Category: Antibiotics

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

Probiotics for Preterm Babies Lowered Antibiotic-resistant Bacteria in the Gut

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Preterm babies with very low birth weight who received a probiotic alongside antibiotics had fewer multidrug resistant bacteria and a more typical gut microbiome, a new study shows.

The paper published in Nature Communications is the result of a trial testing probiotics among a group of 34 pre-term babies born with a very low birth weight, under 1500g representing around 1-1.5% of babies born around the world. The study sequenced gut bacteria from the babies during the first three weeks after birth.

The collaborative study led by Professor Lindsay Hall and Dr Raymond Kiu from the University of Birmingham found that among babies who received a probiotic treatment of a certain strain including Bifidobacterium alongside antibiotics, levels of typical bacterial strains associated with early-life gut microbiota were at levels typical among full-term babies, reducing both the abundance of antibiotic resistance genes and the number of multi-drug resistant bacteria in the gut.

In the context of the global AMR crisis, this is a major finding, especially for NICUs where preterm infants are especially vulnerable. Probiotics are now used in many neonatal ICUs around the UK, and the WHO have recommended probiotic supplementation in preterm babies. Our paper shows how beneficial this intervention can be for babies born prematurely to help them give their gut a kickstart, and reduce the impact of concerning pathogens taking hold.Professor Lindsay Hall – University of Birmingham

There were lower levels of drug-resistant pathogens including Enterococcus associated with risks of infections and longer hospital stays. Babies who received probiotics also saw higher levels of certain positive bacteria found naturally in the gut.

Among babies who didn’t receive probiotics, analysis of the gut bacteria found that while some differences occurred between those receiving antibiotics or not, both groups saw a dominant microbiome develop that included key bacteria (pathobionts) that can cause health problems including life-threatening infections during the crucial period after birth, as well as in later life.

Professor Lindsay Hall from the University of Birmingham and a group leader at Quadram Institute Bioscience, and senior corresponding author of the study said: “We have already shown that probiotics are highly effective in protecting vulnerable preterm babies from serious infections, and this study now reveals that these probiotics also significantly reduce the presence of antibiotic resistance genes and multidrug-resistant bacteria in the infant gut. Crucially, they seem to do so selectively – targeting resistant strains without disrupting non-resistant strains that might be beneficial.

“In the context of the global AMR crisis, this is a major finding, especially for NICUs where preterm infants are especially vulnerable. Probiotics are now used in many neonatal ICUs around the UK, and the WHO have recommended probiotic supplementation in preterm babies.

“Our paper shows how beneficial this intervention can be for babies born prematurely to help them give their gut a kickstart, and reduce the impact of concerning pathogens taking hold.”

Dr Raymond Kiu from the University of Birmingham, first and co-corresponding author of the paper said: “Sequencing technology has now confirmed that probiotic Bifidobacterium rapidly replicates in the preterm gut during the first three weeks of life. Importantly, this successful colonisation drives the maturation of the gut microbiota and is linked to a noticeable reduction in multi-drug-resistant pathogens – pointing to its pivotal role in improving neonatal health. Our findings also shed light on the complex interactions between antibiotics, probiotics, and horizontal gene transfer (HGT) in shaping the early-life microbiome.

“We believe this research lays the groundwork for future studies exploring the role of probiotics in antimicrobial stewardship and infection control among preterm populations.”

Source: University of Birmingham

Bacterial Stress Drives the Development of Antibiotic Resistance

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Antibiotics are supposed to wipe out bacteria, yet the drugs can sometimes hand microbes an unexpected advantage.

A new Nature Communications study from Rutgers Health shows that ciprofloxacin, a staple treatment for urinary tract infections, throws Escherichia coli into an energy crisis that saves many cells from death and speeds the evolution of full‑blown resistance.

“Antibiotics can actually change bacterial metabolism,” said first author Barry Li, a student at Rutgers pursuing a dual doctoral degree for physician–scientists. “We wanted to see what those changes do to the bugs’ chances of survival.”

