Selection of AmpC β-lactamase variants and metallo-β-lactamases leading to ceftolozane/tazobactam and ceftazidime/avibactam-resistance during treatment of MDR/XDR Pseudomonas aeruginosa infections

2021 ◽  
Author(s):  
Alba Ruedas-López ◽  
Isaac Alonso García ◽  
Cristina Lasarte-Monterrubio ◽  
Paula Guijarro-Sánchez ◽  
Eva Gato ◽  
...  
Keyword(s):  
3D Models ◽  
Resistance Mechanisms ◽  
Class 1 ◽  
Long Read ◽  
Cephalosporin Resistance ◽  
One Year ◽  
Clinical Conditions ◽  
Hybrid Assemblies ◽  
Chromosomal Mutations ◽  
The Impact

Infections caused by ceftolozane/tazobactam and ceftazidime/avibactam-resistant P. aeruginosa infections are an emerging concern. We aimed to analyze the underlying ceftolozane/tazobactam and ceftazidime/avibactam resistance mechanisms in all MDR/XDR P. aeruginosa isolates recovered during one year (2020) from patients with a documented P. aeruginosa infection. Fifteen isolates showing ceftolozane/tazobactam and ceftazidime/avibactam resistance were evaluated. Clinical conditions, previous positive cultures and β-lactams received in the previous month were reviewed for each patient. MICs were determined by broth microdilution. MLSTs and resistance mechanisms were determined using short- and long-read WGS. The impact of PDCs on β-lactam resistance was demonstrated by cloning into an ampC -deficient PAO1 derivative (PAOΔC) and construction of 3D models. Genetic support of acquired β-lactamases was determined in silico from high-quality hybrid assemblies. In most cases, the isolates were recovered after treatment with ceftolozane/tazobactam or ceftazidime/avibactam. Seven isolates from different STs owed their β-lactam resistance to chromosomal mutations and all displayed specific substitutions in PDC: Phe121Leu and Gly222Ser, Pro154Leu, Ala201Thr, Gly214Arg, ΔGly203-Glu219 and Glu219Lys. In the other eight isolates, the ST175 clone was overrepresented (6 isolates) and associated with IMP-28 and IMP-13, whereas two ST1284 isolates produced VIM-2. The cloned PDCs conferred enhanced cephalosporin resistance. 3D PDC models revealed rearrangements affecting residues involved in cephalosporin hydrolysis. Carbapenemases were chromosomal (VIM-2) or plasmid-borne (IMP-28, IMP-13), and associated with class-1 integrons located in Tn402-like transposition modules. Our findings highlight that cephalosporin/ß-lactamase inhibitors are potential selectors of MDR/XDR P. aeruginosa strains producing PDC variants or metallo-ß-lactamases. Judicious use of these agents is encouraged.

scholarly journals Effect of ceftiofur cessation and substitution with lincomycin-spectinomycin on extended-spectrum-beta-lactamase/AmpC genes and multidrug resistance in E. coli from a Canadian broiler production pyramid

2019 ◽  
Author(s):  
L. Verrette ◽  
J. M. Fairbrother ◽  
M. Boulianne
Keyword(s):  
Multidrug Resistance ◽  
Multidrug Resistant ◽  
Poultry Production ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Extended Spectrum ◽  
High Prevalence ◽  
Cephalosporin Resistance ◽  
One Year ◽  
The Impact

