Despite stringent infection-control efforts around the world, hospital-acquired infections (HAIs)keep on popping up from new strains of bacteria. In Science Translational Medicine, researchers report evidence pointing to an unexpected source of such bacteria: the hospitalised patients themselves.
From experiments with mice, researchers at Washington University School of Medicine in St. Louis discovered that urinary tract infections (UTIs) can arise after sterile tubes, called catheters, are inserted into the urinary tract, even when no bacteria are detectable in the bladder beforehand. Such tubes are commonly used in hospitals to empty the bladders of people undergoing surgery. In the mice, inserting the tubes activated dormant Acinetobacter baumannii bacteria hidden in bladder cells, triggering them to emerge, multiply and cause UTIs, the researchers said.
The findings suggest that screening patients for hidden reservoirs of dangerous bacteria could supplement infection-control efforts and help prevent deadly HAIs.
“You could sterilise the whole hospital, and you would still have new strains of A. baumannii popping up,” said co-senior author Mario Feldman, PhD, a professor of molecular microbiology. “Cleaning is just not enough, and nobody really knows why. This study shows that patients may be unwittingly carrying the bacteria into the hospital themselves, and that has implications for infection control. If someone has a planned surgery and is going to be catheterised, we could try to determine whether the patient is carrying the bacteria and cure that person of it before the surgery. Ideally, that would reduce the chances of developing one of these life-threatening infections.”
The notoriously multidrug-resistant A. baumannii is a major threat to patients, causing many cases of UTIs in people with urinary catheters, pneumonia in people on ventilators, and bloodstream infections in people with central-line catheters into their veins.
The researchers set out to investigate why so many A. baumannii UTIs develop after people receive catheters.
Most UTIs among otherwise healthy people are caused by the bacterium Escherichia coli. Research has shown that E. coli can hide out in bladder cells for months after a UTI seems to have been cured, and then re-emerge to cause another infection.
The researchers investigated whether A. baumannii can hide inside cells like E. coli can. They studied mice with UTIs caused by A. baumannii. They used mice with weakened immune systems because, like people, healthy mice can fight off A. baumannii.
Once the infections had resolved and no bacteria were detected in the mice’s urine for two months, the researchers inserted catheters into the mice’s urinary tracts with a sterile technique. Within 24 hours, about half of the mice developed UTIs caused by the same strain of A. baumannii as the initial infection.
“The bacteria must have been there all along, hiding inside bladder cells until the catheter was introduced,” said co-senior author Scott J. Hultgren, PhD, a professor and expert on UTIs. “Catheterisation induces inflammation, and inflammation causes the reservoir to activate, and the infection blooms.”
Since A. baumannii rarely causes symptoms in otherwise healthy people, many people who carry the bacteria may never know they’re infected, the researchers said. According to the researchers’ literature search, 2% of healthy people carry A. baumannii in their urine.
“I wouldn’t put much weight on the precise percentage, but I think we can say with certainty that some percentage of the population is walking around with A. baumannii,” Feldman said. “As long as they’re basically healthy, it doesn’t cause any problems, but once they’re hospitalised, it’s a different matter. This changes how we think about infection control. We can start considering how to check if patients already have Acinetobacter before they receive certain types of treatment; how we can get rid of it; and if other bacteria that cause deadly outbreaks in hospitals, such as Klebsiella, hide in the body in the same way. That’s what we’re working on figuring out now.”
In APL Bioengineering, researchers report on an injectable hydrogel that treats infections around hip and knee replacement prosthetics without the problems caused by current treatments. Testing showed that the gel inhibits common bacteria and promotes tissue regrowth.
After hip and knee replacement surgeries, pathogenic bacteria can adhere to the surface of the joint prosthesis and form a dangerous biofilm. Gold standard clinical methods use potent antibiotics and further surgery, including removal of infected tissue and transplantation of new tissue, to treat these infections. However, these strategies run into problems with hyper-resistant bacteria caused by the abuse of antibiotics, persistent damage caused by tissue removal, difficulties in obtaining tissue donors, and toxicity and immune system complications.
