The computer model improves on traditional methods like contact tracing by inferring asymptomatic carriers in the spread of antibiotic-resistant infections
A new analytical tool can improve a hospital’s ability to limit the spread of antibiotic-resistant infections over traditional methods like contact tracing, according to a new study led by researchers at Columbia University Mailman School of Public Health and published in the peer-reviewed journal Nature Communications. The method infers the presence of asymptomatic carriers of drug-resistant pathogens in the hospital setting, which are otherwise invisible.
Antimicrobial resistance (AMR) is an urgent threat to human health. In 2019, 5 million deaths were associated with an AMR infection globally.
The inference framework developed by Columbia Mailman School researchers is the first to combine several data sources – patient mobility data, clinical culture tests, electronic health records, and whole-genome sequence data – to predict the spread of an AMR infection in the hospital setting. In the study, the researchers used five years of real-world data from a New York City hospital. They focused on carbapenem-resistant Klebsiella pneumoniae (CRKP), an AMR bacterium with a high mortality rate. The framework draws on the four data sources to model the spread of CRKP infections, from individual to individual over time.
Levels of CRKP colonisation in healthcare facilities vary by location but can reach up to 22 percent of patients. However, hospitals do not routinely screen for CRKP, and surveillance relies on testing patients who are either symptomatic or suspected of coming into contact with symptomatic patients, overlooking asymptomatic colonisers.
“Many antimicrobial-resistant organisms colonise people without causing disease for long periods of time, during which these agents can spread unnoticed to other patients, healthcare workers, and even the general community,” says the study’s first author, Sen Pei, PhD, assistant professor of environmental health sciences at Columbia Mailman School. “Our inference framework better accounts for these hidden carriers.”
The researchers used the inference framework to estimate CRKP infection probabilities despite limited data on infections. They found that combining the four data sources led to more accurate carrier identification. Furthermore, using data simulations, they found that the framework was more successful at preventing the spread of infections after isolating carriers than traditional approaches based on an individual’s time in the hospital, the number of people they came in contact with, and/or whether the people they came in contact with were identified as having infections.
Using the inference model, isolating 1% of patients on the first day of each week (10–13 patients per week) reduces 16% of positive cases and 15% of colonisation; isolating 5% of patients on the first day of each week (50–65 patients per week) reduces 28% of positive cases and 23% of colonisation. For comparison, using contact tracing – a typical approach in clinical settings (ie, screening close contacts of positive patients) – isolating 1% of patients reduces 10% of positive cases and 8% of colonisation; isolating 5 percent of patients reduces 20% of positive cases and 16% of colonisation.
The new study builds on a study in PNAS that introduced a method that more accurately predicts the likelihood that individuals in hospital settings are colonised with methicillin-resistant Staphylococcus aureus (MRSA) than existing approaches. The new study is a significant advance over the previous study because it now includes patient-level electronic health records and whole-genome sequence data, which allows more precise identification of silent spreaders. While the inference model improves on traditional methods, it remains challenging to eliminate AMR pathogens in hospitals due to their widespread community circulation, limited hospital surveillance, and high false-negative rates in clinical culture tests. However, there is room for improvement; a future study aims to look at the spread of AMR using ultra-dense sequencing.
In Pakistan, 50% of strains of a common milk bacterium, Staphylococcus epidermidis, were multi-drug resistant
Cultured Staphylococcus epidermidis isolates from raw milk samples on MSA. Image credit: Inamullah and colleagues, Abdul Wali Khan University Mardan, Pakistan, CC-BY 4.0
Raw cow and sheep milk is frequently contaminated with antibiotic-resistant bacteria that could pose a threat to human and animal health, reports a new study led by Tahir Usman of Abdul Wali Khan University Mardan, Pakistan, published November 12, 2025 in the open-access journal PLOS One.
In Pakistan, over 95% of milk is consumed in its raw form, which has not been pasteurized to kill off harmful bacteria. Milk can become contaminated by bacteria through improper handing or from infections in the teat, called subclinical mastitis. The overuse of antibiotics to treat subclinical sumastitis has led to the emergence of multidrug-resistant bacterial strains, which could then be transmitted to humans through raw milk.
In the new study, researchers investigated the risk posed by Staphylococcus epidermidis, a subclinical mastitis-causing bacteria that often does not lead to visible symptoms in the cow, but results in contaminated, lower-quality milk. They collected 310 milk samples, about half from cattle and half from ewes, and tested them for subclinical mastitis. They also isolated strains of Staphylococcus epidermidis from the milk samples and screened them for antibiotic resistance. About one quarter of the samples showed evidence of subclinical mastitis and almost 13% (1 in 8) were contaminated with Staphylococcus epidermidis. Strikingly, 95% of Staphylococcus epidermidis bacteria isolated from the milk were resistant to penicillin and erythromycin, and half were resistant to three or more antibiotics.
