Ceftazidime–avibactam and cefiderocol are two of the latest generation β-lactam agents that possess expanded activity against highly drug-resistant bacteria, including carbapenem-resistant Enterobacterales. Here we show that structural changes in AmpC β-lactamases can confer reduced susceptibility to both agents. A multidrug-resistant Enterobacter cloacae clinical strain (Ent385) was found to be resistant to ceftazidime–avibactam and cefiderocol without prior exposure to either agent. The AmpC β-lactamase of Ent385 (AmpC^Ent385) contained an alanine–proline deletion at positions 294–295 (A294_P295del) in the R2 loop. AmpC^Ent385 conferred reduced susceptibility to ceftazidime–avibactam and cefiderocol when cloned into Escherichia coli TOP10. Purified AmpC^Ent385 showed increased hydrolysis of ceftazidime and cefiderocol compared with AmpC^Ent385Rev, in which the deletion was reverted. Comparisons of crystal structures of AmpC^Ent385 and AmpC^P99, the canonical AmpC of E. cloacae, revealed that the two-residue deletion in AmpC^Ent385 induced drastic structural changes of the H-9 and H-10 helices and the R2 loop, which accounted for the increased hydrolysis of ceftazidime and cefiderocol. The potential for a single mutation in ampC to confer reduced susceptibility to both ceftazidime–avibactam and cefiderocol requires close monitoring.

Importance Ceftazidime–avibactam and cefiderocol are newly approved β-lactam agents that possess broad spectrum activity against multidrug-resistant (MDR) Gram-negative bacteria. We show here that a two amino-acid deletion in the chromosomal AmpC β-lactamase, identified in a clinical strain of Enterobacter cloacae, confers reduced susceptibility to both agents. By crystallographic studies of free and drug-bound forms of enzyme, we demonstrate that this deletion in AmpC induces slanting of the H-9 helix that is directly connected with the R2 loop, and disappearance of the H-10 helix, is directly responsible for increased hydrolysis of ceftazidime and cefiderocol. These findings provide novel insights into how MDR Gram-negative bacteria may evolve their β-lactamases to survive selective pressure from these newly developed β-lactam agents.

Treatment of Mycobacterium avium complex pulmonary disease (MAC-PD) is challenging partly due to high efflux pump expression. Thioridazine might block these efflux pumps. We explore thioridazine's efficacy against M. avium using minimum inhibitory concentrations (MICs), time-kill combination assays, ex vivo macrophage infection assays and efflux assays. Thioridazine is bactericidal against M. avium, inhibits intracellular growth at 2x MIC and blocks ethidium bromide efflux. However, its toxicity and low plasma concentrations, make it unlikely to add efficacy to MAC-PD therapy.

Globally, mutations in the katG gene account for the majority of isoniazid-resistant strains of Mycobacterium tuberculosis. Buyankhishig et al analyzed a limited number of Mycobacterium tuberculosis strains in Mongolia and found that isoniazid resistance was mainly attributable to inhA mutations. The GenoType® MTBDRplus assay was performed for isolates collected in the First National Tuberculosis Prevalence Survey and the Third Anti-Tuberculosis Drug Resistance Survey to investigate genetic mutations associated with isoniazid resistance in Mycobacterium tuberculosis in Mongolia. Of the 409 isoniazid-resistant isolates detected by the GenoType® MTBDRplus assay, 127 (31.1%) were resistant to rifampicin, 294 (71.9%) had inhA mutations without katG mutations, 113 (27.6%) had katG mutations without inhA mutations, and two (0.5%) strains had mutations in both the inhA and katG genes. Of the 115 strains with any katG mutation, 114 (99.1%) had mutations in codon 315 (S315T). Of the 296 trains with any inhA mutation, 290 (98.0%) had a C–15T mutation. The proportion of isoniazid-resistant strains with katG mutations was 25.3% among new cases and 36.2% among retreatment cases (p=0.03), as well as 17.0% among rifampicin-susceptible strains and 52.8% among rifampicin-resistant strains (p<0.01). Rifampicin resistance was significantly associated with the katG mutation (adjusted odds ratio 5.36, 95% CI 3.3–8.67, p<0.001). Mutations in inhA predominated in isoniazid-resistant tuberculosis in Mongolia. However, the proportion of katG mutations in isolates from previously treated cases was higher than that among new cases, and that in cases with rifampicin resistance was higher than that in cases without rifampicin resistance.

