scholarly journals Daptomycin treatment impacts resistance in off-target populations of vancomycin-resistant Enterococcus faecium

PLoS Biology ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. e3000987
Author(s):  
Clare L. Kinnear ◽  
Elsa Hansen ◽  
Valerie J. Morley ◽  
Kevin C. Tracy ◽  
Meghan Forstchen ◽  
...  
Keyword(s):  
Enterococcus Faecium ◽  
Evolutionary Dynamics ◽  
Temporal Dynamics ◽  
Phenotypic Diversity ◽  
Target Selection ◽  
Quantitative Measure ◽  
Target Population ◽  
Control Group ◽  
Antibiotic Exposure ◽  
Hospital System

The antimicrobial resistance crisis has persisted despite broad attempts at intervention. It has been proposed that an important driver of resistance is selection imposed on bacterial populations that are not the intended target of antimicrobial therapy. But to date, there has been limited quantitative measure of the mean and variance of resistance following antibiotic exposure. Here we focus on the important nosocomial pathogen Enterococcus faecium in a hospital system where resistance to daptomycin is evolving despite standard interventions. We hypothesized that the intravenous use of daptomycin generates off-target selection for resistance in transmissible gastrointestinal (carriage) populations of E. faecium. We performed a cohort study in which the daptomycin resistance of E. faecium isolated from rectal swabs from daptomycin-exposed patients was compared to a control group of patients exposed to linezolid, a drug with similar indications. In the daptomycin-exposed group, daptomycin resistance of E. faecium from the off-target population was on average 50% higher than resistance in the control group (n = 428 clones from 22 patients). There was also greater phenotypic diversity in daptomycin resistance within daptomycin-exposed patients. In patients where multiple samples over time were available, a wide variability in temporal dynamics were observed, from long-term maintenance of resistance to rapid return to sensitivity after daptomycin treatment stopped. Sequencing of isolates from a subset of patients supports the argument that selection occurs within patients. Our results demonstrate that off-target gastrointestinal populations rapidly respond to intravenous antibiotic exposure. Focusing on the off-target evolutionary dynamics may offer novel avenues to slow the spread of antibiotic resistance.

scholarly journals Antimicrobial treatment impacts resistance in off-target populations of a nosocomial bacterial pathogen: a case-control study

2020 ◽  
Author(s):  
Clare L. Kinnear ◽  
Elsa Hansen ◽  
Meghan Forstchen ◽  
Andrew F. Read ◽  
Robert J. Woods
Keyword(s):  
Evolutionary Dynamics ◽  
Case Control Study ◽  
Temporal Dynamics ◽  
Phenotypic Diversity ◽  
Target Selection ◽  
Case Control ◽  
Antimicrobial Treatment ◽  
Control Group ◽  
Hospital System ◽  
Control Study

AbstractThe antimicrobial resistance crisis has persisted despite broad attempts at intervention. Detailed studies of the population dynamics that lead to resistance could identify additional intervention points. An important driver of resistance in the most concerning antibiotic resistant pathogens can be selection imposed on bacterial populations that are not the intended target of antimicrobial therapy. Here we focus on the important nosocomial pathogen Enterococcus faecium in a hospital system where resistance to daptomycin is evolving despite standard interventions. We hypothesized that the intravenous use of daptomycin generates off-target selection for resistance in transmissible gastrointestinal (carriage) populations of E. faecium. We performed a case-control study in which the daptomycin resistance of E. faecium isolated from rectal swabs from daptomycin-exposed patients was compared to a control group of patients exposed to linezolid, a drug with similar indications. In the daptomycin-exposed group, daptomycin resistance of E. faecium from the off-target population was on average 50% higher than resistance in the control group (n=428 independent E. faecium clones from 22 patients). There was also greater phenotypic diversity in daptomycin resistance within daptomycin-exposed patients. Multiple samples over time were available from a subset of patients, and these demonstrate wide variability in temporal dynamics, from long-term maintenance of resistance to rapid return to sensitivity after daptomycin treatment stopped. Our results demonstrate that off-target gastrointestinal populations rapidly respond to intravenous antibiotic exposure. Gastrointestinal populations are the source for faecal transmission and so can be the driver for hospital-wide population level increases in resistance. Focusing on the off-target evolutionary dynamics may offer novel avenues to slow the spread of antibiotic resistance.

