Tag: Staphyloccous areus

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Global Trial Shows Safer Antibiotic Option for Staph Blood Infection

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Methicillin resistant Staphylococcus aureus (MRSA) – Credit: CDC

A landmark international clinical trial, led in the UK by University College London researchers, has identified the optimal antibiotics for staph blood infection, a breakthrough that is set to reshape treatment for the life-threatening condition.

The SNAP trial found that a little used antibiotic, cefazolin, is as effective as and safer than the current UK standard therapy, flucloxacillin, for treating life-threatening staph blood infections.  More than half of staph blood infections lead to sepsis and 15% to 25% of those who get these infections die within three months.

The researchers also found that a commonly used antibiotic, penicillin, can be used when the staph is treatable with this in the laboratory. And that similarly this is probably as effective as flucloxacillin, and safer.

The findings from the SNAP trial, published in the New England Journal of Medicine (NEJM) and The Lancet, challenge the long-held assumption that flucloxacillin should remain the default treatment and provide important new evidence to guide treatment strategy.

Staph (Staphylococcus aureus) is a leading cause of deadly blood infection, associated with over 1 million deaths worldwide each year. While effective antibiotic treatments exist, there has been no clear agreement about which antibiotic leads to the best outcomes for patients.

The NEJM results – Comparing cefazolin and flucloxacillin

In the trial published in the NEJM, researchers compared antibiotics used to treat meticillin-susceptible Staphylococcus aureus (MSSA) infections (i.e. blood infections that are not resistant to the meticillin antibiotic). It found cefazolin is at least as good as flucloxacillin for helping people to survive this infection, and associated with fewer side effects and a lower risk of kidney injury. It compared cefazolin and flucloxacillin in 1341 adults with staph blood infections across eight countries taking part in this part of the trial.

In patients who received cefazolin there were fewer cases of changes in how the kidneys are working (as measured by blood tests). Such kidney changes can cause long-term health problems and occurred in fewer of those given cefazolin compared to those given flucloxacillin.

The Lancet results – Comparing benzylpenicillin and flucloxacillin

In the paper published in The Lancet, the trial evaluated whether penicillin could be used to treat penicillin-susceptible Staphylococcus aureus (PSSA) infections where laboratory testing confirmed the susceptibility to penicillin.

This trial compared penicillin and flucloxacillin in 281 adults with staph blood infections. Penicillin was found to be likely to be at least as good for helping people to live with this infection as flucloxacillin.

In patients who received penicillin there were similarly fewer cases of changes in how the kidneys are working (as measured by blood tests). These occurred in 11% of those given penicillin compared to 22% of those given flucloxacillin. Mortality was also 14% in the penicillin group compared with 22% in the flucloxacillin group.

Professor Anna Goodman, UK lead of the SNAP trial at the UCL Innovative Clinical Trials, said: “This trial fills a major research gap. Our results strongly support cefazolin as the new first treatment for most adults with these infections. They also show a role for penicillin in some cases. It’s been helpful to deliver it in collaboration with researchers around the world and patients who have been affected by the condition, who we found via the UK Sepsis Trust.

“The results represent huge progress in the management of this disease with the first change in our approach to antibiotics in decades. Not only are cefazolin and penicillin as effective as flucloxacillin at treating penicillin- and meticillin-susceptible staph blood infection, but they also lead to significantly fewer abnormal blood tests.”

Staph infections are caused by bacteria called Staphylococcus aureus. They most often affect the skin and cause relatively minor problems. However, if the bacteria enter the bloodstream or other parts of the body, they can cause serious infections such as blood poisoning, blood infection or sepsis.

These more serious infections can affect anyone, but individuals at higher risk include people with catheters in their veins (as happens when people receive renal replacement therapy also called haemodialysis) or implanted devices (such as pacemakers), and people with diabetes. Those living with cancer and on immune suppressing medication, those who cannot get out of bed, and those who inject drugs are also more vulnerable to these infections.

The Royal Melbourne Hospital’s Professor Steven Tong, an infectious diseases physician at the Doherty Institute in Australia and global co-lead investigator of the SNAP Trial, said the results provide clear evidence that cefazolin should be considered the first-line option to treat MSSA blood infections.

“In the treatment of MSSA blood infections, there is an 89% probability that cefazolin is associated with lower mortality,” said Professor Tong.

