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Tag: antibiotic resistance

  • Urban Birds Are Harboring Antibiotic-Resistant Bacteria

    Urban Birds Are Harboring Antibiotic-Resistant Bacteria

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    This story originally appeared in The Guardian and is part of the Climate Desk collaboration.

    Urban ducks and crows might offer us a connection to nature, but scientists have found wild birds that live near humans are more likely to harbor bacteria resistant to important antibiotics.

    Antimicrobial resistance (AMR) is largely caused by the overuse of drugs such as antibiotics among humans and livestock.

    The issue is of serious concern: According to data for 2019, about 4.95 million deaths globally were associated with bacterial AMR, including 1.27 million directly caused by such resistance.

    Researchers say species of wild birds that tend to turn up in urban settings are reservoirs for bacteria with the hallmarks of resistance to a host of drugs.

    “Basically what we’re seeing are genes that confer resistance to antimicrobials that would be used to treat human infections,” said Samuel Sheppard, coauthor of the research from the Ineos Oxford Institute for Antimicrobial Research.

    The team say their findings are important as wild birds have the capacity to travel over considerable distances. Sheppard said a key concern was that these birds could pass antimicrobial-resistant bacteria to captive birds destined to be eaten by humans—such as those kept in poultry farms.

    Writing in the journal Current Biology, Sheppard and colleagues report how they analyzed the genomes of bacteria found in 700 samples of bird poo from 30 wild bird species in Canada, Finland, Italy, Lithuania, Japan, Sweden, the UK, and the US.

    The team looked specifically at the presence of different strains of Campylobacter jejuni—a type of bacteria that are ubiquitous in birds as a natural part of their gut microbiome. Such bacteria are a leading cause of human gastroenteritis, although antibiotics are generally only used in severe cases.

    Sheppard added that, in general, each wild bird would be expected to harbor a single strain of C. jejuni, specific to that species.

    However, the team found wild birds that turn up in urban settings contain many more strains of C. jejuni than those that live away from humans.

    What’s more, the strains found in urban-dwelling species contained about three times as many genes known to result in antimicrobial resistance, with these genes also associated with resistance to a broader range of antimicrobials.

    The authors suggest that wild birds may pick up antimicrobial-resistant bacteria in a number of ways: Gulls and crows, for example, are known to lurk at landfill sites, while ducks and geese may pick them up in rivers and lakes that are contaminated with human wastewater.

    Thomas Van Boeckel, an expert in antimicrobial resistance at ETH Zurich who was not involved in the work, said the research was unusual as it focused on the impact of antimicrobial use by humans on animals.

    “What are the consequences of that for the birds? We don’t really know but it seems like we humans are responsible for this change,” he said.

    Danna Gifford from the University of Manchester added the findings could have implications for human health.

    “While alarming, the risk of direct transmission of resistance from urban birds to humans is unclear. Poultry-to-human transmission, however, is well documented,” she said. “With urban development encroaching on agricultural land, increasing contact between urban birds and poultry raises significant concerns about indirect transmission through the food chain.”

    Andrew Singer, of the UK Centre for Ecology & Hydrology, said more samples were needed to ensure the results stood up, but that precautions could be taken.

    “The most obvious place to start is to ensure birds do not congregate in our landfills, wastewater treatment plants, and animal muck piles, where both pathogens and AMR are abundant,” he said. “Moreover, we must also eliminate the discharge of untreated sewage into our rivers, which exposes all river-using wildlife—and humans—to human-associated pathogens and AMR.”

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    Nicola Davis

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  • New antibiotic from ‘dark matter’ targets superbugs

    New antibiotic from ‘dark matter’ targets superbugs

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    Newswise — A new powerful antibiotic, isolated from bacteria that could not be studied before, seems capable to combat harmful bacteria and even multi-resistant ‘superbugs’. Named Clovibactin, the antibiotic appears to kill bacteria in an unusual way, making it more difficult for bacteria to develop any resistance against it. Researchers from Utrecht University, Bonn University (Germany), the German Center for Infection Research (DZIF), Northeastern University of Boston (USA), and the company NovoBiotic Pharmaceuticals (Cambridge, USA) now share the discovery of Clovibactin and its killing mechanism in the scientific journal Cell.