scholarly journals Antibiotics at birth and later antibiotic courses: effects on gut microbiota

2021 ◽  
Author(s):  
Sofia Ainonen ◽  
Mysore V Tejesvi ◽  
Md. Rayhan Mahmud ◽  
Niko Paalanne ◽  
Tytti Pokka ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Control Group ◽  
List Type ◽  
Antibiotic Exposure ◽  
Microbiota Composition ◽  
Long Term Effects ◽  
The Impact ◽  
Antibiotic Courses ◽  
Gut Microbiota Composition

Abstract Background Intrapartum antibiotic prophylaxis (IAP) is widely used, but the evidence of the long-term effects on the gut microbiota and subsequent health of children is limited. Here, we compared the impacts of perinatal antibiotic exposure and later courses of antibiotic courses on gut microbiota. Methods This was a prospective, controlled cohort study among 100 vaginally delivered infants with different perinatal antibiotic exposures: control (27), IAP (27), postnatal antibiotics (24), and IAP and postnatal antibiotics (22). At 1 year of age, we performed next-generation sequencing of the bacterial 16S ribosomal RNA gene of fecal samples. Results Exposure to the perinatal antibiotics had a clear impact on the gut microbiota. The abundance of the Bacteroidetes phylum was significantly higher in the control group, whereas the relative abundance of Escherichia coli was significantly lower in the control group. The impact of the perinatal antibiotics on the gut microbiota composition was greater than exposure to later courses of antibiotics (28% of participants). Conclusions Perinatal antibiotic exposure had a marked impact on the gut microbiota at the age of 1 year. The timing of the antibiotic exposure appears to be the critical factor for the changes observed in the gut microbiota. Impact Infants are commonly exposed to IAP and postnatal antibiotics, and later to courses of antibiotics during the first year of life. Perinatal antibiotics have been associated with an altered gut microbiota during the first months of life, whereas the evidence regarding the long-term impact is more limited. Perinatal antibiotic exposure had a marked impact on the infant’s gut microbiota at 1 year of age. Impact of the perinatal antibiotics on the gut microbiota composition was greater than that of the later courses of antibiotics at the age of 1 year.

Combined administration of bacteriocin- -producing, probiotic strain Enterococcus faecium CCM7420 with Eleutherococcus senticosus and their effect in rabbits

2013 ◽  
Vol 16 (4) ◽  
pp. 619-627 ◽  
Author(s):  
M. Pogány Simonová ◽  
A. Lauková ◽  
L. Chrastinová ◽  
I. Plachá ◽  
V. Strompfová ◽  
...  
Keyword(s):  
Growth Performance ◽  
Enterococcus Faecium ◽  
Average Daily Gain ◽  
Probiotic Strain ◽  
Cholesterol Concentration ◽  
Control Group ◽  
Feed Conversion ◽  
Eleutherococcus Senticosus ◽  
Commercial Diet ◽  
And Control

Abstract The effect of Enterococcus faecium CCM7420 (EF) - enterocin-producing and probiotic strain of rabbit origin, Eleutherococcus senticosus extract (ES) and their combination (ES+EF) was determined on selected bacteria in faeces and caecum content, leukocytes phagocytosis, blood biochemistry and growth performance. Ninety-six weaned rabbits were divided into 3 experimental (ES, EF, ES+EF) and control group (CG). The rabbits in the groups ES and EF+ES were fed commercial diet enriched with E. senticosus extract (30 g/100 kg feed), rabbits in groups EF and CG were fed untreated diet. The rabbits in the EF and ES+EF groups were administered with an overnight culture of E. faecium CCM7420 strain (500 μl/animal/day into water, 109 CFU/ml). The treatment period lasted 21 days. The microbiological examinations in faecal samples confirmed the presence of E. faecium CCM7420 strain. In groups EF and ES+EF, the reduction of faecal coliforms, Pseudomonas-like sp., Clostridium-like sp. and S. aureus was recorded. Leucocyte phagocytosis significantly increased in all experimental groups (P<0.0001) compared to CG. The lowest GPx values were measured in the ES+EF group. Higher total protein, triglycerides and calcium concentrations were detected in experimental groups compared to CG. The cholesterol concentration decreased in the ES group. The highest average daily gain was recorded in EF group; in ES+EF the better feed conversion ratio and no mortality was recorded. These results indicated that the dietary supplementation with the E. faecium CCM7420 and E. senticosus extract stimulate the leukocytes phagocytosis and reduces the potential pathogens in rabbits digestive tract without oxidative stress and improve the growth performance.

