Tag: antibiotic resistance

Antibiotic Resistance is Putting SA’s Newborns at Risk

Photo by Christian Bowen on Unsplash

By Sue Segar

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.”

Republished from Spotlight under a Creative Commons licence.

Read the original article.

Using Blue Light to Fight Drug-resistant Infections

Pseudomonas aeruginosa. Source: Wikimedia Commons

Researchers at the University of Oklahoma have made a breakthrough discovery that could potentially revolutionise treatments for antibiotic-resistant infections, cancer and other challenging gram-negative pathogens without relying on precious metals.

Currently, precious metals like platinum and rhodium are used to create synthetic carbohydrates, which are vital components of many approved antibiotics used to combat gram-negative pathogens, including Pseudomonas aeruginosa, a notorious hospital-acquired infection responsible for the deaths of immunocompromised patients. However, these elements require harsh reaction conditions, are expensive to use and are harmful to the environment when mined. In an innovative study published in the journal Nature Communications, an OU team led by Professor Indrajeet Sharma has replaced these precious metals with either blue light or iron, achieving similar results with significantly lower toxicity, reduced costs, and greater appeal for researchers and drug manufacturers.

By using abundant, inexpensive, iron or metal-free, non-toxic blue light, the team can more easily and rapidly synthesize these important carbohydrates. Since most antibiotics rely on a carbohydrate molecule to penetrate the thin, external layer of the gram-negative bacteria, this discovery could transform the way doctors treat multi-drug-resistant pathogens.

“Drug-resistant infections are a major problem and are expected to rise unless something is done,” Sharma said. “By using our methods to make late-stage drug modifications, synthetic carbohydrate-based antibiotics could help treat these infections. Furthermore, since carbohydrates can also increase a drug’s solubility, they can be easily deployed as a pro-drug that a patient can simply take it with water.”

A pro-drug is a medication that it less active when administered and metabolized into its active form. To help drug molecules last longer in the body and work more effectively, Sharma’s team is exploring ways to attach specially designed sugars or unnatural sugar to them. They are using a unique blue light-based method, developed by Surya Pratap Singh, a lead researcher and doctoral student in Dr. Sharma’s lab, that does not require metals.

“If a drug molecule is broken down too quickly, it loses its potency. By replacing an oxygen atom in the carbohydrate molecule with a sulfur one, enzymes in the human body won’t recognise the molecule as a carbohydrate and won’t break it down as quickly,” Sharma said. “These modified compounds, commonly called thiosugars, could be used to more effectively treat infections and diseases like cancer.”

Source: University of Oklahoma

Antibiotic Resistance Among Key Bacterial Species Plateaus Over Time


Use of antibiotics was weakly associated with resistance, indicating additional factors may be at play

Photo by CDC on Unsplash

Antibiotic resistance tends to stabilise over time, according to a study published April 3, 2025 in the open-access journal PLOS Pathogens by Sonja Lehtinen from the University of Lausanne, Switzerland, and colleagues. 

Antibiotic resistance is a major public health concern, contributing to an estimated 5 million deaths per year. Understanding long-term resistance patterns could help public health researchers to monitor and characterise drug resistance as well as inform the impact of interventions on resistance.

In this study, researchers analysed drug resistance in more than 3 million bacterial samples collected across 30 countries in Europe from 1998 to 2019. Samples encompassed eight bacteria species important to public health, including Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae. 

They found that while antibiotic resistance initially rises in response to antibiotic use, it does not rise indefinitely. Instead, resistance rates reached an equilibrium over the 20-year period in most species. Antibiotic use contributed to how quickly resistance levels stabilised as well as variability in resistance rates across different countries. But the association between changes in drug resistance and antibiotic use was weak, suggesting that additional, yet unknown, factors are at play.

The study highlights that continued increase in antibiotic resistance is not inevitable and provides new insights to help researchers monitor drug resistance.