AbstractCeftiofur, a cephalosporin antimicrobial, was used systematically in Canadian hatcheries for many years to prevent early mortality in chicks leading to a high prevalence of cephalosporin resistance in Escherichia coli in chickens. Preventive use of ceftiofur in hatcheries ceased in 2014. We examined the effect of ceftiofur cessation and replacement with lincomycin-spectinomycin at the hatchery on the proportion of E. coli positive for extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase related genes, and on the multidrug resistance profiles of ESBL/AmpC positive E. coli in broilers and their associated breeders, at one year post-cessation. For indicator E. coli from non-enriched media, a significant decrease post-cessation in the proportion of samples harboring E. coli isolates positive for blaCMY-2 and/or blaCTX-M was observed. In contrast, following enrichment in medium containing ceftriaxone (1mg/L) to facilitate recovery of ESBL/AmpC β-lactamase producing E. coli colonies, both pre- and post-cessation, 99% of the samples harbored E. coli positive for blaCMY-2 or blaCTX-M. Flocks receiving lincomycin-spectinomycin after cessation of ceftiofur showed a significantly greater non-susceptibility to aminoglycoside, folate inhibitor, phenicol, tetracycline and possible extensively drug resistant E. coli compared to those receiving ceftiofur or no antimicrobial at hatchery. This study clearly demonstrates an initial decrease in ESBL/AmpC positive E. coli following the cessation of ceftiofur in hatchery but an increase in multidrug resistant E. coli following replacement with lincomycin-spectinomycin.ImportanceAntimicrobial resistance is a global problem. The antimicrobial ceftiofur has been used worldwide for disease prevention in poultry production resulting in a greatly increased resistance to this antimicrobial important in poultry and human medicine. Our study examines the impact of ceftiofur cessation and its replacement with the antimicrobial combination lincomycin-spectinomycin, a common practice in the industry. Our study demonstrated a decrease in ceftiofur resistance after the cessation of its use, although the resistance genes remain ubiquitous in all phases of poultry production, showing that poultry remains a reservoir for ceftiofur resistance and requiring continued vigilance. We also observed a decrease in multidrug resistance after cessation of ceftiofur although the contrary finding following use of lincomycin-spectinomycin indicates that the use of these antimicrobials should be questioned. Reduced resistance to ceftiofur in poultry may translate to better treatment efficacy, decreased morbidity, mortality, duration and cost of hospitalization in humans.

scholarly journals In Vitro Glioblastoma Models: A Journey into the Third Dimension

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2449
Author(s):  
Mayra Paolillo ◽  
Sergio Comincini ◽  
Sergio Schinelli
Keyword(s):  
Tumor Cells ◽  
Single Cell Analysis ◽  
3D Models ◽  
Primary Brain Tumor ◽  
Molecular Features ◽  
Third Dimension ◽  
One Year ◽  
The Impact

Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults, with an average survival time of about one year from initial diagnosis. In the attempt to overcome the complexity and drawbacks associated with in vivo GBM models, together with the need of developing systems dedicated to screen new potential drugs, considerable efforts have been devoted to the implementation of reliable and affordable in vitro GBM models. Recent findings on GBM molecular features, revealing a high heterogeneity between GBM cells and also between other non-tumor cells belonging to the tumoral niche, have stressed the limitations of the classical 2D cell culture systems. Recently, several novel and innovative 3D cell cultures models for GBM have been proposed and implemented. In this review, we first describe the different populations and their functional role of GBM and niche non-tumor cells that could be used in 3D models. An overview of the current available 3D in vitro systems for modeling GBM, together with their major weaknesses and strengths, is presented. Lastly, we discuss the impact of groundbreaking technologies, such as bioprinting and multi-omics single cell analysis, on the future implementation of 3D in vitro GBM models.

scholarly journals An Effectiveness Trial of STEADI in an Outpatient, Primary Care Practice

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 774-774
Author(s):  
David Rein ◽  
Madeleine Hackney ◽  
Michele Dougherty ◽  
Camille Vaughan ◽  
Laurie Imhof ◽  
...  
Keyword(s):  
Primary Care ◽  
Medication Review ◽  
Primary Care Practice ◽  
Controlled Trial ◽  
Care Practice ◽  
Strength Assessment ◽  
Randomized Controlled ◽  
Study Team ◽  
One Year ◽  
The Impact