scholarly journals THE IMPORTANCE OF EDUCATION TO REDUCE SELF-DESTRUCTIVE NAIL HABITS

2021 ◽  
Vol 4 ◽  
pp. 491-499
Author(s):  
Ilze Upeniece ◽  
Monta Beltiņa
Keyword(s):  
Clinical Practice ◽  
General Education ◽  
Statistical Significance ◽  
Target Population ◽  
Control Group ◽  
Age Related ◽  
Nail Changes ◽  
Group 2 ◽  
And Control ◽  
Traumatic Damage

Onychophagia and onychotillomania are rarely seen in clinical practice and are considered undervalued. The study aims were to determine the prevalence of onychophagia and onychotillomania habit in the patient group with hand nail damage and control group, to determine which would be the target population to educate. Patients were interviewed about self-destructive habits. Excel and SPSS were used for data analysis. In the nail damage group, 28.6% of the respondents showed self-destructive habits and past habits – 31.4%. In the control group, the result was 22.9% and 31.4%. For 74.3% of patients the cause of nail damage was skin disease (including 61.54% of respondents with nail damage who have psoriasis), for 5.7% it was age-related nail changes, for 20% traumatic damage and for 57.14% of them it was a result of self-destructive habit. In the nail damage group both – present and past self-destructive habits are higher than in the control group, but it has no statistical significance (p=0.785). 1)The prevalence of onychophagia and onychotillomania does not differ between patients and control group. 2)General education of the population is necessary to actualize this problem, which can worsen nail changes.

scholarly journals Utilizing Pharmacy Records to Assess Antibiotic Prescribing Patterns on the Incidence of Community-Acquired Methicillin-Resistant Staphylococcus aureus Infections in Children

2007 ◽  
Vol 12 (2) ◽  
pp. 91-101
Author(s):  
Peter N. Johnson ◽  
Robert P. Rapp ◽  
Christopher T. Nelson ◽  
J.S. Butler ◽  
Sue Overman ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Therapy ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Prescribing Patterns ◽  
Control Group ◽  
Antibiotic Prescribing ◽  
Antibiotic Exposure ◽  
Pharmacy Records ◽  
Methicillin Resistant ◽  
Prior Antibiotic Therapy

OBJECTIVE To assess the effect of prior antibiotic therapy on the incidence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in children. METHODS This was a concurrent and retrospective review of antibiotic records for children &lt; 18 years of age with documented CA-MRSA infection identified between January 1, 2004, and December 31, 2005. Antibiotic records were compared against a control group. The primary outcome was the incidence of CA-MRSA using linear regression as a function of age and prior antibiotic therapy (i.e., 3 months prior to admission). Secondary objectives included a comparison of antibiotic courses and classes and a description of antibiotic susceptibilities in patients with CA-MRSA RESULTS Data from 26 patients were included. Nine out of 51 patients (18%) with CA-MRSA were included. Another 17 children were enrolled in the control group. The median age was approximately 1.75 years (0.08–14 years) in the CA-MRSA group versus 2.75 years (0.005-15 years) in the control group. A statistical difference was noted in the number of patients with prior antibiotic exposure between the CA-MRSA and control group, 8 (88.9%) versus 6 (35.3%), respectively (P = .01). Antibiotic exposure was found to be a significant independent risk factor (P = .005; 95% CI, 0.167–0.846) for the development of CA-MRSA. The interaction between antibiotic exposure and age &lt; 3 was the most significant predictor of CA-MRSA (P = .019; 95% CI, 0.139–1.40). CONCLUSIONS Prior antibiotic therapy in patients &lt; 3 years of age was associated with a significant risk of developing CA-MRSA. A comprehensive assessment of CA-MRSA patients should include objective methods of measuring prior antibiotic exposure such as pharmacy records.

scholarly journals Feasibility of an 8-week Yoga Intervention among Middle-aged and Older Adults

2020 ◽  
Vol 4 (4) ◽  
Author(s):  
Neha P. Gothe ◽  
Emily Erlenbach ◽  
Keyword(s):  
Older Adults ◽  
Adverse Events ◽  
Controlled Trial ◽  
Critical Role ◽  
Feasibility Studies ◽  
Target Population ◽  
Control Group ◽  
Middle Aged ◽  
Yoga Intervention ◽  
Enrollment Rates