Meropenem/vaborbactam resistance in Klebsiella pneumoniae is associated with loss of function mutations in the OmpK35 and OmpK36 porins. Here we identify two previously unknown loss of function mutations that confer cefuroxime resistance in K. pneumoniae. The proteins lost were NlpD and KvrA; the latter is a transcriptional repressor controlling capsule production. We demonstrate that KvrA loss reduces OmpK35 and OmpK36 porin production, which confers reduced susceptibility to meropenem/vaborbactam in a KPC-3 producing K. pneumoniae isolate.

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.

Background: MRSA pose significant therapeutic challenges, related to their: frequency in clinical infections; innate virulence properties; and propensity for multi-antibiotic resistance. MRSA are among the most common causes of endovascular infections, including infective endocarditis (IE).

Objective: To employ transthoracic echocardiography (TTE) to evaluate the effect of exebacase, a novel direct lytic agent, in experimental aortic valve MRSA IE.

Study Design: TTE was utilized to evaluate the in vivo effect of exebacase on MRSA-infected vegetation progression when combined with daptomycin (vs daptomycin alone). Primary intravegetation outcomes were: maximum size; weights at sacrifice; and MRSA counts at infection baseline vs after 4 days of daptomycin treatment (alone or in addition to exebacase administered once on treatment Day 1).

Results: A single dose of exebacase in addition to daptomycin cleared significantly more intravegetation MRSA than daptomycin alone. This was associated with a statistical trend toward reduced maximum vegetation size in the exebacase + daptomycin vs the daptomycin-alone therapy groups (p = 0.07). Also, mean vegetation weights in the exebacase-treated group were significantly lower vs daptomycin-alone (p < 0.0001). Maximum vegetation size by TTE correlated with vegetation weight (p = 0.005). In addition, intravegetation MRSA counts in the combination group were significantly lower vs untreated controls (p<0.0001) and the daptomycin-alone group (p<0.0001).

Conclusion: This study suggests that exebacase has a salutary impact on MRSA-infected vegetation progression when combined with daptomycin, especially in terms of vegetation MRSA burden, size and weight. Moreover, TTE appears to be an efficient non-invasive tool to assess therapeutic efficacies in experimental MRSA IE.

Florfenicol belongs to a class of phenicol antimicrobials widely used as feed additives and for the treatment of respiratory infections. In recent years, increasing resistance to florfenicol has been reported in Campylobacter spp., the leading foodborne enteric pathogen causing diarrheal diseases worldwide. Here, we reported the identification of fexA, a novel mobile florfenicol resistance gene in Campylobacter. Of the 100 Campylobacter jejuni strains isolated from poultry in Zhejiang, China, nine of them were shown to be fexA positive, and their whole genome sequences were further determined by integration of Illumina short-read and MinION long-read sequencing. The fexA gene was found in the plasmid of one strain and chromosomes of eight strains, and its location was verified by S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting. Based on comparative analysis, the fexA gene was located within a region with the tet(L)-fexA-catA-tet(O) gene arrangement, demonstrated to be successfully transferrable among C. jejuni strains. Functional cloning indicated that acquisition of the single fexA gene significantly increased resistance to florfenicol, whereas its inactivation resulted in increased susceptibility to florfenicol in Campylobacter. Taken together, these results indicated that the emerging fexA resistance is horizontally transferable, which might greatly facilitate the adaptation of Campylobacter in food producing environments where florfenicols are frequently used.

Methicillin-resistant Staphylococcus aureus (MRSA) has grown to become a major burden on healthcare systems. The cumulation of limited therapeutic options and worsened patient outcomes with persistent MRSA bacteremia has driven research in optimizing its initial management. The guidelines published by the Infectious Disease of America currently recommend combination therapy for refractory MRSA bacteremia, but the utility of combining antibiotics from the start of therapy is under investigation. The alternative strategy of early use of a β-lactam antibiotics in combination with vancomycin upon initial MRSA bacteremia detection has shown promise. While this concept has gained international attention, providers should give this strategy serious consideration prior to implementation. The objective of this review is to examine retrospective and prospective evidence for early combination with vancomycin and β-lactam antibiotics, as well as explore potential consequences of combination therapy.

Six sources confirmed Apple changed its mind on end-to-end encrypted backups two years ago following an FBI complaint and concerns users could lose access to their own data.

Oil prices made a spectacular comeback Thursday as fresh US-Iran tensions erupted, also helping equities advance after US labour market figures provided a glimmer of hope for the world's top economy.

