Clostridioides difficile, the leading cause of nosocomial infections, is an urgent health threat worldwide. The increased incidence and severity of disease, the high recurrence rates, and the dearth of effective anticlostridial drugs have created an urgent need for new therapeutic agents. In an effort to discover new drugs for treatment of Clostridioides difficile infections (CDIs), we investigated a panel of FDA-approved antiparasitic drugs against C. difficile and identified diiodohydroxyquinoline (DIHQ), an FDA-approved oral antiamoebic drug. DIHQ exhibited potent activity against 39 C. difficile isolates, inhibiting growth of 50% and 90% of these isolates at the concentrations of 0.5 μg/mL and 2 μg/mL, respectively. In a time-kill assay, DIHQ was superior to vancomycin and metronidazole, reducing a high bacterial inoculum by 3-log₁₀ within six hours. Furthermore, DIHQ reacted synergistically with vancomycin and metronidazole against C. difficile in vitro. Moreover, at subinhibitory concentrations, DIHQ was superior to vancomycin and metronidazole in inhibiting two key virulence factors of C. difficile, toxin production and spore formation. Additionally, DIHQ did not inhibit growth of key species that compose the host intestinal microbiota, such as Bacteroides, Bifidobacterium and Lactobacillus spp. Collectively, our results indicate that DIHQ is a promising anticlostridial drug that warrants further investigation as a new therapeutic for CDIs.

Omadacycline is a novel aminomethylcycline with activity against Gram-positive and -negative organisms, including Haemophilus influenzae, which is one of the leading causes of community-acquired bacterial pneumonia (CABP). The evaluation of antimicrobial agents against H. influenzae using standard murine infection models is challenging due to the low pathogenicity of this species in mice. Therefore, 24-hour dose-ranging studies using a one-compartment in vitro infection model were undertaken with the goal of characterizing the magnitude of the ratio of the area under the concentration-time curve (AUC) to the MIC (AUC/MIC ratio) associated with efficacy for a panel of five clinical H. influenzae isolates. These five isolates, which had MIC values of 1 or 2 mg/L, were exposed to omadacycline total-drug epithelial lining fluid (ELF) concentration-time profiles based on those observed in healthy volunteers following intravenous omadacycline administration. Relationships between change in log₁₀ colony forming units (CFU) from baseline at 24 hours and total-drug ELF AUC/MIC ratio for each isolate and the isolates pooled together were evaluated using Hill-type models and non-linear least squares regression. As evidenced by the high coefficient of determination (r²) of 0.88 to 0.98, total-drug ELF AUC/MIC ratio described the data well for each isolate and the isolates pooled together. The median total-drug ELF AUC/MIC ratio associated with net bacterial stasis and 1- and 2-log₁₀ CFU/mL reductions from baseline at 24 hours was 6.91, 8.91, and 11.1, respectively. These data were useful to support the omadacycline dosing regimens selected for the treatment of patients with CABP, as well as susceptibility breakpoints for H. influenzae.

Tedizolid has demonstrated its efficacy and safety in clinical trials, however, data concerning its tolerability in long-term treatments is scarce. The aim of the study was to assess the indications and to describe the long-term safety profile of tedizolid.

A multicentric, retrospective study of patients who received tedizolid for more than 6-days was conducted. Adverse events (AEs) were identified from patients' medical records and laboratory data. The World Health Organization causality categories were used to discern AEs probably associated with tedizolid.

Eighty-one patients, treated with tedizolid 200mg once-daily for a median (IQR) duration of 28 (14-59) days, were included, 36 (44.4%) had previously received linezolid. Most common reasons for selecting tedizolid were to avoid linezolid potential toxicities or interactions (53.1%) or due to previous linezolid-related toxicities (27.2%). Most common indications were off-label, including prosthetic joint infections, osteomyelitis and respiratory infections (77.8%). Overall, 9/81 patients (11.1%) experienced a probably associated AE. Two patients (2.5%) developed gastrointestinal disorders, 1 (1.2%) anemia and 6 thrombocytopenia (7.4%) after a median (IQR) duration of treatment of 26.5 (17-58.5) days. Four (5%) patients discontinued tedizolid due to AEs. Among 23 patients with chronic renal failure (CRF) the rate of mielotoxicity was 17.4% and only 8.7% had to stop tedizolid and 20 out of 22 with previous linezolid-associated toxicity had no AE.

