Omadacycline is a broad-spectrum aminomethylcycline approved in October 2018 by the U.S. Food and Drug Administration for treating acute bacterial skin and skin structure infections and community-acquired pneumonia as both an oral and intravenous once-daily formulation. In this report, the activities of omadacycline and comparators were tested against 49,000 nonduplicate bacterial isolates collected prospectively during 2016 to 2018 from medical centers in Europe (24,500 isolates, 40 medical centers [19 countries]) and the United States (24,500 isolates, 33 medical centers [23 states and all 9 U.S. census divisions]). Omadacycline was tested by broth microdilution following the methods in Clinical and Laboratory Standards Institute document M07 (Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, 11th ed., 2018). Omadacycline (MIC_50/90, 0.12/0.25 mg/liter) inhibited 98.6% of Staphylococcus aureus isolates at ≤0.5 mg/liter, including 96.3% of methicillin-resistant S. aureus isolates and 99.8% of methicillin-susceptible S. aureus isolates. Omadacycline potency was comparable for Streptococcus pneumoniae (MIC_50/90, 0.06/0.12 mg/liter), viridans group streptococci (MIC_50/90, 0.06/0.12 mg/liter), and beta-hemolytic streptococci (MIC_50/90, 0.12/0.25 mg/liter), regardless of species and susceptibility to penicillin, macrolides, or tetracycline. Omadacycline was active against all Enterobacterales tested (MIC_50/90, 1/8 mg/liter; 87.5% of isolates were inhibited at ≤4 mg/liter) except Proteus mirabilis (MIC_50/90, 16/>32 mg/liter) and indole-positive Proteus spp. (MIC_50/90, 8/32 mg/liter) and was most active against Escherichia coli (MIC_50/90, 0.5/2 mg/liter), Klebsiella oxytoca (MIC_50/90, 1/2 mg/liter), and Citrobacter spp. (MIC_50/90, 1/4 mg/liter). Omadacycline inhibited 92.4% of Enterobacter cloacae species complex and 88.5% of Klebsiella pneumoniae isolates at ≤4 mg/liter. Omadacycline was active against Haemophilus influenzae (MIC_50/90, 0.5/1 mg/liter), regardless of β-lactamase status, and against Moraxella catarrhalis (MIC_50/90, ≤0.12/0.25 mg/liter). The potent activity of omadacycline against Gram-positive and -negative bacteria indicates that omadacycline merits further study in serious infections in which multidrug resistance and mixed Gram-positive and Gram-negative bacterial infections may be a concern.

Capsid assembly is a critical step in the hepatitis B virus (HBV) life cycle, mediated by the core protein. Core is a potential target for new antiviral therapies, the capsid assembly modulators (CAMs). JNJ-56136379 (JNJ-6379) is a novel and potent CAM currently in phase II trials. We evaluated the mechanisms of action (MOAs) and antiviral properties of JNJ-6379 in vitro. Size exclusion chromatography and electron microscopy studies demonstrated that JNJ-6379 induced the formation of morphologically intact viral capsids devoid of genomic material (primary MOA). JNJ-6379 accelerated the rate and extent of HBV capsid assembly in vitro. JNJ-6379 specifically and potently inhibited HBV replication; its median 50% effective concentration (EC₅₀) was 54 nM (HepG2.117 cells). In HBV-infected primary human hepatocytes (PHHs), JNJ-6379, when added with the viral inoculum, dose-dependently reduced extracellular HBV DNA levels (median EC₅₀ of 93 nM) and prevented covalently closed circular DNA (cccDNA) formation, leading to a dose-dependent reduction of intracellular HBV RNA levels (median EC₅₀ of 876 nM) and reduced antigen levels (secondary MOA). Adding JNJ-6379 to PHHs 4 or 5 days postinfection reduced extracellular HBV DNA and did not prevent cccDNA formation. Time-of-addition PHH studies revealed that JNJ-6379 most likely interfered with postentry processes. Collectively, these data demonstrate that JNJ-6379 has dual MOAs in the early and late steps of the HBV life cycle, which is different from the MOA of nucleos(t)ide analogues. JNJ-6379 is in development for chronic hepatitis B treatment and may translate into higher HBV functional cure rates.

