scholarly journals Impact of Candida auris infection in a neutropenic murine model

2019 ◽  
Author(s):  
Steven R. Torres ◽  
Amber Pichowicz ◽  
Fernando Torres-Velez ◽  
Renjie Song ◽  
Navjot Singh ◽  
...  

AbstractCandida auris has become a global public health threat due to its multidrug resistance and persistence in hospital and nursing home settings. Although a skin colonizer, C. auris can cause fatal bloodstream infections and most patients succumb to multi-organ failure. Currently, there are limited animal models to study the progression of C. auris infection. Here we compare two murine models of neutrophil depletion using monoclonal antibodies 1A8, anti-Ly6G+ and RB6-8C5 anti-Ly6G+-Ly6C+. We also compare inoculums of 107 and 108 as well as the intravenous and gavage routes of infection. The results reveal that neutrophil depletion in BALB/c mice is sustained long-term with the 1A8 antibody and short-term with RB6-8C5. Target organs were kidney, heart and brain as these had the highest organ fungal burden in neutrophil depleted and to some extent in infected control mice. We found that C. auris is shed in urine and feces for neutrophil depleted mice. The gavage model is not an ideal route as dissemination was not detected. Eight days post C. auris infection all surviving mice display a unique behavioral phenotype characterized by torticollis and tail spin that progresses to head bobbing and body curling like phenotype by day 22, that continues to persist even 104 days post infection. Lastly, we found C. auris remains in tissues of infected control mice, 34 plus days post infection suggesting that C. auris stays present in the host without causing disease but becomes opportunistic upon a change in the hosts immune status such as neutrophil depletion.

2019 ◽  
Vol 11 (1) ◽  
pp. 48-54 ◽  
Author(s):  
Ashley Bond ◽  
Paul Chadwick ◽  
Trevor R Smith ◽  
Jeremy M D Nightingale ◽  
Simon Lal

Catheter-related bloodstream infections (CRBSIs) commonly arise from a parenteral nutrition catheter hub. A target for a Nutrition Support Team is to have a CRBSI rate of less than 1 per 1000. The diagnosis of CRBSI is suspected clinically by a temperature shortly after setting up a feed, general malaise or raised blood inflammatory markers. It is confirmed by qualitative and quantitative blood cultures from the catheter and peripherally. Treatment of inpatients may involve central venous catheter removal and antibiotics for patients needing short-term parenteral nutrition, but catheter salvage is generally recommended for patients needing long-term parenteral nutrition, where appropriate.


Pathogens ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1470
Author(s):  
Daniel J. J. Carr ◽  
Amanda Berube ◽  
Edward Gershburg

Vaccines to viral pathogens in experimental animal models are often deemed successful if immunization enhances resistance of the host to virus challenge as measured by cumulative survival, reduction in virus replication and spread and/or lessen or eliminate overt tissue pathology. Furthermore, the duration of the protective response against challenge is another important consideration that drives a vaccination regimen. In the current study, we assessed the durability of two related vaccines, 0∆NLS and 0∆RING, against ocular herpes simplex virus type 1 (HSV-1) challenge in mice thirty days (short-term) and one year (long-term) following the vaccine boost. The short-term vaccine efficacy study found the 0∆RING vaccine to be nearly equivalent to the 0∆NLS vaccine in comparison to vehicle-vaccinated mice in terms of controlling virus replication and preserving the visual axis. By comparison, the long-term assessment of the two vaccines found notable differences and less efficacy overall as noted below. Specifically, the results show that in comparison to vehicle-vaccinated mice, the 0∆NLS and 0∆RING vaccinated groups were more resistant in terms of survival and virus shedding following ocular challenge. Moreover, 0∆NLS vaccinated mice also possessed significantly less infectious virus in the peripheral and central nervous systems but not the cornea compared to mice vaccinated with vehicle or 0∆RING which had similar levels. However, all vaccinated groups showed similar levels of blood and lymphatic vessel genesis into the central cornea 30 days post infection. Likewise, corneal opacity was also similar among all groups of vaccinated mice following infection. Functionally, the blink response and visual acuity were 25–50% lower in vaccinated mice 30 days post infection compared to measurements taken prior to infection. The results demonstrate a dichotomy between resistance to infection and functional performance of the visual axis that collectively show an overall loss in vaccine efficacy long-term in comparison to short-term studies in a conventional prime-boost protocol.


