Category: Antibiotics

Targeted Steroid Use Might Offer a Universal Complementary Treatment for TB

Tuberculosis bacteria. Credit: CDC

While steroids like dexamethasone are used in certain tuberculosis cases (eg, TB meningitis), their impact on immune cells is not well understood. Given the renewed interest in the steroid dexamethasone, as a host-directed treatment during the COVID-19 pandemic, a Trinity College Dublin team provides evidence that treating patients with steroids may enhance the function of their macrophages to kill the mycobacteria, while diminishing pathways of inflammatory damage. The study is published now in the journal Scientific Reports.

The team’s goal was to determine whether dexamethasone impacts the macrophage’s ability to fight TB. Although glucocorticoids can reactivate TB, they are paradoxically the only adjunctive host-directed therapies that are recommended by the World Health Organization for TB. Steroids are given to patients alongside antimicrobials in certain circumstances, however, scientists don’t fully understand the effect of these drugs on the immune system, especially innate immune cells such as macrophages.

The researchers studied immune cells called macrophages derived from the blood of healthy volunteers or isolated from lung fluid donated by patients undergoing routine bronchoscopies. By treating and infecting these macrophages in the lab with Mycobacterium tuberculosis (Mtb), the scientists could examine and understand how dexamethasone affects the immune response that protects the lungs during infection.

Key findings from the study

  • Dexamethasone a potent glucocorticoid reduces glycolysis in human lung and blood derived macrophages. This reduces the amount of energy available in the cell.
  • Dexamethasone reduced the production of both pro and anti-inflammatory cytokines measured in the study, IL-1β, TNF, IL-6, IL-8 and IL-10. Although helpful for immunity, limiting the production can also limit damage from excessive inflammation.
  • Mtb-infected macrophages have increased survival when they were treated with dexamethasone. This suggests that dexamethasone may protect macrophages from dying due to the harmful effects of infection or detrimental immune responses to infection.
  • Dexamethasone reduces bacterial burden in infected macrophages, and we have identified that this is at least partly mediated by autophagy and phagosomal acidification. Dexamethasone can enhance the macrophages’ ability to degrade and clear bacteria helping to overcome infection with Mtb.

This study identifies that macrophages from different sources have differential responses to glucocorticoids. This highlights that tissue origin can influence how macrophages react to drugs, which may be important for targeting treatment strategies. This is one of the first studies to show that dexamethasone can reduce inflammation while preserving or enhancing antimicrobial function in primary human lung macrophages infected with Mtb.

How could this research change a patient’s life?

The findings support the use of steroids as an extra therapy in conjunction with existing antimicrobial therapies in TB treatment, especially in cases with excessive inflammation. Steroids might also be useful with antimicrobials in TB preventative therapy, to reduce progression from latent TB infection to active TB disease. This study opens avenues for macrophage-targeted steroid therapies that balance inflammation control with antimicrobial defence.

For now, researchers hope this study will hasten the recovery of TB patients who experience debilitating symptoms, often for months into existing therapy.

Dr Donal Cox, Senior Research Fellow, Clinical Medicine, Trinity College Dublin said:

“Our study shows that dexamethasone, which is known to dampen inflammation, can also help macrophages fight tuberculosis more effectively. This challenges the assumption that steroids always suppress immunity and opens the door to smarter, targeted adjunctive therapies that balance inflammation control with antimicrobial defence.”

Prof Joseph Keane, Professor of Medicine, Trinity College Dublin and Consultant Respiratory Physician, St James Hospital said:

“In clinical practice, steroids are the most under-used adjunctive therapy for TB. We often rely on steroids to manage inflammation in tuberculosis, particularly in severe forms like TB meningitis. What’s reassuring from this study, is that dexamethasone not only tempers inflammation but also appears to support the macrophage’s ability to control infection. This study provides new evidence to help us redefine steroid use in TB care—targeting inflammation without compromising antimicrobial defence.”

Next steps for this research

Developing steroid therapies that can be specifically targeted to lung macrophages via mechanisms such as inhaled nanoparticles might be an option to translating this into better therapy. The team also wants to identify how steroids altered different metabolic pathways in human lung macrophages and not in blood derived macrophages so they can exploit this to make steroid therapies better in the future.