BACKGROUND:

The ability of the decades-old Boston and Philadelphia criteria to accurately identify infants at low risk for serious bacterial infections has not been recently reevaluated.

Today you can save up to 30 percent on select laptops, networking devices, and storage drives at Amazon. Also, the highly anticipated game Cyberpunk 2077 is $10 off when you pre-order it.

When Celtic arrived home after their defeat by Feyenoord on May 6, 1970, everyone at Parkhead was understandably deflated, while the fans were in mourning for the lost chance of glory.

Graham A. Colditz
Jul 1, 1995; 96:29-35
ARTICLES

Julie A. Jaskiewicz
Sep 1, 1994; 94:390-396
COMMENTARY

Payback

The top-rated Kindle Paperwhite, a PCMag Editors' Choice product, is available right now from $84.99 ($45 off) and the new Kindle is on sale starting at $59.99 ($30 off).

The Culture, Tourism, Europe and External Affairs Committee has today issued a call for views from the culture and tourism industry on the current Covid-19 crisis.

House leaders may hold off on a final vote on a Republican-backed bill to rewrite the No Child Left Behind law, amid pushback from powerful GOP lobbying groups

Europe's most famous footballing families are supporting a new TV campaign by UEFA which calls on dads to encourage their daughters to play football.

Finals ambassadors Erin Cuthbert and Jo Love are excited to welcome WU19 EURO to their native Scotland.

By Sr. Joan L. Roccasalvo, C.S.J.

“It’s back to school,” the many ads remind us.  The noble work of education will soon begin anew.  

The word, educate, from the Latin educere, means to lead out of. Educators worthy of the name lead their students out of the darkness of ignorance to the light of truth, knowledge and wisdom. 

The Catholic Philosophy of Education

To realize its Divine mission, the Church has developed a view of education that claims the right over all other agencies to make final decisions about the education of its youth. 

There are several principles of the Catholic philosophy of education that mark it with distinction.  With the obvious age-appropriate adaptations, they affect all ages and academic levels. 

Belief in a Personal God

First, that belief in a personal God is essential to all Catholic thinking in any and every phase of human activity. This includes formal education which proclaims Jesus as its primary Exemplar.  It follows that the Church rejects any philosophy of education or position that sacrifices the eternal and supernatural to the temporal and natural (V.P. Lannie, “Catholic Education IV,” The New Encyclopedia 5: 168).

Academic Excellence

Second, Catholic education imparts far more than amassing facts and information.  Scholarship and faith belong together, the whole person, seeking ultimate Truth, Goodness, and Beauty.  Students should be taught to wonder at the goodness and truth surrounding them. Catholic education builds character. It develops in its students a Catholic moral compass and a Catholic sensibility to understand how society and democracies function. The curriculum’s first order of business is academic formation and excellence. Students must learn correct grammar and use language skillfully, even artfully. This means reading well, writing with imagination, precision and power, and speaking the country’s predominant language correctly. It is typically true that whoever uses the right word thinks precisely and persuasively as in the famous Hopkins’ poetic line, “The world is charged with the grandeur of God.” 

English is a difficult language to master, but it must be said that immigrants to this country often learn to speak better English than those who are born here. In the musical, “My Fair Lady,” the character of Henry Higgins sings, “Why Can’t the English Teach Their Children How to Speak.”  He lampoons Americans’ mutiliation of English with the line, “Well, in America, they haven’t used it in years.” A playful jab, but jab it is.

Catholic and Christian Humanism

Third, in Catholic humanism, God is found not just in the sacred but also in the secular where Christian values and virtue can be uncovered.  The religious and the profane are mutually inclusive, “charged with the grandeur of God.” Whatever is human is inherently Christian.  No enterprise, no matter how secular, is merely secular for we live in a universe of grace and promise. 

The humanities are associated with depth, richness, feelings, character and moral development. This is why the literary and refining arts are so important.  Their purpose is to impart wonder and enjoyment, sensitize the feelings of students and eventually influence their behavior.  The humanities are intended for all students and not just for the elite.

The Student and the Educator

Fourth, St. Thomas Aquinas puts it concisely: Education is a lifelong process of self-activity, self-direction, and self-realization. The child is the center of attention, the “principal agent,” in the educational process. 