“Patients treated with cefazolin fare better, with fewer deaths within 90 days (15% compared to 17% for those who received flucloxacillin). Cefazolin was also associated with fewer cases of acute kidney injury, at 14%, compared to 20% with flucloxacillin.

“The results are sufficiently compelling that I immediately made the switch in my own clinical practice.”

A shift away from flucloxacillin

Researchers said these results mark a turning point in the treatment of MSSA and PSSA blood infections, signalling a shift in clinical practice.

Penicillin was once widely used to treat Staphylococcus aureus, but antibiotic resistance of staph led clinicians to adopt flucloxacillin as the standard treatment for MSSA and PSSA blood infections. The findings support moving away from flucloxacillin as the default treatment for MSSA and PSSA blood infections, given safer alternatives are available.

The new results mark the first major finding from the ongoing SNAP trial, which aims to improve treatment for Staphylococcus aureus infections around the world. These parts of the trial took place in Australia, Canada, Israel, the Netherlands, New Zealand, Singapore, South Africa and the UK – each supported by regional funders working together to form one global network.

Global leadership was provided by the University of Melbourne trial team led by Professor Steven Tong and Professor Josh Davis.

So far, over 6000 participants have been enrolled in over 150 sites in those countries stated, and more recently in Germany and Sweden, Germany, Japan, Malaysia, and the United States.  The trial will continue testing new approaches to improve outcomes for patients facing this serious infection.

Translating the findings

Researchers say the next challenge will be translating the findings into routine clinical practice.

While cefazolin availability may need to increase in some countries, researchers say implementation will ultimately depend on hospitals, laboratories and guideline groups incorporating the findings into clinical care. 

Professor Goodman said: “Sepsis and staph blood infections are devastating for those affected and those who care for them. We are grateful to all those who took part and supported these two trials which will change practice.  The platform trial continues as we ask further important questions in this area.”

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Source: University College London

Categories : DermatologyTags :

Testosterone Increases Severity of Staph Skin Infections

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Study led by UTSW researchers defines how skin hormones influence bacteria and results in potential treatment for Staph infections

This laboratory image shows Staphylococcus aureus bacteria streaked in the shape of a sex steroid, like testosterone. The left shape is of wild-type S. aureus, with the lighter halo around the shape indicating haemolysis, or the breakdown of red blood cells, releasing their haemoglobin into the surrounding fluid. The right shape is a quorum-sensing mutant strain of S. aureus, which cannot damage blood cells.

Men are more susceptible than women to skin infections caused by Staphylococcus aureus bacteria, but the biological basis for this disparity has remained unclear. A new study led by UT Southwestern Medical Center researchers is the first to reveal that testosterone as a key driver of infection. The sex steroid activates a bacterial communication pathway known as quorum sensing, increasing skin cell death and promoting the destruction of red blood cells and white blood cells called neutrophils. 

Published in Nature Microbiology, the study also reported that a mirror-image form of testosterone, known as an enantiomer (ent-T), blocks quorum sensing and prevents S. aureus from damaging tissue in mouse models.

Senior author Tamia Harris-Tryon, MD, PhD, Associate Professor of Dermatology and Immunology at UT Southwestern, and first author Maria S. John, PhD, a UTSW postdoctoral researcher, have a patent pending for an ent-T-based therapeutic along with collaborators at the University of Colorado.

“This research has important implications for treating Staph skin infections and conditions complicated by Staphylococcus, such as atopic dermatitis, pemphigus, abscesses, and wound infections, including the deadliest skin infections caused by methicillin-resistant Staphylococcus aureus [MRSA],” Dr Harris-Tryon said. “It also explains why men are more susceptible to Staph infections.” 

S. aureus is the leading cause of skin infections. When it enters the bloodstream, it can cause septicaemia, a life-threatening infection that may lead to organ failure.

During infection, the bacteria use quorum sensing to detect neighbouring cells of the same species. As bacterial density rises, they produce short signalling molecules called auto-inducing peptides (AIP), which activate virulence programs and trigger toxin release, resulting in host-cell damage. 

The research team found that male skin cells consistently secrete higher levels of testosterone than female skin cells. They also found the same is true for male mice, which were significantly more susceptible to S. aureus colonisation and skin damage than female mice when exposed to a strain of MRSA. However, mice engineered to secrete less testosterone displayed greater resistance to the bacteria, while applying testosterone to the skin of female mice increased MRSA’s severity. 