A team from Shanghai Jiao Tong University School of Medicine created ablack phosphorus-enhanced antibacterial injectable hydrogel to re-establish biological barriers in soft tissue and suppress persistent infections. The gel has a porous structure, excellent injectability, and rapid self-healing properties.
“It is important to explore a new strategy for treatment of infected soft tissue wounds because it is directly related to prognosis,” said author Ruixin Lin. “We aspire to develop a simpler, safer method to help more patients avoid suffering and help more doctors make the right choices.”
In vitro tests showed the hydrogel had good stability and low toxicity to tissue cells. Irradiating the gel with near infrared light causes it to release silver ions. This process was highly efficient at inhibiting the common bacteria S. aureus.
“Furthermore, an in vivo infected wound model showed that the hydrogel could not only inhibit the persistent infection of the wound, but also accelerate the deposition of collagen fibres and angiogenesis, thereby realizing the repair of the natural barrier of soft tissue,” said Lin.
The novel hydrogel provides a safe and feasible synergistic antibacterial strategy for infected soft tissue healing. The team believes that it solves current clinical problems, such as stubborn infections caused by antibiotic resistance, and provides new ideas for minimally invasive treatment. They hope to see it used in the clinic after conducting sufficient studies on its underlying mechanisms.
In Asia, researchers found that antibiotic residues in wastewater and wastewater treatment plants risk contributing to antibiotic resistance, and the drinking water may pose a threat to human health. Published in The Lancet Planetary Health, their comprehensive analysis also determined the relative contribution of various sources of antibiotic contamination in waterways, such as hospitals, municipals, livestock, and pharmaceutical manufacturing.
“Our results can help decision-makers to target risk reduction measures against environmental residues of priority antibiotics and in high-risk sites, to protect human health and the environment,” says first author Nada Hanna, researcher at the Department of Global Public Health at Karolinska Institutet. “Allocating these resources efficiently is especially vital for resource-poor countries that produce large amounts of antibiotics.”
Antibiotics can enter the environment during their production, consumption and disposal. Antibiotic residues in the environment, such as in wastewater and drinking water, can contribute to the emergence and spread of resistance.
Major antibiotics producers and users
The researchers looked for levels of antibiotic residues that are likely to contribute to antibiotic resistance from different aquatic sources in the Western Pacific Region (WPR) and the South-East Asia Region (SEAR), regions as defined by the World Health Organization. China and India, among the world’s largest producers and consumers of antibiotics, fall within these regions.
To find the data, researchers made a systematic review of the literature published between 2006 and 2019, including 218 relevant reports from the WPR and 22 from the SEAR. They also employed a method called Probabilistic Environmental Hazard Assessment to determine where the concentration of antibiotics is high enough to likely contribute to antibiotic resistance.
Ninety-two antibiotics were detected in the WPR, and forty five in the SEAR. Antibiotic concentrations exceeding the level considered safe for resistance development (Predicted No Effect Concentrations, PNECs) were observed in wastewater, influents and effluents of wastewater treatment plants and in receiving aquatic environments. Wastewater and influent of wastewater treatment plants had the highest risks. The relative impact of various contributors, such as hospital, municipal, livestock, and pharmaceutical manufacturing was also determined.
Potential threat to human health
In receiving aquatic environments, the highest likelihood of levels exceeding the threshold considered safe for resistance development was observed for the antibiotic ciprofloxacin in drinking water in China and the WPR.
“Antibiotic residues in wastewater and wastewater treatment plants may serve as hot spots for the development of antibiotic resistance in these regions and pose a potential threat to human health through exposure to different sources of water, including drinking water,” says Nada Hanna.
Limitations to be considered when interpreting the results are the lack of data on the environmental occurrence of antibiotics from many of the countries in the regions and the fact that only studies written in English were included.
Antibiotics play a vital role in the management of bacterial infections, reducing morbidity, and preventing mortality. A 2011 report from the United Kingdom estimated that they have increased life expectancy by 20 years. However, the extensive use of antibiotics has resulted in drug resistance that threatens to reverse their life-saving power and if the situation is not reversed, it has been estimated that by 2050, 10 million people will die annually of drug-resistant infections.
