Invasive methicillin-resistant Staphylococcus aureus (MRSA) in children is associated with high morbidity and mortality. Although reductions in health care–associated MRSA infection among adults are documented, it is unclear if a similar trend is occurring among children.

Data from population-based surveillance were analyzed to assess changes in invasive MRSA infection incidence over time. This analysis describes the epidemiology and trends of invasive MRSA infections among children in 9 US metropolitan areas and estimates national burden. (Read the full article)

Tapentadol is used in the treatment of chronic pain, specifically diabetic neuropathy. It has known action on the μ-opioid receptor leading to drowsiness and apneas. There is no published information on the effects of tapentadol in small children.

After an accidental overdose in a child, tapentadol may be expected to cause μ-opioid clinical effects similar to other opioids. While the opioid effects predominate sympathomimetic effects are also seen. The risk of respiratory depression and dyspnea should be acknowledged. (Read the full article)

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Objectives. The aim of this study was to assess the safety of early oral switch (EOS) prior to 14 days for low-risk Staphylococcus aureus bacteremia (LR-SAB), which is the primary treatment strategy employed at our institution. Usually recommended therapy is 14 days of intravenous (IV) antibiotics.

Methods. All patients with SAB at our hospital were identified between 1 January 2014 and 31 December 2018. Those meeting low-risk criteria (healthcare-associated, no evidence of deep infection or demonstrated involvement of prosthetic material, and no further positive blood cultures after 72-hours) were included in the study. The primary outcome was occurrence of a SAB-related complication within 90 days.

Results. There were 469 SAB episodes during the study period, 100 (21%) of whom met inclusion criteria. EOS was performed in 84 patients. In this group, line infection was the source in 79%, methicillin-susceptible S. aureus caused 95% of SABs and 74% of patients received IV flucloxacillin. The median duration of IV and oral antibiotics in the EOS group was 5 (IQR 4-6) and 10 days (IQR 9-14), respectively. Seventy-one percent of patients received flucloxacillin as their EOS agent. Overall, 86% of oral step-down therapy was with beta-lactams. One patient (1%) undergoing EOS had SAB relapse within 90 days. No deaths attributable to SAB occurred within 90 days.

Conclusions. In this low MRSA prevalence LR-SAB cohort, EOS was associated with a low incidence of SAB-related complications. This was achieved with oral beta-lactam therapy in most patients. Larger prospective studies are needed to confirm these findings.

Recent studies highlight the abundance of commensal coagulase-negative staphylococci (CoNS) on healthy skin. Evidence suggests that CoNS actively shape the skin immunological and microbial milieu to resist colonization or infection by opportunistic pathogens, including methicillin resistant Staphylococcus aureus (MRSA), in a variety of mechanisms collectively termed colonization resistance. One potential colonization resistance mechanism is the application of quorum sensing, also called the Accessory Gene Regulator (agr) system, which is ubiquitous among staphylococci. Common and rare CoNS make autoinducing peptides (AIPs) that function as MRSA agr inhibitors, protecting the host from invasive infection. In a screen of CoNS spent media we found that Staphylococcus simulans, a rare human skin colonizer and frequent livestock colonizer, released potent inhibitors of all classes of MRSA agr signaling. We identified three S. simulans agr classes, and have shown intraspecies cross-talk between non-cognate S. simulans agr types for the first time. The S. simulans AIP-I structure was confirmed, and the novel AIP-II and AIP-III structures were solved via mass spectrometry. Synthetic S. simulans AIPs inhibited MRSA agr signaling with nanomolar potency. S. simulans in competition with MRSA reduced dermonecrotic and epicutaneous skin injury in murine models. Addition of synthetic AIP-I also effectively reduced MRSA dermonecrosis and epicutaneous skin injury in murine models. These results demonstrate potent anti-MRSA quorum sensing inhibition by a rare human skin commensal, and suggest that cross-talk between CoNS and MRSA may be important in maintaining healthy skin homeostasis and preventing MRSA skin damage during colonization or acute infection.

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.