    Urgent need for new antibiotics

    Antimicrobial resistance is a major problem for human health and researchers worldwide are looking for new solutions. “We urgently need new antibiotics to combat bacteria that become increasingly resistant to most clinically used antibiotics,” says Dr. Markus Weingarth, a researcher from the Chemistry Department of Utrecht University.

    However, the discovery of new antibiotics is a challenge: few new antibiotics have been introduced into the clinics over the last decades, and then they often resemble older, already known antibiotics.

    “Clovibactin is different,” says Weingarth. “Since Clovibactin was isolated from bacteria that could not be grown before, pathogenic bacteria have not seen such an antibiotic before and had no time to develop resistance.”

    Antibiotic from bacterial dark matter

    Clovibactin was discovered by NovoBiotic Pharmaceuticals, a small US-based early-stage company, and microbiologist Prof. Kim Lewis from Northeastern University, Boston. Earlier, they developed a device that allows to grow ‘bacterial dark matter’, which are so-called unculturable bacteria. Intriguingly, 99% of all bacteria are ‘unculturable’ and could not be grown in laboratories previously, hence they could not be mined for novel antibiotics. Using the device, called iCHip, the US researchers discovered Clovibactin in a bacterium isolated from a sandy soil from North Carolina: E. terrae ssp. Carolina.

    In the joint Cell publication, NovoBiotic Pharmaceuticals shows that Clovibactin successfully attacks a broad spectrum of bacterial pathogens. It was also successfully used to treated mice infected with the superbug Staphylococcus aureus. 

    A broad target spectrum

    Clovibactin appears to have an unusual killing mechanism. It targets not just one, but three different precursor molecules that are all essential for the construction of the cell wall, an envelope-like structure that surrounds bacteria. This was discovered by the group of Prof. Tanja Schneider from the University of Bonn in Germany, one of the Cell paper’s co-authors.

    Schneider: “The multi-target attack mechanism of Clovibactin blocks bacterial cell wall synthesis simultaneously at different positions. This improves the drug’s activity and substantially increases its robustness to resistance development.”

    A cage-like structure

    How exactly Clovibactin blocks the synthesis of the bacterial cell wall was unraveled by the team of Dr. Markus Weingarth from Utrecht University. They used a special technique called solid-state nuclear magnetic resonance (NMR) that allows to study Clovibactin’s mechanism under similar conditions as in bacteria.

    “Clovibactin wraps around the pyrophosphate like a tightly sitting glove. Like a cage that encloses its target” says Weingarth. This is was gives Clovibactin its name, which is derived from Greek word “Klouvi”, which means cage. The remarkable aspect of Clovibactin’s mechanism is that it only binds to the immutable pyrophosphate that is common to cell wall precursors, but it ignores that variable sugar-peptide part of the targets. “As Clovibactin only binds to the immutable, conserved part of its targets, bacteria will have a much harder time developing any resistance against it. In fact, we did not observe any resistance to Clovibactin in our studies.”

    Fibrils capture the targets

    Clovibactin can do even more. Upon binding the target molecules, it self-assembles into large fibrils on the surface of bacterial membranes. These fibrils are stable for a long time and thereby ensure that the target molecules remain sequestered for as long as necessary to kill bacteria.

    “Since these fibrils only form on bacterial membranes and not on human membranes, they are presumably also the reason why Clovibactin selectively damages bacterial cells but is not toxic to human cells,” says Weingarth. “Clovibactin hence has potential for the design of improved therapeutics that kill bacterial pathogens without resistance development.”.

     

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    Utrecht University

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  • Troubling Signs TB Is Gaining Resistance Against Combo Antibiotics

    Troubling Signs TB Is Gaining Resistance Against Combo Antibiotics

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    By Cara Murez 

    HealthDay Reporter

    MONDAY, Jan. 30, 2023 (HealthDay News) — New drugs may be needed to fight the deadliest form of tuberculosis, because it may no longer respond to current treatments.

    An animal study by Johns Hopkins University researchers found that an approved antibiotic regimen may not work for TB meningitis due to multidrug-resistant strains. Small human studies have also provided evidence that a new combination of drugs is needed.

