Tag Archives: Dog skin disorders

Resistant bacteria are a global problem. Now researchers may have found the solution

Staphylococcus aureus. You may have had it in connection with a wound infection. In most cases, it will pass without treatment, while severe cases may require antibiotics, which kills the bacteria. This is the case for the majority of the population. In fact, many of us — though we feel perfectly fine — carry staphylococci in the nose, a good, moist environment in which the bacteria thrive.

However, more and more staphylococci are becoming resistant to antibiotics (also known as multi resistant staphylococcus aureus or MRSA), and these infections can be difficult to treat.

“Antibiotics resistance is an increasing problem, especially on a global scale. And when you have this relatively simple infection which suddenly cannot be treated with antibiotics, the situation can turn serious, sometimes life-threatening,” says Professor Niels Ødum from the LEO Foundation Skin Immunology Research Center at the University of Copenhagen.

Therefore, all over the world, a lot of resources are being invested in fighting antibiotics resistance in staphylococcus aureus infections, and a new study among skin lymphoma patients has produced positive results. A new substance called endolysins has proven capable of killing both resistant and non-resistant staphylococcus aureus — without the need for antibiotics. But we will get back to that.

The discovery is good news to patients with a weak immune system to whom a staphylococcus aureus infection can be serious and, at worst, fatal. But it also adds to the knowledge we have of other forms of treatment.

“To people who are severely ill with e.g. skin lymphoma, staphylococci can be a huge, sometimes insoluble problem, as many are infected with a type of staphylococcus aureus that is resistant to antibiotics,” says Niels Ødum and adds:

“That is why we are careful not to give antibiotics to everyone, because we do not want to have to deal with more resistant bacteria. Therefore, it is important that we find new ways of treating — and not the least to prevent — these infections.”

New substance may be the answer

In some patients, a staphylococcus aureus will cause the cancer to worsen. And even though antibiotics appear to work in some cases, it is not without its problems.

“We can tell that giving high doses of antibiotics to patients with serious infections causes their health, skin and cancer symptoms to improve. But once we stop giving them antibiotics, the symptoms and staphylococci quickly return. Patients experience many adverse effects, and some risk getting resistant bacteria,” says Niels Ødum.

Therefore, treating staphylococcus aureus can be tricky. At worst, cancer patients may die of an infection which doctors are unable to treat.

And this is where endolysins enter the scene, as this new substance may be part of the solution to antibiotics resistance like MRSA.

“This particular endolysin is a brand new, artificially produced enzyme that has been improved several times and designed as a new drug,” explains Postdoc Emil Pallesen, who is first author of the study. He adds:

“The great thing about this enzyme is that it has been designed to penetrate the wall of staphylococcus aureus. This enables it to target and kill the harmful staphylococcus and leave harmless skin bacteria unharmed.”

And that is what made the researchers decide to test the new substance; they expected it to be able to kill both resistant and non-resistant staphylococcus bacteria.

“We have been testing the substance on skin samples from patients, and it does appear to kill staphylococcus aureus from patients. Endolysins do not care whether the bacterium is resistant to antibiotics or not, because it does not work in the same way as antibiotics,” says Niels Ødum and adds:

“The really good news is that our lab tests have showed that endolysins do not just eradicate staphylococcus aureus; they also inhibit their ability to promote cancer growth.”

  • Emil M.H. Pallesen, Maria Gluud, Chella K. Vadivel, Terkild B. Buus, Bob de Rooij, Ziao Zeng, Sana Ahmad, Andreas Willerslev-Olsen, Christian Röhrig, Maria R. Kamstrup, Lene Bay, Lise Lindahl, Thorbjørn Krejsgaard, Carsten Geisler, Charlotte M. Bonefeld, Lars Iversen, Anders Woetmann, Sergei B. Koralov, Thomas Bjarnsholt, Johan Frieling, Mathias Schmelcher, Niels Ødum. Endolysin inhibits skin colonization by patient-derived Staphylococcus aureus and malignant T cell activation in cutaneous T cell lymphoma. Journal of Investigative Dermatology, 2023; DOI: 10.1016/j.jid.2023.01.039
  • University of Copenhagen – The Faculty of Health and Medical Sciences

    Hydrogel injections treat antibiotic-resistant infections after hip, knee replacements

    Total hip and knee replacements are challenging enough for patients. When an infection occurs in the aftermath, the results are often disastrous, requiring potent antibiotics and revisionary surgery.

    In APL Bioengineering, by AIP Publishing, researchers from Shanghai Jiao Tong University School of Medicine developed an injectable hydrogel that treats infections around prosthetics without the problems caused by current treatments. Testing showed that the gel inhibits common bacteria and promotes tissue regrowth.