The comparative efficacy of ceftazidime-avibactam and meropenem-vaborbactam for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections remains unknown. This was a multicenter, retrospective cohort study of adults with CRE infections who received ceftazidime-avibactam or meropenem-vaborbactam for ≥72 hours from February 2015 to October 2018. Patients with a localized urinary tract infection and repeat study drug exposures after the first episode were excluded. The primary endpoint was clinical success compared between treatment groups. Secondary endpoints included 30- and 90-day mortality, adverse events (AE), 90-day CRE infection recurrence, and development of resistance in patients with recurrent infection. A post hoc subgroup analysis was completed comparing patients who received ceftazidime-avibactam monotherapy, ceftazidime-avibactam combination therapy, and meropenem-vaborbactam monotherapy. A total of 131 patients were included (ceftazidime-avibactam, n = 105; meropenem-vaborbactam, n = 26), 40% of whom had bacteremia. No significant difference in clinical success was observed between groups (62% versus 69%; P = 0.49). Patients in the ceftazidime-avibactam arm received combination therapy more often than patients in the meropenem-vaborbactam arm (61% versus 15%; P < 0.01). No difference in 30- and 90-day mortality resulted, and rates of AE were similar between groups. In patients with recurrent infection, development of resistance occurred in three patients that received ceftazidime-avibactam monotherapy and in no patients in the meropenem-vaborbactam arm. Clinical success was similar between patients receiving ceftazidime-avibactam and meropenem-vaborbactam for treatment of CRE infections, despite ceftazidime-avibactam being used more often as a combination therapy. Development of resistance was more common with ceftazidime-avibactam monotherapy.

Nacubactam is a novel β-lactamase inhibitor with dual mechanisms of action as an inhibitor of serine β-lactamases (classes A and C and some class D) and an inhibitor of penicillin binding protein 2 in Enterobacteriaceae. The safety, tolerability, and pharmacokinetics of intravenous nacubactam were evaluated in single- and multiple-ascending-dose, placebo-controlled studies. Healthy participants received single ascending doses of nacubactam of 50 to 8,000 mg, multiple ascending doses of nacubactam of 1,000 to 4,000 mg every 8 h (q8h) for up to 7 days, or nacubactam of 2,000 mg plus meropenem of 2,000 mg q8h for 6 days after a 3-day lead-in period. Nacubactam was generally well tolerated, with the most frequently reported adverse events (AEs) being mild to moderate complications associated with intravenous access and headache. There was no apparent relationship between drug dose and the pattern, incidence, or severity of AEs. No clinically relevant dose-related trends were observed in laboratory safety test results. No serious AEs, dose-limiting AEs, or deaths were reported. After single or multiple doses, nacubactam pharmacokinetics appeared linear, and exposure increased in an approximately dose-proportional manner across the dose range investigated. Nacubactam was excreted largely unchanged into urine. Coadministration of nacubactam with meropenem did not significantly alter the pharmacokinetics of either drug. These findings support the continued clinical development of nacubactam and demonstrate the suitability of meropenem as a potential β-lactam partner for nacubactam. (The studies described in this paper have been registered at ClinicalTrials.gov under NCT02134834 [single ascending dose study] and NCT02972255 [multiple ascending dose study].)

Nine hundred Haemophilus influenzae clinical isolates from 83 U.S. and European medical centers were tested for susceptibility by reference broth microdilution methods against ceftolozane-tazobactam and comparators. Results were stratified by β-lactamase production and infection type. Overall, ceftolozane-tazobactam MIC_50/90 values were 0.12/0.25 mg/liter, and 99.0% of isolates were inhibited at the susceptible breakpoint of ≤0.5 mg/liter; the highest MIC value was only 2 mg/liter. Our results support using ceftolozane-tazobactam to treat H. influenzae infections.

If you have been looking for a luxury, convenient but cozy accommodation, you are right to choose The Infiniti at Riviera Point - A newly developed project of Keppel Land - a leading Singapore developer. Inspired by Hawaii's spectacular landscape, The Infiniti combines the elemen...

According to Batdongsan.com.vn’s real estate market Q3-2019, Ho Chi Minh City’s District 1 saw the highest housing listing prices in the third quarter due to limited supply.

Government of Central province Khanh Hoa has just asked a property developer to terminate 20 contracts selling apartments to foreigners as the sale was unauthorized.

Competition ushers in new era to recognise the country’s standout real estate projects and senior leaders.

Three marketing experts share their unconventional means of capturing the attention of potential homeowners of today.

Bearing in mind that maintaining a united front against the virus can bode well for the country.

Honouring real estate developers who are relentless in their pursuit to be socially and environmentally responsible.

As they implement stricter measures and distribute millions worth of donations to communities in need.

Hearing the kingdom’s cry for help, these developers are offering their resources to everyone in need.

The amended 2014 Housing Law, which took effect from July 1, 2015, allows foreign individuals and organizations to own property in Vietnam. The more "open" regulations of the Law have created new demand and momentum for the local real estate market. Here are the latest updates on Vietnam property foreign ownership that you need to know.

If you do not want to pay appraisal fee to the third party nor incur losses, here are 4 ways to determine value of a property yourself before entering a transaction.