Such estimates of future deaths are obviously uncertain, but there is strong evidence the problem is already very serious. A major study published earlier this year in the Lancet estimated that globally around 1.27 million deaths in 2019 were directly due to antibiotic resistance. The study identified sub-Saharan Africa as the hardest-hit region.
What is AMR?
Sham Moodley, a community pharmacist from Durban and the vice chairperson of the Independent Community Pharmacy Association (ICPA) explains that antimicrobial resistance (AMR) is the ability of microorganisms (bacteria, viruses, fungi, and protozoa) to withstand treatment with antimicrobial drugs. “It is vitally important as it directly impacts our ability to treat and cure common infectious diseases, including pneumonia, urinary tract infections, gonorrhoea and tuberculosis,” he says.
According to Professor Olga Perovic, Principal Pathologist at the National Institute of Communicable Diseases’ Centre for Healthcare-associated Infections, Antimicrobial Resistance and Mycoses (CHARM), there are six factors fuelling the AMR crisis. These are over-prescribing and dispensing of antibiotics by health workers, patients not finishing their full treatment course of antibiotics, poor infection control in hospitals and clinics, lack of hygiene and poor sanitisation in the community, lack of new antibiotics being developed, and the overuse of antibiotics in livestock and fish farming.
Under overuse, she stresses the misuse of antibiotics to treat upper respiratory tract infections, which are typically viral rather than bacterial. Antibiotics are powerless against viruses. Another driver of inappropriate or overprescribing of antibiotics, she says, may be the lack of testing of specimens for the presence of bacteria and their susceptibility to treatment.
How can we prevent AMR?
Dr Marc Mendelson, Professor of Infectious Diseases and Head of the Division of Infectious Diseases and HIV Medicine at Groote Schuur Hospital, the University of Cape Town as well as chairperson of the Ministerial Advisory Committee on Antimicrobial Resistance, says reducing the use of antibiotics is about preventing the need for prescription in the first place. (Mendelson’s recent SAMJ article provides excellent further reading on AMR in South Africa.)
“So, reducing the burden of infections through the provision of clean water and safe sanitation (reduces diarrhoeal diseases) and vaccination programmes (reduces diarrhoea and pneumonia for instance),” he says. “Education and awareness raising of the public and (sadly) healthcare professionals as to the correct use of antibiotics is also critical.”
Broadly speaking, all the experts we interviewed agreed that we should use far fewer antibiotics and only use them when they are absolutely necessary. But actually making this happen is surprisingly complex.
Part of the complexity, for example, is that resistance profiles and disease profiles are different in different places. Geraldine Turner, a pharmacist at Knysna Hospital in the Western Cape, says there is a need for guidelines tailored to the South African context or linked to the local epidemiology. This, she says, can play an important role in determining the correct antibiotics to be used.
It is also not just an issue of what antibiotics are prescribed for humans.
“A big driver of antimicrobial resistance is overuse in agriculture and collaboration with stakeholders in this regard is required,” says Turner. She says we need policies that facilitate improved integration among environmental, animal, and human sector interventions.
Moodley agrees that a multidisciplinary, One Health approach is needed at every level of care and in both human and animal health sectors.
“It is important we reinforce the principle that antimicrobial medicines for human use are only supplied on the authority of a healthcare professional and that antimicrobial medicines for either human or animal use are only supplied in accordance with country legislation and regulations,” he says.
The role of stewardship programmes
One response to the AMR crisis is antimicrobial stewardship programmes or ASPs. Moodley describes ASPs as a systematic approach used “to optimise appropriate use of all antimicrobials to improve patient outcome and limit the emergence of resistant pathogens whilst ensuring patient safety.”
Perovic says, “In healthcare institutions, resistant bacteria can spread easily within and from patient to patient. That is why there are guidelines, which we call ASPs in the medical and veterinary fields, on how and when antibiotics are prescribed as well as how to implement infection prevention and control measures, particularly for patients with health risks such as diabetes, high blood pressure, and cancer.”