In humans, Staphylococcus epidermidis is a common, generally harmless inhabitant of the skin, but the researchers point out that multi-drug resistant Staphylococcus epidermis bacteria in raw milk could spread antimicrobial resistance to more harmful pathogens, like Staphylococcus aureus, the MRSA pathogen.
The study’s findings underscore the high rates of subclinical mastitis in cattle and ewes, and indicate that Staphylococcus epidermidis might be an important pathogen impacting both animal health and food safety. The high rates of antibiotic resistance observed in the samples also emphasize the urgent need for improved antibiotic stewardship in agriculture to prevent the rise of multi-drug resistant strains.
The authors add: “The presence of multidrug-resistant Staphylococcus epidermidis in raw milk highlights how on-farm antibiotic use directly shapes public health risks. These findings emphasize the urgent need for responsible antibiotic use and improved hygiene practices in the dairy sector to reduce the risk of antimicrobial resistance transmission through the food chain.”
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.”
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.
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.
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.
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.”
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.
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.”
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 Escherichiacoli 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.
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.
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 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.
Experts say bacterial infections are responsible for more infant deaths than is generally recognised, and things may get worse as more of the bugs become resistant to commonly used antibiotics. We asked local experts about this growing threat to newborns.
A two-week-old baby is referred to the Red Cross War Memorial Children’s Hospital (RCWMCH) in Cape Town. The infant, who was born prematurely at six months, has come from a nearby neonatal hospital.
She’s developed complications, including a feed intolerance and constant vomiting. On investigation, she is found to have a bowel perforation and a condition called necrotising enterocolitis. Surgeons conclude she needs an operation to repair the perforation. A sample of pus from inside her abdomen is sent to a laboratory to identify any infections. While the tests are being done, the infant is started on second-line antibiotics. The doctors suspect she picked up an infection due to pathogens that may be resistant to first-line antibiotics while in the neonatal hospital.
“But 48 hours later, when the results are available, they may show that the antibiotics we’ve been treating the baby with are not treating the bacteria that have now been detected in the lab,” says Associate Professor James Nuttall, a paediatric infectious diseases sub-specialist at RCWMCH and the University of Cape Town.
“In response to those results, we’d change to a different set of antibiotics to try and target the bacteria that have been detected. In the meantime, the child has deteriorated and requires a second operation. Throughout all the subsequent treatments, we are testing samples for infections she might – and frequently will – acquire along the way.”
From then on, he says it’s a case of trying to keep up with the sequence of infections that the baby might develop. Some of these infections may have originated at the neonatal hospital, while others could have been acquired during her treatment in the Intensive Care Unit (ICU) at RCWMCH, possibly from the operating theatre, intravenous lines, or healthcare workers’ hands.
“This is the kind of scenario we are faced with all the time,” says Nuttall. “The fact is, an infant might come into hospital with one infection and, unfortunately, pick up a bunch of other infections while in the hospital from transmission of pathogens that may be resistant to one or more of the commonly used first- or second-line antibiotics.”
Sitting in a boardroom at the Red Cross Hospital, close to the paediatric wards and clinics in which he treats sick children referred from other hospitals in Cape Town and beyond, Nuttall says there are two possible outcomes for this baby.
“She might turn the corner and respond to the new antibiotics, together with interventions from the surgical doctors and expert management in an ICU. Or she might not respond to the treatment, and die two days later, because of ongoing infection that doesn’t respond to treatment.”
Nuttall is discussing the ongoing issue of rising antibiotic resistance, particularly among neonates, the group most vulnerable to this. He’s responding to Spotlight’s main question: Will the antibiotics used to treat bacterial infections, such as Klebsiella pneumoniae – which have seen hundreds of babies die in hospitals in recent years – keep working? And, how big is the risk of antibiotic resistance to infants?
“The short answer to whether the antibiotics we currently use to treat bacterial infections will keep working is no,” he says.
‘Almost endemic’
In some South African healthcare facilities, especially in the public sector, antibiotic-resistant bacteria have become “almost endemic”, says Professor Shabir Madhi, director of the Wits Vaccines and Infectious Diseases Analytics Unit at University of Witwatersrand (WITS VIDA).