Long-term tedizolid treatments had good tolerance with rates of gastrointestinal AE and hematological toxicity lower than those reported with linezolid, particularly in patients with CRF and in those with a previous history of linezolid-associated toxicity.

Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are associated with substantial morbidity and mortality. Monotherapy with first-line antimicrobials such as vancomycin (VAN; glycopeptide) and daptomycin (DAP; lipopeptide) are inadequate in some cases due to reduced antibiotic susceptibilities or therapeutic failure. In recent years, β-lactam antibiotics have emerged as a potential option for combination therapy with VAN/DAP that may meet an unmet therapeutic need for MRSA BSI. Ceftaroline (CPT), the only commercially available β-lactam in the United States with intrinsic in vitro activity against MRSA, has been increasingly studied in the setting of VAN and DAP failures. Novel combinations of first-line agents (VAN and DAP) with β-lactams have been the subject of many recent investigations due to in vitro findings such as the "see-saw effect", where β-lactam susceptibility may be improved in the presence of decreased glycopeptide and lipopeptide susceptibility. The combination of CPT and DAP, in particular, has become the focus of many scientific evaluations, due to intrinsic anti-MRSA activities and potent in vitro synergistic activity against various MRSA strains. This article reviews the available literature describing these innovative therapeutic approaches for MRSA BSI, focusing on preclinical and clinical studies, and evaluates the potential benefits and limitations of each strategy.

The currently unfolding coronavirus pandemic threatens health systems and economies worldwide....

A case of M. leprae rifampicin resistance after irregular anti-leprosy treatments since 1971 is reported. Whole-genome sequencing from four longitudinal samples indicated relapse due to acquired rifampicin resistance and not to reinfection with another strain. A putative compensatory mutation in rpoC was also detected. Clinical improvement was achieved using an alternative therapy.

Exploring different ways of minimising linezolid toxicity without compromising efficacy is a major quest in the treatment of drug resistant tuberculosis (TB)....

We thank Kim and colleagues for their interest in our study....

Funders have been both fast and thoughtful about how to work with national and local partners to listen to needs from the field, identify best practices, and deploy resources quickly, says Celine Coggins.

BACKGROUND AND OBJECTIVES:

Antibiotic therapy is often prescribed for suspected community-acquired pneumonia (CAP) in children despite a lack of knowledge of causative pathogen. Our objective in this study was to investigate the association between antibiotic prescription and treatment failure in children with suspected CAP who are discharged from the hospital emergency department (ED).

Two Erling Braut Haaland strikes have given Dortmund an advantage to take to Paris, although Neymar's away goal could prove crucial.

Penn State Health has enrolled its first COVID-19 patient into an experimental treatment program called convalescent plasma therapy.

Matthew J. Lipshaw
Apr 1, 2020; 145:e20193138-e20193138
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Don't wait until you have a large amount of money to invest: the key to building wealth is just starting somewhere and letting your returns generate over time, says Ebrahim Moola of Bobats Wealth Solutions.

By the end of February, most taxpayers are looking for every opportunity to reduce their tax liabilities.

The "scare" reaction in the markets due to the coronavirus pandemic, has removed "froth" and returned risk markets to much fairer valuations, says an investment expert.

Hazleton native Megan Bobish has joined the Penn State Hazleton Athletics Department as the newest member of its team.

When the novel coronavirus pandemic prompted the transition to remote learning at Penn State, faculty and administrators in the Department of Mechanical Engineering were prepared for the challenge.

Despite being rebuked by Congress in its bid to do so last year, the U.S. Department of Education says it will use Education Innovation and Research funds for teacher professional development vouchers.

Paul L. Aronson
Oct 1, 2014; 134:667-677
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G. C. Liggins
Oct 1, 1972; 50:515-525
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C. Michael Cotten
Jan 1, 2009; 123:58-66
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Quiz Yourself: What are today's biggest challenges to teacher recruitment?

The Penn State Board of Trustees Committee on Finance, Business and Capital Planning today (May 7) advanced a plan to adjust tuition schedules for the summer 2020 semester due to the ongoing financial challenges many students and families are experiencing as a result of COVID-19 disruptions. The measure will go to the full board for a final vote on Friday, May 8.