Senior author Francois Blanquart notes: “When we looked into the dynamics of antibiotic resistance in many important bacterial pathogens all over Europe and in the last few decades, we often found that resistance frequency initially increases and then stabilises to an intermediate level. The consumption of the antibiotic in the country explained both the speed of initial increase and the level of stabilisation.”

Senior author Sonja Lehtinen summarises: “In this study, we were interested in whether antibiotic resistance frequencies in Europe were systematically increasing over the long-term. Instead, we find a pattern where, after an initial increase, resistance frequencies tend to reach a stable plateau.”

Provided by PLOS

Diabetes Can Drive the Evolution of Antibiotic Resistance

Photo by CDC on Unsplash

Staphylococcus aureus is a leading cause of antibiotic resistance associated infections and deaths. It is also the most prevalent bacterial infection among those with diabetes mellitus, a chronic condition that affects blood sugar control and reduces the body’s ability to fight infections.

Microbiologists at the UNC School of Medicine have just shown that people with diabetes are more likely to develop antibiotic-resistant strains of Staph, too. Their results, which were published in Science Advances, show how the diabetic microbial environment produces resistant mutations, while hinting at ways antibiotic resistance can be combatted in this patient population.

“We found that antibiotic resistance emerges much more rapidly in diabetic models than in non-diabetic models of disease,” said Brian Conlon, PhD, associate professor of immunology. “This interplay between bacteria and diabetes could be a major driver of the rapid evolution and spread of antibiotic resistance that we are seeing.”

 Staph feeds off the high levels of blood glucose in diabetes, allowing it to reproduce more rapidly. The bacterium can also grow without consequence, as diabetes also impairs the immune system’s ability to destroy cells and control infection.

As the numbers of bacteria increase in a diabetic infection, so does the likelihood of resistance. Random mutations appear and some build up resistance to external stressors, like antibiotics. Once a resistant mutant is present in a diabetic infection, it rapidly takes over the population, using the excess glucose to drive its rapid growth.

Staphylococcus aureus is uniquely suited to take advantage of this diabetic environment,” said Lance Thurlow, PhD, assistant professor of microbiology and immunology. “Once that resistant mutation happens, you have excess glucose and you don’t have the immune system to clear the mutant and it takes over the entire bacterial population in a matter of days.”

Conlon, an expert on antibiotic treatment failure, and Thurlow, an expert on Staph pathogenesis in diabetes, have long been interested in comparing the effectiveness of antibiotics in a model with and without diabetes. Using their connections within the Department of Microbiology and Immunology, the researchers brought their labs together to perform a study with antibiotics in a diabetic mouse model of S. aureus infection.

First, the team prepared a mouse model with bacterial infection in the skin and soft tissue. The mouse models were divided into two groups: one half was given a compound that selectively kills cells in the pancreas, rendering them diabetic, and the other half was not given the compound. Researchers then infected both diabetic and non-diabetic models with S. aureus and treated them with rifampicin, an antibiotic where resistance evolves at a high rate.

After five days of infection, it was time to observe the results.

Conlon and Thurlow were quick to notice that the rifampicin had practically no effect in diabetic models. So, they took some samples to investigate. Researchers were shocked to find that the bacteria had evolved to become resistant to rifampicin, with the infection harboring over a hundred million rifampicin resistant bacteria. There were no rifampicin resistant bacteria in the non-diabetic models.

Their new findings have left Conlon and Thurlow with many questions; however, they are certain that the evolution of antibiotic resistance in people with diabetes could spell trouble for the population at large.

And, even more surprisingly, the mutation had taken over the entire infection in just four days. They next inoculated diabetic and non-diabetic models with Staphylococcus aureus as before, but this time supplemented with a known number of rifampicin resistant bacteria. Again, these bacteria rapidly took over the diabetic infection, but remained as only a sub-population in non-diabetic models after 4 days rifampicin treatment.