“There are a large number of deaths occurring on an ongoing basis. We still have clusters of outbreaks, but those are underpinned by a really widespread dissemination of these antibiotic-resistant bacteria, and persistently high rates of hospital-acquired infections, especially in the first month of life,” he says. “Despite the best of efforts, we haven’t been able to get on top of this.”
Madhi headed up a study at the Chris Hani Baragwanath Academic Hospital in Soweto in which they used molecular testing to look at evidence of infections in 153 babies who had passed away. The researchers found that infections were the immediate or underlying cause of death in 58% of all the neonatal deaths, including the immediate cause in 70% of neonates with complications of prematurity as the underlying cause.
Overall, 74.4% of 90 infection-related deaths were hospital-acquired, mainly due to multidrug-resistant Acinetobacter baumannii (52.2%), Klebsiella pneumoniae (22.4%), and Staphylococcus aureus (20.9%).
Also asked whether the antibiotics used to treat Klebsiella and other bacterial infections will keep working, Madhi says: “The short answer is that we’ve already run out of antibiotics in the public sector that can treat all of these different bacteria.”
He says that there are two bacteria that are of particular concern in South Africa.
“The one is Klebsiella pneumoniae, which that has become resistant to almost all of the antibiotic classes that are available for use, except perhaps for colistin, (a reserve antibiotic which is seen as a last-resort treatment for multidrug-resistant Gram-negative infections), but even antibiotic resistance to colistin in bacteria is emerging.
“The other big one is Acinetobacter baumannii, which is also a common cause of hospital-acquired infections. Here the bacteria have become resistant to all classes of antibiotics including colistin.”
Madhi says compared to other African countries, South Africa is better equipped to provide high-level care, including intensive care, to prematurely-born babies.
“Consequently, we end up spending a mini fortune to get these very premature children to survive the first few days of life, only for them then to succumb to hospital-acquired infections. Whereas in other settings many of these babies will die in the first few hours of life.”
He adds: “The single leading cause of neonatal mortality in South Africa is antibiotic resistant bacterial infections, but that is underpinned by other conditions which increases the susceptibility of babies to eventually succumb to these hospital-acquired infections.”
In the public sector, Madhi says hospital-acquired infections are a major reason why children are dying. In the private sector, there is more attention on identifying these infections, along with better resources, which helps reduce the problem.
Meanwhile, physicians like Nuttall are put in impossible situations at Red Cross.
“When doing blood tests on an infant to check for infection, you can’t wait for those results. You have to start treatment with what you think is the appropriate treatment. That’s the empirical treatment,” explains Nuttall.
“Then, when you isolate a bacterium and know its resistance profile (or antibiotic susceptibility profile), you must redirect your treatment to what’s known as ‘directed’ or definitive treatment. But there’s now been a time gap of 24 to 72 hours where the infant is on treatment, and you don’t know if it’s the right treatment. That’s a critical issue, because the baby might deteriorate in that time because they’re not on the right treatment,” he says.
He says the choice of empiric antibiotics is becoming more difficult, “as what we previously used as empiric antibiotic treatment is less and less reliable to treat serious infections, particularly in patients who acquire resistant infections in hospital”.
In a position paper, Nuttall and his colleagues write that growing antibiotic resistance is linked to the increased use of “reserve” and “watch” antibiotics. The WHO classifies antibiotics into three groups. Access antibiotics are the common ones used to treat everyday infections in the community. Watch antibiotics are broad-spectrum antibiotics that carry a higher risk of causing resistance, so their use must be carefully monitored and limited. Reserve antibiotics are last-resort treatments for infections caused by multi-drug-resistant bacteria and should only be used when all other options have failed.
‘Totally underestimated’
Following the research described earlier, Madhi says they convened an expert panel, to deliberate on what the causes of death was in children.
Unfortunately, he says, it’s become completely monotonous in that there’s a clear series of events for children born prematurely, who die: They’re admitted to hospital, they usually require ICU, they improve in ICU, and two to three days later, they appear very sick again. “Often you don’t actually identify the bacteria causing the clinical deterioration when you investigate ante-mortem, and you only realise the child actually succumbed to antimicrobial resistant bacterial infections after you’ve done the postmortem sampling”. Postmortem sampling is not done systematically across the country.
“What the post-mortem sampling has unmasked, is that we’ve totally underestimated the contribution of antibiotic-resistant bacteria in relation to causes of neonatal death. If we were to do the same investigations in other facilities, there would be much greater heightened awareness of what is really an unrecognised endemic public health crisis across our healthcare facilities,” says Madhi.
Professor Angela Dramowski, Head of the Clinical Unit: General Paediatrics at Tygerberg Hospital, agrees that outbreaks in low- and middle-income country hospitals, including South Africa are under-reported.