Staphylococcus aureus osteomyelitis is a debilitating infection of bone. Treatment of osteomyelitis is impaired by the propensity of invading bacteria to induce pathologic bone remodeling that may limit antibiotic penetration to the infectious focus. The nonsteroidal anti-inflammatory drug diflunisal was previously identified as an osteoprotective adjunctive therapy for osteomyelitis, based on the ability of this compound to inhibit S. aureus quorum sensing and subsequent quorum-dependent toxin production. When delivered locally during experimental osteomyelitis, diflunisal significantly limits bone destruction without affecting bacterial burdens. However, because diflunisal's "quorum-quenching" activity could theoretically increase antibiotic recalcitrance, it is critically important to evaluate this adjunctive therapy in the context of standard of care antibiotics. The objective of this study is to evaluate the efficacy of vancomycin to treat osteomyelitis during local diflunisal treatment. We first determined that systemic vancomycin effectively reduces bacterial burdens in a murine model of osteomyelitis, and identified a dosing regimen that decreases bacterial burdens without eradicating infection. Using this dosing scheme, we found that vancomycin activity is unaffected by the presence of diflunisal in vitro and in vivo. Similarly, locally-delivered diflunisal still potently inhibits osteoblast cytotoxicity in vitro and bone destruction in vivo in the presence of sub-therapeutic vancomycin. However, we also found that the resorbable polyurethane foams used to deliver diflunisal serve as a nidus for infection. Taken together, these data demonstrate that diflunisal does not significantly impact standard of care antibiotic therapy for S. aureus osteomyelitis, but also highlight potential pitfalls encountered with local drug delivery.

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.

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.

Background

Optimal concentrations of unbound antimicrobials are essential for maximum microbiological effect. Although hypoalbuminemia and albumin fluid resuscitation are common in critical care, the effects of different albumin concentrations on the unbound concentrations of highly protein-bound antimicrobials are not known. The aim of this study was to compare effects of different albumin states on total and unbound concentrations of ertapenem and ceftriaxone using an ovine model.

Methods

Design

Prospective, three phase intervention observational study.

Subjects

Healthy Merino sheep.

Interventions

Eight sheep were subject to three experimental phases; normoalbuminemia, hypoalbuminemia using plasmapheresis and albumin replacement using a 25% albumin solution. In each phase, ceftriaxone 40 mg/kg and ertapenem 15 mg/kg were given intravenously. Blood samples were collected at pre-defined intervals and analyzed using an ultra-high-performance liquid chromatography tandem mass spectrometry method. Pharmacokinetic parameters such as area under the curve (AUC_0-24), plasma clearance (CL) and apparent volume of distribution in the terminal phase (V_d) were estimated and compared between the phases.

Results

The protein and albumin concentrations were significantly different between phases. Hypoalbuminemia resulted in a significantly lower AUC_0-24 and higher CL of total and unbound concentrations of ceftriaxone compared to the other phases. Whereas albumin replacement led to higher AUC_0-24 and lower CL compared to other phases for both drugs. The V_d for total drug concentrations for both drugs were significantly lower with albumin replacement.

Conclusions

For highly protein-bound drugs such as ceftriaxone and ertapenem, both hypoalbuminemia and albumin replacement may affect unbound drug exposure.

T. Michael O'Shea
Jul 1, 1999; 104:15-21
ARTICLES

Start your new year off right by getting some new customized items for your business, or just treat yourself to a unique 2020 calendar of your own design, all for a fantastic price.

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

It’s a wonderful phenomenon—yeast.  It permeates lifeless flour and causes it to rise and expand.  The power of yeast effects the brewing of beer and the making of wine.   The yeast plant is a fungus that grows without limits to its borders.  Only if yeast is alive and active will it interact with the dough.

On her TV program, “Martha Bakes,” the talented Ms. Stewart cannot contain her delight when she makes yeast dough: “Look at the sheen—so soft and shiny! The aroma is “bee-you-tee-ful,” and the fragrance gratifies all the senses!” Follow these instructions: proof active yeast, blend it into the flour mixture, and let it rise to double the size.  From yeast dough come baked goods such as breads, sticky buns and sugar buns, and monkey bread.  “Soo pretty, soo delicious,” Ms. Stewart swoons over her culinary works of art.

