Common Skin Bacteria Found Beneficial Against Drying, Aging

Add Staphylococcus epidermidis to the list of common human bacteria undergoing an image change: From the bad reputation of “disease-causing” to something helpful – and likely interesting to probiotic users.

Scanning electron micrograph of a clump of Staphylococcus epidermidis bacteria (green) in the extracellular matrix, which connects cells and tissue.
Credit: NIAID

S. epidermidis is known as a bacterium that usually colonizes harmlessly on the skin, but can be dangerous when it invades deeper, says through a cut or – more commonly – a surgical implant, such as a catheter. Once established internally, the bacterium can form biofilms that are difficult to treat with antibiotics. S. epidermidis is of particular concern in healthcare settings because it often spreads easily in people who are ill or have weakened immune systems.

The bacterium’s new image is aided by research findings just published by NIAID scientists and colleagues in Cell Host and Microbe. The group showed that S. epidermidis produces enzymes, known as sphingomyelinase, that help the bacteria acquire nutrients and colonize the skin. But the bacterial enzymes also help the skin produce ceramides, which are important components of the outer skin layers that prevent drying and aging of the skin. Low ceramide levels contribute to many skin diseases, such as atopic dermatitis, commonly called eczema. With colleagues from Shanghai Jiaotong University in China, the NIAID scientists identified how the mutually beneficial relationship works.

The study used research mice and samples from the faces and armpits of human volunteers to verify that S. epidermidis produces sphingomyelinase and that the enzyme is not harmful. In the mice, they then found that the presence of S. epidermidis on the skin significantly increases ceramide levels and prevents water loss from damaged skin. Then they discovered that these processes are entirely dependent on the sphingomyelinase that the bacteria secrete.

Their study points out that – much like in the gut, where scientists are learning about the balance between good and bad bacteria – the same type of harmony takes place on the skin.

“Our study underlines the potential translational use of S. epidermidis in a probiotic fashion to promote skin health during aging or in people suffering from skin diseases such as atopic dermatitis,” the authors state. Such an undertaking would involve a complex clinical trial involving hospitals and clinicians, so nothing is set, though the scientists plan to discuss how and where such a study could proceed. Another NIAID research team has shown in a small study that probiotic therapy reduced the severity of eczema symptoms in children.  

Rapid diagnostic for gonorrhea wins $19 million federal prize competition to combat antibiotic resistance

A diagnostic test capable of accurately and reliably detecting the microorganism that causes gonorrhea and rapidly determining in under 30 minutes if the microorganism is susceptible to a single-dose antibiotic is the winner of the Antimicrobial Resistance (AMR) Diagnostic Challenge. Visby Medical, Inc., will receive $19 million as a prize for its winning diagnostic.

Colorized scanning electron micrograph of Neisseria gonorrhoeae bacteria, which causes gonorrhea. NIAID

According to the Centers for Disease Control and Prevention, more than 2.8 million antibiotic-resistant infections occur in the United States each year, and more than 35,000 people die as a result. The AMR Diagnostic Challenge is co-sponsored by the National Institutes of Health and the Biomedical Advanced Research and Development Authority (BARDA) of the HHS Office of the Assistant Secretary for Preparedness and Response, with each contributing $10 million over the course of the competition.

“Antibiotic-resistant bacteria are a growing and concerning public health risk against which we have few effective deterrents,” said NIH Director Francis S. Collins, M.D., Ph.D. “Challenge prizes spur innovation and we saw many innovative concepts throughout this competition. I want to congratulate Visby Medical for their winning technology, which could help reduce the unnecessary use of antibiotics, a major driver of antimicrobial resistance.”

“One of the challenges healthcare providers face in combating the growing threat of antimicrobial resistant infections is identifying which drugs will be effective in treating the initial infection, and fixing that problem starts with rapid, accurate, easy-to-use, point of care diagnostics,” said BARDA Acting Director Gary Disbrow, Ph.D. “Innovative technologies that can rapidly detect and diagnose drug resistant infections have the potential to measurably improve our response in a public health emergency caused by a drug resistant pathogen. Congratulations to Visby Medical on their winning technology.”

The company’s diagnostic, known as Patient-side, Disposable, Molecular PCR Diagnostic Device for Neisseria gonorrhoeae and Drug Resistance Markers, is a palm-size, single-use, disposable device for the detection of Neisseria gonorrhoeae (N. gonorrhoeae), the microorganism that causes gonorrhea. This diagnostic gives results quickly, allowing clinicians to treat patients immediately and with the correct medication. Gonorrhea is one of the most frequently seen sexually transmitted infections (STIs), which represent a major public health crisis worldwide and in the United States. There were more than 580,000 cases of gonorrhea reported nationwide in 2018 according to the CDC, a 63% increase from 2014.