Feasibility studies play a critical role in determining whether the target population is likely to engage with larger scale efficacy and effectiveness trials. Feasibility data for yoga interventions designed and conducted with older adults is limited. In this paper we present feasibility and acceptability data from an 8-week randomized controlled trial (RCT) conducted with middle aged and older adults. Participants n=118 (Mean age: 62.0 years) were randomized to either a Hatha yoga or Stretching Control group with hour long group exercise classes held 3x/week for 8 weeks. Herein we report feasibility and acceptability, including enrollment rates, attendance, attrition and adverse events, participant feedback and satisfaction data. Of the 265 adults screened, 118 were eligible and randomized. Session attendance was high for both groups (80.82 to 81.29 %) and only 10 people were lost to follow-up. Program satisfaction for both groups was high (4.8 and 4.86 out of 5) and no adverse events were reported. Participants’ feedback regarding most and least helpful aspects of the program as well as suggestions for future yoga interventions are summarized. Overall, the yoga intervention was highly feasible and acceptable. The feasibility parameters from this trial can aid researchers in estimating desired sample sizes to successfully recruit, randomize and retain older adults in short- and long-term yoga based RCTs.

scholarly journals The Genomic Ecosystem of Transposable Elements in Maize

2019 ◽  
Author(s):  
Michelle C. Stitzer ◽  
Sarah N. Anderson ◽  
Nathan M. Springer ◽  
Jeffrey Ross-Ibarra
Keyword(s):  
Transposable Elements ◽  
Evolutionary Dynamics ◽  
Phenotypic Diversity ◽  
Flowering Plant ◽  
Genome Wide ◽  
Family Level ◽  
Genomic Environment ◽  
Single Category ◽  
The Impact

Transposable elements (TEs) constitute the majority of flowering plant DNA, reflecting their tremendous success in subverting, avoiding, and surviving the defenses of their host genomes to ensure their selfish replication. More than 85% of the sequence of the maize genome can be ascribed to past transposition, providing a major contribution to the structure of the genome. Evidence from individual loci has informed our understanding of how transposition has shaped the genome, and a number of individual TE insertions have been causally linked to dramatic phenotypic changes. But genome-wide analyses in maize and other taxa have frequently represented TEs as a relatively homogeneous class of fragmentary relics of past transposition, obscuring their evolutionary history and interaction with their host genome. Using an updated annotation of structurally intact TEs in the maize reference genome, we investigate the family-level ecological and evolutionary dynamics of TEs in maize. Integrating a variety of data, from descriptors of individual TEs like coding capacity, expression, and methylation, as well as similar features of the sequence they inserted into, we model the relationship between these attributes of the genomic environment and the survival of TE copies and families. Our analyses reveal a diversity of ecological strategies of TE families, each representing the evolution of a distinct ecological niche allowing survival of the TE family. In contrast to the wholesale relegation of all TEs to a single category of junk DNA, these differences generate a rich ecology of the genome, suggesting families of TEs that coexist in time and space compete and cooperate with each other. We conclude that while the impact of transposition is highly family- and context-dependent, a family-level understanding of the ecology of TEs in the genome can refine our ability to predict the role of TEs in generating genetic and phenotypic diversity.‘Lumping our beautiful collection of transposons into a single category is a crime’-Michael R. Freeling, Mar. 10, 2017

Abstract TP376: Director, Comprehensive Stroke Program

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Michele J Patterson ◽  
Tracy Moore ◽  
Paula Cline
Keyword(s):  
Private Insurance ◽  
Retrospective Chart Review ◽  
Target Population ◽  
Community Response ◽  
Treatment Rate ◽  
Hospital System ◽  
Early Presentation ◽  
Stroke Type ◽  
Poverty Levels ◽  
Treatment Window