In laboratory experiments, testosterone activated quorum sensing even in the absence of AIPs. Other sex steroids, including progesterone and oestrogen, had no measurable effect on quorum sensing. 

While using ent-T as an experimental control, the researchers unexpectedly identified its therapeutic potential. In lab tests, ent-T inhibited quorum sensing and reduced the bacteria’s virulence. The molecule also inhibited quorum sensing on male and female mice when applied to their skin. 

Dr Harris-Tryon won an Innovation Award from the UTSW Office for Technology Development in 2024 to fund development of an ent-T-based transdermal therapeutic for Staph.

“Our exciting finding suggests we can inhibit S. aureus virulence rather than killing the bacteria directly, an approach that prevents infection, preserves beneficial skin microbes, and reduces the selective pressure that drives antibiotic resistance while offering a potential new strategy to treat infections, including MRSA,” Dr. John said.

This work builds on Dr Harris-Tryon’s studies in 2023 and 2025 with Jeffrey McDonald, PhD, Professor in the Center for Human Nutrition and of Molecular Genetics at UTSW, which demonstrated sex-specific differences in skin hormone production. The team also has previously uncovered how the immune system stimulates testosterone production in skin cells. Dr Harris-Tryon said the current research builds on UT Southwestern’s longstanding leadership in steroid and skin hormone biology, a field in which the institution has been a global leader for decades.

Source: UT Southwestern

Categories : Infection ControlTags :

New Approach Halves Bacteriaemia Mortality from Staphylococcus Aureus

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The study reveals that the combination of antibiotics reduces mortality in patients with high-risk Staphylococcus aureus bacteriaemia by half, if applied in a personalised way

Methicillin resistant Staphylococcus aureus (MRSA) – Credit: CDC

A study led by researchers from the Infectious Diseases Service of the Bellvitge University Hospital (HUB), the Bellvitge Biomedical Research Institute (IDIBELL) and the University of Barcelona (UB) shows for the first time that the combination of antibiotics can significantly improve the prognosis of patients with high-risk Staphylococcus aureus bacteriaemia, if it is applied selectively and in a personalised way.

The article has been published in the prestigious scientific journal The Lancet Regional Health – Europe and is the result of the collaboration of a dozen Spanish hospitals.

A reanalysis that redefines the strategy against bacteriaemia

Bacteraemia for S. aureus is a frequent and serious infection, with mortality reaching 30%. Its management requires prolonged intravenous antibiotherapy, the removal of possible infected devices and a thorough evaluation to rule out complications such as endocarditis or metastatic focus. In recent years, several clinical trials evaluating the combination of antibiotics had failed to demonstrate clear benefits in the global set of patients, a fact that the authors of the present study attributed to the lack of stratification according to risk.

For this reason, the study has carried out a reanalysis of the individualised data of two previously performed randomised clinical trials, differentiating patients according to their risk profile. This stratification was done through the FEN-AUREUS classification – a recently developed clinical tool that allows estimating the risk of mortality with information available during the first 24 hours of evolution – and the complication criteria of the Infectious Diseases Society of America (IDSA).

A personalised medicine according to individual risk

The re-evaluated trials include, on the one hand, a study with 155 patients from 18 Spanish hospitals that compared the use of daptomycin with the combination of daptomycin and phosphomycin; and, on the other, a study with 215 patients from 19 hospitals that compared cloxacillin in monotherapy with the combination of cloxacillin and phosphomycin. In both cases, the initial conclusions had shown no significant benefits of combined therapy in the overall set of patients, beyond a reduction in the duration of bacteraemia in patients treated with phosphomycin.

After the new risk group analysis, the work shows that low-risk and uncomplicated patients do not obtain significant benefits from combined therapy. On the other hand, high-risk patients showed remarkable therapeutic success at eight weeks (69.2% vs. 25.8%) and lower mortality at 60 days (23.1% vs. 45.2%).

According to first author Dr Francesc Escrihuela-Vidal, “the integration of risk and complications criteria can help identify patients who can really benefit from combined therapy.”.

In the same vein, co-author Dr Jordi Carratalà points out that “the results represent a real paradigm shift in the approach to this infection: we move from a uniform strategy for all patients to a precision medicine based on individual risk”. In addition, it highlights that this approach allows to avoid unnecessary intensive treatments in low-risk patients and will contribute to improving the design of future clinical trials.

