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].)

The RESTORE-IMI 1 phase 3 trial demonstrated the efficacy and safety of imipenem-cilastatin (IMI) combined with relebactam (REL) for treating imipenem-nonsusceptible infections. The objective of this analysis was to compare the outcomes among patients meeting eligibility requirements based on central laboratory susceptibility versus local laboratory susceptibility. Patients with serious infections caused by imipenem-nonsusceptible, colistin-susceptible, and imipenem-REL-susceptible pathogens were randomized 2:1 to IMI-REL plus placebo or colistin plus IMI for 5 to 21 days. The primary endpoint was a favorable overall response. Key endpoints included the clinical response and all-cause mortality. We compared outcomes between the primary microbiological modified intent-to-treat (mMITT) population, where eligibility was based on central laboratory susceptibility testing, and the supplemental mMITT (SmMITT) population, where eligibility was based on local, site-level testing. The SmMITT (n = 41) and MITT (n = 31) populations had similar baseline characteristics, including sex, age, illness severity, and renal function. In both analysis populations, favorable overall response rates in the IMI-REL treatment group were >70%. Favorable clinical response rates at day 28 were 71.4% for IMI-REL and 40.0% for colistin plus IMI in the mMITT population, whereas they were 75.0% for IMI-REL and 53.8% for colistin plus IMI in the SmMITT population. Day 28 all-cause mortality rates were 9.5% for IMI-REL and 30.0% for colistin plus IMI in the mMITT population, whereas they were 10.7% for IMI-REL and 23.1% for colistin plus IMI in the SmMITT population. The outcomes in the SmMITT population were generally consistent with those in the mMITT population, suggesting that outcomes may be applicable to the real-world use of IMI-REL for treating infections caused by imipenem-nonsusceptible Gram-negative pathogens. (This study has been registered at ClinicalTrials.gov under identifier NCT02452047.)

Enterococcus faecium strains are commonly resistant to vancomycin and β-lactams. In addition, E. faecium often causes biofilm-associated infections and these infections are difficult to treat. In this context, we investigated the activity of dosing regimens using daptomycin (DAP) (8, 10, 12, and 14 mg/kg of body weight/day) alone and in combination with ceftaroline (CPT), ampicillin (AMP), ertapenem (ERT), and rifampin (RIF) against 2 clinical strains of biofilm-producing vancomycin-resistant Enterococcus faecium (VREfm), namely, strains S447 and HOU503, in an in vitro biofilm model. HOU503 harbors common LiaS and LiaR substitutions, whereas S447 lacks mutations associated with the LiaFSR pathway. MIC results demonstrated that both strains were susceptible to DAP and resistant to CPT, AMP, ERT, and RIF. The 168-h pharmacokinetic/pharmacodynamic (PK/PD) CDC biofilm reactor models (simulating human antibiotic exposures) were used with titanium and polyurethane coupons to evaluate the efficacy of antibiotic combinations. DAP 12 and 14 achieved bactericidal activity against S447 but lacked such effect against HOU503. Addition of ERT and RIF enhanced DAP activity, allowing DAP 8 and 10 plus ERT or RIF to produce bactericidal activity against both strains at 168 h. While DAP 8 and 10 plus CPT improved killing, they did not reach bactericidal reduction against S447. Combination of AMP, CPT, ERT, or RIF resulted in enhanced and bactericidal activity for DAP against HOU503 at 168 h. Our data provide further support for the use of combinations of DAP with AMP, ERT, CPT, and RIF in infections caused by biofilm producing VREfm. Further research involving DAP combinations against biofilm-producing enterococci is warranted.

A 4-year surveillance of carbapenem-resistant Acinetobacter spp. isolates in Argentina identified 40 strains carrying bla_NDM-1. Genome sequencing revealed that most were Acinetobacter baumannii, whereas seven represented other Acinetobacter spp. The A. baumannii genomes were closely related, suggesting recent spread. bla_NDM-1 was located in the chromosome of A. baumannii strains and on a plasmid in non-A. baumannii strains. A resistance gene island carrying bla_PER-7 and other resistance determinants was found on a plasmid in some A. baumannii strains.