“In hospitals,” explains Mendelson, “ASPs will consist of a governance body such as an AS Committee that directs a work programme of stewardship, often with AS teams as the implementers of policy. AS teams can involve anything from single pharmacists or physicians, through one to two dedicated individuals, through to all-singing all-dancing multi-disciplinary teams in academic teaching hospitals, comprising infectious diseases specialists, microbiologists, pharmacists, [and] infection prevention and control nurses.”
ASPs are not only important at institutional levels, adds Moodley, but imperative for every individual prescriber/practitioner to implement to reduce AMR in our population.
Critical role for pharmacists
Mendelson stresses that pharmacists are integral to antibiotic stewardship in South Africa and globally. “Community pharmacists give advice to patients seeking symptomatic relief and reduce doctors’ visits, which can result in antibiotic prescriptions when not needed,” he says. In hospitals, dispensing pharmacists help optimise the antibiotics prescribed to patients by checking indication for the antibiotic, dose, dosing frequency, and duration. “Some hospitals have pharmacists on the wards, again, checking and helping to optimise the use of antibiotics,” he says.
“Pharmacists play an important role in recommending symptomatic treatments for non-specific symptoms and particularly, the common cold, which is a major cause of inappropriate antibiotic prescribing, requiring simple paracetamol with or without decongestants. Unfortunately, a recent pilot study suggests that a small number of community pharmacies are dispensing antibiotics without a prescription, which is not allowed in South Africa,” says Mendelson.
Turner concurs that pharmacists play a crucial role in ensuring that the correct antibiotics are used appropriately and only if indicated. She says pharmacistsare also in a good position to counsel and advise patients on the correct use of antibiotics.
Strategy framework
The key policy document setting out South Africa’s response to AMR is the South Africa Antimicrobial Resistance Strategy Framework of 2018-2024. The framework outlines nine strategic objectives – they include improving the appropriate use of diagnostic investigations to identify pathogens, guiding patient and animal management and ensuring good quality laboratory, enhancing infection prevention and control, promoting appropriate use of antimicrobials in humans and animals as well as legislative and policy reform for health systems strengthening.
Mendelson is positive about what has been achieved so far. “There have been major improvements to the surveillance and reporting of antibiotic resistance and antibiotic use in humans and animals, development of a greater one health (human, animal, and environmental health) response. There was a formation of national training centres for antibiotic stewardship and empowerment of under-resourced provinces to train and develop Antimicrobial Stewardship programmes and there have been improvements in governance and delivery of infection prevention and control measures in hospitals and development of education programmes for healthcare workers in South Africa,” he says.
But Mendelson also says that challenges remain in promoting prescribing behaviour change amongst the health workforce in SA and the expectations and social position that antibiotics hold in society.
As with several other health policies, there are questions on whether the plan has been backed up with funding.
“The national strategic framework remains largely unfunded (shared by most low- and middle-income countries) but this does hamper progress in developing programmes of interventions,” says Mendelson. “In food production, reducing [the] use of antibiotics is an important goal but will require investment in reducing drivers of infection in the animals that produce food. Legislation to bring all antibiotic prescribing in food production under veterinarian control will be an important intervention,” says Mendelson.
A major clinical trial found that the risk of gastrointestinal bleeding caused by long-term aspirin use can be reduced with a short course of antibiotics, potentially improving the safety of aspirin when used to prevent heart attacks, strokes and possibly some cancers.
The results of the HEAT (Helicobacter pylori Eradication Aspirin) trial, which was led by Professor Chris Hawkey from the University of Nottingham, are published in The Lancet.
Aspirin in low doses is a very useful preventative drug in people at high risk of strokes or heart attacks. However, on rare occasions, its blood thinning effect can provoke internal ulcer bleeding. These ulcers may be caused by Helicobacter pylori.
The STAR (Simple Trials for Academic Research) team from the University of Nottingham investigated whether a short course of antibiotics to remove these bacteria would reduce the risk of bleeding in aspirin users.
The HEAT trial, conducted in 1208 UK general practices, was a real-life study which used clinical data routinely stored in GP and hospital records, instead of bringing patients back for follow up trial visits.
The researchers recruited 30 166 who were taking aspirin. Those who tested positive for H. pylori were randomised to receive antibiotics or placebos (dummy tablets) and were followed for up to 7 years.
