Sentinel Case of Candida auris in the Western United States Following Prolonged Occult Colonization in a Returned Traveler from India.

Candida auris is an emerging multidrug-resistant yeast with high mortality. We report the sentinel C. auris case on the United States West Coast in a patient who relocated from India. We identified close phylogenetic relatedness to the South Asia clade and ERG11 Y132F and FKS1 S639Y mutations potentially explaining antifungal resistance

Effects of dietary Cu, Zn, and ractopamine-HCl on finishing pig growth performance, carcass characteristics, and antimicrobial susceptibility of enteric bacteria

Citation: Feldpausch, J. A., Amachawadi, R., Tokach, M. D., Scott, H. M., Dritz, S. S., Nagaraja, T. G., . . . DeRouchey, J. M. (2016). Effects of dietary Cu, Zn, and ractopamine-HCl on finishing pig growth performance, carcass characteristics, and antimicrobial susceptibility of enteric bacteria. Journal of Animal Science, 94, 73-74. doi:10.2527/msasas2016-157A total of 480 pigs (PIC 327 × 1050; initially 48.7 kg) were used to determine the interactive effects of supplemental Cu, Zn, and ractopamine HCl on finishing pig growth, carcass characteristics, and antimicrobial susceptibility of enteric bacteria. Treatments were arranged in a 2 × 2 × 2 factorial with main effects of added copper (CuSO4; 0 vs. 125 ppm Cu), added zinc (ZnO; 0 vs. 150 ppm Zn) and ractopamine HCl (0 vs. 10 ppm during the last 28 d before marketing; Paylean®; Elanco Animal Health, Greenfield, IN). All diets contained 11 ppm Cu and 73 ppm Zn from the trace mineral premix. Pens of pigs were balanced and blocked on initial BW then randomly allotted to 1 of the 4 mineral treatment diets. Twenty-eight d before marketing, pens within each block and mineral treatment were randomly assigned to receive either 0 or 10 ppm ractopamine in addition to the mineral treatment. Adding either Cu or Zn alone did not improve ADG or ADFI yet resulted in numerical improvements in overall G:F and caloric efficiencies but improvements were not additive (Cu × Zn, P = 0.057, 0.068 and 0.064 for G:F and caloric efficiency on a ME and NE basis, respectively). Ractopamine improved (P < 0.001) overall ADG, G:F, and caloric efficiency thereby increasing final BW by 3% with no change in ADFI. Ractopamine increased (P < 0.001) HCW, percent carcass yield, HCW G:F, loin depth, and percent fat-free lean and decreased (P = 0.014) backfat. An interaction existed whereby adding Zn or Cu alone to diets containing ractopamine numerically improved percent carcass yield and HCW G:F, but no improvement was observed when the Cu or Zn was added to the control diet or when Cu and Zn were fed in combination in the ractopamine diets (Cu × Zn × ractopamine, P = 0.011 and 0.018 for yield and HCW G:F, respectively). Fecal samples were collected on d 0 and at the conclusion of the finishing period (d 90) for bacterial isolation and antimicrobial susceptibility determinations according to minimal inhibitory concentration breakpoints. Escherichia coli and Enterococcus spp. isolates displayed varying levels of resistance to certain antibiotics before initiation of treatments on d 0. Resistance to most antibiotics decreased (P < 0.05) over time or was stable for those that had a low base-line percentage of resistance. Ractopamine and Zn did not adversely affect antimicrobial resistance but extended feeding of 125 ppm Cu throughout the finishing period appeared to antagonize any time-associated decrease in enterococcal resistance to tetracycline, tylosin, and quinupristin/dalfopristin

Effects of dietary copper, zinc, and ractopamine hydrochloride on finishing pig growth performance, carcass characteristics, and antimicrobial susceptibility of enteric bacteria

