced performance was observed for Simplexa C. difficile Direct Assay (100% specificity, 88% sensitivity), Gene Xpert CD/Epi Assay (86% specificity, 83% sensitivity), and Quick Check Complete Tox A/B (100% specificity, 30% sensitivity). Genomic analysis additionally revealed variability in toxin gene sequences among C. difficile strains, phylogenomic equivalency between isolates from affected patients and carriers, and patient carriage with uncommon environmentally derived C. difficile lineages, as well as presenting opportunities for tracing pathogen transmission events., Conclusion: These results highlight the variable performance of clinical stool-based testing approaches as well as the potential diagnostic utility of whole-genome sequencing as an alternative to conventional testing algorithms., (Copyright © 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the associated costs related to the diagnosis and treatment of meningitis and encephalitis (ME) in adult patients in the USA., Methods: A retrospective observational study design was used to assess the use and costs of diagnostic tests and antimicrobial treatment and the total hospitalization costs for adult patients with suspected ME, who received a lumbar puncture procedure during an emergency department visit or during the first two service days of an inpatient stay. Related costs were calculated by timing of lumbar puncture performed and infectious etiology., Results: A total 26429 adult patients with suspected ME diagnosed between 2011 and 2014 were included in the study. The mean hospitalization cost was $15 572±27168, with antimicrobial medication cost of $1144±4052 and laboratory test cost of $210±244. The total visit cost increased with delayed lumbar puncture procedure, intensive care unit stay, and if the etiology was fungi, arbovirus, or bacteria., Conclusions: Higher diagnostic and treatment costs are associated with a delayed lumbar puncture procedure, the etiological agent, and the requirement for an intensive care unit stay., (Copyright © 2018 BioMerieux, Inc. Published by Elsevier Ltd.. All rights reserved.)

Background: Large epidemiological studies evaluating the etiologies, management decisions, and outcomes of adults with meningitis or encephalitis in the United States (US) are lacking., Methods: Adult patients (≥18 years) with meningitis or encephalitis by International Classification of Diseases, Ninth Revision codes available in the Premier Healthcare Database during 2011-2014 were analyzed., Results: A total of 26429 patients with meningitis or encephalitis were identified. The median age was 43 years; 53% were female. The most common etiology was enterovirus (13463 [51.6%]), followed by unknown (4944 [21.4%]), bacterial meningitis (3692 [14.1%]), herpes simplex virus (2184 [8.3%]), noninfectious (921 [3.5%]), fungal (720 [2.7%]), arboviruses (291 [1.1%]), and other viruses (214 [0.8%]). Empiric antibiotics, antivirals, and antifungals were administered in 85.8%, 53.4%, and 7.8%, respectively, and varied by etiologies. Adjunctive steroids were utilized in 15.9% of all patients and in 39.3% of patients with pneumococcal meningitis, with an associated decrease in mortality (6.67% vs 12.5%, P = .0245). The median length of stay was 4 days, with the longest duration in those with fungal (13), arboviral (10), and bacterial meningitis (7). Overall inpatient mortality was 2.9% and was higher in those with bacterial (8.2%), fungal (8.2%), or arboviral (8.9%) disease. Overall readmission rate at 30 days was 3.2%; patients with arboviral (12.7%), bacterial (6.7%), and fungal (5.4%) etiologies had higher rates., Conclusions: Viruses are the most common cause of meningitis and encephalitis in the United States and are treated with antibiotic therapy in the majority of cases. Adjunctive steroid treatment is underutilized in pneumococcal meningitis, where it has shown to decrease mortality., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com)

Mycobacteria cause significant morbidity in humans. Rapid and accurate mycobacterial identification is important for improvement of patient outcomes. However, identification may be challenging due to the slow and fastidious growth of mycobacteria. Several diagnostic methods, such as biochemical, sequencing, and probe methods, are used for mycobacterial identification. We compared the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) Biotyper system (Bruker Daltonics) to 16S rRNA/hsp65 sequencing and/or DNA probes (Gen-Probe) for mycobacterial identification. One hundred seventy-eight mycobacterial isolates grown on solid and/or broth medium were included in the study. MALDI-TOF MS identified 93.8% of the mycobacteria isolates accurately to the species level and 98.3% to the genus level, independent of the type of medium used for isolation. The identification of mycobacteria directly from cultures using MALDI-TOF MS allows for precise identification in an hour compared to traditional biochemical and phenotypic methods that can take weeks or probes and sequencing that may take a few hours. Identification by MALDI-TOF MS potentially reduces the turnaround time and cost, thereby saving resources within the health care system.

Clostridium difficile is the most important cause of nosocomial diarrhea. Several laboratory techniques are available to detect C. difficile toxins or the genes that encode them in fecal samples. We evaluated the Xpert C. difficile and Xpert C. difficile/Epi (Cepheid, CA) that detect the toxin B gene (tcdB) and tcdB, cdt, and a deletion in tcdC associated with the 027/NAP1/BI strain, respectively, by real-time PCR, and the Illumigene C. difficile (Meridian Bioscience, Inc.) that detects the toxin A gene (tcdA) by loop-mediated isothermal amplification in stool specimens. Toxigenic culture was used as the reference method for discrepant stool specimens. Two hundred prospective and fifty retrospective diarrheal stool specimens were tested simultaneously by the cell cytotoxin neutralization assay (CCNA) and the Xpert C. difficile, Xpert C. difficile/Epi, and Illumigene C. difficile assays. Of the 200 prospective stools tested, 10.5% (n = 23) were determined to be positive by CCNA, 17.5% (n = 35) were determined to be positive by Illumigene C. difficile, and 21.5% (n = 43) were determined to be positive by Xpert C. difficile and Xpert C. difficile/Epi. Of the 50 retrospective stools, previously determined to be positive by CCNA, 94% (n = 47) were determined to be positive by Illumigene C. difficile and 100% (n = 50) were determined to be positive by Xpert C. difficile and Xpert C. difficile/Epi. Of the 11 discrepant results (i.e., negative by Illumigene C. difficile but positive by Xpert C. difficile and Xpert C. difficile/Epi), all were determined to be positive by the toxigenic culture. A total of 21% of the isolates were presumptively identified by the Xpert C. difficile/Epi as the 027/NAP1/BI strain. The Xpert C. difficile and Xpert C. difficile/Epi assays were the most sensitive, rapid, and easy-to use assays for the detection of toxigenic C. difficile in stool specimens.

Clostridium difficile bacteremia is rare. Here, we report two cases of C. difficile bacteremia in patients with significant underlying gastrointestinal pathology. In one case, the bacteremia was caused by the North American pulsed-field gel electrophoresis (PFGE) type 1 (NAP-1) strain, which is responsible for recent outbreaks of C. difficile infections of increased severity.