Yeast as a Metaphor

In the Matthean parable (13:33), the reign of God is like yeast that a woman took and kneaded into three measures of flour.  Eventually the entire mass of dough began to rise.  The image of yeast was a favorite in the Early Church.  Everyone understood the inner power of yeast with its limitless ability to make things grow, even in small beginnings with “three measures of flour.”  They grasped the comparison.  The yeast referred to the Church as an unlimited and growing reality, “destined ultimately to be present everywhere and to affect everything, though by no means to convert everything into itself” (Walter J. Ong, “Yeast: A Parable for Catholic Higher Education,” America Magazine, April 7, 1990).  The Church is catholic because it has always been expanding into new and shiny ‘dough’ without limit. Katholicos, from kata or kath and holos, means “through-the-whole or “throughout-the-whole.”

The Laity: Worldly and Yet Unworldly    

The laity are catholic, yeast in business and finance, entertainment, nursing and medicine, arts and science, law and law enforcement, politics, and sports.  They are the inner power with its limitless ability to make things grow, even in small ways. The laity find their holiness in the world with its financial concerns and family responsibilities.  Those who marry and have children become not just a family but also the Domestic Church.

In 1987, the Catholic Church held a World Synod on the Laity, one of many, beginning with Vatican II in the 1960s.  According to the synod’s final document, the laity are equal with clergy and consecrated religious in the life and mission of the Church.  

The call to holiness of the laity differs from the vocation of consecrated religious.  The laity are to be in the world in an unworldly way.  They approach life with wisdom that teaches the limited and relative value of material things. This would seem to be a contradiction in terms.  How to be worldly and unworldly at the same time?   It cannot be easy, for at times, the challenges seem insurmountable.  Yet, it remains for the lay vocation to find a theology of being present in the world. It is a practical spirituality of the family and the workplace.  For the laity, this is where holiness resides.*  

Holiness of the Laity

The holiness of the laity began with Jesus himself.  He was a rabbi and teacher, as were his disciples. Peter was a married man, and for all we know, so were the other apostles, the exception being John, the Beloved Disciple.  

St. Paul addresses and refers to those he evangelized as ‘saints,’ meaning that they were on their way to becoming saints.  In the Early Church, there were no consecrated institutes of men and women.  All Christians grasped the importance of living as disciples and ambassadors of the Lord.

As increasing numbers of Christians came to view the world as wicked, they flocked to the desert to live alone. When the desert grew so overcrowded with these solitaries, they came together and formed religious communities.  Thus, the start of monastic orders of men and women.

Prayer

Consecrated men and women, and especially those who live in cloisters, spend several hours a day in prayer.

This is not the way of the laity. Their days focus almost entirely on family and the means of supporting it.  Their prayer is measured not in hours but in minutes—two here, five there, perhaps a Holy Hour or Retreat Day on rare occasions.

The conciliar document on the sacred liturgy encourages Catholic families to pray portions of the Liturgy of the Hours (#102-111).  The Hours are not private or devotional prayer but the prayer of the entire Church, the Church at prayer.  Praying the psalms nourishes Catholic family life whose welfare is daily beset with conflicting external forces. If prayer is the underlying power of strong family life, then parents can find ways to incorporate parts of the Hours into their daily schedule. In prayer, married couples derive the strength of God’s grace to live their married vocation.  

As children mature, they too must learn to travel the road to discipleship in the Lord.  Small children can be taught to pray a psalm or two at bed time. If this is not feasible during the week, then prayer on weekend is an alternate possibility.  

A minimal and external Christianity will not fortify today’s Domestic Church but only a vibrant Christianity in which Christ is a living reality.  It takes a few minutes to pray short sections of the Hours, even on public transit.  It is a consoling thought to recall that “in him, we live and move and have our being” (Acts 17:28).  

At Pre-Cana instructions, couples can learn the practice of making the Hours an integral part of their married life.

Can Yeast Corrupt?

The image of yeast is not always positive.  In First Corinthians 5:6-8, St. Paul mentions what all Jews understood.  At the Paschal festival time, they were to destroy all yeasted products because leaven was a metaphor for the corruptive influence of evil, for puffing up the self, leaving no room for God.   

Proofing the yeast in warm water will yield bubbles around the surface, and the yeast will become puffed up if it does not interact with the flour dough.  The puffed up yeast will die.  In this sense, neither the laity, nor any minister in the Church, can afford to be puffed up with pride.