Citation: Feldpausch, J. A., Amachawadi, R. G., Tokach, M. D., Scott, H. M., Nagaraja, T. G., Dritz, S. S., . . . DeRouchey, J. M. (2016). Effects of dietary copper, zinc, and ractopamine hydrochloride on finishing pig growth performance, carcass characteristics, and antimicrobial susceptibility of enteric bacteria. Journal of Animal Science, 94(8), 3278-3293. doi:10.2527/jas2016-0340A total of 480 pigs (PIC 327 × 1050; initially 48.7 ± 2.3 kg) were used to determine the interactive effects of supplemental Cu, Zn, and ractopamine HCl (RAC) on finishing pig growth performance, carcass characteristics, and antimicrobial susceptibility of enteric bacteria. Treatments were arranged in a 2 × 2 × 2 factorial with the main effects of added Cu (CuSO4; 0 vs. 125 mg/kg Cu), Zn (ZnO; 0 vs. 150 mg/kg Zn), and RAC (0 vs. 10 mg/kg during the last 28 d prior to marketing). All diets contained 11 mg/kg Cu and 73 mg/ kg Zn from the trace mineral premix. Pens of pigs were balanced and blocked on initial BW and then randomly allotted to 1 of the 4 mineral treatment diets. At 28 d prior to marketing, pens within each block and mineral treatment were randomly assigned to receive either 0 or 10 mg/kg RAC in addition to the mineral treatment. Adding either Cu or Zn alone did not improve ADG or ADFI yet resulted in numerical improvements in overall G:F and caloric efficiencies, but improvements were not additive (Cu × Zn, P = 0.057, P = 0.068, and P = 0.064 for G:F and caloric efficiency on a ME and NE basis, respectively). Ractopamine improved (P &lt; 0.001) overall ADG, G:F, and caloric efficiency, thereby increasing final BW by 3% with no change in ADFI. Ractopamine also increased (P &lt; 0.001) HCW, percentage carcass yield, G:F, loin depth, and percent fat-free lean and decreased (P = 0.014) backfat. Adding Zn or Cu alone to diets containing RAC numerically improved percent yield and HCW G:F, but this effect was absent when the Cu or Zn was added to the control diet or when Cu and Zn were fed in combination in RAC diets (Cu × Zn × RAC, P = 0.011 and P = 0.018 for yield and HCW G:F, respectively). Fecal samples were collected on d 0 and at the conclusion of the finishing period (d 90) for bacterial isolation and antimicrobial susceptibility determinations according to Clinical and Laboratory Standards Institute minimal inhibitory concentrations breakpoints. Enterococcus spp. and Escherichia coli isolates displayed varying levels of resistance to certain antibiotics prior to initiation of treatments on d 0. Resistance to most antibiotics decreased (P &lt; 0.05) over time or was stable for those that had a low baseline percentage of resistance. Neither Zn nor RAC adversely affected antimicrobial resistance. However, extended feeding of 125 mg/kg Cu throughout the finishing period seems to decrease enterococcal susceptability to tetracycline, tylosin, and quinupristin/dalfopristin. © 2016 American Society of Animal Science. All rights reserved

Secondary Bacterial Pneumonias and Bloodstream Infections in Patients Hospitalized with COVID-19

Group Name: The Emory COVID-19 Quality and Clinical Research Collaborative Background: Patients hospitalized with COVID-19 are at risk of secondary infections—10%–33% develop bacterial pneumonia and 2%–6% develop bloodstream infection (BSI). We conducted a retrospective cohort study to identify the prevalence, microbiology, and outcomes of secondary pneumonias and BSIs in patients hospitalized with COVID-19. Methods: Patients aged ≥18 years with a positive SARS-CoV-2 real-time polymerase chain reaction assay admitted to 4 academic hospitals in Atlanta, Georgia, between February 15 and May 16, 2020, were included. We extracted electronic medical record data through June 16, 2020. Microbiology tests were performed according to standard protocols. Possible ventilator-associated pneumonia (PVAP) was defined according to Centers for Disease Control and Prevention (CDC) criteria. We assessed in-hospital mortality, comparing patients with and without infections using the χ(2) test. SAS University Edition software was used for data analyses. Results: In total, 774 patients were included (median age, 62 years; 49.7% female; 66.6% black). In total, 335 patients (43.3%) required intensive care unit (ICU) admission, 238 (30.7%) required mechanical ventilation, and 120 (15.5%) died. Among 238 intubated patients, 65 (27.3%) had a positive respiratory culture, including 15 with multiple potential pathogens, for a total of 84 potential pathogens. The most common organisms were Staphylococcus aureus (29 of 84; 34.5%), Pseudomonas aeruginosa (16 of 84; 19.0%), and Klebsiella spp (14 of 84; 16.7%). Mortality did not differ between intubated patients with and without a positive respiratory culture (41.5% vs 35.3%; P = .37). Also, 5 patients (2.1%) had a CDC-defined PVAP (1.7 PVAPs per 1,000 ventilator days); none of them died. Among 536 (69.3%) nonintubated patients, 2 (0.4%) had a positive Legionella urine antigen and 1 had a positive respiratory culture (for S. aureus). Of 774 patients, 36 (4.7%) had BSI, including 5 with polymicrobial BSI (42 isolates total). Most BSIs (24 of 36; 66.7%) had ICU onset. The most common organisms were S. aureus (7 of 42; 16.7%), Candida spp (7 of 42; 16.7%), and coagulase-negative staphylococci (5 of 42; 11.9%); 12 (28.6%) were gram-negative. The most common source was central-line–associated BSI (17 of 36; 47.2%), followed by skin (6 of 36; 16.7%), lungs (5 of 36; 13.9%), and urine (4 of 36; 11.1%). Mortality was 50% in patients with BSI versus 13.8% without (p < 0.0001). Conclusions: In a large cohort of patients hospitalized with COVID-19, secondary infections were rare: 2% bacterial pneumonia and 5% BSI. The risk factors for these infections (intubation and central lines, respectively) and causative pathogens reflect healthcare delivery and not a COVID-19–specific effect. Clinicians should adhere to standard best practices for preventing and empirically treating secondary infections in patients hospitalized with COVID-19. Funding: No Disclosures: Non

Large scale enzyme based xenobiotic identification for exposomics.