Source: Trinity College Dublin

Amazing Images Show How Antibiotics Shred Bacterial Armour

Bacteria response to antibiotics

UK researchers have shown for the first time in stunning detail how life-saving antibiotics act against harmful bacteria. The team, led by UCL and Imperial College London, has shown for the first time how a class of antibiotics called polymyxins are able to pierce the armour of E. coli and kill the microbes. 

The findings, published in the journal Nature Microbiology, could lead to new treatments for bacterial infections – especially urgent since drug-resistant infections already kill more than a million people a year.

Polymyxins were discovered more than 80 years ago and are used as a last-resort treatment for infections caused by “Gram negative” bacteria.

These bacteria have an outer surface layer that acts like armour and prevents certain antibiotics from penetrating the cell. Polymyxins are known to target this outer layer, but how they disrupt it and then kill bacteria is still not understood.

Through capturing these incredible images of single cells, we’ve been able to show that this class of antibiotics only work with help from the bacterium, and if the cells go into a hibernation-like state, the drugs no longer work – which is very surprising

Dr Andrew Edwards Department of Infectious Disease

In the new study, the research team revealed in high-resolution images and biochemical experiments how the antibiotic Polymyxin B rapidly caused bumps and bulges to break out on the surface of an E. coli bacterial cell.

These protrusions, which appeared within minutes, were followed by the bacterium rapidly shedding its outer armour.

The antibiotic, the researchers concluded, had triggered the cell to produce and shed its armour.

The more the cell tried to make new amour, the more it lost the amour it was making, at such a rate that it left gaps in its defences, allowing the antibiotic to enter the cell and kill it.

However, the team found that this process – protrusions, fast production and shedding of armour, and cell death – only occurred when the cell was active. In dormant (sleeping) bacteria, armour production is switched off, making the antibiotic ineffective.

Co-senior author Dr Andrew Edwards, from the Department of Infectious Disease at Imperial College London, said: “For decades we’ve assumed that antibiotics that target bacterial armour were able to kill the microbes in any state, whether they’re actively replicating or they were dormant. But this isn’t the case.

“Through capturing these incredible images of single cells, we’ve been able to show that this class of antibiotics only work with help from the bacterium, and if the cells go into a hibernation-like state, the drugs no longer work – which is very surprising.”

Becoming dormant allows bacteria to survive unfavourable conditions such as a lack of food. They can stay dormant for many years and “wake up” when conditions become more favourable. This can allow bacteria to survive against antibiotics, for instance, and reawaken to cause recurrent infections in the body.

Co-senior author Professor Bart Hoogenboom, based at the London Centre for Nanotechnology at UCL, said: “Polymyxins are an important line of defence against Gram-negative bacteria, which cause many deadly drug-resistant infections. It is important we understand how they work.

“Our next challenge is to use these findings to make the antibiotics more effective. One strategy might be to combine polymyxin treatment – counterintuitively – with treatments that promote armour production and/or wake up ‘sleeping’ bacteria so these cells can be eliminated too.

“Our work also shows we need to take into account what state bacteria are in when we are assessing the effectiveness of antibiotics.”

The E. coli cells were imaged at the London Centre for Nanotechnology at UCL. A tiny needle, only a few nanometres wide, was run over the bacterial cell, “feeling” the shape to create an image (a technique called atomic force microscopy) at much higher resolution than would be possible using light.

Co-author Carolina Borrelli, a PhD student at the London Centre for Nanotechnology at UCL, said: “It was incredible seeing the effect of the antibiotic at the bacterial surface in real-time. Our images of the bacteria directly show how much polymyxins can compromise the bacterial armour. It is as if the cell is forced to produce ‘bricks’ for its outer wall at such a rate that this wall becomes disrupted, allowing the antibiotic to infiltrate.”

The team compared how active (growing) and inactive E. coli cells responded to polymyxin B in the lab, finding that the antibiotic efficiently eliminated active cells but did not kill dormant cells.

They also tested the E. coli cells’ response with and without access to sugar (a food source that wakes up dormant cells). When sugar was present, the antibiotic killed previously dormant cells, but only after a delay of 15 minutes – the time needed for the bacteria to consume the sugar and resume production of its outer armour.

In conditions where the antibiotic was effective, the researchers detected more armour being released from the bacteria. They also observed the bulges occurring across the surface of the cell.

In conditions where it was ineffective, the antibiotic bound itself to the outer membrane but caused little damage.