2020 ◽  
Vol 41 (12) ◽  
pp. 1388-1395
Author(s):  
Mireia Puig-Asensio ◽  
Alexandre R. Marra ◽  
Christopher A. Childs ◽  
Mary E. Kukla ◽  
Eli N. Perencevich ◽  
...  

AbstractObjective:To evaluate the effectiveness of chlorhexidine (CHG) dressings to prevent catheter-related bloodstream infections (CRBSIs).Design:Systematic review and meta-analysis.Methods:We searched PubMed, CINAHL, EMBASE, and ClinicalTrials.gov for studies (randomized controlled and quasi-experimental trials) with the following criteria: patients with short- or long-term catheters; CHG dressings were used in the intervention group and nonantimicrobial dressings in the control group; CRBSI was an outcome. Random-effects models were used to obtain pooled risk ratios (pRRs). Heterogeneity was evaluated using the I2 test and the Cochran Q statistic.Results:In total, 20 studies (18 randomized controlled trials; 15,590 catheters) without evidence of publication bias and mainly performed in intensive care units (ICUs) were included. CHG dressings significantly reduced CRBSIs (pRR, 0.71; 95% CI, 0.58–0.87), independent of the CHG dressing type used. Benefits were limited to adults with short-term central venous catheters (CVCs), including onco-hematological patients. For long-term CVCs, CHG dressings decreased exit-site/tunnel infections (pRR, 0.37; 95% CI, 0.22–0.64). Contact dermatitis was associated with CHG dressing use (pRR, 5.16; 95% CI, 2.09–12.70); especially in neonates and pediatric populations in whom severe reactions occurred. Also, 2 studies evaluated and did not find CHG-acquired resistance.Conclusions:CHG dressings prevent CRBSIs in adults with short-term CVCs, including patients with an onco-hematological disease. CHG dressings might reduce exit-site and tunnel infections in long-term CVCs. In neonates and pediatric populations, proof of CHG dressing effectiveness is lacking and there is an increased risk of serious adverse events. Future studies should investigate CHG effectiveness in non-ICU settings and monitor for CHG resistance.


2017 ◽  
Vol 62 (2) ◽  
Author(s):  
M. Cristina Vazquez Guillamet ◽  
Rodrigo Vazquez ◽  
Benjamin Deaton ◽  
Jenny Shroba ◽  
Laia Vazquez ◽  
...  

ABSTRACTPrevious studies have separately emphasized the importance of host, pathogen, and treatment characteristics in determining short-term or in-hospital mortality rates for patients with methicillin-resistantStaphylococcus aureus(MRSA) bloodstream infections. Less is known about the relative importance of these factors and their interactions in determining short-, medium-, and long-term mortality rates. This is an observational cohort study in which data for all patients admitted to the University of New Mexico (UNM) Health Sciences Center (HSC) between July 2002 and August 2013 with MRSA-positive blood cultures were recorded. We collected patients' demographics and treatment data, as well as data on genetic markers of the MRSA isolates. Outcomes of interest were determinants of short-term (within 30 days), medium-term (30 to 90 days), and long-term (>90 days) mortality rates. This study included 273 patients with MRSA bacteremia. Short-, medium-, and long-term mortality rates were 18.7%, 26.4%, and 48%, respectively. Thirty-day mortality rates were influenced by host variables and host-pathogen interaction characteristics. Pitt bacteremia scores, malignancy, and health care exposure contributed to 30- to 90-day mortality rates, while treatment duration of >4 weeks had a protective effect. Age remained a significant risk factor for death at >90 days, while admission leukocytosis was protective. Infection represented the most frequent cause of death for all three time frames; rates varied from 72.6% in the first 30 days and 60% for 30 to 90 days to 35.7% for >90 days (P= 0.003). Host characteristics affect short-, medium-, and long-term mortality rates for MRSA bloodstream infections more than do pathogen genetic markers and treatment factors.


