scholarly journals 1186. Cefazolin inoculum effect predicts reduced susceptibility to other antibiotics and patient outcomes in MSSA endovascular infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S617-S617
Author(s):  
Dan Smelter ◽  
Sue McCrone ◽  
Warren Rose
Keyword(s):  
Infective Endocarditis ◽  
Mortality Rate ◽  
Patient Outcomes ◽  
Treatment Options ◽  
Fold Increase ◽  
Specific Mechanism ◽  
Research Support ◽  
High Burden ◽  
Low Toxicity ◽  
Inoculum Effect

Abstract Background MSSA Infective endocarditis (IE) is inherently a high-burden infection with up to a 30% mortality rate. Cefazolin is an appealing treatment option for IE with low toxicity and a favorable dosing scheme. However, cefazolin has been associated with treatment failure in IE, attributed to an inoculum effect. The specific mechanism underlying the cefazolin inoculum effect (CIE) remains undetermined, but CIE has been linked to both blaZ expression and agr dysfunction. This study aims to determine whether CIE is linked to reduced susceptibility to other antibiotics and worse outcomes regardless of therapy in MSSA endovascular infections. Methods Sixty-four MSSA strains were collected from patients with endovascular infections not treated with cefazolin. To determine CIE phenotype, strains were cultured and MICs assayed for cefazolin, nafcillin, and vancomycin at 107 CFU/mL for high-inocula (HI) and 105 CFU/mL for standard-inocula (SI). This study defined CIE as a ≥ 4-fold increase in MIC at HI compared to SI, with at least an MIC of 4 mg/L at HI. Nitrocefin disks identified blaZ expression, and beta lysin disks were used to determine hemolysin type and agr function. Patient outcomes of mortality and bacteremia duration were assessed across cohorts. Results Twenty-four strains exhibit a CIE (38%), with 10 strains having an MIC of ≥ 32mg/L at HI. Nafcillin and vancomycin also had an inoculum effect, uncoupled from the CIE and occurring at a lower frequency and amplitude at HI. Presence of CIE had a greater association with blaZ expression (71% vs 25%) than agr dysfunction (38% vs 20%). 50% (9/18) of CIE infections were cleared within 48 hours while 77% (20/26) of CIE-negative infections were cleared within 48 hours (P=0.106). However, presence of CIE was not associated with increased mortality (25% CIE-positive vs 35%; P=0.578) Conclusion Previous studies for CIE failed to enrich for isolates from endovascular sources, where inocula are known to be high. This study presents one of the largest endovascular source cohorts for CIE evaluation. It identifies that CIE prevalence (38%) is higher than reports from diverse infection sources (10-36%). CIE appears to predict bacteremia duration with other MSSA treatment options, suggesting mechanisms independent of blaZ and agr function for this phenomenon. Disclosures Warren Rose, PharmD, MPH, Merck (Grant/Research Support)Paratek (Grant/Research Support)

Potential of Nanoparticles in Combating Candida Infections

2019 ◽  
Vol 16 (5) ◽  
pp. 478-491 ◽  
Author(s):  
Faizan Abul Qais ◽  
Mohd Sajjad Ahmad Khan ◽  
Iqbal Ahmad ◽  
Abdullah Safar Althubiani
Keyword(s):  
Targeted Delivery ◽  
Recent Progress ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Fold Increase ◽  
Antifungal Drugs ◽  
Low Toxicity ◽  
Candida Infections ◽  
Made In

Aims: The aim of this review is to survey the recent progress made in developing the nanoparticles as antifungal agents especially the nano-based formulations being exploited for the management of Candida infections. Discussion: In the last few decades, there has been many-fold increase in fungal infections including candidiasis due to the increased number of immunocompromised patients worldwide. The efficacy of available antifungal drugs is limited due to its associated toxicity and drug resistance in clinical strains. The recent advancements in nanobiotechnology have opened a new hope for the development of novel formulations with enhanced therapeutic efficacy, improved drug delivery and low toxicity. Conclusion: Metal nanoparticles have shown to possess promising in vitro antifungal activities and could be effectively used for enhanced and targeted delivery of conventionally used drugs. The synergistic interaction between nanoparticles and various antifungal agents have also been reported with enhanced antifungal activity.