Over the first two and a half years, those who had antibiotic treatment were less likely to be hospitalised for ulcer bleeding than those taking placebo (6 versus 17). Protection occurred rapidly: with the placebo group, the first hospitalisation for ulcer bleeding occurred after 6 days, compared to 525 days following antibiotic treatment.
Over a longer time period, protection appeared to wane. However, the overall rate of hospitalisation for ulcer bleeding was lower than expected and this in line with other evidence that ulcer disease is on the decline. Risks for people already on aspirin are low. Risks are higher when people first start aspirin, when searching for H. pylori and treating it is probably worthwhile.
Aspirin has many benefits in terms of reducing the risk of heart attacks and strokes in people at increased risk. There is also evidence that it is able to slow down certain cancers. The HEAT trial is the largest UK-based study of its kind, and we are pleased that the findings have shown that ulcer bleeding can be significantly reduced following a one-week course of antibiotics. The long-term implications of the results are encouraging in terms of safe prescribing.
Professor Chris Hawkey, University of Nottingham’s School of Medicine and Nottingham Digestive Diseases Centre
The COVID pandemic has set back years of progress against antimicrobial resistance, with resistant hospital-onset infections and deaths increasing by at least 15% in the first year of the pandemic alone, according to a new report from the US CDC.
About 3 million people in the US are infected with antimicrobial-resistant pathogens, often acquired in healthcare settings, with about 50 000 people dying. Some estimates predict that by 2050, there could be more deaths from antibiotic resistance than from cancer.
Corrie Detweiler, a professor of molecular, cellular, and developmental biology at CU Boulder, has spent her career trying to develop solutions to antimicrobial-resistance. CU Boulder Today spoke with her about why so many antimicrobial drugs won’t work anymore, how COVID made things worse and what can be done to make things better.
Prior to the pandemic, how were we doing in addressing this issue?
“A lot of progress had been made, particularly in hospital-acquired infections, based on a better understanding of the problem and better guidelines about when to use antibiotics. Between 2012 and 2017, for instance, deaths from antimicrobial resistance fell by 18% overall and nearly 30% in hospitals. That all fell apart during COVID.”
Why? How did COVID spawn an uptick?
We didn’t know how to treat COVID, and, understandably, there was a fair amount of chaos in the medical system. People were using antibiotics more, often inappropriately. About 80% of COVID patients received antibiotics. People were given them prophylactically, prior to knowing they had a lung bacterial infection. That’s not to say that none of (the patients) needed them. Some did. But the more you use antibiotics, the more you select for resistance. And that’s how you eventually get a superbug.
What can society do to address this?
First, we need to go back to this idea of stewardship in hospitals – to only give out antibiotics when there is a clear need. We were doing the right thing. And then something terrible came along and messed it up, and it demonstrated that what we were doing was working well. That’s a good thing. Second, we need to discover and develop novel classes of antibiotics. The last time a new class of antibiotics hit the market was in 1984. The fundamental problem is that they’re not profitable to develop, compared to say a cancer drug. You can go to the drugstore and get a course of amoxicillin for $8. We need programs that reward industry and academic labs like ours for doing the early research.
What does your lab do?
We’re using basic biology to try to figure out new ways to kill bacteria during an infection and identify compounds that work differently than existing drugs.
In a study published in Microbiology Spectrum, researchers detail how they have turned to attacking one of the critical proteins bacteria use to create an infection – adhesins, which confer the ability to adhere to cells. They also suggest that targeting adhesins with ‘anti-ligands’ could form a new class of antibiotics.
As their first decisive step in establishing a foothold in an organism, bacteria adhere to host cells. Infection pathogens use this adhesion to first colonise the host organism, and then to trigger an infection, which as a worst case scenario can end being fatal. Precise understanding of the bacteria’s adhesion to host cells is a key to finding therapeutic alternatives that block this critical interaction in the earliest possible stage of an infection.