    Doctors currently use a regimen of three antibiotics — bedaquiline, pretomanid and linezolid (BPaL) — to treat TB of the lungs due to multidrug-resistant (MDR) strains. The new study showed that is not effective in treating TB meningitis because bedaquiline and linezolid are restricted in crossing the blood-brain barrier, a network of cells that stops germs and toxins from entering the brain.

    About 1% to 2% of TB cases progress into TB meningitis. This leads to brain infection that causes increased fluid and inflammation.

    Tuberculosis is caused by the bacteria Mycobacterium tuberculosis and is considered a global health threat.

    “Most treatments for TB meningitis are based on studies of treatments for pulmonary TB, so we don’t have good treatment options for TB meningitis,” senior author Dr. Sanjay Jain said in a Hopkins news release. He’s director of the university’s Center for Infection and Inflammation Imaging Research in Baltimore.

    The BPaL regimen has been approved for MDR strains of TB since 2019.

    For the study, researchers synthesized a chemically identical version of the antibiotic pretomanid. They conducted experiments with mouse and rabbit models of TB meningitis.

    They used positron emission tomography (PET) imaging to measure penetration of the antibiotic into the central nervous system and used direct drug measurements in mouse brains.

    Imaging showed excellent penetration of pretomanid into the brain or the central nervous system of the mouse and rabbit models. But levels in the cerebrospinal fluid (CSF) that bathes the brain were several times lower than in the brains of mice.

    “When we have measured drug concentrations in the spinal fluid, we have found that many times they have no relation to what’s happening in the brain,” study co-author Dr. Elizabeth Tucker said in the release. She’s an assistant professor of anesthesiology and critical care medicine. “This finding will change how we interpret data from clinical trials and, ultimately, treat infections in the brain.”

    The researchers also compared effectiveness of the BPaL regimen to the standard treatment — a combination of the antibiotics rifampin, isoniazid and pyrazinamide — used to treat drug-susceptible forms of TB.

    The ability to kill bacteria in the brain using the BPaL regimen in the mouse model was about 50 times lower than the standard TB regimen after six weeks of treatment. This was likely due to restricted penetration of bedaquiline and linezolid into the brain, researchers said.

    That means that the “regimen that we think works really well for MDR-TB in the lung does not work in the brain,” Jain said.

    Another experiment involved six healthy adults — three men and three women ages 20 to 53 years. PET imaging was used to show pretomanid distribution to major organs, according to researchers.

    Results in the people were similar to those found in mice.

    “Our findings suggest pretomanid-based regimens, in combination with other antibiotics active against MDR strains with high brain penetration, should be tested for treating MDR-TB meningitis,” said co-author Dr. Xueyi Chen, a pediatric infectious diseases fellow at Hopkins, who is now studying combinations of such therapies.

    The findings were recently published in Nature Communications.

    More information

    The U.S. National Library of Medicine has more on tuberculosis meningitis.

     

    SOURCE: Johns Hopkins Medicine, news release, Jan. 27, 2023

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  • Is Using Antibiotics Before STI Exposure Risky?

    Is Using Antibiotics Before STI Exposure Risky?

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    Dec. 9, 2022 – The use of antibiotics to prevent – not just treat – sexually transmitted infections was a fringe idea just a decade ago. Now, it has the backing of several studies and a green light from a California public health department.

    Jeffrey Klausner, MD, an infectious disease doctor and professor of public health at the University of Southern California, published the first randomized, controlled trial on whether doxycycline – an antibiotic commonly used to treat infections, including syphilis, chlamydia, and others – could prevent STIs back in 2015. At first, he says the National Institutes of Health didn’t want to fund the work, expressing concerns about the potential for antimicrobial resistance.

    In a worst-case scenario, microbes change over time and no longer respond to medicine, and treatments stop working.

    But a growing STI crisis has health care professionals searching for new options to help. 

    “There were more than 170,000 cases of syphilis [in the U.S.] last year, and yearly cases have doubled over the past five years,” says Klausner. 

    Repeated studies, with slightly different designs, also found lower rates of STIs among people who took doxycycline either daily or after sex. The method, known as pre-exposure doxycycline prophylaxis, now has its own name: doxyPEP.

    And in October, the San Francisco Department of Public Health recommended doxyPEP for cisgender men and transgender women who have had a bacterial STI in the past year as well as condomless oral or anal sex with one or more cis men or trans women in the past year.