“What we see in the literature and in the headlines of newspapers is the tip of the iceberg. The vast majority of outbreaks in fact are either undetected or unreported. This is almost an invisible problem because a lot of the deaths are currently labelled due to another cause, for example, prematurity.
“This is a crucial public health crisis. We cannot practice modern medicine without effective antibiotics, and, especially for newborns the situation is perilous as we have very few effective treatment options left.”
‘Existential threat’
Though more acute in some areas, the problem is a global one. Marc Mendelson, Professor of Infectious Diseases at the University of Cape Town, describes antibiotic resistance as an existential global health threat.
“If antibiotic resistance is not mitigated, in the next 25 years, 39 million people globally will die of an antibiotic-resistant bacterial infection. That will dwarf HIV, tuberculosis, and malaria,” he says.
“There are bacteria currently causing infections in our hospitals in South Africa that are totally resistant to antibiotics. Those patients would usually die or need extraordinary measures to keep them alive such as amputating a limb to remove the infection in a bone or joint,” Mendelson says.
“People have always assumed if you get sick with a bacterial infection, there will be an antibiotic to treat it. Doctors in and out of hospitals have been too lax in how they prescribe antibiotics. Now we’re paying the price as some bacterial infections are not easily treatable,” he says.
As Dramowski points out, there is a lot of good science confirming the extent of the problem. A systematic review published in The Lancet found that almost 5 million deaths in 2019 were associated with bacterial infections resistant to antibiotics.
“That huge number is more than deaths from HIV and malaria combined,” she says.
Dramowski also points to another review study that found 3 million cases of neonatal sepsis globally each year, with at least 570 000 deaths (likely an underestimate). Over 95% of deaths from neonatal antibiotic resistance occur in low- and middle-income countries (LMICs).
“In a nutshell, in five big studies … they showed that antibiotic resistance to the World Health Organization-recommended antibiotic treatments ranges anywhere between 40 to 70%, so almost half of all babies with severe bacterial infection have resistance to the recommended antibiotic treatment,” she says.
What to do?
To address the major issue of antibiotic resistance in infants, Dramowski stresses the importance of prevention. This includes improving Water, Sanitation, and Hygiene (WASH) as well as Infection Prevention and Control programmes to reduce the spread of antibiotic-resistant bacteria in communities and healthcare facilities. She also stresses the need to prevent pre-term births as much as possible, as hospital admissions carry a high risk of acquiring antibiotic-resistant bacteria and developing infections.
She says increased surveillance of infections in LMICs is also crucial, along with more antibiotic trials to provide better alternatives. Additionally, there is a strong need for responsible antibiotic use (stewardship) to ensure they are only used when necessary, helping to prevent the development of antibiotic resistance.
A challenge in practicing stewardship is the difference in resources between the public and private sectors, says Professor Vindana Chibabhai, Head of the Centre for Healthcare-associated Infections, Antimicrobial Resistance, and Mycology (CHARM) at the National Institute for Communicable Diseases. Expensive antibiotics are more easily accessible in the private sector, while they are often not available in the public sector.
“Antibiotic stewardship is happening all over the country but we need to have a national monitoring system,” she says.
Chibabhai says that private sector clinicians often work independently and are not required to follow stewardship programmes as strictly as those in public sector hospitals. To address antibiotic resistance, she says we need monitoring systems to track the effectiveness of these programmes and provide support to hospitals struggling with them. Even though some hospitals have dedicated pharmacists, microbiologists, and clinicians, Chibabhai says they may need additional help to strengthen their antibiotic stewardship efforts.
‘Lots of lovely paper’
A major issue highlighted by experts is the lack of a clear AMR strategy in South Africa. The last strategy, which covered 2019 to 2024, was not funded, and its impact has not been evaluated.
“We have lots of lovely paper and lots of committed people doing great work but in terms of interventions, none of it is funded,” says Mendelson, who chaired the Ministerial Advisory Committee on Antimicrobial Resistance for the eight years until 2022. “If these interventions were funded, we could save lives.”
Madhi says the consequences of not implementing South Africa’s AMR plan are exactly what we are seeing now. “The problems have become endemic and entrenched in public healthcare facilities and lead to large numbers of unnecessary deaths which could have been prevented if we implemented a proper strategy in place.”
He says the situation now calls for a multi-faceted approach. “It’s not just about the type of antibiotics that should be available but about mitigating the many contributing factors that resulted in these outbreaks. That requires immense investment in terms of resources and expertise.”