Abstract The STEADI Options trial uses a randomized, controlled-trial design to assess the effectiveness and cost-effectiveness of the STEADI Initiative . Beginning March, 2020, we will randomize 3,000 adults ≥ 65 years of age at risk for falls seen in an Emory Clinic primary care practice to: (1) full STEADI; (2) a STEADI-derived gait, balance, and strength assessment with physical therapy referrals; (3) a STEADI-derived medication review and management; or (4) usual care. This presentation will discuss decisions made by the study team to facilitate implementation of STEADI including electronically conducting screening prior to the date of encounter, the use of dedicated nursing staff to conduct assessments, implementation of strength, balance, orthostatic hypotension, and vision testing, methods to facilitate medication review, and communication of assessment information to providers. The results from this study will be used to estimate the impact of STEADI on falls, service utilization, and costs over one year.

scholarly journals Ventricular arrhythmias in patients with functional mitral regurgitation and implantable cardiac devices: implications of mitral valve repair with Mitraclip

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Benito Gonzalez ◽  
X Freixa ◽  
C Godino ◽  
M Taramasso ◽  
R Estevez-Loureiro ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Mitral Regurgitation ◽  
Mitral Valve Repair ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Functional Mitral Regurgitation ◽  
Valve Repair ◽  
One Year ◽  
The Impact

Abstract Background Limited information has been reported regarding the impact of percutaneous mitral valve repair (PMVR) on ventricular arrhythmic (VA) burden. The aim of this study was to address the incidence of VA and appropriate antitachycardia implantable cardiac defibrillator (ICD) therapies before and after PMVR. Methods We retrospectively analyzed all consecutive patients with heart failure with reduce left ventricular ejection fraction, functional mitral regurgitation grade 3+ or 4+ and an active ICD or cardiac resynchronizer who underwent PMVR in any of the eleven recruiting centers. Only patients with complete available device VA monitoring from one-year before to one year after PMVR were included. Baseline clinical and echocardiographic characteristics were collected before PMVR and at 12-months follow-up. Results 93 patients (68.2±10.9 years old, male 88.2%) were enrolled. PMVR was successfully performed in all patients and device success at discharge was 91.4%. At 12-months follow-up, we observed a significant reduction in mitral regurgitation severity, NT-proBNP and prevalence of severe pulmonary hypertension and severe kidney disease. Patients also referred a significant improvement in NYHA functional class and showed a non-significant trend to reserve left ventricular remodeling. After PMVR a significant decrease in the incidence of non-sustained ventricular tachycardia (VT) (5.0–17.8 vs 2.7–13.5, p=0.002), sustained VT or ventricular fibrillation (0.9–2.5 vs 0.5–2.9, p=0.012) and ICD antitachycardia therapies (2.5–12.0 vs 0.9–5.0, p=0.033) were observed. Conclusion PMVR was related to a reduction in arrhythmic burden and ICD therapies in our cohort. Proportion of patients who presented ven Funding Acknowledgement Type of funding source: None

scholarly journals Infant Safe Sleep Promotion: Increasing Capacity of Child Protective Services Employees

2021 ◽  
Vol 18 (8) ◽  
pp. 4227
Author(s):  
Carolyn R. Ahlers-Schmidt ◽  
Christy Schunn ◽  
Ashley M. Hervey ◽  
Maria Torres ◽  
Cherie Sage ◽  
...  
Keyword(s):  
Infant Death ◽  
Child Protective Services ◽  
Sudden Infant Death ◽  
Sudden Infant ◽  
Protective Services ◽  
Safe Sleep ◽  
Train The Trainer ◽  
Baseline Knowledge ◽  
One Year ◽  
The Impact

Sleep-related infant deaths, including Sudden Infant Death Syndrome (SIDS), are the number one cause of death in infants between 28 days and one year of life. Nearly half of families experiencing a sleep-related infant death in Kansas were involved with the Department of Children and Families Child Protective Services (CPS), making CPS staff a priority for safe sleep training. This study assessed the impact of the two-day Kansas Infant Death and SIDS (KIDS) Network Safe Sleep Instructor (SSI) train-the-trainer program on CPS staffs’ knowledge of the American Academy of Pediatrics safe sleep recommendations. Training was attended by 43 participants, 27 (63%) of whom were employed by CPS. CPS staff had significantly lower baseline knowledge on the 10-item pretest (t = 3.33, p = 0.002), but both CPS and other attendees showed significant improvement by posttest (t = 8.53, p < 0.001 and t = 4.44, p < 0.001, respectively). Following SSI certification, CPS SSIs provided more safe sleep training to professionals than other SSIs (1051 vs. 165, respectively), and both groups of SSIs were able to significantly increase the knowledge of their trainees. Overall, the KIDS Network SSI training was successful. The innovative partnership with CPS allowed for provision of training to a group not historically targeted for safe sleep education.