Co-author Dr Ed Douglas, from Imperial, said: “We observed that disruption of the outermost armour of the bacteria only occurred when the bacteria were consuming sugar. Once we knew that, we could quickly figure out what was happening.”

Co-author Professor Boyan Bonev, of the University of Nottingham, said: “Working together has given us unique insights into bacterial physiology and morphology under stress that have remained hidden for decades. Now we understand better the weak points of bacteria.”

Source: Imperial College London

Could Slime Mould Microbes Be a Source of Potent Antimicrobials?

Photo by National Cancer Institute on Unsplash

The cellular slime mold Dictyostelium discoideum is a soil microbe that produces diverse natural products with potential antibiotic activity. Previously, three chlorinated compounds had been detected in Dictyostelium, but only the most abundant compound (CDF-1) was identified and shown to be almost as effective an antimicrobial as ampicillin.  In research published in FEBS Open Bio, investigators optimised lab culture conditions of Dictyostelium cells to boost the levels of low-abundance chlorinated compounds and to characterise their antimicrobial properties.

The optimized culture conditions took advantage of propionic acid and zinc supplementation to increase the yield of the chlorinated compounds, leading to the identification of CDF-2 and CDF-3 in addition to CDF-1. The molecular structure of CDF-2 and CDF-3 was similar to that of CDF-1, aside from the length of a molecular structure called an acyl side chain. When their antibacterial activity was tested, similarly to CDF-1, CDF-2 and CDF-3 exhibited stronger activity against Gram-positive bacteria than ampicillin but limited activity against Gram-negative bacteria.

Because these compounds are conserved across distantly related Dictyostelium species, CDFs may fulfill a critical role in protecting against harmful bacteria.

“Soil presents both opportunities and dangers for the Dictyostelium amoeba, and we believe this amoeba responds by producing specialised chemicals to attract, repel, or eliminate friends, prey, and predators. We are just starting to discover these chemicals, including this new, potent antibiotic,” said corresponding author Tamao Saito, PhD, of Sophia University, in Japan.

Source: Wiley

‘Alarming’ Rise in Newborn Babies with Antibiotic-resistant Infections, Researchers Find

Photo by Christian Bowen on Unsplash

Researchers are calling for an urgent overhaul of diagnostic and treatment guidelines for infections in newborn babies, after a University of Sydney-led study revealed frontline treatments for sepsis are no longer effective to treat the majority of bacterial infections. 

The study, published in The Lancet Regional Health – Western Pacific, analysed almost 15 000 blood samples collected from sick babies in 2019 and 2020 at 10 hospitals across five countries in Southeast Asia, including Indonesia and the Philippines. 

It found that most infections were caused by bacteria unlikely to respond to the currently applied WHO recommended treatments. These were developed using data from high-income countries, instead of using localised data which could be more accurate and therefore effective. 

“Our study highlights the causes of serious infections in babies in countries across Southeast Asia with high rates of neonatal sepsis, and reveals an alarming burden of AMR that renders many currently available therapies ineffective for newborns,” said senior author Associate Professor Phoebe Williams, a Senior Lecturer and NHMRC Fellow in the Sydney School of Public Health.

“Guidelines must be updated to reflect local bacterial profiles and known resistance patterns. Otherwise, mortality rates are only going to keep climbing.”

The problem is further compounded by a lack of new antimicrobial medications in development for infants and babies, added co-author Michelle Harrison, PhD candidate and Project Coordinator of NeoSEAP in the Sydney School of Public Health. 

“It takes about 10 years for a new antibiotic to be trialled and approved for babies,” Harrison said.

“With so few new drug candidates in the first place, we need a significant investment in antibiotic development.”

Gram-negative bacteria responsible for 80% of infections

For the samples which tested positive for fungal or bacterial infections, the team analysed whether they were caused by gram-positive or gram-negative bacteria – referring to the structure of the bacteria’s cell wall which influences how likely it is to develop and acquire antibiotic resistance. 

Gram-negative bacteria like E. coli, Klebsiella and Acinetobacter were responsible for nearly 80% of infections and are more likely to develop (and spread) antibiotic resistance.

“These bugs have long been considered to only cause infections in older babies, but are now infecting babies in their first days of life,” said Associate Professor Williams. 