2016 ◽  
Vol 39 ◽  
Author(s):  
Mary C. Potter

AbstractRapid serial visual presentation (RSVP) of words or pictured scenes provides evidence for a large-capacity conceptual short-term memory (CSTM) that momentarily provides rich associated material from long-term memory, permitting rapid chunking (Potter 1993; 2009; 2012). In perception of scenes as well as language comprehension, we make use of knowledge that briefly exceeds the supposed limits of working memory.


Author(s):  
D.E. Loudy ◽  
J. Sprinkle-Cavallo ◽  
J.T. Yarrington ◽  
F.Y. Thompson ◽  
J.P. Gibson

Previous short term toxicological studies of one to two weeks duration have demonstrated that MDL 19,660 (5-(4-chlorophenyl)-2,4-dihydro-2,4-dimethyl-3Hl, 2,4-triazole-3-thione), an antidepressant drug, causes a dose-related thrombocytopenia in dogs. Platelet counts started to decline after two days of dosing with 30 mg/kg/day and continued to decrease to their lowest levels by 5-7 days. The loss in platelets was primarily of the small discoid subpopulation. In vitro studies have also indicated that MDL 19,660: does not spontaneously aggregate canine platelets and has moderate antiaggregating properties by inhibiting ADP-induced aggregation. The objectives of the present investigation of MDL 19,660 were to evaluate ultrastructurally long term effects on platelet internal architecture and changes in subpopulations of platelets and megakaryocytes.Nine male and nine female beagle dogs were divided equally into three groups and were administered orally 0, 15, or 30 mg/kg/day of MDL 19,660 for three months. Compared to a control platelet range of 353,000- 452,000/μl, a doserelated thrombocytopenia reached a maximum severity of an average of 135,000/μl for the 15 mg/kg/day dogs after two weeks and 81,000/μl for the 30 mg/kg/day dogs after one week.


2020 ◽  
Vol 29 (4) ◽  
pp. 710-727
Author(s):  
Beula M. Magimairaj ◽  
Naveen K. Nagaraj ◽  
Alexander V. Sergeev ◽  
Natalie J. Benafield

Objectives School-age children with and without parent-reported listening difficulties (LiD) were compared on auditory processing, language, memory, and attention abilities. The objective was to extend what is known so far in the literature about children with LiD by using multiple measures and selective novel measures across the above areas. Design Twenty-six children who were reported by their parents as having LiD and 26 age-matched typically developing children completed clinical tests of auditory processing and multiple measures of language, attention, and memory. All children had normal-range pure-tone hearing thresholds bilaterally. Group differences were examined. Results In addition to significantly poorer speech-perception-in-noise scores, children with LiD had reduced speed and accuracy of word retrieval from long-term memory, poorer short-term memory, sentence recall, and inferencing ability. Statistically significant group differences were of moderate effect size; however, standard test scores of children with LiD were not clinically poor. No statistically significant group differences were observed in attention, working memory capacity, vocabulary, and nonverbal IQ. Conclusions Mild signal-to-noise ratio loss, as reflected by the group mean of children with LiD, supported the children's functional listening problems. In addition, children's relative weakness in select areas of language performance, short-term memory, and long-term memory lexical retrieval speed and accuracy added to previous research on evidence-based areas that need to be evaluated in children with LiD who almost always have heterogenous profiles. Importantly, the functional difficulties faced by children with LiD in relation to their test results indicated, to some extent, that commonly used assessments may not be adequately capturing the children's listening challenges. Supplemental Material https://doi.org/10.23641/asha.12808607


2019 ◽  
Vol 25 ◽  
pp. 114
Author(s):  
Alyssa Dufour ◽  
Setareh Williams ◽  
Richard Weiss ◽  
Elizabeth Samelson

2017 ◽  
Vol 23 ◽  
pp. 50
Author(s):  
Jothydev Kesavadev ◽  
Shashank Joshi ◽  
Banshi Saboo ◽  
Hemant Thacker ◽  
Arun Shankar ◽  
...  

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