Li and senior author Jason Yang focused on adenosine triphosphate (ATP), the molecular fuel of cells. When ATP levels crash, cells experience “bioenergetic stress.” To mimic that stress, the team engineered E. coli with genetic drains that constantly burned ATP or its cousin nicotinamide adenine dinucleotide (NADH). Then, they pitted both the engineered strains and normal bacteria against ciprofloxacin.

The results surprised the researchers. The drug and the genetic drains each slashed ATP, but rather than slowing down, the bacteria revved up. Respiration soared, and the cells spewed extra reactive‑oxygen molecules that can damage DNA. That frenzy produced two troubling outcomes.

First, more of the bacteria cells survived.

In time‑kill tests, ten times as many stressed cells survived a lethal ciprofloxacin dose compared with unstressed controls. These hardy stragglers, called persister cells, lie low until the drug is gone and then rebound to launch a new infection.

People have long blamed sluggish metabolism for persister cell formation.

“People expected a slower metabolism to cause less killing,” Li said. “We saw the opposite. The cells ramp up metabolism to refill their energy tanks, and that turns on stress responses that slow the killing.”

Follow‑up experiments traced the protection to the stringent response, a bacterial alarm system that reprograms the cell under stress.

Second, stressed cells mutated faster to evolve antibiotic resistance.

While persisters keep infections smoldering, genetic resistance can render a drug useless outright. The Rutgers group cycled E. coli through escalating ciprofloxacin doses and found that stressed cells reached the resistance threshold four rounds sooner than normal cells. DNA sequencing and classic mutation tests pointed to oxidative damage and error‑prone repair as the culprits.

“The changes in metabolism are making antibiotics work less well and helping bacteria evolve resistance,” said Yang, an assistant professor at the medical school and Chancellor Scholar of microbiology, biochemistry & molecular genetics.

Preliminary measurements show that gentamicin and ampicillin also drain ATP in addition to ciprofloxacin. The stress effect may span very different pathogens, including the pathogen Mycobacterium tuberculosis, which is highly sensitive to ATP shocks.

If so, the discovery casts new light on a global threat. Antibiotic resistance already contributes to 1.27 million deaths a year. Strategies that ignore the metabolic fallout of treatment may be missing a key lever.

The findings suggest several changes for antibiotic development and use.

First, screen candidate antibiotics for unintended energy‑drain side effects. Second, pair existing drugs with anti‑evolution boosters that block the stress pathways or mop up the extra oxygen radicals. Third, reconsider the instinct to blast infections with the highest possible dose. Earlier studies and the new data both hint that extreme concentrations can trigger the very stress that protects bacteria.

“Bacteria turn our attack into a training camp,” Yang said. “If we can cut the power to that camp, we can keep our antibiotics working longer.”

Li and Yang are planning on testing compounds that soothe bioenergetic stress in the hope of turning the microbial energy crisis back into an Achilles’ heel rather than a shield.

Source: Rutgers University

South Africa Needs to do More to Tackle Antimicrobial Resistance, Warn Experts

This is a “pandemic which is wreaking havoc, is not being attended to properly and not being taken seriously enough”

Source: Unsplash CC0

By Liezl Human

A group of infectious disease and public health experts are calling on the Department of Health and Minister Aaron Motsoaledi to reintroduce a national action plan addressing antimicrobial resistance (AMR).

An open letter from over 70 doctors, scientists and public health advisors states that antibiotic resistance is becoming a “growing threat” in the country and poses a threat to universal health coverage through the National Health Insurance.

Read the open letter

Latest figures show that over one-million deaths a year worldwide are directly caused by AMR. This number is projected to increase. Nearly five-million people die with an antibiotic-resistant infection. Over the next 25 years, nearly 40-million people are projected to die from AMR. 