It is important to know what you want in order to find the right rental property, even if you are only renting a property temporarily while your current home is undergoing renovation works, or if you are in the midst of moving to a new home.

When you view a property to rent, it pays to be as organised as possible. Our rental viewing checklist below should provide you with basic questions to ask and things to look out for at the property. Whether you are viewing a house or a flat, it could be your home for the foreseeable future, so be prepared and make a rational assessment of the property. staircaseAlthough you're going to be renting a house or a flat rather than buying it, remember that it will be your home for the foreseeable future. Of course you'll have an instant emotional reaction to any property, but you should balance this with a rational assessment of the potential of living in the property, including the local area and amenities, the condition of the property both inside and out and the costs that come with living in it. Obviously, your own priorities will vary depending on whether you're viewing houses, flats, studio flats or just rooms, but the checklist should act as a basic guide to help you keep all of your bases covered.

The costs of buying a property are often covered and explained by lenders, advisors and agents. However, there are also costs associated with selling your property.

To help you decide whether selling at auction is right for your property and, if so, how to go about it, we have come up with a step-by-step guide.

Normally, you put your property on the market but the estate agent is the one who actually sells it to buyers. It is a critical decision to choose the right agent and protect you from any future trouble. The questions below may help you.

When it comes to building a retirement nest egg for the future, property is still regarded as one of the safest long-term investments.

With many years of experience in field of real estate, Mr. Le Xuan Truong- CEO of Batdongsan.com.vn has shared very useful advice for those who intend to take part in this market in 2015.

With a budget of 1 billion VND, the best way for investors to get high-return and low-risk investment in Ho Chi Minh property market in 2015 is choosing one of three segments below: project land, apartment or townhouse in suburbs.

Along with the recovery of market, property investment also rebounds with new trends. Here are three new trends of property investment that become more and more popular in 2015.

“The rapid & global spread of coronavirus is a devastating reminder of the consequences of global disorder”: Tharoor

The 36th edition of the European Athletics Indoor Championships is scheduled to take place from March 5 to 7 next year in Torun, Poland.

EU states should guarantee vouchers for travel cancelled during the coronavirus pandemic and start lifting internal border restrictions in a bid to salvage some of the summer tourism season, the bloc's executive will say next week.

“Thanks to future lunar inhabitants, the 1.5 liters of liquid waste a person generates each day could become a promising by-product for space exploration,” the ESA says

Researchers find evidence of piezoelectricity in lab-grown, two-dimensional flakes of molybdenum dioxide.

A new study investigates the impact of the European Union Emissions Trading Scheme (EU ETS), the largest international cap-and-trade system for greenhouse gas emissions in the world, on power plant fuel efficiency.

Read our live coronavirus updates HERE

Read our live coronavirus updates HERE

Coronavirus: the symptoms Read live Covid-19 updates here

A potentially deadly disease affecting olive trees in Europe could take a huge economic toll in the next five decades, researchers have said.

Follow our live coronavirus updates here Coronavirus: the symptoms

2019 was the hottest year on record for Europe as global warming trends continue, major analysis has shown.

Two young children have been stabbed to death at a property in east London.

The drive to ease lockdowns across Europe intensified today as several countries set out blueprints for how to restore normality in everyday life.

The full impact of coronavirus on the UK is set to be revealed as the Government prepares to publish the country's death toll for care homes on a daily basis.

Europe has shown positive signs that it is passing the peak of its coronavirus outbreak, the World Health Organisation (WHO) has said.

People in countries across Europe are gradually regaining some old freedoms as governments start to lift their coronavirus lockdowns after many weeks.

Italians were today enjoying the chance to exercise in parks for the first time in eight weeks as their country took its first significant steps out of its coronavirus lockdown.

A veteran of the Second World War who celebrated victory in Europe with a three-day party in Burma says the lockdown commemorations for the 75th anniversary will still be a "great tribute" to those who lost their lives.

Care home workers say employers are playing "Russian roulette" with their lives as personal protective equipment (PPE) is withheld or rationed amid unclear guidance, according to a union.

The UK has fallen behind many other European countries in its response to coronavirus, a public health expert has said.

The coronavirus death toll in the UK has risen to more than 32,000 - and may now be the highest in Europe.

Boris Johnson will today come under fresh criticism over his handling of the coronavirus crisis as he faces Sir Keir Starmer for the first time during Prime Minister's Questions.

Public Health England medical director Professor Yvonne Doyle said it was "too early" to compare the UK statistics with that of other countries.

Second World War veteran and NHS fundraising champion Captain Tom Moore has recalled the day the "fearsome war in Europe" ended 75 years ago.