Background: Hospital system identified decline in Emergency Medical Services arrivals [EMS-A] and increased Private Vehicle arrivals [PVA]. Purpose: Understand community response and PVA for focused education to increase EMS-A in order to improve treatment rates and decrease disability. Methods: Retrospective chart review to evaluate age, gender, race, poverty levels, stroke type, severity, treatment rates, and outcomes of the Target Population [TP]. Results: Review of 4,264 records [2015-2018] identified 1,612 PVA and 2,652 EMS-A. The largest PVA age group, identified as TP, was age 46-65. The TP was 60% male. Hispanics comprised 59% PVA versus [v] 54% EMS-A. All other races had higher EMS-A. Those with PVA were more likely to have private insurance [39% PVA v 23% EMS-A] and more likely to have zip codes with less than 10% poverty [8% PVA v 1% EMS-A]. Those below poverty had lower PVA [6% PVA v 12% EMS-A]. Stroke type was 90% Ischemic. Eighty-nine percent of PVA had NIHSS 0-7 [NIHSS: 0=24%, 1-5=57%, 6-7=8%]. Time last known well [TLKW] for PVA NIHSS 0-7 was less than or equal to 3.5 hours in 15% and greater than 3.5 hours in 33%. Alteplase treatment rate for NIHSS 0-7 was 4% PVA v 9% EMS-A. Mechanical Endovascular Reperfusion [MER] treatment rate for NIHSS 0-7 was 0% PVA v 1% EMS-A. Discharge [DC] disposition for PVA NIHSS 0-7 showed 21% rehabilitation and 2% death or hospice. DC Modified Rankin Scale [mRS] for PVA NIHSS 0-7 was mRS 2-3 in 17% and mRS 4-5 in 10%. Conclusion: The majority of PVA were middle aged [46-65] and predominantly male. Hispanics were the only ethnic group with higher PVA v EMS-A. The TP majority lived in areas with less than 10% poverty, had private insurance, had ischemic strokes with milder deficits and presented outside the Alteplase treatment window. Treatment rates for Alteplase and MER were 50% greater for NIHSS 0-7 for EMS-A. At DC, 21% PVA with NIHSS 0-7 required rehabilitation and 27% had slight to severe disability. Identifying characteristics of the TP is helpful for focused public education to increase EMS-A and early presentation regardless of severity to increase treatment rates and decrease disability.

Use of Procalcitonin to Reduce Patients’ Exposure to Antibiotics in Intensive Care Units (PRORATA Trial)

2018 ◽  
pp. 276-281
Author(s):  
Alice Gallo De Moraes ◽  
Dante Schiavo
Keyword(s):  
Antibiotic Resistance ◽  
Intensive Care ◽  
Bacterial Infections ◽  
Clinical Case ◽  
Adverse Outcomes ◽  
Control Group ◽  
Antibiotic Exposure ◽  
Icu Patients ◽  
Study Intervention

This chapter provides a summary of the landmark study known as the PRORATA trial. Does a procalcitonin (PCT)-based strategy to treat suspected bacterial infections in ICU patients reduce antibiotic exposure without adverse outcomes? Starting with that question, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case. The study suggests that critically ill patients managed with a PCT-guided antibiotic strategy to treat suspected bacterial infections results in more antibiotic-free days than those managing patients with clinical guidelines alone. The mortality of patients in the PCT arm was non-inferior to those in the control group at day 28 and at day 60. The strategy could be beneficial for reducing antibiotic resistance in the ICU.

scholarly journals The Pre-Deal Phase of Mergers and Acquisitions: A Review and Research Agenda

2019 ◽  
Vol 46 (6) ◽  
pp. 843-878 ◽  
Author(s):  
Xena Welch ◽  
Stevo Pavićević ◽  
Thomas Keil ◽  
Tomi Laamanen
Keyword(s):  
Mergers And Acquisitions ◽  
Research Agenda ◽  
Temporal Dynamics ◽  
Target Selection ◽  
Comprehensive Analysis ◽  
Research Interest ◽  
Theoretical Base ◽  
Topic Area ◽  
High Level

Despite the long-standing research interest in the pre-deal phase of mergers and acquisitions, many important questions remain unanswered. We review and synthesize the extensive but rather fragmented research on this topic area in the fields of management, finance, accounting, and economics. We organize our review according to six themes, that is, deal initiation, target selection, bidding and negotiation, valuation and financing, announcement, and closure, which represent the main categories of activities performed during the pre-deal phase. Our review shows that most of the existing research relies on a rather high-level, simplified, and static conception of the pre-deal phase. On the basis of our review, we put forward a research agenda that calls for a more granular examination of individual activities and decisions, a more comprehensive analysis of the interplay among the different actors involved in the pre-deal phase, a better understanding of the role of the temporal dynamics, and the extension of the theoretical base from variance-based to process-based theorizing.

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