    For those who meet the second criteria but haven’t been diagnosed with an STI in the last year, the department is advising a “shared decision-making approach,” where doctors discuss the benefits and risks of doxyPEP and prescribe it for patients who feel they will benefit, explains Stephanie Cohen, MD, the department’s acting director of disease prevention and control in the Population Health Division. 

    The department also recommends doxyPEP for anyone diagnosed with syphilis, regardless of their gender or sexual partners.

    Cohen says the U.S. has among the highest rates of STIs in the world and that “San Francisco, in particular, has some of the highest rates of sexually transmitted infections in the country.”

    Latest Results

    The most recent study of doxyPEP followed 501 men and trans women in Seattle and San Francisco. About two-thirds were taking HIV pre-exposure prophylaxis (HIV PrEP) and the rest were living with HIV. The results of that study, shared at the International AIDS Society (IAS) Conference earlier this year, found STIs were lower in the group told to take a single dose of doxycycline within 72 hours of unprotected sex. The rate of STI reduction was 66% in the HIV PrEP group and 62% in the HIV-positive group. 

    “It can be a bit of a paradigm shift when you talk about using antibiotics before someone has an infection,” says Annie Luetkemeyer, MD, an infectious disease doctor and STI researcher at the University of California San Francisco, who co-led the study.

    She recalls that when HIV PreP came out, there was pushback that it would lead to riskier sex or increased HIV drug resistance. In reality, “we’ve learned that for some segments of the population, having access to HIV PrEP has absolutely been essential to reduce the risk in HIV.”

    Now, the pushback to doxyPEP is that it could lead to more antimicrobial resistance. But Luetkemeyer points out that the highest-risk populations, for whom the intervention is meant, are already exposed to high rates of antibiotic use, largely to treat STIs. 

    In the study’s control group, the rate of STIs was 32% in a 3-month period, compared to 11% in the doxyPEP  group. But the doxyPEP use wasn’t perfect, and people in the study reported they took it after 87% of unprotected sexual encounters, on average.

    “This isn’t a question of taking doxycycline versus taking no antibiotics,” Luetkemeyer says. In fact, the control group had a 50% higher exposure to ceftriaxone, a broad-spectrum antibiotic that has a higher potential, compared to doxycycline, of spurring drug-resistant gonorrhea.

    Still, Luetkemeyer and Klausner say it’s important to monitor both drug-resistant STIs, as well as other infections, like doxycycline-resistant Staphylococcus aureus, to ensure that doxyPEP isn’t increasing them. 

    Making Things Worse?

    Luetkemeyer and her colleagues are now studying to see whether doxyPEP increases drug-resistant bacteria in those who take it. There are no red flags yet, but the research is ongoing.

    While San Francisco’s public health department has given the first official endorsement of doxyPEP, doctors who work with high-risk populations have been prescribing it off-label for years. Klausner says that when he was treating patients living with HIV or at risk of HIV, he would prescribe prophylactic doxycycline either daily or after sex without a condom, depending on the patient’s frequency of sexual activity. For as-needed use, he would typically start with 15 doses at 200 milligrams, with refills.

    He  also notes that there isn’t one, fixed group of people who need doxyPEP, pointing out that people may benefit for a period in between monogamous or relatively monogamous relationships, for example. 

    “People’s risk profile is dynamic. … doxyPEP isn’t a strategy we’re encouraging people to adopt forever,” he says. 

    And while doxyPEP could increase the risk of drug-resistant infections, it could also theoretically reduce it, by lowering the burden of STIs in the population, and the need for antibiotic treatments, Klausner says.

    “It’s been known since the 1970s that sexually transmitted infections – like chlamydia, gonorrhea, syphilis – are perpetuated by a core group,” he says, typically men who have sex with many male partners over a month. “If you can control that spread of infection in the core group, the rest of the population is more protected.”

    Cohen at the San Francisco Department of Public Health said that while “it’s definitely a priority as we roll it out to do surveillance to see if there’s any concerning signs of antimicrobial resistance,” for now, “the desire from the community to have new tools to protect themselves from STIs outweigh the potential and unknown risks of antimicrobial resistance.”