    After hip and knee replacement surgeries, pathogenic bacteria can adhere to the surface of the joint prosthesis and form a dangerous biofilm. Gold standard clinical methods use potent antibiotics and further surgery, including removal of infected tissue and transplantation of new tissue, to treat these infections. However, these strategies run into problems with hyper-resistant bacteria caused by the abuse of antibiotics, persistent damage caused by tissue removal, difficulties in obtaining tissue donors, and toxicity and immune system complications.

    “It is important to explore a new strategy for treatment of infected soft tissue wounds because it is directly related to prognosis,” said author Ruixin Lin. “We aspire to develop a simpler, safer method to help more patients avoid suffering and help more doctors make the right choices.”

    The team created the black phosphorus-enhanced antibacterial injectable hydrogel to reestablish biological barriers in soft tissue and suppress persistent infections. The gel has a porous structure, excellent injectability, and rapid self-healing properties.

    In vitro tests showed the hydrogel had good stability and low toxicity to tissue cells. Irradiating the gel with near infrared light causes it to release silver ions. This process was highly efficient at inhibiting S. aureus, common bacteria that cause disease in humans.

    “Furthermore, an in vivo infected wound model showed that the hydrogel could not only inhibit the persistent infection of the wound, but also accelerate the deposition of collagen fibers and angiogenesis, thereby realizing the repair of the natural barrier of soft tissue,” said Lin.

    The novel hydrogel provides a safe and feasible synergistic antibacterial strategy for infected soft tissue healing. The team believes that it solves current clinical problems, such as stubborn infections caused by antibiotic resistance, and provides new ideas for minimally invasive treatment. They hope to see it used in the clinic after conducting sufficient studies on its underlying mechanisms.

    Story Source:

    Materials provided by American Institute of Physics. Note: Content may be edited for style and length.

    Journal Reference:

  • Yaochao Zhao, Zhijie Chen, Wenjun Shao, Shu Yang, Wenguo Cui, Zhengwei Cai, Liang Cheng, Ruixin Lin. Black phosphorus-enhanced injectable hydrogel for infected soft tissue healing. APL Bioengineering, 2023; 7 (1): 016103 DOI: 10.1063/5.0121241
  • American Institute of Physics

    Scientists reveal first close-up look at bats’ immune response to live infection

    Scientists at Duke-NUS Medical School and colleagues in Singapore have sequenced the response to viral infection in colony-bred cave nectar bats (Eonycteris spelaea) at single-cell resolution. Published in the journal Immunity, the findings contribute to insights into bat immunity that could be harnessed to protect human health.

    Bats harbour many types of viruses. Even when they are infected with viruses deadly to humans, they show no notable signs or symptoms of disease.

    “It is our hope that by understanding how bats’ immune responses protect them from infections, we may find clues that will help humans to better combat viral infections,” explained Dr Akshamal Gamage, Research Fellow with Duke-NUS’ Emerging Infectious Diseases (EID) Programme and a co-first author of the study.

    “And knowing how to better fight viral infections can aid in the development of treatments that will help us to be more bat-like — by falling sick less and ageing better,” added Mr Wharton Chan, an MD-PhD candidate at Duke-NUS who is also a co-first author of the study.

    In this study, the scientists investigated bat immune responses to Malacca virus, a double-stranded RNA virus that uses bats as its natural reservoir. This virus also causes mild respiratory disease in humans.

    The team used single-cell transcriptome sequencing to study lung immune responses to infections at the cellular level, identifying the different types of immune cells in bats — some of which are different from those in other mammals, including humans — and uncovering what they do in response to such viral infections.

    They found that a type of white blood cell, called neutrophils, showed a very high expression of a gene called IDO1, which is known to play a role in mediating immune suppression in humans. The scientists believe that IDO1 expression in cave nectar bats could play an important role in limiting inflammation following infection.

    Dr Feng Zhu, Research Fellow with the EID Programme and a co-first author of the study, said, “We also found marked anti-viral gene signatures in white blood cells known as monocytes and alveolar macrophages, which — in a sense — consume viral particles and then teach T cells how to recognise the virus. This observation is interesting as it shows that bats clearly activate an immune response following infection despite showing few outward symptoms or pathology.”

    The team also identified an unusual diversity and abundance of T cells and natural killer cells — named for their ability to kill tumour cells and cells infected with a virus — in the cave nectar bat, which are broadly activated to respond to the infection.

    “This is the first study that details the bat immune response to in vivo infection at the single-cell transcriptome level,” said Professor Linfa Wang, senior author of the study from the EID Programme. “We believe that our work serves as a key guide to inform further investigations into uncovering the remarkable biology of bats. Moving forward, besides studies into viral disease tolerance, we also hope to uncover clues to longevity from bats as long-lived mammals and also learn how these nectarivorous bats can live on the high sugar diet in nectar without getting diabetes.”