This type of rapid testing that includes assessment of antibiotic susceptibility has not been available previously as a point-of-care diagnostic device. Antimicrobial resistance in gonorrhea is of increasing concern, and successful treatment of gonorrhea is becoming more difficult. Treatment options have been limited to two drugs, requiring an injection of one drug plus an oral antibiotic.

If approved by the U.S. Food and Drug Administration, the Visby Medical device could be useful in ensuring that patients with gonorrhea receive the right antibiotic so that they can immediately begin treatment, and will allow other antibiotics to be used for patients with drug resistant strains of N. gonorrhoeae.

The easy-to-use format of the device could be helpful in STI clinics, walk-in/urgent care clinics and other facilities without extensive hands-on laboratory staff. Ultimately, this device could have a significant impact in addressing the increasing incidence of gonorrhea and the increasing spread of drug resistant forms of this common STI in the United States and worldwide. Visby Medical currently is exploring how its proprietary technology platform could be adapted to aid in the development of diagnostics for SARS-CoV-2, the virus that causes COVID-19.

The winning diagnostic was chosen from a group of five semifinalists who each received $100,000 in Step 2 of the competition to develop and test prototypes to improve detection of drug-resistant bacteria or differentiate between a bacterial and viral infection. For more information on Visby Medical’s submission and the AMR Diagnostic Challenge, visit: https://dpcpsi.nih.gov/AMRChallenge.

Highly active HIV antibody restricts development of viral resistance

A research team led by Univ.-Prof. Dr. Florian Klein of the Institute of Virology of the University Hospital Cologne and the German Center for Infection Research (DZIF) has identified a new highly active antibody targeting HIV.

They identified a new highly active antibody targeting HIV (left to right): Henning Grüll, Philipp Schommers and Florian Klein.
© Uniklinik Köln/Thies Schöning

Whereas the development of viral resistance limits the efficacy of previously described HIV antibodies, the newly identified antibody 1-18 can continuously suppress viral replication.

1-18 therefore has high potential for successful application in the prevention and treatment of HIV infection. An article describing antibody 1-18 has now been published in Cell.

Antiretroviral drugs are the gold standard for the treatment of HIV infection. They are highly effective in suppressing replication of the virus but require lifelong daily application and can be associated with side effects. Due to the high mutability of HIV and its capacity for rapid adaptation, combinations of antiretroviral agents are required to prevent the development of drug resistance and treatment failure.

Broadly neutralizing antibodies are a focus of ongoing research on novel options for the treatment and prevention of HIV infection. Their mode of action substantially differs from regular antiretroviral drugs, as antibodies target the virus through specific binding of HIV surface proteins.

Clinical trials have demonstrated the potential of broadly neutralizing antibodies by reducing the viral load in the blood of HIV-infected individuals. Similar to antiretroviral drugs, however, the effects of single antibodies were only temporary because of the development of viral resistance.

Scientists at the University Hospital Cologne have now identified a novel antibody called 1-18 that targets HIV. This antibody is highly potent and showed activity against 97% of the tested HIV variants. „1-18 is therefore among the best HIV neutralizing antibodies described to date“, says Dr. Philipp Schommers, resident physician at the Department I of Internal Medicine and one of the first authors of the article.

In collaboration with colleagues at the California Institute of Technology (Pasadena, USA), the researchers identified the mode of action of antibody 1-18 in detail. 1-18 binds and inactivates a surface structure of HIV that is particularly relevant because it is essential for viral infection and replication.

The therapeutic efficacy of the newly identified antibody 1-18 was studied using a mouse model that allows recapitulation of HIV infection as it occurs in humans. In this model, other broadly neutralizing antibodies showed only short-term effects because of the rapid development of viral resistance. In contrast, treatment with the antibody 1-18 resulted in suppression of the viral load that was maintained for the duration of therapy. „These results indicate that development of viral resistance against the new antibody 1-18 is restricted when compared to other antibodies“, says Dr. Henning Grüll, resident physician at the Institute of Virology and also first author of the work.

Due to its high potency, the scientists consider 1-18 a promising candidate for HIV immunotherapy. “In addition, 1-18 has great potential for preventing HIV infection by passive immunization“, adds Prof. Dr. Florian Klein, lead and senior author of the study. Clinical trials are now planned to further investigate antibody 1-18.

Long-term antibiotic use linked with CVD risk in women

Women’s risk for cardiovascular disease (CVD) may increase if they use antibiotics for two months or more, according to a new study.

Researchers looked at data on more than 36,000 women over seven years of follow-up. Compared with women who never used antibiotics, women in their 40s or 50s who used them for two months or longer had a 28% increased risk for CVD, the study found. Women over 60 who used antibiotics for that long had a 32% increased risk.

