Tedizolid (TZD) and daptomycin (DAP) were assessed in a rat endocarditis model against Enterococcus faecalis, Enterococcus faecium (resistant to vancomycin and ampicillin), and Staphylococcus aureus. As a monotherapy, TZD for 5 days was not effective in a comparison with no-treatment controls, while DAP for 5 days was significantly effective against these bacteria. Step-down therapy (DAP for 3 days followed by TZD for 2 days) was as effective as DAP for 5 days and was comparable to 3 days of DAP plus ceftriaxone against all bacteria and to 3 days of DAP plus gentamicin against E. faecalis OG1RF.

Chromosomal resistance islands containing the methicillin resistance gene mecD (McRI_mecD) have been reported in Macrococcus caseolyticus. Here, we identified novel macrolide resistance genes in Macrococcus canis on similar elements, called McRI_msr. These elements were also integrated into the 3' end of the 30S ribosomal protein S9 gene (rpsI), delimited by characteristic attachment (att) sites, and carried a related site-specific integrase gene (int) at the 5' end. They carried novel macrolide resistance genes belonging to the msr family of ABC subfamily F (ABC-F)-type ribosomal protection protein [msr(F) and msr(H)] and the macrolide efflux mef family [mef(D)]. Highly related mef(D)-msr(F) fragments were found on diverse McRI_msr elements in M. canis, M. caseolyticus, and Staphylococcus aureus. Another McRI_msr-like element identified in an M. canis strain lacked the classical att site at the 3' end and carried the msr(H) gene but no neighboring mef gene. The expression of the novel resistance genes in S. aureus resulted in a low-to-moderate increase in the MIC of erythromycin but not streptogramin B. In the mef(D)-msr(F) operon, the msr(F) gene was shown to be the crucial determinant for macrolide resistance. The detection of circular forms of McRI_msr and the mef(D)-msr(F) fragment suggested mobility of both the island and the resistance gene subunit. The discovery of McRI_msr in different Macrococcus species and S. aureus indicates that these islands have a potential for dissemination of antibiotic resistance within the Staphylococcaceae family.

In patients with renal impairment (n = 22 of 39), the median serum concentrations of linezolid, PNU-142300, and PNU-142586 were 1.6-, 3.3-, 2.8-fold higher, respectively, than in patients without renal impairment. Metabolite concentrations in paired samples were poorly correlated with linezolid concentrations (r² = 0.26 for PNU-142300 and 0.06 for PNU-142586). Linezolid and its metabolites share potential toxicophores that deserve characterization to mitigate higher myelosuppression risk in patients with renal impairment.

HER2-targeted therapies are approved only for HER2-positive breast and gastric cancers. We assessed the safety/tolerability and activity of the novel HER2-targeted antibody–drug conjugate trastuzumab deruxtecan (T-DXd) in 60 patients with pretreated, HER2-expressing (IHC ≥ 1+), non-breast/non-gastric or HER2-mutant solid tumors from a phase I trial (NCT02564900). Most common (>50%) treatment-emergent adverse events (TEAE) were nausea, decreased appetite, and vomiting. Two drug-related TEAEs were associated with fatal outcomes. The confirmed objective response rate (ORR) was 28.3% (17/60). Median progression-free survival (PFS) was 7.2 [95% confidence interval (CI), 4.8–11.1] months. In HER2-mutant non–small cell lung cancer (NSCLC), ORR was 72.7% (8/11), and median PFS was 11.3 (95% CI, 8.1–14.3) months. Confirmed responses were observed in six tumor types, including HER2-expressing NSCLC, colorectal cancer, salivary gland cancer, biliary tract cancer, endometrial cancer, and HER2-mutant NSCLC and breast cancer. Results suggest T-DXd holds promise for HER2-expressing/mutant solid tumors.

BRITAIN'S summer holiday destinations will face some of the biggest economic hits of the coronavirus pandemic with fears of massive job losses in coastal communities, a study has claimed.

Two stars in the constellation Sagitta are predicted to smash together in the year 2083, producing an explosion that will outshine every star in the sky

The topography and bathymetry payload for UAV

This is the Popcorn Popping Lid with Butter Vents available from Uncommon Goods ($11). You just fill a microwave-safe 10-inch bowl with your choice of popping corn, set the lid on top, add a pat of butter to each of the lid's butter vents, and let the microwaving begin! Of course if you're anything like me you'll balance as much butter as you can atop each of those vents because, I don't know if you knew this about me, but I love butter. I don't really like it cold but *microwave beeping* sometimes when I'm really feeling down I'll just melt two sticks and drink it. Keep going for a couple more shots because they exist.

The rate of new coronavirus cases is dropping in Australia, largely due to strict travel restrictions, but complacency could cause the virus to get out of hand

Congratulations to Drake, who scores the Official Chart double this week as his Dark Lane Demo Tapes mixtape and song Toosie Slide claim Number 1 on the Official Albums and Singles Charts.