    Story Source:

    Materials provided by Duke-NUS Medical School. Note: Content may be edited for style and length.

    Journal Reference:

  • Akshamal M. Gamage, Wharton O.Y. Chan, Feng Zhu, Yan Ting Lim, Sandy Long, Matae Ahn, Chee Wah Tan, Randy Jee Hiang Foo, Wan Rong Sia, Xiao Fang Lim, Haopeng He, Weiwei Zhai, Danielle E. Anderson, Radoslaw Mikolaj Sobota, Charles-Antoine Dutertre, Lin-Fa Wang. Single-cell transcriptome analysis of the in vivo response to viral infection in the cave nectar bat Eonycteris spelaea. Immunity, 2022; 55 (11): 2187 DOI: 10.1016/j.immuni.2022.10.008
  • Duke-NUS Medical School

    New drug is found effective for treating complicated urinary tract infections

    An international study led by a Rutgers scientist comparing new and older treatments against complicated urinary tract infections has found a new drug combination to be more effective, especially against stubborn, drug-resistant infections.

    Describing the results in the Journal of the American Medical Association (JAMA), researchers in the ALLIUM Phase 3 clinical trial showed that a combination of the drugs cefepime and enmetazobactam was more effective in treating both complicated urinary tract infections and acute pyelonephritis (AP), a bacterial infection causing kidney inflammation, than a standard treatment combining piperacillin and tazobactam. Urinary tract infections are considered complicated when they are associated with risk factors — including fevers, sepsis, urinary obstruction or catheters — that increase the danger of failing antibiotic therapy.

    “This new antibiotic was superior to the standard-of-care therapy,” said Keith Kaye, chief of the Division of Allergy, Immunology and Infectious Diseases and

    a professor of medicine at Rutgers Robert Wood Johnson Medical School.

    “It represents an exciting option for treatment,” said Kaye, the principal investigator of the study and lead author on the publication.

    Kaye added this drug combination also fights an often-dangerous category of bacterial illnesses caused by pathogens known as extended spectrum beta-lactamase (ESBL) infections, named for an enzyme the bacteria produce. ESBL-producing bacteria can’t be killed effectively by many of the antibiotics conventionally used to treat infections, such as penicillins and cephalosporins.

    “We are looking for antibiotics that are active against resistant bacteria, such as ESBLs, and we found this new combination to be highly effective,” Kaye said.

    The trial was conducted at 90 sites in Europe, North and Central America, South America and South Africa from September 2018 to November 2019. More than 1,000 patients participated in the study. Some 79 percent of the patients receiving the new combination of cefepime and enmetazobactam were successfully treated for their illness, as opposed to 58.9 percent of those receiving the conventional treatment of piperacillin and tazobactam.

    Of the 20 percent of patients from the overall group belonging to the subset of those with ESBL infections, 73 percent of the patients receiving cefepime and enmetazobactam achieved a clinical cure, as opposed to 51 percent of the patients on the standard therapy.

    The antibiotic cefepime is a fourth-generation cephalosporin that was approved for use in the 1990s and is available generically. Enmetazobactam, an experimental drug made by the French biopharmaceutical company Allecra Therapeutics, is a beta-lactamase inhibitor, meaning it attacks the beta-lactamases, including the types of enzymes produced by ESBL-producing bacteria. The drug combination has been granted Qualified Infectious Disease Product and Fast Track designation by the U.S. Food and Drug Administration (FDA).

    Kaye said he expected the company to apply for FDA approval early next year.

    More than 2.8 million antimicrobial-resistant infections occur in the U.S. each year, and more than 35,000 people die from them, according to a report from the U.S. Centers for Disease Control and Prevention (CDC). In a 2019 study on antibiotic resistance, the CDC characterized ESBLs as a serious threat to human health.

    A JAMA editorial by Sonali Advani and Kimberly Claeys, both of Duke University School of Medicine, praised the Rutgers-led study: “The clinical trial by Kaye et al presents a promising novel antibiotic therapy that expands the limited armamentarium for resistant organisms and an exciting new therapeutic option for the management of acute pyelonephritis or complicated [urinary tract infection].”

    Story Source:

    Materials provided by Rutgers University. Original written by Kitta MacPherson. Note: Content may be edited for style and length.

    Journal Reference:

  • Keith S. Kaye, Adam Belley, Philip Barth, Omar Lahlou, Philipp Knechtle, Paola Motta, Patrick Velicitat. Effect of Cefepime/Enmetazobactam vs Piperacillin/Tazobactam on Clinical Cure and Microbiological Eradication in Patients With Complicated Urinary Tract Infection or Acute Pyelonephritis. JAMA, 2022; 328 (13): 1304 DOI: 10.1001/jama.2022.17034
  • Rutgers University