Omadacycline, a novel aminomethylcycline antibiotic with activity against Gram-positive and -negative organisms, including tetracycline-resistant pathogens, received FDA approval in October, 2018 for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). A previously-developed population pharmacokinetic (PK) model based on Phase 1 intravenous and oral PK data was refined using data from infected patients. Data from 10 Phase 1 studies used to develop the previous model were pooled with data from three additional Phase 1 studies, a Phase 1b uncomplicated urinary tract infection study, one Phase 3 CABP study, and two Phase 3 ABSSSI studies. The final population PK model was a three-compartment model with first-order absorption using transit compartments to account for absorption delay following oral dosing and first-order elimination. Epithelial lining fluid (ELF) concentrations were modeled as a sub-compartment of the first peripheral compartment. A food effect on oral bioavailability was included in the model. Sex was the only significant covariate identified, with 15.6% lower clearance for females relative to males. Goodness-of-fit diagnostics indicated a precise and unbiased fit to the data. The final model, which was robust in its ability to predict plasma and ELF exposures following omadacycline administration, was also able to predict the central tendency and variability in concentration-time profiles using an external Phase 3 ABSSSI dataset. A population PK model, which described omadacycline PK in healthy subjects and infected patients, was developed and subsequently used to support pharmacokinetic-pharmacodynamic (PK-PD) and PK-PD target attainment assessments.

Linezolid has strong antimicrobial activity against the multidrug-resistant (MDR) strains of Mycobacterium tuberculosis. Little is known about the distribution of linezolid in tuberculosis (TB) lesions in patients with MDR-TB. The aim of this study is to evaluate the distribution of linezolid in TB lesions in patients with spinal MDR-TB. Nine patients with spinal MDR-TB were enrolled prospectively from August 2019 to February 2020. The patients received a linezolid-containing anti-TB treatment regimen and needed surgery for the removal of TB lesions. During the operation, nine blood samples, eight diseased bone tissue samples, seven pus samples and four granulation tissue samples were collected simultaneously and 2 h after the oral administration of 600 mg of linezolid. Linezolid concentrations in plasma, diseased bone tissue, pus, and granulation tissue samples were subjected to high-performance liquid chromatography–tandem mass spectrometry. At sample collection, the mean concentrations of linezolid in plasma, diseased bone tissue, pus, and granulation tissue samples of the nine patients were 11.14 ± 5.82, 5.94 ± 4.27, 11.09 ± 4.58, 14.08 ± 10.61 mg/L, respectively. The mean ratios of linezolid concentration in diseased bone/plasma, pus/plasma, and granulation/plasma were 53.84%, 91.69%, and 103.57%, respectively. The mean ratios of linezolid concentration in pus/plasma and granulation/plasma were higher than those in diseased bone/plasma, and the difference was statistically significant (t =-2.810, p = 0.015; t =-4.901, p = 0.001). In conclusion, linezolid had different concentration distributions in different types of TB infected tissues in patients with spinal MDR-TB.

Treatment of exacerbations of chronic Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) is highly challenging due to hypermutability, biofilm formation and an increased risk of resistance emergence. We evaluated the impact of ciprofloxacin and meropenem as monotherapy and in combination in the dynamic in vitro CDC biofilm reactor (CBR). Two hypermutable P. aeruginosa strains, PAOmutS (MIC_{ciprofloxacin} 0.25 mg/L, MIC_meropenem 2 mg/L) and CW44 (MIC_{ciprofloxacin} 0.5 mg/L, MIC_meropenem 4 mg/L), were investigated for 120h. Concentration-time profiles achievable in epithelial lining fluid (ELF) following FDA-approved doses were simulated in the CBR. Treatments were ciprofloxacin 0.4g every 8h as 1h-infusions (80% ELF penetration), meropenem 6 g/day as continuous infusion (CI; 30% and 60% ELF penetration) and their combinations. Counts of total and less-susceptible planktonic and biofilm bacteria and MICs were determined. Antibiotic concentrations were quantified by UHPLC-PDA. For both strains, all monotherapies failed with substantial regrowth and resistance of planktonic (≥8log₁₀ CFU/mL) and biofilm (>8log₁₀ CFU/cm²) bacteria at 120h (MIC_{ciprofloxacin} up to 8 mg/L, MIC_meropenem up to 64 mg/L). Both combination treatments demonstrated synergistic bacterial killing of planktonic and biofilm bacteria of both strains from ~48h onwards and suppressed regrowth to ≤4log₁₀ CFU/mL and ≤6log₁₀ CFU/cm² at 120h. Overall, both combination treatments suppressed amplification of resistance of planktonic bacteria for both strains, and biofilm bacteria for CW44. The combination with meropenem at 60% ELF penetration also suppressed amplification of resistance of biofilm bacteria for PAOmutS. Thus, combination treatment demonstrated synergistic bacterial killing and resistance suppression against difficult-to-treat hypermutable P. aeruginosa strains.