Candida albicans endocarditis involving a normal native aortic valve in an immunocompetent patient

2020 ◽  
Vol 13 (11) ◽  
pp. e236902
Author(s):  
Taha Sheikh ◽  
Jeremy C Tomcho ◽  
Mohammed T Awad ◽  
Syeda Ramsha Zaidi
Keyword(s):  
Candida Albicans ◽  
Mortality Rate ◽  
Aortic Valve ◽  
High Mortality ◽  
Treatment Options ◽  
Immunocompetent Patient ◽  
Fungal Endocarditis ◽  
Appropriate Treatment ◽  
Mechanical Valves ◽  
Serious Infection

Fungal endocarditis, specifically from Candida species, is a rare but serious infection with a high mortality rate. Most cases occur in bioprosthetic or mechanical valves and are uncommon in native, structurally normal valves. When Candida endocarditis is detected and appropriate treatment is initiated earlier, there is an improvement in mortality. While the recommendation is usually to treat with a combination of surgery and antifungal medications, patient comorbidities may limit treatment options.

scholarly journals A metabolomic endotype of bioenergetic dysfunction predicts mortality in critically ill patients with acute respiratory failure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raymond J. Langley ◽  
Marie E. Migaud ◽  
Lori Flores ◽  
J. Will Thompson ◽  
Elizabeth A. Kean ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Acute Respiratory Failure ◽  
Patient Outcomes ◽  
Medical Intensive Care Unit ◽  
Close Association ◽  
Treatment Options ◽  
Feature Model ◽  
High Morbidity ◽  
Medical Intensive Care ◽  
Poor Outcomes

AbstractAcute respiratory failure (ARF) requiring mechanical ventilation, a complicating factor in sepsis and other disorders, is associated with high morbidity and mortality. Despite its severity and prevalence, treatment options are limited. In light of accumulating evidence that mitochondrial abnormalities are common in ARF, here we applied broad spectrum quantitative and semiquantitative metabolomic analyses of serum from ARF patients to detect bioenergetic dysfunction and determine its association with survival. Plasma samples from surviving and non-surviving patients (N = 15/group) were taken at day 1 and day 3 after admission to the medical intensive care unit and, in survivors, at hospital discharge. Significant differences between survivors and non-survivors (ANOVA, 5% FDR) include bioenergetically relevant intermediates of redox cofactors nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP), increased acyl-carnitines, bile acids, and decreased acyl-glycerophosphocholines. Many metabolites associated with poor outcomes are substrates of NAD(P)-dependent enzymatic processes, while alterations in NAD cofactors rely on bioavailability of dietary B-vitamins thiamine, riboflavin and pyridoxine. Changes in the efficiency of the nicotinamide-derived cofactors’ biosynthetic pathways also associate with alterations in glutathione-dependent drug metabolism characterized by substantial differences observed in the acetaminophen metabolome. Based on these findings, a four-feature model developed with semi-quantitative and quantitative metabolomic results predicted patient outcomes with high accuracy (AUROC = 0.91). Collectively, this metabolomic endotype points to a close association between mitochondrial and bioenergetic dysfunction and mortality in human ARF, thus pointing to new pharmacologic targets to reduce mortality in this condition.

scholarly journals History of the Military Nurse Corps and the 1918 Influenza Pandemic: Lessons for the 2019 Coronavirus Pandemic

2020 ◽  
Author(s):  
Laura A Talbot ◽  
E Jeffrey Metter ◽  
Heather King
Keyword(s):  
World War I ◽  
Patient Outcomes ◽  
Influenza Pandemic ◽  
Treatment Options ◽  
Primary Therapy ◽  
World War ◽  
Military Nursing ◽  
History Of ◽  
1918 Influenza ◽  
The Military

ABSTRACT During World War I, the 1918 influenza pandemic struck the fatigued combat troops serving on the Western Front. Medical treatment options were limited; thus, skilled military nursing care was the primary therapy and the best indicator of patient outcomes. This article examines the military nursing’s role in the care of the soldiers during the 1918 flu pandemic and compares this to the 2019 coronavirus pandemic.

scholarly journals Infective endocarditis caused by HACEK group bacteria—a registry-based comparative study

2021 ◽  
Author(s):  
Anna Bläckberg ◽  
Christian Morenius ◽  
Lars Olaison ◽  
Andreas Berge ◽  
Magnus Rasmussen
Keyword(s):  
Staphylococcus Aureus ◽  
Infective Endocarditis ◽  
Mortality Rate ◽  
Haemophilus Influenzae ◽  
Comparative Study ◽  
Clinical Characteristics ◽  
Prosthetic Valve ◽  
Prosthetic Valve Endocarditis ◽  
Common Cause ◽  
Prosthetic Valves