Élisabeth Leseur (1866-1914) and Félix Leseur (1861-1950)

The story of Élisabeth Arrighi Leseur exemplifies the limitless power of marital love.  Élisabeth was born into a wealthy French Catholic family of Corsican descent.  As a child, she had contracted hepatitis, a disease from which she suffered all her life.  At twenty-one, she met Félix Leseur, a medical doctor, who also came from an affluent Catholic family.  Shortly before they were to be married, Élisabeth discovered that Félix was no longer a practicing Catholic.  Soon he became well known as the editor of an anti-clerical, atheistic newspaper.  

Despite the circumstances, the couple married, for Élisabeth was deeply in love with Félix.  They were unable to have children, a fact that made their marriage all the more difficult.  His attack on her religious devotion prompted an even more serious fidelity to the faith. She bore the brunt of his hatred of the Church with patient love.  At thirty-two years of age, Élisabeth experienced the grace to a deeper form of prayer.  She was convinced that her task now was to love her husband and pray for his conversion while remaining steadfast during his taunts against religion, and the Church in particular.

Homebound and Bed-Ridden

Élisabeth’s deteriorating health forced her to lead a sedentary life.  She received visitors and was able to conduct a vibrant apostolate from the confines of her home.  She became a devotee of St. Francis de Sales who wrote for the layperson in the seventeenth century. His Introduction to the Devout Life, perhaps the most famous spiritual guide of all time, is an offshoot of the Ignatian Exercises. During this period, Élisabeth kept a secret spiritual diary.  

When, at the age of forty-five, Élisabeth underwent surgery and radiation for the removal of a malignant tumor, she recovered and continued to receive visitors to her home. Three years later, she succumbed to cancer.  Her life has been recommended for sainthood. Why?  We turn the page to continue the narrative of her husband.

Dr. Félix Leseur

After Élisabeth’s death, Félix found a note addressed to him.  Not only did it predict his conversion, but he would also become a Dominican priest.  His hatred of the Church prompted him to expose her note as a fake, and he decided to do so at Lourdes, the famous Marian shrine in France.  There, something prevented him from carrying out his intended project—call it God’s intervening grace. As Élisabeth had predicted, he experienced a conversion and published her spiritual journal.  In 1919, Félix entered the Dominican Order, was ordained a priest four years later, and spent his remaining years speaking about his wife’s difficult yet remarkable life with him.  

In 1924, the future Archibishop Fulton J. Sheen made a retreat under Fr. Leseur’s direction.  It was at this time that he learned of Élisabeth’s life and her husband’s conversion.  In 1934, Fr. Leseur, O.P. worked to begin the cause for her canonization, and the Archbishop shared the story of this remarkable married couple in many presentations.  Élisabeth is currently a Servant of God, the first step in the cause for sainthood.

Élisabeth Leseur’s suffering was not wasted. On the contrary, her lifelong devotion to Félix was central to his conversion.  She became the yeast that permeated the lifeless soul of her husband.  It forever transformed his life so that he could affect change in the lives of others. Love begets love.

*The Ignatian “Prayer for Finding God in All Things” by Joan L. Roccasalvo, C.S.J. can help the busy person find God throughout the day.  Copies are available from the Institute of Jesuit Sources, Boston, MA.

Dover, DE – Just in time for the holidays, the happiest season of all will now also be the “hoppiest” with the addition of four new craft breweries to the Delaware on Tap mobile app. Each location offers a unique atmosphere and special take on the brewmaster’s art. They bring the number of craft breweries, wineries, […]

Brands tap regional celebrities to go hyperlocal. Does it translate into higher ROI?

Last year, PepsiCo, too, had reduced the salt content in two of its Lay’s chips variants and introduced Kurkure Multigrain packs with 21% lesser sodium.

OTT platforms are partnering with travel agencies, airlines and cruises to tap on-the-go audiences

A new phrase in marketing which started in the US a few years back is now catching on in India as well.

Conversational commerce, as it is more popularly known, is any form of online communication that takes place during an e-commerce purchase.

Brands are tapping regional influencers for higher engagement.