Their new findings have left Conlon and Thurlow with many questions; however, they are certain that the evolution of antibiotic resistance in people with diabetes could spell trouble for the population at large. Antibiotic-resistant strains of bacteria spread from person to person in the same ways as other bacteria and viruses do – in the air, on doorknobs, and the food that we eat – which makes preventing these types of infections a major priority.

So, what can be done to prevent it? Well, the Conlon and Thurlow labs showed that reducing blood sugar levels in diabetic models (through administration of insulin) deprived bacteria of their fuel, keeping their numbers at bay, and reducing the chances of antibiotic-resistant mutations from occurring. Their findings suggest that controlling blood sugar through insulin use could be key in preventing antibiotic resistance.

“Resistance and its spread are not only associated with the prescription of drugs, but also the health status of those that are taking antibiotics,” said Conlon. “Controlling blood glucose then becomes really important. When we gave our mice insulin, we were able to bring their blood sugar back to normal and we didn’t get this rapid proliferation of resistant bacteria.”

Now, Conlon and Thurlow are expanding their efforts to study the evolution of resistance in humans (with and without diabetes) and other antibiotic-resistant bacteria of interest, including Enterococcus faecalisPseudomonas aeruginosa, and Streptococcus pyogenes. Recognizing how large a role the host plays a role in the evolution of antibiotic resistance, the researchers plan to perform similar studies in patients undergoing chemotherapy and recent transplant recipients to see if those populations are also prone to antibiotic resistant infections.

Source: University of North Carolina Health Care

Study Finds Three New Safe, Effective Ways to Treat Drug-resistant TB

Tuberculosis bacteria. Credit: CDC

An international clinical trial has found three new safe and effective drug regimens for tuberculosis that is resistant to rifampin, the most effective of the first-line antibiotics used to treat TB. The research, published in the New England Journal of Medicine, was led by researchers at Harvard Medical School and other members of the endTB project.

The newly identified regimens take advantage of recently discovered drugs to expand the treatment arsenal and give physicians new ways to shorten and personalise treatment, minimise side effects, and treat patients using only pills instead of daily injections. They also offer alternatives in case of drug intolerance, medication shortages or unavailability, or drug resistance, the researchers said.

The endTB trial is one of four recent efforts to use randomised controlled trials to test new, shorter, less toxic regimens for drug-resistant TB. endTB uses two new drugs – bedaquiline and delamanid — which, when brought to market in 2012-2013, were the first new TB medicines developed in nearly 50 years.

To find shorter, injection-free drug combinations for people infected with TB resistant to rifampin, endTB tested five new, all-oral 9-month regimens using the two new drugs in combination with older medications.

A third drug, pretomanid, received emergency authorisation from the FDA for specific use within a regimen against highly drug-resistant TB in 2019, after the endTB clinical trial was underway, and is not included in the regimens used in these trials.

Trial regimens were considered effective if they performed at least as well as the control group, which received a well-performing standard of care composed in accordance with a stringent interpretation of World Health Organization (WHO) recommendations.

The three successful new regimens were successful for between 85 and 90% of patients, compared with 81% success for people in the control group. The control group was treated with longer treatments, which also included the recently discovered medicines.

The trial launched in 2017 and enrolled 754 patients across seven countries: Georgia, India, Kazakhstan, Lesotho, Pakistan, Peru, and South Africa. The goal was to improve treatment for patients with tuberculosis resistant to rifampin. The WHO estimates that some 410 000 people become sick with rifampin-resistant TB each year, including people who have multidrug-resistant TB (MDR-TB). Only 40% are diagnosed and treated, 65%of them successfully.

The study population included children as well as people infected with HIV or hepatitis C, both common in populations with high rates of TB. In another innovation, women who became pregnant while on treatment were included in the endTB trial. These groups are often excluded from clinical trials. In a special report published in August 2024, the WHO added the three noninferior regimens from the endTB trial to the list of treatment options for rifampin-resistant and multidrug-resistant TB (MDR-TB) treatment; the recommendations extend to these neglected groups as well as to pregnant women.