The off-label use of third generation cephalosporin (3GC) during in ovo vaccination or vaccination of newly hatched chicks, was a common practice worldwide. CMY-2-producing Escherichia coli have been disseminated among broiler production. The objectives of this study were to determine the epidemiological linkage of bla_CMY-2-positive plasmids among broilers both within and outside Japan because grandparent stock and parent stock were imported in Japan. We examined the whole genome sequences of 132 3GC-resistant E. coli isolates collected from healthy broilers during 2002-2014. The predominant 3GC-resistance gene was bla_CMY-2, which was detected in the plasmids of 87 (65.9%) isolates. The main plasmid replicon types were IncI1-I (n=21; 24.1%), IncI (n=12; 13.8%), IncB/O/K/Z (n=28; 32.2%), and IncC (n=22; 25.3%). Those plasmids were subjected to gene clustering and network analyses and plasmid multi-locus sequence typing (pMLST). The chromosomal DNA of isolates was subjected to MLST and single nucleotide variant (SNV)-based phylogenetic analysis.

MLST and SNV-based phylogenetic analysis revealed high diversity of E. coli isolates. ST429 harboring bla_CMY-2-positive IncB/O/K/Z was closely related to isolates from broiler in Germany harboring bla_CMY-2-positive IncB/O/K/Z. pST55-IncI and pST12-IncI1-I and pST3-IncC were prevalent in western Japan. pST12-IncI1-I and pST3-IncC were closely related to those detected in E. coli isolates from chicken in American continent, whereas 26 IncB/O/K/Z were related to those in Europe. These data will be useful to reveal the whole picture of transmission of CMY-2-producing bacteria in and out of Japan.

Background

Optimal concentrations of unbound antimicrobials are essential for maximum microbiological effect. Although hypoalbuminemia and albumin fluid resuscitation are common in critical care, the effects of different albumin concentrations on the unbound concentrations of highly protein-bound antimicrobials are not known. The aim of this study was to compare effects of different albumin states on total and unbound concentrations of ertapenem and ceftriaxone using an ovine model.

Methods

Design

Prospective, three phase intervention observational study.

Subjects

Healthy Merino sheep.

Interventions

Eight sheep were subject to three experimental phases; normoalbuminemia, hypoalbuminemia using plasmapheresis and albumin replacement using a 25% albumin solution. In each phase, ceftriaxone 40 mg/kg and ertapenem 15 mg/kg were given intravenously. Blood samples were collected at pre-defined intervals and analyzed using an ultra-high-performance liquid chromatography tandem mass spectrometry method. Pharmacokinetic parameters such as area under the curve (AUC_0-24), plasma clearance (CL) and apparent volume of distribution in the terminal phase (V_d) were estimated and compared between the phases.

Results

The protein and albumin concentrations were significantly different between phases. Hypoalbuminemia resulted in a significantly lower AUC_0-24 and higher CL of total and unbound concentrations of ceftriaxone compared to the other phases. Whereas albumin replacement led to higher AUC_0-24 and lower CL compared to other phases for both drugs. The V_d for total drug concentrations for both drugs were significantly lower with albumin replacement.

Conclusions

For highly protein-bound drugs such as ceftriaxone and ertapenem, both hypoalbuminemia and albumin replacement may affect unbound drug exposure.

Deep and lasting learning can best come from the relationship between teachers and their students.

The U.S. education system isn't adequately preparing students to use technology for problem-solving, according to a newly released analysis.

The "elephant in the room" has everything to do with technology but is not really about technology at all.

Elizabeth Stringer Keefe, Becky Shiring, Katie Robinson, Dr. Sonny Magana and Dr. Monica Burns contribute their suggestions on using tech to differentiate instruction.

Second year teacher, Christine Pinto, shares some reasons she integrates technology in her classroom.

Writing, reading, focusing, and remembering have all been transformed in ways we don't yet fully understand, writes psychologist Elias Aboujaoude.

Although educational apps for preschoolers abound, many don't include sound teaching strategies, says a new study in the journal Learning, Media and Technology.

The lack of access to technology and internet connectivity at home is especially severe among poor, rural, and minority students, according to a new survey from ACT's nonprofit Center for Equity in Learning.

One-to-one technology programs may boostmath scores over time, finds a new study in the Educational Evaluation and Policy Analysis journal.

If we truly want educational technology to take root in schools and finally live up to the promise we've been expecting for more than a decade, schools need to develop a cadre of well-trained tech instructional coaches.

More than two-thirds of districts are very confident in their networks' ability to support a digital device for every student, and nearly a quarter of districts now average two devices for each student, finds the latest annual report of the Consortium for School Networking.

A massive international analysis finds more screen time is associated with a lower sense of well-being among teenagers, but the effects are too small to require policy changes, according to a study in the journal Nature Human Behavior.