A majority of sugar companies decided to make hand sanitisers to supply to hospitals by using a part of the ethanol/ENA production, thereby ensuring that the country does not face any shortage of good quality hand sanitisers.

“Keeping it open-ended and on-tap would be a better idea than conducting the operation on a pre-decided date. Banks should get enough leeway in deciding how much they want to borrow and when to borrow,” said an expert.

The three year NCD issue of Indiabulls Housing Finance opened on April 29. Although, the base issue size was Rs 100 crore, but it had a greeshoe option of Rs 900 crore.

Bengali actor-politician Tapas Pal, who died of a cardiac arrest at 61, will be remembered as Kedar Chatterjee. That is the name of the character the actor and former Trinamool Congress lawmaker...

visit News18 Urdu for latest news, breaking news, news headlines and updates from Pratapgarh on politics, sports, entertainment, cricket, crime and more.

visit News18 Urdu for latest news, breaking news, news headlines and updates from Sitapur on politics, sports, entertainment, cricket, crime and more.

Here’s the latest wrinkle in the battery boom: National Grid Plc is paying consumers to tap electricity from their power-storage systems.

POWERGEN International Week truly begins Monday, Nov. 18 with POWERGEN University. This year’s set of three, four and eight-hour PGU classes include detail educations on crucial power generation topics such as effective project management, gas turbine long-term service agreements, safety processes, digitalization, business plans for emerging markets, microgrids, cogeneration, machine learning, boiler technologies, building the generation fleet of the future and the consideration of natural gas vs. diesel for on-site power gen-sets.

POWERGEN International Week truly begins Monday, Nov. 18 with POWERGEN University. This year’s set of three, four and eight-hour PGU classes include detail educations on crucial power generation topics such as effective project management, gas turbine long-term service agreements, safety processes, digitalization, business plans for emerging markets, microgrids, cogeneration, machine learning, boiler technologies, building the generation fleet of the future and the consideration of natural gas vs. diesel for on-site power gen-sets.

Here’s the latest wrinkle in the battery boom: National Grid Plc is paying consumers to tap electricity from their power-storage systems.

Brazil's Institute of the Environment and Natural Resources, Ibama, has decided not to award an environmental license for the Sao Luiz do Tapajos hydroelectric plant, effectively ending development of the controversial 8,000 MW project.

Brazil's Institute of the Environment and Natural Resources, Ibama, has decided not to award an environmental license for the Sao Luiz do Tapajos hydroelectric plant, effectively ending development of the controversial 8,000 MW project.

Here’s the latest wrinkle in the battery boom: National Grid Plc is paying consumers to tap electricity from their power-storage systems.

In visualizing microgrids as smaller versions of the existing grid, we ignore a whole new dimension of the impending electricity revolution that I wish to call “microgrid as metaphor,” and distinguish it from “microgrid as fact.” Let me elaborate.

The global strategy for mitigating climate change is no secret. Most countries have embarked on an initiative to transition to clean energy sources. According to a study by scientists from the universities of Oxford and Utrecht, we will almost certainly pass a point of no return for dealing with global warming if governments worldwide don’t transition away from fossil fuels, such as coal and natural gas, towards renewable energy by 2035. This would mean that renewables would need to see their total share of power generation increase by at least two percent per year.

Prime Minister Shinzo Abe is pushing Japan’s coal industry to expand sales at home and abroad, undermining hopes among environmentalists that he’d use the Fukushima nuclear accident to switch the nation to renewables.

The Chancellor has announced some important changes to the capital gains tax (CGT) regime. These changes may have a significant impact on the tax payable by your employees holding shares in your company traded on the full list. Abolition of taper r...

Australia’s economy has become too reliant on China as a result of a government push for domestic industry to maximise exports to the world’s second largest economy, industry submissions to a government inquiry say.Business groups also singled out Australian government policies, including management of bilateral relationships with Indonesia and India, as hurting access to alternative markets.While some Australian export industries are not reliant on demand from China, companies like those in…

A rigorous randomised trial has put to bed the idea that tapping or flicking a can of beer makes bubbles come to the top and prevents the liquid fizzing out

Fancy bidding on a Christmas present steeped in science history? Find out what they'll set you back, and which present-day artefacts might be worth investing in

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