The study, published in the European Heart Journal on Thursday April 24, 2019, found that women aged 60 or older who took antibiotics for two months or more had the greatest risk of cardiovascular disease, but long duration of antibiotic use was also associated with an increased risk if taken during middle age (aged 40-59). The researchers could find no increased risk from antibiotic use by younger adults aged between 20-39.

Professor Lu Qi, director of the Tulane University Obesity Research Centre, Tulane University, New Orleans, and adjunct professor of nutrition at Harvard T.C. Chan School of Public Health, Boston, USA, who led the research, says that a possible reason why antibiotic use is linked to an increased risk of cardiovascular disease is because antibiotics alter the balance of the micro-environment in the gut, destroying “good” probiotic bacteria and increasing the prevalence of viruses, bacteria or other micro-organisms that can cause disease.

“Antibiotic use is the most critical factor in altering the balance of microorganisms in the gut. Previous studies have shown a link between alterations in the microbiotic environment of the gut and inflammation and narrowing of the blood vessels, stroke and heart disease,” he said.

After adjustments to take account of factors that could affect their results, such as age, race, sex, diet and lifestyle, reasons for antibiotic use, overweight or obesity, other diseases and medication use, the researchers found that women who used antibiotics for periods of two months or longer in late adulthood were 32% more likely to develop cardiovascular disease than women who did not use antibiotics. Women who took antibiotics for longer than two months in middle age had a 28% increased risk compared to women who did not.

These findings mean that among women who take antibiotics for two months or more in late adulthood, six women per 1,000 would develop a cardiovascular disease, compared to three per 1,000 among women who had not taken antibiotics.

The first author of the study is Dr Yoriko Heianza. a research fellow at Tulane University. She said: “By investigating the duration of antibiotic use in various stages of adulthood we have found an association between long-term use in middle age and later life and an increased risk of stroke and heart disease during the following eight years. As these women grew older they were more likely to need more antibiotics, and sometimes for longer periods of time, which suggests a cumulative effect may be the reason for the stronger link in older age between antibiotic use and cardiovascular disease.”

The most common reasons for antibiotic use were respiratory infections, urinary tract infections and dental problems.

The study is the largest prospective study to investigate the link between antibiotic use and risk of heart disease and stroke, and this is one of the strengths of the study, as well as the long follow-up and comprehensive information on factors that could affect the results such as life style, diet, age, other diseases and medication use.

Limitations include the fact that the participants reported their use of antibiotics and so this could be mis-remembered. However, as they were all health professionals, they were able to provide more accurate information on medication use than the general population. The researchers did not have information on the different classes of antibiotics used, but believe that the most common type of prescription tends to depend on the infections it is treating, and information on these was included in their analysis. As the study only looked at middle-aged and elderly women, the results cannot necessarily be extrapolated to younger ages and to men.

Prof Qi concluded: “This is an observational study and so it cannot show that antibiotics cause heart disease and stroke, only that there is a link between them. It’s possible that women who reported more antibiotic use might be sicker in other ways that we were unable to measure, or there may be other factors that could affect the results that we have not been able take account of.

“Our study suggests that antibiotics should be used only when they are absolutely needed. Considering the potentially cumulative adverse effects, the shorter time of antibiotic use the better.”

Physicians may overprescribe antibiotics to children during telemedicine visits

Children are more likely to be overprescribed antibiotics for colds, sinus infections and sore throats during telemedicine visits than during in-person visits to primary care providers or urgent care facilities, suggests a study funded by the Eunice Kennedy ShriverNational Institute of Child Health and Human Development (NICHD), part of the National Institutes of Health. The study, conducted by Kristin Ray, M.D., of the University of Pittsburgh School of Medicine and colleagues, appears in Pediatrics.

Many companies offer visits in which patients can connect with physicians outside of their primary care practice through audio-video conferencing, often on their cell phones or personal devices. The researchers compared antibiotic prescribing practices from the billing data of 4,604 telemedicine visits, 38,408 urgent care visits, and 485,201 primary care visits for children up to 17 years old with respiratory infections. They found that children were more likely to receive prescriptions for antibiotics during telemedicine visits (52%), compared to urgent care visits (42%) and visits with primary care providers (31 percent). Clinical guidelines for antibiotic prescriptions were less likely to be followed after telemedicine visits (59%), compared to urgent care (67%) or primary care visits (78%). These clinical guidelines are intended to prevent inappropriate use of antibiotics, such as to treat viral infections for which they are ineffective, and to guide selection of the most appropriate antibiotic for bacterial infections. Inappropriate antibiotic use(link is external) increases bacterial resistance to these drugs, eventually making many infections difficult to treat.