With recent efforts to end patent exclusivity on bedaquiline, two of the endTB regimens and the WHO-recommended pretomanid-containing regimen can all be purchased for less than $500, an access target set by activists more than 10 years ago, which has only just now been achieved. All of these innovations together mean the new shortened, all-oral regimens are available to more people than ever.

Source: Harvard Medical School

The Spread of a Highly Drug-resistant Cholera Strain

Scanning electron micrograph image of cholera bacteria.

Scientists from the National Reference Center for Vibrios and Cholera at the Institut Pasteur, in collaboration with the Centre hospitalier de Mayotte, have revealed the spread of a highly drug-resistant cholera strain from Yemen down through Africa. The study was published in the New England Journal of Medicine.

Cholera is caused by the bacteria Vibrio cholerae and in its most severe forms, it is one of the most rapidly fatal infectious diseases: in the absence of treatment, patients can die within hours. Treatment primarily involves replacing lost water and electrolytes, but antibiotics are also used in addition to rehydration therapy. They are essential in reducing the duration of infection and breaking chains of transmission as quickly as possible.

A strain resistant to ten antibiotics – including azithromycin and ciprofloxacin, two of the three recommended for treating cholera – was identified for the first time in Yemen during the cholera outbreak in 2018-2019[1].

Scientists have now been able to trace the spread of this strain by studying the bacterial genomes. After Yemen, it was identified again in Lebanon in 2022[2], then in Kenya in 2023, and finally in Tanzania and the Comoros Islands – including Mayotte, a French département off the south-east coast of Africa – in 2024. Between March and July 2024, the island of Mayotte was affected by an outbreak of 221 cases caused by this highly drug-resistant strain.

“This study demonstrates the need to strengthen global surveillance of the cholera agent, and especially to determine how it reacts to antibiotics in real time. If the new strain that is currently circulating acquires additional resistance to tetracycline, this would compromise all possible oral antibiotic treatment,” concludes Professor François-Xavier Weill, Head of the Vibrios CNR at the Institut Pasteur and lead author of the study.

[1] Press release 19/08/2023 – Genes fuelling antibiotic resistance in Yemen cholera outbreak uncovered

[2] https://www.nature.com/articles/s41467-024-51428-0

Source: Institut Pasteur

Research Shines a Light on Emerging Virulent Streptococcus Subspecies

This illustration depicts a 3D computer-generated image of a group of Gram-positive, Streptococcus pneumoniae bacteria. The artistic recreation was based upon scanning electron microscopic (SEM) imagery. Credit: CDC on Unsplash

A concerning increase in global rates of severe invasive infections becoming resistant to key antibiotics has a team of infectious disease researchers at the Houston Methodist Research Institute studying a recently emerged strain of bacteria, Streptococcus dysgalactiae subspecies equisimilis (SDSE). SDSE infects humans via the skin, throat, gastrointestinal tract and female genital tract to cause infections ranging in severity from pharyngitis to necrotising fasciitis. The findings of this study are described in a paper appearing in the journal mBio

Though closely related to group A streptococcus (also commonly known as Streptococcus pyogenes), which has been very well studied, little is known about SDSE.

“Given its great emerging importance to human health, our limited understanding of SDSE molecular pathogenesis is remarkable,” said Jesus M. Eraso, PhD, an assistant research professor of pathology & genomic medicine with Houston Methodist and lead author on the study.

To close this knowledge gap, the Houston Methodist team used a sophisticated integrative approach to study 120 human isolates of a particular SDSE subtype, called stG62647. They analysed the subtype’s genome, where the information of its DNA is stored, its transcriptome, which provides a snapshot of the complete gene expression profile at the time the SDSE cells were collected, and its virulence, which refers to the degree of damage it causes to its host. The stG62647 SDSE strains are important to study because they have been reported to cause unusually severe infections, and understanding the relationships and interplay between these three entities gave the researchers a richer understanding of how it causes disease.