AbstractInfective endocarditis (IE) caused by bacteria within Haemophilus (excluding Haemophilus influenzae), Aggregatibacter, Cardiobacterium, Eikenella and Kingella (HACEK) is rare. This study aimed to describe clinical features of IE caused by HACEK genera in comparison with IE due to other pathogens. Cases of IE due to HACEK were identified through the Swedish Registry of Infective Endocarditis (SRIE). Clinical characteristics of IE cases caused by HACEK were compared with cases of IE due to other pathogens reported to the same registry. Ninety-six patients with IE caused by HACEK were identified, and this corresponds to 1.8% of all IE cases. Eighty-three cases were definite endocarditis, and the mortality rate was 2%. The median age was 63 years, which was lower compared to patients with IE caused by other pathogens (66, 70 and 73 years respectively, p ≤ 0.01). Patients with IE caused by Haemophilus were younger compared to patients with IE due to Aggregatibacter (47 vs 67 years, p ≤ 0.001). Patients with IE due to HACEK exhibited longer duration from onset of symptoms to hospitalization and had more prosthetic valve endocarditis compared to patients with IE due to Staphylococcus aureus (10 vs 2 days, p ≤ 0.001, and 35 vs 14%, p ≤ 0.001). This is, to date, the largest study on IE due to HACEK. Aggregatibacter was the most common cause of IE within the group. The condition has a subacute onset and often strikes in patients with prosthetic valves, and the mortality rate is relatively low.

scholarly journals 168. Efficacy of the Novel gwt1 Inhibitor APX2039 in a Rabbit Model of cryptococcus Meningitis

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S213-S213
Author(s):  
Karen J Shaw ◽  
Charles D Giamberardino ◽  
Quinlyn A Soltow ◽  
Jennifer Tenor ◽  
Dena Toffaletti ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Oral Treatment ◽  
Treatment Options ◽  
Rabbit Model ◽  
Experimental Period ◽  
Control Group ◽  
Log10 Reduction ◽  
Research Support ◽  
Rapid Reduction ◽  
Geographical Regions

Abstract Background Cryptococcal meningitis (CM), caused primarily by Cryptococcus neoformans, is uniformly fatal if not treated. Treatment options are limited especially in resource-poor geographical regions, and mortality rates remain high despite current therapies. New oral treatment options are needed that demonstrate rapid reductions in CFU in CSF and brain tissue. APX2039 is a novel inhibitor of the fungal Gwt1 enzyme, which catalyzes an early step in glycosylphosphatidyl inositol (GPI) anchor biosynthesis. It is highly active against both C. neoformans and C. gattii and has previously demonstrated significant efficacy in a mouse delayed-treatment model of CM. CSF Fungal Burden in Rabbits Methods Male New Zealand White rabbits were inoculated with C. neoformans H99 (1.4 ×106 CFU) directly into the cisterna magna. Rabbits were immunosuppressed with cortisone acetate at 7.5 mg/kg (i.m.), starting on Day -1 relative to inoculation and then administered drug daily throughout the 14-day experimental period. Treatment was initiated on Day 2 postinfection and continued through Day 14 consisting of: 50 mg/kg APX2039 PO (BID), 80 mg/kg fluconazole (FLU) PO (QD), c) 1 mg/kg amphotericin B deoxycholate (AMB) IV (QD); and vehicle control. CSF was removed via an intracisternal tap on Days 2, 7, 10 and 14 post-infection and CFU/ml was assessed. Animals were sacrificed on Day 14 and CFU/g brain tissue was assessed. Results APX2039 demonstrated rapid reduction in CFU in both CSF and brain tissue. The range in CFU values in rabbit CSF is shown (Figure). Reductions in CFU were statistically different from the control group for all treatment groups. APX2039 was also different from both FLU and AMB and resulted in sterilization in CSF by Day 10. Brain harvested on Day 14 demonstrated a reduction in CFU/g tissue vs control of 1.8 log10 and 3.4 log10 for FLU and AMB, respectively, while a > 6 log10 reduction (tissue sterilization) was observed for APX2039. Conclusion APX2039 demonstrated potent efficacy in a rabbit model of CM. The more rapid clearance in CSF than either AMB or FLU, as well as > 6 log10 reduction in brain CFU highlights the unique properties of this drug, warranting further investigation of this molecule for the treatment of CM. Disclosures Karen J. Shaw, PhD, Amplyx (Consultant)Forge Therapeutics (Consultant) Charles D. Giamberardino, Jr., MR, Box (Shareholder) John R. Perfect, MD, amplyx (Grant/Research Support)astellas (Grant/Research Support)astellas (Grant/Research Support)