When treating babies, doctors don’t have time to wait for lab tests to confirm the exact cause of the infection, and often make an educated guess from published data, most often based on high-income populations, to guide treatment. These tests are also frequently delayed or falsely negative due to the difficulty of collecting blood samples.

Harrison explained that the findings showcase the importance of locally relevant data to guide routine medical decision-making.

“We need more region-specific surveillance to guide treatment decisions. Otherwise, we risk reversing decades of progress in reducing child mortality rates,” she said.

“Our results also revealed fungal infections caused nearly one in 10 serious infections in babies – a much higher rate than in high-income countries. 

“We need to ensure doctors are prescribing treatments that have the best chance at saving a baby’s life.”

Source: University of Australia

Study Finds Caffeine Can Weaken Effectiveness of Certain Antibiotics

Photo by Mike Kenneally on Unsplash

Ingredients of our daily diet – including caffeine – can influence the resistance of bacteria to antibiotics. This has been shown in a new study by a team of researchers at the Universities of Tübingen and Würzburg led by Professor Ana Rita Brochado. They discovered bacteria such as Escherichia coli (E. coli) orchestrate complex regulatory cascades to react to chemical stimuli from their direct environment which can influence the effectiveness of antimicrobial drugs such as ciprofloxacin.

In a systematic screening, Brochado’s team investigated how 94 different substances – including antibiotics, prescription drugs, and food ingredients – influence the expression of key gene regulators and transport proteins of the bacterium E. coli, a potential pathogen. Transport proteins function as pores and pumps in the bacterial envelope and control which substances enter or leave the cell. A finely tuned balance of these mechanisms is crucial for the survival of bacteria.

Researchers describe phenomenon as an ‘antagonistic interaction’

“Our data show that several substances can subtly but systematically influence gene regulation in bacteria,” says PhD student Christoph Binsfeld, first author of the study. The findings suggest even everyday substances without a direct antimicrobial effect – eg, caffeinated drinks – can impact certain gene regulators that control transport proteins, thereby changing what enters and leaves the bacterium. “Caffeine triggers a cascade of events starting with the gene regulator Rob and culminating in the change of several transport proteins in E. coli – which in turn leads to a reduced uptake of antibiotics such as ciprofloxacin,” explains Ana Rita Brochado. This results in caffeine weakening the effect of this antibiotic. The researchers describe this phenomenon as an ‘antagonistic interaction.’

“Caffeine triggers a cascade of events starting with the gene regulator Rob and culminating in the change of several transport proteins in E. coli – which in turn leads to a reduced uptake of antibiotics such as ciprofloxacin,” says Prof Brochado.

This weakening effect of certain antibiotics was not detectable in Salmonella enterica, a pathogen closely related to E. coli. This shows that even in similar bacterial species, the same environmental stimuli can lead to different reactions – possibly due to differences in transport pathways or their contribution to antibiotic uptake.

The study, which has been published in the scientific journal PLOS Biology, makes an important contribution to the understanding of what is called ‘low-level’ antibiotic resistance, which is not due to classic resistance genes, but to regulation and environmental adaptation. This could have implications for future therapeutic approaches, including what is taken during treatment and in what amount, and whether another drug or food ingredient – should be given greater consideration.

Source: University of Tübingen

New Antibiotic to Fight C. Diff Proves Effective in Clinical Trial

Clostridioides difficile. Credit: CDC

As the effectiveness of antibiotics meant to fight the deadly superbug Clostridioides difficile wanes, a research team at the University of Houston is seeing positive results of a new antibiotic on the scene – ibezapolstat – which is proving successful in fighting these infectious bacteria in clinical trials.

C. diff is a leading cause of death from gastroenteritis, causing gastrointestinal illness ranging from diarrhoea and abdominal pain to toxic megacolon, sepsis and death.

Until now the frontline treatments for C. diff have been the antibiotics vancomycin, with a sustained clinical cure of 42% to 71%, and fidaxomicin at 67%.

And yet, a superbug would not be so deadly if it was not able to outlive the very medicines meant to destroy it.

“Both vanco and fidaxo are associated with emerging antimicrobial resistance. C. difficile infection recurrence is associated with increased mortality, decreased quality of life and higher healthcare costs. New antibiotics are urgently needed,” said Kevin Garey, Professor of Drug Discovery at the University of Houston College of Pharmacy and senior author on recent clinical trial results with ibezapolstat published in Lancet Microbe.