Alphabet Inc's Google said on Friday it has asked employees to take a day off on May 22, to address work-from-home-related burnout during the coronavirus pandemic.

Temperatures in parts of Britain are likely to soar to 24C over the Easter Bank Holiday weekend, but the sunshine could be interrupted by some April showers.

Follow our live Covid-19 updates HERE Coronavirus: The symptoms

Brits should not book summer holidays because there is no end in sight to the lockdown, the Government has suggested.

The US state of Missouri is suing the Chinese government over its handling of the coronavirus as Beijing calls for solidarity and less "finger pointing" during the pandemic.

Retailer also doubles staff discounts and commits to guaranteeing time off for employees over Christmas period

Greece's tourism minister today told Britons he wants them to holiday in his country this summer as he declared they could be safer there than here.

English schools will reopen after coronavirus lockdown in a "phased manner", the Education Secretary confirmed.

The UK is braced for a wet weekend with sunny spells as temperatures drop ahead of the May Bank Holiday.

Britons will enjoy another mini heatwave as temperatures soar to an unseasonably high 25C just in time for the Bank Holiday weekend.

Brits are set to bask in two days of glorious sunshine over the May Bank Holiday weekend, with temperatures creeping up to 26C.

Mayor Sadiq Khan today made an urgent appeal to Londoners not to relax their "monumental effort" to beat coronavirus as the death toll in the capital's hospitals rose to 5,414.

Brits have been urged to stick to the coronavirus lockdown rules over the Bank Holiday weekend as temperatures are set to soar.

Cabinet Secretary Oliver Dowden admitted on Friday morning that the lockdown is facing a major test from the sunny weekend ahead.

For the first time, Virgin Galactic's SpaceShipTwo rocket plane flew free in the skies over New Mexico's Spaceport America, its new base of operations. The SpaceShipTwo plane, known as VSS Unity, has made rocket-powered flights beyond the 50-mile space milestone during tests at California's Mojave Air and Space Port, but today's unpowered test flight was the first to be flown from Spaceport America. "Today's VSS Unity flight is another exciting milestone for Virgin Galactic's progress in New Mexico," Dan Hicks, executive director of the New Mexico Spaceport Authority, said in a news release. "We are extremely happy and proud of… Read More

Meltwater caused a 500-metre slab of ice to cascade down an Alaskan valley — and researchers say warmer summers are making similar events more likely

John Nichols

The post Bernie Sanders Reflects on the Power of International Solidarity appeared first on The Nation.

Not once, but twice

He invited Sylvester Stallone and Arnold Schwarzenegger to also take part.

Period dramas, real life spycraft thrills, epic stadium tours and freestyle rap battles all feature.

From accidentally making money due to currency fluctuations, to paying down debt, for some Australians cancelled overseas trips have had surprising windfalls

From June 2018 to June 2019, the Australian Bureau of Statistics says Australians made a record 11.3 million trips overseas – double the number of trips just 10 years ago. In the wake of the Covid-19 pandemic, millions of Australians have been forced to cancel or alter their international travel plans.

This has left many Australians struggling to get refunds from travel providers. Flight Centre was charging $300 in processing fees per person, in some cases leading to fees that cost more than the value of the refund, until the Australian Competition and Consumer Commission stepped in and threatened legal action, causing the company to waive fees for trips cancelled by travel providers. The ACCC also warned travel providers against retroactively changing their cancellation policies after tour companies including Topdeck and Intrepid attempted to retrospectively apply updated refund policies that would force customers to take credit rather than cash for cancelled trips.

Price said her 'phobia of water' made things difficult during the tough course

The best bit? It's completely free

There isn't long to wait until the next Bank Holiday

There isn't long to wait until the next Bank Holiday

Lizzie Edmonds speaks to travel expert Simon Calder about whether we should book summer holidays and how travel will be different

Manchester United star Paul Pogba has opened up on his injury frustration, but says his time on the sidelines has reminded him how much he loves football.

Arsenal's former transfer chief Dick Law has revealed just how close the club came to signing Leicester City striker Jamie Vardy.

Barcelona head coach Quique Setien has lifted the lid on his side's pursuit of Inter Milan star Lautaro Martinez.

The artists deliver slow beats and fast cars.

From gift-card rackets to online fraud, consumers are under near-constant assault amid what some analysts are calling the country's first-ever trillion-dollar holiday season.

Resist the urge to sunbath and socialise despite hints from the PM lockdown might be eased soon, Dominic Raab said.

Since the 1970s, the Degenhardts dreamed of retiring to Gerroa. Their dream became a reality — but retirement got tougher this month when they were told their supposedly guaranteed monthly income would not be paid until July due to coronavirus.

Jobless international hospitality workers deemed ineligible for the Federal Government's JobKeeper and JobSeeker programs are "heartbroken" at their treatment and turning to restaurants providing free meals during the coronavirus pandemic.

The major online platforms say rental listings are up 8-10 per cent compared to last year, as thousands of Airbnbs and other short-term rentals are expected to move to the long-term market as coronavirus halts travel.