Source: Bellvitge Biomedical Research Institute

Categories : AntibioticsTags :

Antibiotic Resistance Among Key Bacterial Species Plateaus Over Time

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Use of antibiotics was weakly associated with resistance, indicating additional factors may be at play

Photo by CDC on Unsplash

Antibiotic resistance tends to stabilise over time, according to a study published April 3, 2025 in the open-access journal PLOS Pathogens by Sonja Lehtinen from the University of Lausanne, Switzerland, and colleagues. 

Antibiotic resistance is a major public health concern, contributing to an estimated 5 million deaths per year. Understanding long-term resistance patterns could help public health researchers to monitor and characterise drug resistance as well as inform the impact of interventions on resistance.

In this study, researchers analysed drug resistance in more than 3 million bacterial samples collected across 30 countries in Europe from 1998 to 2019. Samples encompassed eight bacteria species important to public health, including Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae. 

They found that while antibiotic resistance initially rises in response to antibiotic use, it does not rise indefinitely. Instead, resistance rates reached an equilibrium over the 20-year period in most species. Antibiotic use contributed to how quickly resistance levels stabilised as well as variability in resistance rates across different countries. But the association between changes in drug resistance and antibiotic use was weak, suggesting that additional, yet unknown, factors are at play.

The study highlights that continued increase in antibiotic resistance is not inevitable and provides new insights to help researchers monitor drug resistance.

Senior author Francois Blanquart notes: “When we looked into the dynamics of antibiotic resistance in many important bacterial pathogens all over Europe and in the last few decades, we often found that resistance frequency initially increases and then stabilises to an intermediate level. The consumption of the antibiotic in the country explained both the speed of initial increase and the level of stabilisation.”

Senior author Sonja Lehtinen summarises: “In this study, we were interested in whether antibiotic resistance frequencies in Europe were systematically increasing over the long-term. Instead, we find a pattern where, after an initial increase, resistance frequencies tend to reach a stable plateau.”

Provided by PLOS

Categories : Dermatology ImmunologyTags :

Topical Mupirocin Reduces Cutaneous Lupus Inflammation

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A woman with Systemic Lupus Erythematosus. Source: Wikimedia CC0

Researchers have found that topical mupirocin is effective in reducing rashes caused by systemic lupus erythematosus. Instead of directly lowering inflammation, the treatment kills bacteria that promote it. The findings are published in Arthritis & Rheumatology.

Cutaneous lupus erythematosus is a common manifestation of systemic lupus erythematosus, caused by the autoimmune conditions. The condition is characterised by rashes on various parts of the body including the face and scalp, hair loss and scarring of the skin.

The standard treatment for cutaneous lupus erythematosus is using immunosuppressants and biologic drugs to reduce inflammation. While the medications can be helpful, many patients with systemic lupus erythematosus already take several drugs and are looking for alternatives to pills.

J. Michelle Kahlenberg, MD, PhD, a professor of internal medicine in the Division of Rheumatology at University of Michigan Health led a team of researchers investigating topical mupirocin which is one such alternatives.

This trial was based on Kahlenberg’s previous discovery that cutaneous lupus rashes are often colonised with a common skin bacteria, Staphyloccous areus, also known as staph, and contributes to inflammation in the rashes. Mupirocin kills this type of bacteria.

The study randomly selected systemic lupus erythematosus patients currently experiencing cutaneous lupus erythematosus flares to treat their skin lesions with mupirocin or with an inactive control, petrolatum jelly.

Samples from the nose and lesional skin were used to determine baseline and post treatment Staphylococcus abundance and microbial community profiles. Paired samples collected prior to treatment with the topical solution and seven days after treatment showed decreases in lesional staphylococcus aureus in the mupirocin treated samples.

Importantly, the reduction in staph also was accompanied by a reduction in inflammatory signals, including interferon-driven gene expression, in the lesions.

“In addition to decreasing the inflammation by decreasing lesional staphylococcus aureus, the mupirocin treatment also lowered skin monocyte levels, which are important in driving cutaneous lupus,” said Kahlenberg.

Mupirocin is a prescription treatment, and while this early study showed signs of decreasing inflammation, the study wasn’t designed to see if it can decrease the rash of cutaneous lupus erythematosus.

“Additional larger studies are needed to determine whether topical antibiotics will be helpful to make rashes go away,” Kahlenberg said.

“However, this is an exciting first step to show that there may be additional treatments that can improve inflammation beyond our usual immunosuppressant and biologic drugs.”

Source: Michigan Medicine – University of Michigan