scholarly journals THU0652-HPR ONLINE EDUCATION YIELDS SIGNIFICANT GAINS IN RHEUMATOLOGISTS’ KNOWLEDGE OF BIOLOGICS AND BIOSIMILARS BUT A SUBSTANTIAL GAP REMAINS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 570.2-571
Author(s):  
A. Stan ◽  
E. Bell ◽  
P. Schoonheim ◽  
E. Mysler
Keyword(s):  
Online Education ◽  
Statistical Significance ◽  
Treatment Options ◽  
Educational Activity ◽  
Round Table Discussion ◽  
Knowledge Gain ◽  
Regulatory Requirements ◽  
Research Support ◽  
Significance Level ◽  
Post Assessment

Background:Biologics are complex proteins which have revolutionized the treatment of many serious diseases. Due to their complexity and manufacturing which involves living organisms, it is not possible to create identical versions of reference biologics, but it is possible to create biosimilar drugs. Biosimilars have the potential to yield high cost savings and expand treatment options to meet the growing demand for biological therapies.Objectives:This study assessed whether the online CME-accredited round-table-discussion titled “Understanding Biologics: from protein to clinical practice” improved physicians’ understanding of the inherent variability of biologics and what similarity means in the context of biologics as well as the analytical assessment of quality that applies to both biologics and biosimilars.Methods:Rheumatologists participated in an online CME activity (www.medscape.org/viewarticle/900121) consisting of a 30-minute video discussion between 4 experts with accompanying slides. Educational effect was assessed using a 4-question repeated pairs, pre-/post-assessment. A chi-square test was used to determine if a statistically significant improvement (P<.05 significance level) existed in the number of pre-/post-test correct responses. Cramer’s V was used to estimate the level of impact of the education. The CME activity launched on 22 Aug 2018, and the data were collected through 9 Oct 2018.Results:A total of 622 rheumatologists participated in the educational activity, and 87 completed the pre- and postassessment. Overall the activity had a signficiant impact (P<.001) on rheumatologists’ understanding of the inherent variability of biologics and the regulatory requirements for approval of a biosimilar. The Cramer’s V value of 0.186 indicates a considerable effect of the education. The average perecentage of correct responses rose from 33% pre-activity to 51% post-activity. A linked learning assessment (individual responses matched pre- and post-education) showed that 25% of learners improved their knowledge and 26% reinforced their knowledge. The change in percentage of correct responses from pre- to post-assessment achieved statistical significance (P<.05) in 2 of the 3 questions presented: (i) understanding the type of studies needed to demonstrate comparability of a biosimilar to an originator (11% at baseline; 45% post activity), (ii) understanding the type of variability considered acceptable for a biologic (46% at baseline; 63% post activity). However, no knowledge gain was observed regarding basic analytic attributes evaluated to ensure batch to batch consistency (37% at baseline; 38% post activity). Almost 45% of rheumatologists gained confidence in their ability to describe the regulatory requirements for approval of a biosimilar.Conclusion:This online CME activity significantly improved rheumatologists’ understanding of the inherent variability of complex biologic medicines and the role of analytical studies in the regulatory approval of biosimilars. However, there is room for further improving physicians’ knowledge, especially of basic analytics of biologics and biosimilars.Acknowledgments:This CME-certified activity was supported by independent funding from Sandoz.Disclosure of Interests:Adriana Stan Grant/research support from: The CME-certified activity was supported by anindependent educational grant from Sandoz., Elaine Bell: None declared, Peter Schoonheim Grant/research support from: This CME-certified activity was supported by independent funding from Sandoz., Eduardo Mysler Grant/research support from: AbbVie, Lilly, Pfizer, Roche, BMS, Sandoz, Amgen, and Janssen., Consultant of: AbbVie, Lilly, Pfizer, Roche, BMS, Sandoz, Amgen, and Janssen.