C. diff infections often return when the natural balance in the gut stays disrupted – good bacteria like Bacillota, Bacteroidota, and Actinomycetota are reduced, while harmful types like Pseudomonadota increase. These changes can weaken the gut’s defences, causing a loss of the kind of bacteria that helps break down bile acids. When that happens, harmful bacteria can easily take over.

“Ibezapolstat’s mechanism of action helps restore the healthy microbiota that causes C. diff recurrence” said study lead author Taryn A. Eubank, research assistant professor of Pharmacy Practice and Translational Research at UH.

Enter ibezapolstat

Ibezapolstat has a way of working that kills harmful C. difficile bacteria without harming the good bacteria in the gut that protect against C. diff infections.

“A randomized, double-blind, active-controlled study showed high rates of initial clinical cure in participants treated with ibezapolstat, with no recurrence,” reports Garey.

“Ibezapolstat was found to be safe, well tolerated, and was associated with the preservation of key health-promoting bacteria responsible for bile acid homoeostasis, a key component in preventing recurrent C. difficile infection.”

Eubank added, “This helps confirm the important anti-C diff recurrence properties of Ibezapolstat.”

Ibezapolstat is being developed by Acurx Pharmaceuticals progressing towards phase III clinical trials. The study was conducted at 15 centres, primarily outpatient clinics and hospitals in the United States. Participants were aged 18–90 years, with diarrhoea and a confirmed diagnosis of mild or moderate C. difficile infection.

“The findings of our study support further clinical development of ibezapolstat into phase III clinical trials and eventual use in our patients,” said Garey.

Source: University of Houston

Special Lactic Acids Reduce Antibiotic Resistance in Infants

Photo by William Fortunato on Pexels

Infants with high levels of antibiotic-resistant bacteria face a greater risk to their health if they need to be treated with antibiotics when they contract infectious diseases during their first year of life. Now, researchers at the Technical University of Denmark have discovered a way to combat antibiotic-resistant bacteria by nourishing a special subgroup of bifidobacteria found in the gut.

The research project, recently published in the renowned journal Nature Communications, points to a new, natural strategy for combating antibiotic resistance: supporting the good bacteria in the gut from the very first months of life.

“We document that special lactic acids produced by bifidobacteria play a key role in keeping antibiotic-resistant bacteria at bay, which is important for reducing the risk of resistance genes being transferred to other bacteria in the gut. Resistance genes can jump from one type of bacteria to another, and the more bacteria with resistance that are present in the gut, the greater the chance that they will encounter other bacteria and transfer resistance genes to them,” says postdoc Ioanna Chatzigiannidou from DTU Bioengineering, who participated in the research project.

The study of gut bacteria is based on 547 stool samples from 56 children and their mothers, who were followed over a five-year period.

A matter of life and death for infants

Professor Susanne Brix Pedersen from DTU Bioengineering is the head of the research project and explains that the new knowledge about bifidobacteria can be better utilized in society when researchers have developed a rapid test for use in the first weeks of a child’s life, so that parents can check whether their child already has these bifidobacteria naturally or would benefit from receiving a supplement containing them.

“It will be very important if we can strengthen their ability to handle antibiotic-resistant bacteria from the first weeks of a child’s life. This is especially true in the first year of life where infants are exposed to many infectious diseases due to an immature immune system, and when it is a matter of life and death if they have many antibiotic-resistant bacteria, for instance the pneumonia bacteria Klebsiella pneumoniae, making it difficult to treat pneumonia with certain antibiotics,” says Susanne Brix Pedersen.

There is a lot of research into antibiotic resistance, and Susanne Brix Pedersen is also involved in another study, BEGIN, which is based in the paediatric department at Aarhus University Hospital, where researchers are investigating whether a dietary supplement containing beneficial bifidobacteria can strengthen the immune system of newborn babies. So far, the trial has involved 300 women and their newborn babies, who are given either a placebo or a dietary supplement containing the special bifidobacteria.

Source: Technical University of Denmark

One Dose of Antibiotic Treats Early Syphilis as Well as Three Doses 

NIH-funded clinical trial shows potential to simplify treatment for early syphilis.