    What is certain is that decades of experience shows that the only other prevention tool, condoms, aren’t going to be widely adopted by everyone, due to partner or personal preferences. 

    “For some populations, with really soaring rates of sexually transmitted infections, what we currently have to offer isn’t working, so we really need new tools,” says Luetkemeyer.

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  • COVID Infection Disrupts the Gut’s Microbiome

    COVID Infection Disrupts the Gut’s Microbiome

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    By Dennis Thompson 

    HealthDay Reporter


    TUESDAY, Nov. 1, 2022 (HealthDay News) — COVID-19 is known to mess with a person’s lungs, and can have long-term effects on the brain.

    Now doctors have found another way COVID harms your health — through your gut.

    A COVID infection can reduce the number of bacterial species in the gut, creating an opportunity for dangerous antibiotic-resistant bacteria to thrive, according to a new study in the journal Nature Communications.

    “Our findings suggest that coronavirus infection directly interferes with the healthy balance of microbes in the gut, further endangering patients in the process,” said study co-senior author Ken Cadwell, a microbiologist at NYU Grossman School of Medicine in New York City.

    An unhealthy gut leaves a person vulnerable to life-threatening diarrhea from harmful bacteria like C. difficile. It also can cause other health problems like bloating and acid reflux.

    The study is the first to show that COVID alone damages the gut microbiome, researchers said. Before now, doctors had suspected that the use of antibiotics to treat COVID had been damaging gut bacteria.

    Analysis of nearly 100 men and women hospitalized with COVID in 2020 found that most patients had low gut microbiome diversity. In fact, full quarter had guts dominated by a single type of bacteria, the researchers found.

    At the same time, populations of several potentially harmful microbes increased. Some antibiotic-resistant bacteria had migrated into the bloodstream of 20% of patients.

    “Now that we have uncovered the source of this bacterial imbalance, physicians can better identify those coronavirus patients most at risk of a secondary bloodstream infection,” Cadwell said in an NYU news release.
     

    The findings were published Nov. 1.


    More information

    The Cleveland Clinic has more about gut health.

     

    SOURCE: NYU Grossman School of Medicine, news release, Nov. 1, 2022



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  • Most National Grocery Chains Fail Antibiotics-in-Meat Test

    Most National Grocery Chains Fail Antibiotics-in-Meat Test

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    Oct. 12, 2022 — Three-quarters of the largest grocery chains in the U.S. are failing to limit the use of antibiotics in their house-brand fresh meat, thus contributing to the spread of antibiotic resistance. 

    That’s according to a new report, “Superbugs in Stock,” produced by members of a coalition of public health, animal protection, and consumer groups known as Antibiotics Off the Menu. Of the nation’s top food retailers, Target fared the best — but even it only received a C grade.

    About half of the fresh meat sold in this country is purchased in stores. 

    “That means the grocery industry has a potentially major impact on how antibiotics are used in meat production,” says Matthew Wellington, public health campaigns director at U.S. PIRG, a member of the coalition. “This report shows a dire need for more progress in the grocery sector.”


    A Report Card for Supermarkets

    For the past 6 years, the coalition focused on restaurants, with an annual report about the practices of major fast-food and fast-casual chains. In the wake of these reports, several chains announced changes to their policies, though not all have followed through. 

    “We saw there was progress with the restaurant chains, so we wanted to look at the other place people get most of their food,” says Steven Roach of the Food Animal Concerns Trust, lead author of the report. “And coming through the pandemic, where there had been a shift from people eating out to eating at home, we thought it was good time to look at grocery chains.”

    Roach and his co-authors gathered information about the supermarket chains’ policies on antibiotic use in private-label chicken, turkey, pork, and beef through a survey as well as company websites and published materials. They assigned points for various scoring criteria — things like having a meaningful and transparent public policy that links to animal welfare, enforcement of that policy, and using third-party verification.

    Their findings don’t exactly inspire confidence. Of the dozen major grocery retailers in the U.S., eight received an F grade, with 10 points or fewer out of a possible 100. That group includes Kroger, Walmart, and Albertsons, three of the five top-earning grocers in the U.S. While many of the failing companies do carry some house-brand meat labeled “raised without antibiotics,” none have strong policies to cover the entire range of their private-label fresh meat.

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