The instructor is the “essential mover” who teaches by the witness of his or her example and consistently brings to their lessons a high degree of preparedness. The teacher’s role is critical to Catholic education (Ibid).  The students’ real life situations initiate the process of learning.   Educators lead their students out beyond their life setting—their Sitz-im-Leben.  Experience teaches students to discover for themselves by engaging the five senses. This includes, for example, making or doing beautiful art forms or listening to beautiful music. Affectivity must be channeled in socially-accepted ways. For the most part, “Rap” culture exalts anti-social affectivity.

In his apostolic exhortation, “Evangelii nuntiandi,” Pope Paul VI reflected: “Today students do not listen seriously to teachers but to witnesses, and if they do listen to teachers, it is because they are witnesses.”  

Catholic educators teaching in public schools can adapt Catholic principles to the public school curriculum especially when these are also embraced by other faith-traditions.    

The Benedict Effect

At his papal election in 2003, why did Joseph Cardinal Ratzinger take the papal name Benedict?  It was the Benedictine monks, who, systematically and comprehensively, rebuilt Europe after the barbaric invasions of Rome in the 5th century. Some European leaders refuse to acknowledge Europe’s Christian roots and, specifically, the Church’s role in building on Greco-Roman culture, Christianizing it, and handing it on to future generations. At a time when Europe was cast in darkness, the Church led it out of the darkness; the Church was Europe’s light. Not opinion, but fact.

St. Benedict, the Benedictine Order, and the Monastic Centuries

In the middle of the sixth century, a small movement changed the landscape of the European world.  Benedict of Nursia (480-547) introduced a new way of life and thinking that has brought vitality to contemporary men and women. He laid the foundation of Benedictine monastic life with his monks first at Subiaco and Rome, and then at Monte Cassino.  

Benedict composed his Rule of disciplined balance that fostered order and peace.  If “pray and work” (ora et labora) was the Benedictine motto, the way to live it was through beauty, piety, and learning.  Every monastery was built on an expansive tract of land, and  eventually, it became a miniature civic center for the townspeople.  One could say that the monks sacralized the landscape.  

Monastic Schools

Of the many contributions the Benedictine monks made to European culture, education remained a prominent value. In the Middle Ages, education was conducted within the confines of the monastery by monks, and later, by nuns.  They offered religious and general education to youth who intended to enter the monastic or clerical life and to youth who were preparing for public life.  They lived at home.  Young children of six or seven years of age were taught the basics. The majority, especially potential monks and nuns, were taught to read Latin, writing, chant, arithmetic, and learning how to read time on the sundial. The main text was the Psalter.  From the eighth century onward, students were taught the seven liberal arts, the trivium, grammar, logic, and rhetoric, and the quadrivium, arithmetic, astronomy, geometry, and music.  The ideal monastery of the Benedictine Order was that of Saint Gall in present-day Switzerland where the town flourished around the monastery.

In our century, Catholic education continues to flourish across the world in developed and in developing countries.

Conclusion: Catholic Education in the United States

The Encyclopedia of Catholicism asserts that “throughout history, there is likely no more compelling instance of Catholic commitment to education than the school system created by the U.S. Catholic community.  The story of American Catholicism goes back to the very first Catholic settlers in the New World.” 

Despite the various declarations of freedom in early American history, anti-Catholicism prevailed through groups such as the Know-Nothing Society of the 1850s.  They existed to eradicate Popery, Jesuitism, and Catholicism.  

Between 1840 and 1900, at least sixty European religious orders of women and men were teaching in this country’s parochial schools. 

Conclusion

Finally, the philosophy of Catholic education integrates several aspects of the faith into the curriculum but always in age-appropriate ways: Biblical tradition, Early Christian Church plus heresies and the results,  Spirituality and prayer, Liturgy,  Doctrine, Ecumenism:  a study of the world religions and the Third World.

Today, apologetics is needed more than ever to defend the Church against old and new approaches to anti-Catholicism.  Our students should be taught the art and skill of civil debate—to learn the principles, internalize them, anticipate opposing views, and then defend the principles. 

(This précis of the philosophy of Catholic education has been presented in its ideal conception and not necessarily as it exists with the integrity described.)

A poor family's dreams are dashed by a father's illness but brought back to life by OM Bangladesh's tailoring programme.

OM team members and former electrical training programme students help a disabled man get back into business after two teenagers steal his motorised rickshaw.

A Bangladeshi woman sees God answer prayer in an unlikely way. Her new faith teaches her to trust that God hears her.

The organization hopes the change, which will take place starting with the next round of exams in November, will make it more affordable for students to take the tests.

Researchers in Penn State’s College of Engineering, College of Agricultural Sciences and College of Medicine say direct LTP treatment and plasma-activated media are effective treatments against bacteria found in liquid cultures and have devised a way to create plasma directly in liquids.