The data from this integrative analysis provided much new data about this important emerging human bacterial pathogen and are useful in vaccine research. It also raised many new questions and generated new hypotheses to be studied in this ongoing line of investigation.

Source: Houston Methodist Research Institute

Bacteria able to Overcome Cost of Vancomycin Resistance in Lab Setting

Compensatory mutations enabled vancomycin resistance to persist through several generations

Methicillin resistant Staphylococcus aureus (MRSA) – Credit: CDC

Staphylococcus aureus has the potential to develop durable vancomycin resistance, according to a study published August 28, 2024, in the open-access journal PLOS Pathogens by Samuel Blechman and Erik Wright from the University of Pittsburgh, USA.

Despite decades of widespread treatment with the antibiotic vancomycin, vancomycin resistance among the bacterium S. aureus is extremely uncommon – only 16 such cases have reported in the US to date. Vancomycin resistance mutations enable bacteria to grow in the presence of vancomycin, but they do so at a cost. Vancomycin-resistant S. aureus (VRSA) strains grow more slowly and will often lose their resistance mutations if vancomycin is not present. The reason behind vancomycin’s durability and the potential for VRSA strains to further adapt have not been adequately explored.

In this study, researchers took four VRSA strains and grew them in the presence and absence of vancomycin to see how the strains would evolve. They found that strains grown in the presence of vancomycin developed additional mutations in the ddl gene, which has previously been associated with vancomycin dependence. These mutations enabled VRSA strains to grow faster when vancomycin was present. Unlike the original strains, which quickly lost vancomycin resistance, the evolved strains maintained resistance through several generations, even when vancomycin was no longer present.

The study shows that durability of vancomycin susceptibility to date should not be taken for granted. The trade-off that often comes with vancomycin resistance can be overcome if the bacteria is allowed to grow in the presence of vancomycin. As antibiotic resistance continues to grow as a public health threat, studies like this underscores the importance of developing new antibiotics.

The authors add: “The superbug MRSA has been held off by the antibiotic vancomycin for decades. A new study shows we will not be able to count on vancomycin forever.”

Provided by PLOS

Klebsiella Thrives in Nutrient-deprived Hospital Environments

Photo by Hush Naidoo Jade Photography on Unsplash

Scientists at ADA Forsyth Institute (AFI) have identified a critical factor that may contribute to the spread of hospital-acquired infections (HAIs), shedding light on why these infections are so difficult to combat. Their study reveals that the dangerous multidrug resistant (MDR) pathogen, Klebsiella, thrives under nutrient-deprived polymicrobial community conditions found in hospital environments.

According to the World Health Organization, HAIs pose significant risks to patients, often resulting in prolonged hospital stays, severe health complications, and a 10% mortality rate. One of the well-known challenging aspects of treating HAIs is the pathogens’ MDR. In a recent study published in Microbiome, AFI scientists discovered that Klebsiella colonising a healthy person not only have natural MDR capability, but also dominate the bacterial community when starved of nutrients.

“Our research demonstrated that Klebsiella can outcompete other microorganisms in its community when deprived of nutrients,” said Batbileg Bor, PhD, associate professor at AFI and principal investigator of the study. “We analysed samples of saliva and nasal fluids to observe Klebsiella‘s response to starvation conditions. Remarkably, in such conditions, Klebsiella rapidly proliferates, dominating the entire microbial community as all other bacteria die off.”

Starvation environments

Klebsiella is one of the top three pathogens responsible for HAIs, including pneumonia and irritable bowel disease. As colonising opportunistic pathogens, they naturally inhabit the oral and nasal cavities of healthy individuals but can become pathogenic under certain conditions. “Hospital environments provide ideal conditions for Klebsiella to spread,” explained Dr Bor. “Nasal or saliva droplets on hospital surfaces, sink drains, and the mouths and throats of patients on ventilators, are all starvation environments.”