When it comes to a key international test, there's little evidence that technology use benefits student scores and some evidence that it could drag them down, according to a new report by the nonprofit Reboot Foundation.

Anne Jenks, Michelle Shory, Ed.S, Irina V. McGrath, Ph.D, Kim Jaxon, Dr. Beth Gotcher, Elizabeth Stringer Keefe, Ph.D., and Keisha Rembert share their suggestions for using tech effectively in class.

From blended learning to computerized testing, digital and online technologies are reshaping the classroom experience for millions of students.

Yuanyuan Dong
Apr 8, 2020; 0:peds.2020-0702v2-e20200702
ARTICLES

Comixology Unlimited lets you dive into more than 20,000 digital comics for just $5.99 per month. Make the most of your subscription by starting with these 10 titles.

The Synology DiskStation DS419slim is a small but powerful four-bay network-attached storage device that offers many of the same features found on bigger, more expensive models.

The Logitech C920 1080p webcam is back down to its Prime Day price, the 65-inch Vizio P-Series Quantum 4K TV is on sale for less than $1,000, and you can grab the new Dell Inspiron 15 5000 plus a $100 Visa prepaid card for just $600.

Two Penn State University Libraries employees at Berks Thun Library, Penn State Berks, have been awarded the American Library Association’s 2020 Emerging Technologies Section 2020 Best Emerging Technology Application (BETA) Award, which recognizes a technology application that directly benefits library users.

Douglas K. Richardson
Mar 1, 1993; 91:617-623
ARTICLES

Paul W. Newacheck
Jul 1, 1998; 102:117-123
ARTICLES

A Penn State Abington faculty member is teaching students enrolled to integrate the content into their daily lives to help them manage the impact of the coronavirus.

Senior Steven Shalamanda began his education at Penn State Schuylkill knowing he was interested in becoming an optometrist. But it was this high-achieving biology student’s internship with a local practice that affirmed his vision for the future. In fall 2020, Shalamanda will begin his doctor of optometry program at the Pennsylvania College of Optometry.

In a study published in the latest Proceedings of Computer-Human Interaction, a team of Penn State researchers identified a dozen subtle — but powerful — reasons that may shed light on why people talk a good game about privacy, but fail to follow up in real life.

A multi-disciplinary collaborative relationship, developed between Penn State EMS Energy Institute researchers and a Pittsburgh-based start-up company, may hold the answer to reducing global greenhouse gas (GHG) emissions while also paving the way to disrupt the chemical and material industries.

When she began the biology program at Penn State Schuylkill, senior Dominique Varra thought she wanted to study plants. But after conducting field research studying gray catbirds with Luke Redmond, assistant professor of biology, she has discovered a passion for ornithology. And all of her accomplishments have inspired the next generation of scientists, chiefly her five-year-old daughter Hayden, who hopes to follow in her mother’s footsteps.

As the two big groups of states craft common-assessment systems, experts warn that the smallest details could undermine their work.

Penn State Beaver students will give a special performance of Eve Ensler’s "The Vagina Monologues" at 5 p.m. Feb. 13 in the Penn State Beaver auditorium. The event is open to the public.

Penn State faculty are going beyond using traditional video in their courses by incorporating virtual-reality immersive experiences. They are discovering how those experiences help enhance active learning and focus students' attention on critical lessons in their courses.

The International Crisis Group congratulates the members of the Tunisian National Dialogue Quartet as this year’s recipient of the Nobel Peace Prize. It is an apt recognition of its achievement in allowing the spirit of inclusion and compromise to triumph over the polarisation and violence that has been all too prevalent in the region, and of the central role civil society can play at moments of crisis.

On Friday, USA Swimming CEO Chuck Wielgus offered a formal apology for not doing more to prevent sexual abuse by coaches.

An initiative to improve the use of apps and mobile technology in the instruction of special education students finds that teachers aren't receiving the professional development they want.

Today, 98% of households with 2- to 8-year-old children include a mobile device, like smartphones, tablets, and iPods or other smart-mobile devices, an increase from 75% in 2013. We are really connected, but not connecting at all.

034 - Wednesday 26 June 2013 at 11.30 at the Pavillon Cambon Capucines in Paris

A Scottish Parliament Committee will take evidence from a leading microbiologist, Professor Hugh Pennington, as it begins its scrutiny of the Government’s response to COVID-19.

Regulation moves at a snail's pace, so it's up to CEOs, executives, and employees to reject projects that put profit over privacy. Clearview AI facial-recognition tech is just the latest example of 'innovation' that could quickly get out of hand.

Source: www.youtube.com - Wednesday, May 06, 2020

Four top European players feature in the first episode of UEFA's new weekly vlog series designed to increase the visibility of women's football to teenage girls.

UEFA's ground-breaking weekly vlog Press Play has now had over three million views on the Together #WePlayStrong Youtube channel.