Education Week's BookMarks blog is back! The authors may be different, but the heart of the blog remains the same.

Nearly half of all Mzansi accounts, created in 2004 as a means of having more people bank, are dormant but SA’s top banks won’t abandon the system.

Lead historic-site-interpreter Gavin Malone will portray a World War I veteran discussing the differences in American society between the 1910s and the early 1920s.

Delaware’s First Lady Tracey Quillen Carney and Delaware Libraries celebrated libraries and reading during Summer Library Reading Celebrations at the Milford Public Library and Route 9 Library and Innovation Center. The First Lady, Delaware Libraries, United Way and other partners encourage all children and teens to continue to use their most valuable school supply, a […]

The real challenge with regulations is that of implementation and compliance.

The US women's national team on Friday filed an appeal against a legal setback in their equal pay lawsuit, saying they are being paid less than the men even though they win twice as much.

Virat Kohli posted a throwback picture of him posing with Anushka in a balcony with snow-clad mountains in the background.

Sonakshi, a renowned television actress of a popular show, and Rohit, a highly successful cardiologist, cross paths and develop a unique bond even as they struggle with their demanding careers.   

<strong>New Delhi:</strong> Gauri Khan took a stroll down her memory lane and shared a throwback family picture from their vacation featuring husband and megastar Shah Rukh Khan and their two kids. However, it is the doting father and a husband's response over the adorable picture which will just melt

Yuvraj Singh had one of the finest arrays of shots during his playing days, making him one of the most attractive batsmen to watch.

Shan Masood was video-chatting with teammates when they grabbed their cricket gear and pretended to play a match.

The ECB took to Twitter to share a throwback video of Virat Kohli's dismissal from India's 2018 tour of England.

CSK's cheeky dig at Shikhar Dhawan on his throwback picture with Suresh Raina left fans in splits.

"In remembrance of the two that have left us," wrote Amitabh Bachchan

The picture also features Alia Bhatt, Abhishek Bachchan, Neetu Kapoor and others

The Indian Embassy here has started to contact the Indian nationals who wish to return home once the international travel lockdown due to the coronavirus pandemic is lifted.

The picture also features Alia Bhatt, Abhishek Bachchan, Neetu Kapoor and others

The Delaware Department of Agriculture is urging farmers to participate in the two major mid-year surveys, the June Agricultural Survey and the June Area Survey, conducted by USDA’s National Agricultural Statistics Service (NASS). NASS will survey nearly 400 farmers across Delaware to determine crop production and supply levels in 2017. “As an $8 billion industry, agriculture plays a major role in Delaware’s economy,” said Secretary of Agriculture Michael Scuse. “The information that our farmers provide is critical to helping everyone – from fellow farmers to lawmakers to extension professionals – make decisions that will impact our industry. It is critical that NASS has the most accurate data, so I urge Delaware farmers to participate in the June Surveys.”

Delaware Secretary of Agriculture Michael Scuse is reminding farmers to complete the small grain production survey that has been sent out to nearly 300 producers by the USDA’s National Agricultural Statistics Service (NASS). The agency is taking a comprehensive look into the 2017 production and supply of small grains, which include wheat, oats, barley, and rye. 

During the next several weeks, U.S. Department of Agriculture’s National Agricultural Statistics Service (NASS) will conduct two major mid-year surveys, the June Agricultural Survey and the June Area Survey. The agency will contact around 350 producers across Delaware to determine crop acreage and stock levels as of June 1, 2018.

Delaware will hold its 16th Drug Take-Back Day on Saturday, April 28, 2018, to help reduce the risk of prescription medications being diverted for misuse. Delawareans can discard their expired or unused medications at 24 locations statewide between 10 a.m. and 2 p.m.

Op-ed by Rick Geisenberger, Secretary of the Delaware Department of Finance Over the next several weeks, as we complete another budget debate in Dover, we should not lose sight of Delaware’s long-term challenges and of one issue in particular: the rising cost of health care. The projected growth rate for state spending on health care […]

The Delaware Division of Public Health (DPH) has advised the operator of Broadkiln Beach Water Company located in Sussex County to issue a boil water notice to customers after water samples collected from the system tested positive for the presence of E-coli bacteria on Friday, July 20. Because the Broadkiln Beach Water Company shares a connection with PrimeHook Water Company, anyone who uses drinking water from either system should not drink the water without boiling it first.