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.

In India and China, indigenous drug manufacturers market arbitrarily combined parenteral β-lactam and β-lactamase inhibitors (BL-BLIs). In these fixed-dose combinations, sulbactam or tazobactam is indiscriminately combined with parenteral cephalosporins, with BLI doses kept in ratios similar to those for the approved BL-BLIs. Such combinations have been introduced into clinical practice without mandatory drug development studies involving pharmacokinetic/pharmacodynamic, safety, and efficacy assessments being undertaken. Such unorthodox combinations compromise clinical outcomes and also potentially contribute to resistance development.

Từ gương thông minh cho phép con người đọc báo trong khi vệ sinh cá nhân, bồn tắm giúp làm giảm căng thẳng hay bồn cầu với tính năng sưởi ấm nắp ngồi... tất cả góp phần tạo nên phòng tắm tương lai tiện nghi, an toàn và thoải mái.

Chúng ta đang ở trong những ngày đầu năm 2020, một thập kỷ mới đã mở ra và đây chính là thời khắc lý tưởng để mỗi người có thể hiện thực hóa những điều mà bản thân đã ấp ủ bấy lâu. Liệu tân trang phòng tắm có phải là những gì bạn muốn làm trong năm nay?

Phòng tắm màu trắng luôn được nhiều người lựa chọn vì tạo cảm giác nhẹ nhàng, yên bình, dễ trang trí, dễ phối kết hợp với đồ nội thất. Dưới đây là những ý tưởng thiết kế phòng tắm màu trắng đơn giản mà không đơn điệu.

Bạn đã từng ao ước được đắm chìm trong không gian phòng tắm hoang dã, mộc mạc và gần gũi với thiên nhiên? Những mẫu phòng tắm lộ thiên dưới đây sẽ cho bạn thấy rằng mùa hè là khoảng thời gian lý tưởng nhất để đưa hơi thở thiên nhiên vào trong nhà.

Tôi thấy đất trên Tam Đảo ở cũng thích mà kinh doanh cũng có nhiều ý tưởng. Các bạn cho tôi hỏi giá cả đất thổ canh, thổ cư trên đó như nào ạ? Tôi tính đầu tư 1 mảnh trên đó làm nhà vườn cũng hay, gần HN, tiện cuối tuần về nghỉ dưỡng, hít thở không khí trong lành. Xin ý kiến về giá cả, về thuận lợi, khó khăn, tương lai ra sao...

Tôi có anh bạn cần mua đất đầu tư, tầm tiền 2-6 tỷ, đất ở nội thành và ngoại thành miễn ưng là xuống tiền luôn. Ai biết chỉ tôi. Xin cám ơn và hậu tạ? đt: 0868 37 0004

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Là một trong những không gian cơ bản phục vụ nhu cầu sinh hoạt gia đình nhưng phòng tắm lại chỉ chiếm một diện tích khiêm tốn trong nhà. Vì lẽ đó, nhiều gia đình thường đánh giá thấp tầm quan trọng của không gian này mà không biết rằng những sai lầm khi bài trí phòng tắm có thể tạo ra trải nghiệm không thoải mái trong suốt quá trình sử dụng.

Phòng tắm có diện tích khiêm tốn thường mang lại cảm giác ấm cúng, nhỏ xinh. Tất nhiên, phòng tắm nhỏ sẽ chỉ thật hoàn hảo nếu chúng ta lựa chọn nội thất, đồ dùng phù hợp và áp dụng chiến lược bài trí thông minh.

Giữ phòng tắm luôn sạch đẹp không hề đơn giản chút nào, đòi hỏi bạn phải dành rất nhiều thời gian, công sức. Cống thoát nước bị tắc vì tóc rụng, nấm mốc ẩm ướt, cửa phòng tắm bị bám bẩn… và vô vàn các vấn đề khó chịu khác khiến việc vệ sinh phòng tắm trở thành nỗi ám ảnh của nhiều người.