scholarly journals The Impact of Energy Storage along with the Allocation of RES on the Reduction of Energy Costs Using MILP

Energies ◽  
2021 ◽  
Vol 14 (13) ◽  
pp. 3783
Author(s):  
Mateusz Andrychowicz
Keyword(s):  
Energy Storage ◽  
Mixed Integer Linear Programming ◽  
Distribution Systems ◽  
Operating Costs ◽  
Mixed Integer ◽  
Energy Costs ◽  
Power Exchange ◽  
Local Initiatives ◽  
One Year ◽  
The Impact

The paper shows a method of optimizing local initiatives in the energy sector, such as energy cooperatives and energy clusters. The aim of optimization is to determine the structure of generation sources and energy storage in order to minimize energy costs. The analysis is carried out for the time horizon of one year, with an hourly increment, taking into account various RES (wind turbines (WT), photovoltaic installations (PV), and biogas power plant (BG)) and loads (residential, commercial, and industrial). Generation sources and loads are characterized by generation/demand profiles in order to take into account their variability. The optimization was carried out taking into account the technical aspects of the operation of distribution systems, such as power flows and losses, voltage levels in nodes, and power exchange with the transmission system, and economic aspects, such as capital and fixed and variable operating costs. The method was calculated by sixteen simulation scenarios using Mixed-Integer Linear Programming (MILP).

Malnutrition and biological frailty are independent and complementary predictors of one-year mortality in women after primary angioplasty for ST-segment elevation myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Arroyo-Espliguero ◽  
M.C Viana-Llamas ◽  
A Silva-Obregon ◽  
A Estrella-Alonso ◽  
C Marian-Crespo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Mortality Rate ◽  
Primary Angioplasty ◽  
Prognostic Impact ◽  
St Segment Elevation ◽  
Segment Elevation Myocardial Infarction ◽  
Kaplan Meier ◽  
St Segment ◽  
One Year ◽  
The Impact

Abstract Background Malnutrition and sarcopenia are common features of frailty. Prevalence of frailty among ST-segment elevation myocardial infarction (STEMI) patients is higher in women than men. Purpose Assess gender-based differences in the impact of nutritional risk index (NRI) and frailty in one-year mortality rate among STEMI patients following primary angioplasty (PA). Methods Cohort of 321 consecutive patients (64 years [54–75]; 22.4% women) admitted to a general ICU after PA for STEMI. NRI was calculated as 1.519 × serum albumin (g/L) + 41.7 × (actual body weight [kg]/ideal weight [kg]). Vulnerable and moderate to severe NRI patients were those with Clinical Frailty Scale (CFS)≥4 and NRI&lt;97.5, respectively. We used Kaplan-Meier survival model. Results Baseline and mortality variables of 4 groups (NRI-/CFS-; NRI+/CFS-; NRI+/CFS- and NRI+/CFS+) are depicted in the Table. Prevalence of malnutrition, frailty or both were significantly greater in women (34.3%, 10% y 21.4%, respectively) than in men (28.9%, 2.8% y 6.0%, respectively; P&lt;0.001). Women had greater mortality rate (20.8% vs. 5.2%: OR 4.78, 95% CI, 2.15–10.60, P&lt;0.001), mainly from cardiogenic shock (P=0.003). Combination of malnutrition and frailty significantly decreased cumulative one-year survival in women (46.7% vs. 73.3% in men, P&lt;0.001) Conclusion Among STEMI patients undergoing PA, the prevalence of malnutrition and frailty are significantly higher in women than in men. NRI and frailty had an independent and complementary prognostic impact in women with STEMI. Kaplan-Meier and Cox survival curves Funding Acknowledgement Type of funding source: None

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