Within days of the University's shift to remote learning, faculty, instructors and teaching assistants in the Department of Geography moved 35 resident instruction courses into remote delivery mode to teach 1,947 students.

Sprint will need to divest to Boost Mobile, Virgin Mobile and its prepaid business to Dish Network, a satellite TV provider, so Dish can become a viable fourth competitor in the market.

Penn State York student-athlete Austin Lehman has received the Chancellor's Award for Academic Character, the most prestigious athletic award given by the campus.

Nedbank, FirstRand and Anglo Platinum have received the highest scores in the Public Investment Corporation's new corporate governance rating system.

College of Education student teachers in the Professional Development School program and their mentors in the State College Area School District had to make the quick switch to remote learning when the coronavirus pandemic closed schools.

The start of a good financial plan is not to react to tax hike announcements, but to match our income and our expenditure, says Errol Meyer, Head Advisory Propositions at Standard Bank.

New believers in the village of Sunkapur have started meeting together regularly to study God's Word.

Consumers must be careful simply to assume their fortune lies in investment property, cautions Steven van Rooyen, Principal at Leapfrog Milnerton.

Governor Markell will attend the ribbon cutting ceremony at Heron Run Apartments in Smyrna.

Governor Jack Markell joined Delaware State Housing Authority (DSHA) Director Anas Ben Addi, Representative Stephanie Bolden, in addition to representatives from the City of Wilmington, The Michaels Development Company, Bank of America and Architectural Alliance, for a tour of Jazz Court Apartments, a new affordable 44-unit three-story apartment building located in Wilmington. This project is part of a master plan created by Banc of America Community Development Corporation and its development partners, utilizing a former Brownfield site remediated and donated by Bank of America to its partners. The project will also include 17 homeownership townhomes to be built by Inter-Neighborhood Foundation and Habitat for Humanity of New Castle County.

University Police and Public Safety Deputy Chief Stephanie Delaney has been appointed as the district commander at the University Park campus, according to UPPS Assistant Vice President Charlie Noffsinger.

The department currently has a fleet of 810 drones, which are used to monitor federal lands. Of those, 786 are Chinese-made and 121 come from DJI, the leading provider of consumer drones. DJI denies that its technology poses a threat.

Money market funds are about managing income.

Should a life policy also include an investment component? A financial planner gives his take.

Two new international studies look at how parents judge how to invest in their children's education, and what happens to children's academic progress when one parent can't be involved.

Additional victims encouraged to contact Consumer Protection Unit The Delaware Department of Justice’s Consumer Protection Unit today announced three indictments, including separate criminal charges against two brothers, in a series of home improvement frauds targeting older Delawareans. Isaac K. Lovell, 44, of Bear was indicted on July 8, 2019 on charges including Racketeering, Conspiracy to […]

  FOR IMMEDIATE RELEASE September 9, 2019                                                     MEDIA ADVISORY WHAT:  Delaware Insurance Commissioner Trinidad Navarro will be hosting a ribbon cutting and ceremony to commemorate the opening of the […]

FOR IMMEDIATE RELEASE September 10, 2019 Delaware Department of Insurance Opens New Building in Dover, Delaware   Delaware Insurance Commissioner Trinidad Navarro cut the ribbon during a ceremony held this morning at 11 AM to commemorate the opening of the Delaware Department of Insurance’s new Dover office location at 1351 West North Street, Suite 101 […]

Investigations result in discovery and correction of issues impacting consumers The Delaware Department of Insurance’s Market Conduct Examinations resulted in the receipt of nearly $700,000 in fines during 2019 from more than a dozen companies found to violate the Insurance Code or other related regulations. The fines are contributed to the General Fund, providing funding […]

The Delaware Department of Insurance made great strides in fraud detection and response during 2019. Throughout the year, 6 criminal arrests that included 21 charges were recommended from the Department’s Fraud Prevention Bureau to the Department of Justice, and 16 civil cases were brought forward resulting in more than $21,000 in fines. The Bureau received 551 referral cases in 2019.

Kobe and Gianna Bryant were among nine people who died in the January 26 helicopter crash in the mountains west of Los Angeles.