The second edition of the South African Antimicrobial Resistance National Strategy Framework, from 2018-2024, has expired. The plan acknowledged that antimicrobial resistance is “a serious and growing global health security risk”.

The open letter also called on the department to reinstate a ministerial advisory committee on AMR or to establish a similar scientific body.

“The lack of a robust scientific advisory body limits the government’s capacity to develop evidence-based policies,” the letter reads. The establishment of a scientific body would “empower the government to make strategic, data-driven decisions to combat this pressing health threat effectively”.

The former Ministerial Advisory Committee was disbanded in November 2023.

Marc Mendelson, an infectious disease specialist at Groote Schuur Hospital who has been outspoken about the threat of AMR for many years, said: “AMR is a current pandemic which is wreaking havoc, is not being attended to properly and not being taken seriously enough in South Africa.”

Mendelson said that there are “more and more people having to be treated for highly resistant bacterial infections in our healthcare system”. AMR leads to an increase in morbidity, mortality, hospital costs, and also has socio-economic consequences, he said. Common medical interventions such as surgery “becomes much riskier” with AMR.

Department of Health spokesperson Foster Mohale said that the department would only comment once the letter was formally presented, which is expected to happen at 5pm on Thursday.

Republished from Spotlight under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Read the original article.

Antibiotics Taken During Pregnancy May Reduce Preterm Births

Photo by SHVETS production

A study of almost 1000 pregnant women in Zimbabwe found that a daily dose of a commonly used, safe and inexpensive antibiotic may have led to fewer babies being born early. Among women living with HIV, those who received the antibiotic had larger babies who were less likely to be preterm.

One in four live-born infants worldwide is preterm (born at 37 weeks’ gestation or before), is small for gestational age, or has a low birth weight. The mortality rate for these small and vulnerable newborns is high, with prematurity now the leading cause of death among children younger than 5 years of age. Maternal infections and inflammation during pregnancy are linked to adverse birth outcomes, particularly for babies born to mothers living with HIV, who have a greater risk of being born too small or too soon. 

An international group of researchers, led by Professor Andrew Prendergast from Queen Mary University of London, and Bernard Chasekwa from the Zvitambo Institute for Maternal and Child Health Research in Zimbabwe, conducted the Cotrimoxazole for Mothers to Improve Birthweight in Infants (COMBI) randomised controlled trial, to examine whether prescribing pregnant women a daily dose of trimethoprim–sulfamethoxazole (a broad-spectrum antimicrobial agent with anti-inflammatory properties, widely used in sub-Saharan Africa) would result in heavier birth weights, decreased premature births, and better health outcomes for their babies.  

993 pregnant women were recruited from three antenatal clinics in Shurugwi, a district in central Zimbabwe, and received either 960 mg of the drug or a placebo daily. The participants received regular antenatal care during their pregnancies and data regarding their birth outcomes were recorded. 

The study, published in the New England Journal of Medicine, found that although birthweight did not differ significantly between the two groups, the trimethoprim–sulfamethoxazole group showed a 40% reduction in the proportion of preterm births, compared to the placebo group. Overall, 6.9% of mothers receiving the drug had babies born preterm, compared to 11.5% of mothers receiving the placebo, and no women receiving antibiotics had babies born prior to 28 weeks. For babies born to a small group of 131 women with HIV, the reduction in premature births was especially marked, with only 2% of births in the trimethoprim–sulfamethoxazole group preterm, as compared with 14% in the placebo group. Babies exposed to antibiotics during pregnancy also showed a 177 gram increase in their birth weight. 

Bernard Chasekwa, first author, said: “Our trial, conducted within routine antenatal care and enrolling women predominantly from rural areas, showed that trimethoprim-sulfamethoxazole did not improve birthweight, which was our main outcome. However, there was an intriguing suggestion that it may have improved the length of pregnancy and reduced the proportion of preterm births. We now need to repeat this trial in different settings around the world to see whether antibiotics during pregnancy can help reduce the risk of prematurity.”  

Source: Queen Mary University of London