The international collaborative effort has now explained the exact bacterial adhesion mechanism using the human-pathogenic bacterium Bartonella henselae. This pathogen causes ‘cat-scratch disease‘, which affects the lymph nodes draining the area where a cat scratch or bite occurs, causing regional lymphadenopathy. The bacterial adhesion mechanism was deciphered with the help of a combination of in-vitro adhesion tests and high-throughput proteomics. Proteomics is the study of all the proteins present in a cell or a complex organism.
The research group, led by University Hospital Frankfurt and Goethe University Frankfurt, shed light on a key mechanism: the bacterial adhesion to the host cells can be traced back to the interaction of a certain class of adhesins, trimeric autotransporter adhesins, with fibronectin, a common protein in human tissue. Adhesins are components on the surface of bacteria which enable the pathogen to adhere to the host’s biological structures. Homologues of the adhesin identified here as critical are also present in many other human-pathogenic bacteria, such as the multi-resistant Acinetobacter baumannii, which the World Health Organization (WHO) has classified as the top priority for research into new antibiotics.
The researchers visualised the exact points of interaction between the proteins using cutting-edge protein analytics. They also demonstrated that experimental blocking of these processes almost entirely prevents bacterial adhesion. Therapeutic approaches that aim to prevent bacterial adhesion in this way could represent a promising treatment alternative as a new class of antibiotics (known as ‘anti-ligands’) to treat the constantly growing array of multi-resistant bacteria.
Lessening sepsis’s deadly effects means quickly recognising its signs and symptoms, and initiating antibiotic treatments, but some experts have wondered whether this may contribute to antibiotic overuse, especially with time-to-treatment performance measures. A new study published in JAMA Internal Medicine showed that it was possible to effectively treat sepsis while engaging in antibiotic stewardship.
The study led by Hallie Prescott, MD, of the University of Michigan Health Division of Pulmonary and Critical Care and Vincent Liu, MD, of Kaiser Permanente Division of Research, looked at data from more than 1.5 million patients from 2013–2018. Patients included came to the emergency department with signs of systemic inflammatory response syndrome (SIRS), which includes increased heart rate, abnormal body temperature, among other signs.
The research team analysed antibiotics use in these patients, including number receiving antibiotics, when treatment started, treatment duration medications and the broadness of spectrum of the antibiotics.
“We showed in the overall cohort, that antibiotic use decreased. There was a slight decrease in the proportion treated within 48 hours, a more impressive decrease in the average number of days of antibiotic treatment, and also a decrease in the use of broad-spectrum antibiotics,” said Dr Prescott.
About half of the people who met the criteria for SIRS received antibiotics within 12 to 48 hours after admission, a practice that decreased slightly over time. At the same time, 30-day mortality, length of hospitalisation, and the development of multi-drug resistant bacteria also decreased.
“This study adds to our national conversation about how to combat sepsis most effectively. It also confirms that we now need to look for new opportunities to mitigate sepsis by finding patients at high risk before they arrive at the hospital, identifying hospitalised patients most likely to benefit from specific treatments, and enhancing their recovery after they survive sepsis,” said Dr Liu.
Dr Prescott agrees: “The pushback has been [time-to-treatment for sepsis] should not be a performance measure because it’s going to cause more harm than good, and I think our data shows it probably does more good than harm. We have shown that 152 hospitals have been able to make improvements in stewardship and sepsis treatment at the same time, contrary to popular belief.”
Bacteria causing Typhoid fever are becoming increasingly resistant to the macrolide and quinone antibiotic classes, according to a study published in The Lancet Microbe. The largest genome analysis of Salmonella enterica serovar Typhi also reveals that resistant strains, mostly from South Asia, have spread to other countries nearly 200 times since 1990.
Typhoid fever is a global public health concern, causing 11 million infections and more than 100 000 deaths per year. While it is most prevalent in South Asia, making 70% of global cases, it also has significant impacts in sub-Saharan Africa, Southeast Asia, and Oceania, highlighting the need for a global response.
Typhoid fever infections are treatable with antibiotics, but their effectiveness is threatened by the emergence of resistant S. Typhi strains. Thus far, little is known about the rise and spread of resistant S. Typhi has so far been limited, with most studies based on small samples, prompting researchers led by Stanford University to conduct a wider spread study.