The authors theorize that physicians providing telemedicine visits may overprescribe antibiotics because they cannot closely examine patients or perform tests, potentially limiting their ability to distinguish between bacterial and viral infections.

Of all human diseases, 60% originate in animals – “One Health” is the only way to keep antibiotics working

Antibiotic resistance is a growing threat to global health. As a result of infection with drug-resistant bacteria an estimated 700 000 people die each year worldwide. A total of around 33 000 die annually in the European Union and European Economic Area, and this number is increasing all the time.

Many of the same microbes (e.g. bacteria, viruses, fungi, parasites) affect both animals and humans via the environment they share and 60% of all human diseases originate in animals. This means that when microbes develop drug resistance in animals, they can easily go on to affect humans, making it difficult to treat diseases and infections.

“Human, animal and environment health are all equally responsible for the correct use of antimicrobials and to avert the threat of antimicrobial resistance,” said Dr Zsuzsanna Jakab, WHO Regional Director for Europe. “As we strive to ensure that antibiotics are rightly used in the community and in health-care settings, one sector alone will not solve the problem. A ‘One Health’ approach brings together professionals in human, animal, food and environment health as one force, and as such is the only way to keep antibiotics working. I call on all European countries to secure the highest commitment to this approach from the whole of society and the whole of government.”

“With 33 000 deaths each year as a consequence of an infection due to bacteria resistant to antibiotics and €1 billion in annual health-care expenditure, we need to ensure that antibiotics are used prudently and that infection prevention measures are in place in all settings across Europe,” stated Andrea Ammon, Director of the European Centre for Disease Prevention and Control (ECDC). She added, “Since the rates of antibiotic resistance and the rates of antibiotic consumption as well as infection prevention practices vary from country to country, it is essential to tailor strategies to address specific needs. ECDC calls for continued action at all levels”.

This year, the WHO European Region will mark the 4th annual World Antibiotic Awareness Week on 12–18 November, by committing to closer collaboration across sectors to protect human, animal and environment health, in the spirit of One Health.

Fecal microbiota transplantation helps restore beneficial bacteria in cancer patients

NIAID-funded study could offset harsh effects of antibiotics.

Researchers at Memorial Sloan Kettering Cancer Center have shown that autologous fecal microbiota transplantation (auto-FMT) is a safe and effective way to help replenish beneficial gut bacteria in cancer patients who require intense antibiotics during allogenic hematopoietic stem cell transplantation.

Left: Streptococcus; microbial biofilm of mixed species in a human; Bacillus; Malassezia lopophilis. Jonathan Bailey, NHGRI

In their study, patients who underwent the procedure were randomly assigned into two groups: one group received standard care and the other received auto-FMT. The researchers found that auto-FMT resulted in the recovery of beneficial gut bacteria to near baseline levels within days, thus restoring patients’ digestive, immune and other essential functions.  With standard care, beneficial bacteria typically take many weeks to recover from antibiotic treatment, leaving patients at risk of other infectious diseases, including Clostridium difficile.

The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, provided funding for part of the project. The study report appears in Science Translational Medicine.

“This important study suggests that clinical intervention using auto-FMT can safely reverse the disruptive effects of broad-spectrum antibiotic treatment,” says NIAID Director Anthony S. Fauci, M.D. “If validated in larger studies, this approach may prove to be a relatively simple way to quickly restore a person’s healthy microbiome following intensive antimicrobial therapy.”

Allogenic hematopoietic cell transplantation involves a donor — often but not exclusively a family member — who gives the recipient stem cells that re-establish bone marrow production of blood cells and immune function to combat cancer. Antibiotics are essential to prevent bacterial infections in stem cell recipients. However, antibiotics also destroy beneficial bacteria that enhance immune function and resistance to infection. The loss of beneficial bacteria increases the risk of certain life-threatening infectious diseases and graft-versus-host disease (GVHD).

The study involved cancer patients who provided their own fecal sample, which was frozen and stored prior to their cell transplantation procedure. Weeks later, when physicians confirmed that the transplanted cells were growing, they assessed the status of the patients’ beneficial gut bacteria. The first 25 patients who lacked known beneficial bacteria were enrolled into the study and randomly assigned to the different treatment groups: 14 received auto-FMT by enema and 11 received standard-of-care.

The patients who received auto-FMT consistently regained bacterial diversity, composition and function; recovery of beneficial bacteria in the 11 control patients was delayed.

The researchers are continuing to monitor the study patients to determine if auto-FMT improves patient outcomes, such as the incidence and severity of bacterial, viral and fungal infections and the incidence and severity of GVHD. Whether FMT from a healthy donor would be as beneficial as the patient’s own fecal sample at restoring beneficial bacteria remains to be studied.