scholarly journals Establishment of a Pretreatment Nomogram to Predict the 6-Month Mortality Rate of Patients with Advanced Biliary Tract Cancers Undergoing Gemcitabine-Based Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3139
Author(s):  
Chiao-En Wu ◽  
Wen-Kuan Huang ◽  
Wen-Chi Chou ◽  
Chia-Hsun Hsieh ◽  
John Wen-Cheng Chang ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
Mortality Rate ◽  
Biliary Tract ◽  
Mortality Risk ◽  
Treatment Options ◽  
Univariate Analysis ◽  
Cytotoxic Agents ◽  
Response To Treatment ◽  
Tract Cancer ◽  
Additional Information

Background: The estimation of mortality risk among patients diagnosed with advanced cancer provides important information for clinicians and patients in clinical practice. Currently, gemcitabine-based chemotherapy regimens are the standard treatment for patients with advanced biliary tract cancer (BTC). We aimed to develop a nomogram to predict the 6-month mortality rate among patients with advanced BTC to help physicians evaluate treatment options and outcomes. Patients: We conducted a retrospective analysis to evaluate the 6-month mortality rate among patients with advanced BTC who underwent gemcitabine-based chemotherapy from 2012 to 2018. Data regarding pretreatment factors and the clinical response to treatment were collected. Univariate and multivariate analyses were performed to identify independent factors for nomogram creation. Results: A total of 202 advanced BTC patients who were treated with gemcitabine-based chemotherapy were included in this analysis. No difference in survival was identified between patients undergoing gemcitabine monotherapy and those treated with gemcitabine combined with other cytotoxic agents. The univariate analysis revealed 10 significant factors, while the multivariate analysis identified four independent factors, including gender, monocyte to lymphocyte ratio (MLR), alkaline phosphatase (ALP), and liver metastasis, which were used to establish the nomogram. The performance of this nomogram for the prediction of 6-month mortality risk was found to be promising and feasible based on logistic regression. Conclusion: A nomogram based on four independent pretreatment factors, including gender, MLR, ALP, and liver metastasis, was established to predict the 6-month mortality risk in patients with advanced BTC; it can provide clinicians and patients with additional information when evaluating treatment outcomes.

Abstract TP252: Using Hospital Door-to-Needle Times to Individualize Hospital Bypass Times in Order to Minimize Regional Onset-to-Needle Times

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Jin-Moo Lee ◽  
Andria Ford ◽  
Jo-Ann Burns ◽  
Peter Panagos
Keyword(s):  
Patient Outcomes ◽  
Treatment Options ◽  
Stroke Care ◽  
Smartphone Application ◽  
System Level ◽  
Acute Stroke Care ◽  
Web Based ◽  
Arrival Times ◽  
Get With The Guidelines ◽  
Individual Hospital

Introduction: With enhanced treatment options but limited resources, acute stroke care is becoming regionalized. Regional pre-hospital triage plans are being developed to permit bypass of certain hospitals in order to deliver patients to hospitals with higher-level resources for advanced treatment options. One of the most contentious issues in these plans is the “bypass time”_time allowed for EMS to bypass one hospital in order to transport to a hospital with presumed higher level stroke care. Hypothesis: Incorporating transport times and individual hospital door-to-needle times (DNTs) into regional pre-hospital triage bypass plans will expedite regional treatment times which may lead to improved patient outcomes at the system level. Methods: To minimize onset-to-needle times (ONTs), it is essential not only to find the fastest route to the nearest capable hospital, but to find the nearest capable hospital with the shortest DNTs. We examined specific time components comprising ONT, including Onset-to-Arrival times (OATs) and DNTs using Get-with-the-Guidelines data (GWTG), comparing the hospital with fastest DTN times (Hospital A) with that of the average in the St. Louis metropolitan area. Results: Hospital A had a mean DNT that was 20 min faster than the average St. Louis DNT (31 min vs. 51 min, p<.0.001), while OATs were not different. This 20 min advantage might be translated into a longer bypass time specifically for hospital A, to provide equivalent or faster ONTs for patients in the region. Conclusion: The incorporation of hospital DNTs into regional pre-hospital triage plans can individualize bypass times for each hospital. This practice may accelerate treatment times throughout a region, and could be trialed with the aid of web-based smartphone application that could provide EMS with important information that could minimize both transport times and DNTs.

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