Delirium is a common and morbid condition in elderly hospitalized patients. Its pathophysiology is poorly understood but inflammation has been implicated based on a clinical association with systemic infection and surgery and preclinical data showing that systemic inflammation adversely affects hippocampus-dependent memory. However, clinical manifestations and imaging studies point to abnormalities not in the hippocampus but in cortical circuits. We therefore tested the hypothesis that systemic inflammation impairs prefrontal cortex function by assessing attention and executive function in aged animals. Aged (24-month-old) Fischer-344 rats received a single intraperitoneal injection of lipopolysaccharide (LPS; 50 μg/kg) or saline and were tested on the attentional set-shifting task (AST), an index of integrity of the prefrontal cortex, on days 1–3 post-injection. Plasma and frontal cortex concentrations of the cytokine TNFα and the chemokine CCL2 were measured by ELISA in separate groups of identically treated, age-matched rats. LPS selectively impaired reversal learning and attentional shifts without affecting discrimination learning in the AST, indicating a deficit in attention and cognitive flexibility but not learning globally. LPS increased plasma TNFα and CCL2 acutely but this resolved within 24–48 h. TNFα in the frontal cortex did not change whereas CCL2 increased nearly threefold 2 h after LPS but normalized by the time behavioral testing started 24 h later. Together, our data indicate that systemic inflammation selectively impairs attention and executive function in aged rodents and that the cognitive deficit is independent of concurrent changes in frontal cortical TNFα and CCL2. Because inattention is a prominent feature of clinical delirium, our data support a role for inflammation in the pathogenesis of this clinical syndrome and suggest this animal model could be useful for studying that relationship further.

C andida auris is an emerging public health threat. Since initial identification (1), it has become a global pathogen, causing outbreaks in various health care settings. Despite its capacity for health care-associated transmission, rapid, accurate identification remains challenging in clinical laboratories. This poses a public health threat, as early identification is crucial for initiating infection control measures in order to limit transmission and for guiding antifungal therapy, as most C. auris strains are resistant to one or more antifungal drugs. Over 200 C. auris cases have been reported in the United States (2), though the worldwide burden of C. auris is largely unknown. As an emerging pathogen, C. auris may be mischaracterized and underreported due to unreliable identification in automated systems, as C. auris biochemical fingerprints have not yet been incorporated into many microbiology databases. In commercially available automated systems, C. auris has been misidentified as other Candida species, Rhodotorula glutinis, and Saccharomyces cerevisiae (3-10). RapID Yeast Plus (Remel, Thermo Fisher Scientific, Lenexa, KS) is a commercial, manual, biochemical enzyme-based system used in many clinical laboratories to identify medically important yeasts. RapID relies on several chromogenic reactions and the Electronic RapID Coded Compendium (ERIC) for organism identification. To date, C. auris isolation has not been validated by this system and is not included in the electronic coded compendium. We obtained a reference panel of 10 C. auris isolates from the U.S. Centers for Disease Control and Prevention designed to assist clinical laboratories in the identification of this organism. The isolates were subcultured to Sabouraud dextrose agar (Emmons formulation; BD, Sparks, MD). Cultures used for inoculum preparation were incubated at 30°C for 48 h. Using a cotton swab, sufficient growth from the agar plate culture was suspended in RapID inoculation fluid (2 ml) to achieve the appropriate visual turbidity according to the manufacturer's package insert. The inoculum fluid was transferred into reaction cavities within the panel, which was incubated at 30°C in a non-CO 2 incubator for 4 h. The preformulated reagents were added according to the manufacturer's instructions. Based on pH and chromogenic changes, a microcode, which was entered into the ERIC database for species identification with an associated probability, was assigned to each panel. Testing was performed in duplicate for each reference isolate. If disagreement occurred between the first two rounds of testing for any isolate, a third test was performed for adjudication. Glucose utilization, the enzymatic hydrolysis of p-nitrophenyl-␣-D-glucoside, and the hydrolysis of proline-␤-naphthylamide were common to all C. auris reference isolates (Table 1). Nine isolates were misidentified as Candida parapsilosis, with satisfactory

A 27-year-old woman presented with elevated transaminase levels and a positive hepatitis B surface antigen test result. How do you interpret these test results?

BackgroundFosfomycin is among the limited treatment options for carbapenem-resistant Enterobacteriaceae (CRE) infections. Despite its use, prevalence of fosfomycin resistance among CRE in the United States is largely unknown. In 2017, submission of Enterobacteriaceae isolates resistant to ≥1 carbapenem became mandated in Connecticut (CT), allowing further characterization at the state public health laboratory (SPHL). We analyzed fosfomycin resistance among CRE isolates in CT during 2017, and explored demographic and molecular factors potentially associated with resistance.MethodsAfter confirming carbapenem resistance, SPHL tests fosfomycin susceptibility using disk diffusion. For each CRE patient, the isolate most resistant to fosfomycin was included in this analysis. We used the Clinical and Laboratory Standards Institute (CLSI) fosfomycin breakpoint for Escherichia coli (nonsusceptible <16 mm) to evaluate associations among fosfomycin resistance and demographic factors, carbapenemase activity (modified carbapenem inactivation method, mCIM) and carbapenemase genes tested at SPHL. We report fosfomycin resistance rate by European Committee on Antimicrobial Susceptibility Testing (EUCAST, resistance <24 mm for E. coli) criteria for comparison.ResultsAmong 138 CRE isolates, 39 (28.3%) were fosfomycin nonsusceptible by CLSI criteria. Most nonsusceptible isolates were Enterobacter cloacae (18; 46.2%) or Klebsiella pneumoniae (17; 43.6%). Isolates from patients aged ≥65 years were more likely to be fosfomycin nonsusceptible than isolates from patients aged <65 years (χ2 = 3.8; P = 0.050). No other demographic characteristics were statistically significant. Of fosfomycin nonsusceptible isolates, 12 (30.8%) produced a carbapenemase (mCIM-positive), and 9 (23.1%) had the blaKPC gene. By EUCAST criteria, 96 (69.6%) CRE isolates were fosfomycin resistant.ConclusionA substantial proportion of CRE in CT during 2017 were fosfomycin nonsusceptible, and nonsusceptibility was associated with older patient age. Fosfomycin resistance risk factors and molecular mechanisms need further exploration. The substantial proportion of isolates with results falling between CLSI and EUCAST breakpoints warrants evaluation.Disclosures All authors: No reported disclosures.