The study researchers genetically sequenced 3489 S. Typhi isolates obtained from blood samples collected between 2014 and 2019 from people in Bangladesh, India, Nepal, and Pakistan with confirmed cases of typhoid fever. A collection of 4169 S. Typhi samples isolated from more than 70 countries between 1905 and 2018 was also sequenced and included in the analysis.
Resistance-conferring genes in the 7658 sequenced genomes were identified using genetic databases. Strains were classified as multidrug-resistant (MDR) if they contained genes giving resistance to classical front-line antibiotics ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole. The authors also traced the presence of genes conferring resistance to the crucially important macrolides and quinolones.
The analysis shows resistant S. Typhi strains have spread between countries at least 197 times since 1990. While these strains most often occurred within South Asia and from South Asia to Southeast Asia, East and Southern Africa, they have also been reported in the UK, USA, and Canada.
Since 2000, MDR S. Typhi has declined steadily in Bangladesh and India, and remained low in Nepal (less than 5% of Typhoid strains), though it has increased slightly in Pakistan. However, these are being replaced by strains resistant to other antibiotics.
For example, gene mutations giving resistance to quinolones have arisen and spread at least 94 times since 1990, with nearly all of these (97%) originating in South Asia. Quinolone-resistant strains accounted for more than 85% of S. Typhi in Bangladesh by the early 2000s, increasing to more than 95% in India, Pakistan, and Nepal by 2010.
Azithromycin resistance mutations have emerged at least seven times in the past 20 years. In Bangladesh, strains with these mutations emerged around 2013, and since then their population size has steadily increased. The findings add to recent evidence of the rapid rise and spread of S. Typhi strains resistant to third-generation cephalosporins, another class of antibiotics critically important for human health.
“The speed at which highly-resistant strains of S. Typhi have emerged and spread in recent years is a real cause for concern, and highlights the need to urgently expand prevention measures, particularly in countries at greatest risk. At the same time, the fact resistant strains of S. Typhi have spread internationally so many times also underscores the need to view typhoid control, and antibiotic resistance more generally, as a global rather than local problem.”
Dr Jason Andrews, Study Lead Author Stanford University
The authors acknowledge some limitations to their study. S. Typhi sequences are underrepresented in several regions, particularly many countries in sub-Saharan Africa and Oceania, where typhoid is endemic. More sequences from these regions are needed to improve understanding of timing and patterns of spread.
Even in countries with better sampling, most isolates come from a small number of surveillance sites and may not be representative of the distribution of circulating strains. As S. Typhi genomes only cover a fraction of all typhoid fever cases, estimates of resistance-causing mutations and international spread are likely underestimated. These potential underestimate highlight the need to expand genomic surveillance to provide a more comprehensive window into the emergence, expansion, and spread of antibiotic-resistant organisms.
Research just published in Clinical Infectious Diseaseshas found that Faecal Microbiota Transplantation, or FMT, is an optimal cost-effective treatment for first recurrent Clostridioides difficile infection (CDI).
“The most effective therapies for CDI are also the cost effective therapies,” said co-investigator Radha Rajasingham, MD. “FMT should be moved earlier in the treatment algorithm for CDI. Our model suggests it is effective and cost effective when used in patients after a single episode of recurrent CDI.”
Mathematical modelling was used to understand both the effectiveness and cost effectiveness of earlier use of FMT in the treatment of CDI, which normally arises from the disruption of healthy gut bacteria.
While this disease is caused by antibiotics, it is often treated with antibiotics, including fidaxomicin for initial, non-severe CDI or vancomycin for severe CDI, followed by FMT for any recurrent CDI.s. Unfortunately in many cases, CDI recurs in the same person again. This cycle of infection is called recurrent CDI.
Current guidelines recommend using FMT as a last resort for people with recurrent CDI. The goal of this research was to examine the benefits of using FMT earlier in the cycle of CDI.
“Based on this analysis, we would recommend that rather than waiting for multiple recurrent CDI, providers should consider FMT use for any recurrent CDI,” said co-author Byron Vaughn, MD, MS.
The authors suggest future research examine the role of FMT to prevent all recurrent CDI or even as primary prevention of CDI in high risk individuals.