Dr Bor further elaborated, “When a patient is placed on a ventilator, they stop receiving food by mouth, causing the bacteria in their mouth to be deprived of nutrients and Klebsiella possibly outcompete other oral bacteria. The oral and nasal cavities may serve as reservoirs for multiple opportunistic pathogens this way.”

Additionally, Klebsiella can derive nutrients from dead bacteria, allowing it to survive for extended periods under starvation conditions. The researchers found that whenever Klebsiella was present in the oral or nasal samples, they persisted for over 120 days after being deprived of nutrition.

Other notable findings from the study include the observation that Klebsiella from the oral cavity, which harbours a diverse microbial community, was less prevalent and abundant than those from the nasal cavity, a less diverse environment. These findings suggest that microbial diversity and specific commensal (non-pathogenic) saliva bacteria may play a crucial role in limiting the overgrowth of Klebsiella species. 

The groundbreaking research conducted by AFI scientists offers new insights into the transmission and spread of hospital-acquired infections, paving the way for more effective prevention and treatment strategies.

Source: Forsyth Institute

Temperature may be a New Weapon in the Battle against Antibiotic Resistance

Scientists from the University of Groningen in the Netherlands, together with colleagues from other European universities, have tested how a fever could affect the development of antimicrobial resistance. In laboratory experiments, they found that a small increase in temperature from 37 to 40 degrees Celsius drastically changed the mutation frequency in E. coli bacteria, which facilitates the development of resistance. If these results can be replicated in human patients, fever control could be a new way to mitigate the emergence of antibiotic resistance.

There are two ways to fight the threat of antimicrobial resistance: by developing new drugs, or by preventing the development of resistance. ‘We know that temperature affects the mutation rate in bacteria’, explains Timo van Eldijk, co-first author of the paper published in JAC-Antimicrobial Resistance. ‘What we wanted to find out was how the increase in temperature associated with fever influences the mutation rate towards antibiotic resistance.’

‘Most studies on resistance mutations were done by lowering the ambient temperature, and none, as far as we know, used a moderate increase above normal body temperature,’ Van Eldijk reports. Together with Master’s student Eleanor Sheridan, he cultured E. coli bacteria at 37 or 40 degrees Celsius, and subsequently exposed them to three different antibiotics to assess the effect. ‘Again, some previous human trials have looked at temperature and antibiotics, but in these studies, the type of drug was not controlled.’ In their laboratory study, the team used three different antibiotics with different modes of action: ciprofloxacin, rifampicin, and ampicillin.

The results showed that for two of the drugs, ciprofloxacin and rifampicin, increased temperature led to an increase in the mutation rate towards resistance. However, the third drug, ampicillin, caused a decrease in the mutation rate toward resistance at fever temperatures. ‘To be certain of this result, we replicated the study with ampicillin in two different labs, at the University of Groningen and the University of Montpellier, and got the same result,’ says Van Eldijk.

The researchers hypothesized that a temperature dependence of the efficacy of ampicillin could explain this result, and confirmed this in an experiment. This explains why ampicillin resistance is less likely to arise at 40 degrees Celsius. ‘Our study shows that a very mild change in temperature can drastically change the mutation rate towards resistance to antimicrobials,’ concludes Van Eldijk. ‘This is interesting, as other parameters such as the growth rate do not seem to change.’

If the results are replicated in humans, this could open the way to tackling antimicrobial resistance by lowering the temperature with fever-suppressing drugs, or by giving patients with a fever antimicrobial drugs with higher efficacy at higher temperatures. The team concludes in the paper: ‘An optimized combination of antibiotics and fever suppression strategies may be a new weapon in the battle against antibiotic resistance.’

Source: University of Groningen