Hỏi: Tôi sinh năm 1969 (Kỷ Dậu) dự định xây nhà vào năm 2020. Tuy nhiên, tôi tìm hiểu được biết năm này tuổi tôi phạm hạn Tam tai, vậy tôi có xây nhà được không?

Đối với các hộ dân bị thu hồi đất, UBND TP.HCM sẽ hỗ trợ chi phí thuê nhà tạm cư với mức cao nhất là 24 triệu đồng/hộ/tháng.

Các công trình kiến trúc nhà ở được phân chia theo từng loại để dễ quản lý và mỗi loại nhà lại có những tiêu chuẩn riêng khi thiết kế, thi công. Chúng ta cần tìm hiểu kỹ lưỡng nhà cấp 1, 2, 3, 4, biệt thự, nhà tạm là gì, các tiêu chuẩn nhà trong xây dựng như thế nào để có những lựa chọn phù hợp.

Royal Enfield (रॉयल एनफील्ड) मोटरसाइकिल बाइकर्स की पसंद होने के साथ साथ बाइक मॉडिफाई करने वालों में भी लोकप्रिय है। देशभर में ऐसी कई स्टार्ट-अप कंपनियां खुल गई हैं जिन्हें एनफील्ड को कस्टमाइज करने में महारथ हासिल हैं।

Tech firms are making record profits but paying little tax. Now global leaders are discussing ways to make them pay their fair share

While you're going to gaming jail, you'll want to listen to our show so you know what games to bring with you. Fallout 76 has a new update, perhaps it'll be a good choice for you. Phantasy Star Online 2 had a wonderful beta, maybe it's the way to go. Unfortunately, Metal Max Xeno: Reborn was delayed so you'll have to wait a bit for that one.

To avoid arsenic contamination, many Bangladeshi households access water via private wells drilled to 300 feet or less, beneath impermeable clay layers. Such clay layers have been thought to protect groundwater in the underlying aquifers from the downward flow of contaminants. However, a new study suggests that such clay layers do not always protect against arsenic, and could even be a source of contamination in some wells.

The stranded people hail from Tamil Nadu and they were working in the United Arab Emirates.

Chennai, May 09: About 359 people arrived in Tamil Nadu early on Saturday from Dubai in two Air India flights as part of the government's Vande Bharat Mission to bring home Indian nationals stranded in various countries. Among the passengers

Chennai, May 09: Tamil Nadu government has announced some relaxations in the Coronavirus lockdown in non-containment zones from May 11. The extension includes working hours of standalone and neighbourhood shops and allowing private establishments to function with a reduced number of employees

Researchers analyzed patient data from 10 countries. The team found a correlation between low vitamin D levels and hyperactive immune systems. Vitamin D strengths innate immunity and prevents overactive immune responses. The finding could explain several mysteries, including why children are unlikely to die from COVID-19.

A new study has found an association between low average levels of vitamin D and high numbers of COVID-19 cases and mortality rates across 20 European countries.

A new set of stamps is being issued to mark the 75th anniversary of the end of the Second World War.

Thousands of firms today rushed to get "bounce back" loans of up to £50,000 to avoid going bust within weeks as the coronavirus crisis wreaked havoc in the economy.

Sasha Abramsky

The post Why Are Republicans Stampeding to Reopen? appeared first on The Nation.

Public Health England has updated its advice on vitamin D

'Never, ever, ever, ever intended to make anyone feel uncomfortable – ever. It's just not who I am'

Health experts have reissued guidelines on the supplement as the population faces more time indoors

It's a wonder ingredient – and not just for fending off illness

Marco van Ginkel has revealed local Chelsea players remain able to train at Stamford Bridge, although the club insist on individual sessions only.

Legendary centre-back Jaap Stam believes 2018 Golden Boy winner Matthijs De Ligt must stay at Juventus, stating it's the 'only way he will improve' as a player.

The Glazer family - owners of the NFL's Buccaneers and Premier League giants Manchester United - are helping in the fight against coronavirus by donating five million meals to a food rescue and distribution organisation in Tampa Bay, Florida.