Advances in genomics have revealed many of the genetic underpinnings of human disease, but exposomics methods are currently inadequate to obtain a similar level of understanding of environmental contributions to human disease. Exposomics methods are limited by low abundance of xenobiotic metabolites and lack of authentic standards, which precludes identification using solely mass spectrometry-based criteria. Here, we develop and validate a method for enzymatic generation of xenobiotic metabolites for use with high-resolution mass spectrometry (HRMS) for chemical identification. Generated xenobiotic metabolites were used to confirm identities of respective metabolites in mice and human samples based upon accurate mass, retention time and co-occurrence with related xenobiotic metabolites. The results establish a generally applicable enzyme-based identification (EBI) for mass spectrometry identification of xenobiotic metabolites and could complement existing criteria for chemical identification

The Adversarial Robustness of Sampling

Random sampling is a fundamental primitive in modern algorithms, statistics, and machine learning, used as a generic method to obtain a small yet "representative" subset of the data. In this work, we investigate the robustness of sampling against adaptive adversarial attacks in a streaming setting: An adversary sends a stream of elements from a universe $U$ to a sampling algorithm (e.g., Bernoulli sampling or reservoir sampling), with the goal of making the sample "very unrepresentative" of the underlying data stream. The adversary is fully adaptive in the sense that it knows the exact content of the sample at any given point along the stream, and can choose which element to send next accordingly, in an online manner. Well-known results in the static setting indicate that if the full stream is chosen in advance (non-adaptively), then a random sample of size $\Omega(d / \varepsilon^2)$ is an $\varepsilon$-approximation of the full data with good probability, where $d$ is the VC-dimension of the underlying set system $(U,R)$. Does this sample size suffice for robustness against an adaptive adversary? The simplistic answer is \emph{negative}: We demonstrate a set system where a constant sample size (corresponding to VC-dimension $1$) suffices in the static setting, yet an adaptive adversary can make the sample very unrepresentative, as long as the sample size is (strongly) sublinear in the stream length, using a simple and easy-to-implement attack. However, this attack is "theoretical only", requiring the set system size to (essentially) be exponential in the stream length. This is not a coincidence: We show that to make Bernoulli or reservoir sampling robust against adaptive adversaries, the modification required is solely to replace the VC-dimension term $d$ in the sample size with the cardinality term $\log |R|$. This nearly matches the bound imposed by the attack

(Young Scholars) Effects of feed truck unloading and swine barn feed line location on pellet quality and nutrient segregation

Citation: De Jong, J. A., DeRouchey, J. M., Tokach, M. D., Goodband, R. D., Woodworth, J. C., Jones, C. K., . . . Haberl, B. (2016). (Young Scholars) Effects of feed truck unloading and swine barn feed line location on pellet quality and nutrient segregation. Journal of Animal Science, 94, 78-78. doi:10.2527/msasas2016-166Two experiments were conducted at a commercial feed mill and 6 commercial wean to finish pig sites to determine the effects of feed truck unloading auger RPM on pellet quality and unloading time, and the effects of feed line location on pellet quality and nutrient concentration of intact pellets and their fines. In Exp. 1, pelleted feed was unloaded using 3 speeds (900, 1150, and 1400 RPM) from each of 8 compartments of a feed truck (Walinga Inc., Guelph, ON, Canada). Six samples per compartment were collected creating 16 replications/unloading speed. There was an unloading speed × trailer compartment interaction (P = 0.031; SEM = 17.4). The difference in unloading time from the front to rear compartment was greatest at the slowest unloading speed and similar at the 2 highest unloading speeds (70 vs. 35 and 37 s). The percentage of fines formed during unloading was not influenced by unloading speed, but tended to increase (quadratic; P = 0.081; SEM = 2.27) from the front (8.2%) to the rear compartment (10.7%). In Exp. 2, pelleted feed samples were collected during unloading into a commercial feed bin at 6 finishing pig sites with 2 feed lines, resulting in 12 replications per feed line location. Samples were collected from the feed line at 6, 35, and 76 m from the feed bin. There were no interactions between feed line location and nutrient profile of the fines and pellets. There was no effect of feed line location on pellet durability index, percentage fines, percentage fines formed, or the nutrient profile of pellets or fines. Across locations, fines had decreased (P < 0.05) CP (12.4 vs. 15.3%; SEM = 0.14) and P (0.37 vs. 0.40%; SEM = 0.006), but greater (P < 0.05) ADF (3.7 vs. 3.2%; SEM = 0.24), crude fiber (2.7 vs. 2.2%; SEM = 0.09), Ca (0.47 vs. 0.44%; SEM = 0.012), ether extract (6.2 vs. 5.2%; SEM = 0.11), and starch (47.4 vs. 44.7%; SEM = 0.42) for the fines and pellets, respectively. In conclusion, the front compartments closer to the truck cab resulted in fewer fines formed from loading to unloading. Decreasing unloading speed significantly increased the amount of time taken to unload a feed truck but did not alter fines formed. Feeder distance from the bin did not influence fines formation. There were significant differences in nutrient profile between fines and pellets. Understanding the location of fines creation during the feed delivery process may allow for alternative methods to reduce the formation of fines and subsequent nutrient segregation