Photo by Raghavendra V Konkathi on Unsplash

Researchers funded by the National Institutes of Health (NIH) have found that a single injection of the antibiotic benzathine penicillin G (BPG) successfully treated early syphilis just as well as the three-injection regimen used by many clinicians in the United States and elsewhere. These findings from a late-stage clinical trial suggest the second and third doses of conventional BPG therapy do not provide a health benefit. The results were published in The New England Journal of Medicine.

“Benzathine penicillin G is highly effective against syphilis, but the three-dose regimen can be burdensome and deter people from attending follow-up visits with their healthcare providers,” said Carolyn Deal, PhD, chief of the enteric and sexually transmitted infections branch of NIH’s National Institute of Allergy and Infectious Diseases (NIAID). “The new findings offer welcome evidence for potentially simplifying treatment with an equally effective one-dose regimen, particularly while syphilis rates remain alarmingly high.”

Syphilis is a common sexually transmitted infection (STI) caused by the bacterium Treponema pallidum. The United States reported 209 253 total syphilis cases and 3882 congenital syphilis cases in 2023, representing 61% and 108% increases over 2019 numbers, respectively. Without treatment, syphilis can result in neurological and organ damage as well as severe pregnancy complications and congenital abnormalities. Syphilis can also increase a person’s likelihood of acquiring or transmitting HIV.

BPG is one of the few antibiotics known to effectively treat syphilis, and stockouts are common worldwide. The antibiotic is currently being imported to the United States to resolve a nationwide shortage.

The study was conducted at ten U.S. sites and enrolled 249 participants with early syphilis, which encompasses the primary, secondary, and early latent stages of disease. Sixty-four percent of participants were living with HIV and 97% were men. The participants were randomly assigned to receive either a single intramuscular (IM) injection of BPG 2.4 million units (MU) or a series of three IM injections of BPG 2.4 MU at weekly intervals. All participants were monitored for safety. Biological markers of successful treatment in the blood – known as the serologic response to therapy – were examined at six months following treatment.

Seventy-six percent of participants in the single-dose group had a serologic response to treatment compared to 70% of participants in the three-dose group. The difference between groups was not statistically significant, even when participants were stratified by HIV status. One participant developed signs of neurosyphilis three days after starting BPG therapy and was excluded from the analysis. Three serious adverse events were reported but were not related to BPG.

“Syphilis has been studied and treated for more than a century, and BPG has been in use for more than 50 years, yet we are still acquiring knowledge to help us optimise treatment,” said Principal Investigator Edward W. Hook III, MD, emeritus professor of medicine and epidemiology at the University of Alabama at Birmingham. “We hope these promising results will be complemented by scientific advances in syphilis prevention and diagnosis.”

According to the study authors, the results from this trial provide substantial evidence that single-dose BPG 2.4 MU is as effective as three doses in treating early syphilis. More research is needed to understand the full potential of this abbreviated treatment strategy and to evaluate therapeutic approaches for all stages of syphilis, including late syphilis, latent syphilis of unknown duration, and clinical neurosyphilis.

The study was conducted through the NIAID-funded Sexually Transmitted Infections Clinical Trials Group.

For more information about this trial, please visit ClinicalTrials.gov using the study identifier  NCT03637660.

Source: National Institutes of Health

Paracetamol and Ibuprofen Linked to Antibiotic Resistance

Study evaluated nine common medications used in old age care homes

Photo by Kampus Production

New research from the University of South Australia shows that the trusted staples of paracetamol and ibuprofen are quietly fuelling one of the world’s biggest health threats: antibiotic resistance.

In the first study of its kind, researchers found that ibuprofen and paracetamol are not only driving antibiotic resistance when used individually but amplifying it when used together.

Assessing the interaction of non-antibiotic medications, the broad-spectrum antibiotic ciprofloxacin, and Escherichia coli, researchers found that ibuprofen and paracetamol significantly increased bacterial mutations, making E. coli highly resistant to the antibiotic.

It’s an important finding that has serious health implications, particularly for people in aged care homes, where multiple medications are regularly administered.

The World Health Organization reports that antimicrobial resistance is a global threat to public health, and that bacterial resistance was directly responsible for 1.27 million global deaths in 2019.

Lead researcher UniSA’s Associate Professor Rietie Venter says the findings raise important questions about the risks of polypharmacy in aged care.

“Antibiotics have long been vital in treating infectious diseases, but their widespread overuse and misuse have driven a global rise in antibiotic-resistant bacteria,” Assoc Prof Venter says.