EspA Acts as a Critical Mediator of ESX1-Dependent Virulence in Mycobacterium tuberculosis by Affecting Bacterial Cell Wall Integrity

Mycobacterium tuberculosis (Mtb) requires the ESX1 specialized protein secretion system for virulence, for triggering cytosolic immune surveillance pathways, and for priming an optimal CD8+ T cell response. This suggests that ESX1 might act primarily by destabilizing the phagosomal membrane that surrounds the bacterium. However, identifying the primary function of the ESX1 system has been difficult because deletion of any substrate inhibits the secretion of all known substrates, thereby abolishing all ESX1 activity. Here we demonstrate that the ESX1 substrate EspA forms a disulfide bonded homodimer after secretion. By disrupting EspA disulfide bond formation, we have dissociated virulence from other known ESX1-mediated activities. Inhibition of EspA disulfide bond formation does not inhibit ESX1 secretion, ESX1-dependent stimulation of the cytosolic pattern receptors in the infected macrophage or the ability of Mtb to prime an adaptive immune response to ESX1 substrates. However, blocking EspA disulfide bond formation severely attenuates the ability of Mtb to survive and cause disease in mice. Strikingly, we show that inhibition of EspA disulfide bond formation also significantly compromises the stability of the mycobacterial cell wall, as does deletion of the ESX1 locus or individual components of the ESX1 system. Thus, we demonstrate that EspA is a major determinant of ESX1-mediated virulence independent of its function in ESX1 secretion. We propose that ESX1 and EspA play central roles in the virulence of Mtb in vivo because they alter the integrity of the mycobacterial cell wall

Fecal Microbiota Transplantation Is Safe and Effective in Patients With Clostridioides difficile Infection and Cirrhosis

Background & Aims Clostridioides difficile infection (CDI) harms a large proportion of patients with cirrhosis. Fecal microbiota transplantation (FMT) is recommended for recurrent CDI, but its effects in patients with cirrhosis have not been established. We performed a multicenter observational study to evaluate the efficacy and safety of FMT for CDI in patients with cirrhosis. Methods We performed a retrospective study of 63 adults with cirrhosis (median model for end-stage liver disease score, 14.5; 24 patients with decompensated cirrhosis) who underwent FMT for CDI from January 2012 through November 2018 at 8 academic centers in the United States, Canada, and Italy. We collected data on patient demographics and characteristics of cirrhosis, CDI, and FMT from medical records and compared differences among patients with different severities of cirrhosis, and FMT successes vs failures at the 8-week follow-up evaluation. We also obtained data on adverse events (AEs) and severe AEs within 12 weeks of FMT. Results Patients underwent FMT for recurrent CDI (55 of 63; 87.3%), severe CDI (6 of 63; 9.5%), or fulminant CDI (2 of 63; 3.2%) primarily via colonoscopy (59 of 63; 93.7%) as outpatients (47 of 63; 76.8%). FMT success was achieved for 54 patients (85.7%). Among FMT failures, a higher proportion used non-CDI antibiotics at the time of FMT (44.4% vs 5.6%; P < .001), had Child–Pugh scores of B or C (100% vs 37.7%; P < .001), used probiotics (77.8% vs 24.1%; P = .003), had pseudomembranes (22.2% vs 0; P = .018), and underwent FMT as inpatients (45.5% vs 19%; P = .039), compared with FMT successes. In multivariable analysis, use of non-CDI antibiotics at the time of FMT (odds ratio, 17.43; 95% CI, 2.00–152.03; P = .01) and use of probiotics (odds ratio, 11.9; 95% CI, 1.81–78.3; P = .01) were associated with a greater risk of FMT failure. FMT-related AEs occurred in 33.3% of patients (21 of 63)—most were self-limited abdominal cramps or diarrhea. There were only 5 severe AEs that possibly were related to FMT; none involved infection or death. Conclusions In a retrospective study, we found FMT to be safe and effective for the treatment of CDI in patients with cirrhosis