“This is especially prevalent in residential aged care facilities, where older people are more likely to be prescribed multiple medications – not just antibiotics, but also drugs for pain, sleep, or blood pressure – making it an ideal breeding ground for gut bacteria to become resistant to antibiotics.

“In this study we looked at the effect of non-antibiotic medicines and ciprofloxacin, an antibiotic which is used to treat common skin, gut or urinary tract infections.

“When bacteria were exposed to ciprofloxacin alongside ibuprofen and paracetamol, they developed more genetic mutations than with the antibiotic alone, helping them grow faster and become highly resistant. Worryingly, the bacteria were not only resistant to the antibiotic ciprofloxacin, but increased resistance was also observed to multiple other antibiotics from different classes.

“We also uncovered the genetic mechanisms behind this resistance, with ibuprofen and paracetamol both activating the bacteria’s defences to expel antibiotics and render them less effective.”

The study assessed nine medications* commonly used in residential aged care: ibuprofendiclofenacparacetamolfurosemidemetforminatorvastatintramadoltemazepam, and pseudoephedrine.

Assoc Prof Venter says the study shows how antibiotic resistance is a more complex challenge than previously understood, with common non-antibiotic medications also playing a role.

“Antibiotic resistance isn’t just about antibiotics anymore,” Assoc Prof Venter says.

“This study is a clear reminder that we need to carefully consider the risks of using multiple medications – particularly in aged care where residents are often prescribed a mix of long-term treatments.

“This doesn’t mean we should stop using these medications, but we do need to be more mindful about how they interact with antibiotics – and that includes looking beyond just two-drug combinations.”

The researchers are calling for further studies into drug interactions among anyone on long-term medication treatment regimes so we can gain a greater awareness of how common medications may impact antibiotic effectiveness.

Source: University of South Australia

Study Suggests No Link Between Antibiotic Exposure and Autoimmune Diseases in Children

Korean children with early life exposure to antibiotics were not diagnosed with autoimmune diseases at higher rates

Photo by Chayene Rafaela on Unsplash

The global incidence of autoimmune diseases among children has increased over the past few decades. A study published August 21st in the open-access journal PLOS Medicine by Ju-Young Shin at Sungkyunkwan University, Republic of Korea, and colleagues suggests that early life antibiotic exposure is not associated with an increased risk of autoimmune diseases in children.

Previous research has suggested that exposure to antibiotics as a foetus or infant may contribute to the development of autoimmune diseases among children. However, confounding variables limit the validity of prior studies and the association of antibiotics to autoimmune disease remains poorly understood.

In order to investigate whether antibiotics may increase risk of autoimmune diseases, researchers conducted a retrospective cohort study comprised of over 4 million children born in the Republic of Korea between April 1, 2009, and December 31, 2020. They accessed a mother-child linked insurance claims database from the South Korea National Health Insurance Service-National Health Insurance Database (NHIS-NHID) to identify children whose mothers had received antibiotic prescriptions during pregnancy or while breastfeeding their infant. The researchers then retrospectively analysed the health outcomes of each cohort for a period of over 7 years, tracking all diagnoses of Type 1 diabetes, Juvenile idiopathic arthritis, Inflammatory bowel disease (ulcerative colitis, Crohn’s disease), Systemic lupus erythematosus, and Hashimoto’s thyroiditis.

The researchers found no relationship between antibiotic exposure during pregnancy or early infancy and the overall incidence of autoimmune diseases in children. Future research is needed, however, to replicate the outcomes in other populations and to further investigate potential effects on subgroups.

According to the authors, “Our findings suggest no association between antibiotic exposure during the prenatal period or early infancy and the development of autoimmune diseases in children. This observation contrasts with several previous studies reporting increased risks and underscores the importance of carefully considering the underlying indications for antibiotic use and genetic susceptibility when interpreting such associations. While the potential benefits of antibiotic treatment in managing infections during pregnancy or early infancy likely outweigh the minimal risk of autoimmune outcomes, our findings also highlight the need for cautious and clinically appropriate use of antibiotics during these critical developmental periods in specific subgroups.”

The authors note, “Exposure to antibiotics during pregnancy or early infancy was not associated with an increased risk of autoimmune diseases in children. Nevertheless, the importance of follow-up studies to confirm and extend these findings cannot be overstated.”

Provided by PLOS