Antibiotic overuse is a key driver in the rise of antimicrobial resistance (AMR), a major global health crisis. Researchers from the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine) and Duke-NUS Medical School have provided compelling evidence that short-course antibiotic treatments can be a game-changer in tackling ventilator-associated pneumonia (VAP), a serious infection common in critically ill patients.
The findings from the landmark REGARD-VAP trial, published in Lancet Respiratory Medicine, and the accompanying economic analyses published in Lancet Global Health, highlight how prudent antibiotic use can curb resistance, effectively safeguarding patients as well as combatting the global threat of antimicrobial resistance while reducing healthcare costs.
Led by the NUS Medicine research team, the clinical trial examined over 450 patients across intensive care units (ICUs) in Singapore, Thailand, and Nepal. Results revealed that short-course antibiotics. carefully tailored to individual patients’ recovery, are just as effective as traditional longer treatments in preventing death and recurrence of pneumonia. “By shortening the duration of antibiotics, we can reduce the risks of side effects and resistance without compromising patient outcomes,” added Dr Mo Yin, Junior Academic Fellow at the Department of Medicine, NUS Medicine, and principal investigator of the clinical trial, and co-author of the economic analysis.
The economic analyses accompanying the trial were just published in the prestigious journal Lancet Global Health. They demonstrated that adopting short-course antibiotics offers significant value for healthcare systems. In Singapore, the strategy is cost-saving, reducing hospital expenditure while maintaining excellent outcomes for patients. In Thailand and Nepal, short-course antibiotics were highly cost-effective, with health gains outweighing the modest additional costs incurred. “Short-course antibiotics are a pragmatic solution that benefits patients and healthcare systems alike, particularly in resource-limited settings,” said Assistant Professor Yiying Cai, lead researcher from the Health Services and Systems Research Programme at Duke-NUS.
The REGARD-VAP study’s findings have practical implications for hospitals worldwide. Short-course antibiotics can streamline treatment in ICUs, where managing infections efficiently is vital. The approach is effective across high-income (Singapore), middle-income (Thailand), and low-income (Nepal) settings, making it a scalable solution for diverse healthcare systems. These results provide robust evidence including cost-effectiveness data for policymakers to adopt short-course antibiotics into national and institutional guidelines.
The team hopes to disseminate their findings globally to encourage the adoption of short-course antibiotics, particularly in regions with limited resources. They also advocate for integrating cost-effectiveness studies into future clinical trials to strengthen both clinical and economic decision-making processes. By reducing unnecessary antibiotic exposure, short-course treatments help preserve the effectiveness of existing drugs for future generations. Every additional day of antibiotic use increases the risk of drug resistance by 7%. Reducing treatment duration is a critical step in combating this silent epidemic. “Prudent antibiotic use is essential to combat antimicrobial resistance and optimise healthcare outcomes. Our findings make a strong case for adopting short-course antibiotics as the new standard of care,” concluded Dr Mo Yin.
Credit: Darryl Leja National Human Genome Research Institute National Institutes Of Health
A multi-institutional clinical trial led by Weill Cornell Medicine and NewYork-Presbyterian investigators showed that a newer technique for collecting prostate biopsy samples reduced the risk of infection compared with traditional biopsy approaches and removed the need for prophylactic antibiotics. The results of the study appear in JAMA Oncology.
The technique, called transperineal prostate biopsy, collects prostate tissue via a needle through the skin of the perineum, the area between the rectum and the scrotum. The procedure, which uses local anesthesia to numb the area, allows physicians to bypass the traditional and more infection-prone route of collecting prostate biopsy tissue with a needle through the rectum.
The PReclude infection EVEnts with No prophylaxis Transperineal (PREVENT) trial, funded by the National Cancer Institute, part of the National Institutes of Health, was conducted at multiple sites, including NewYork-Presbyterian/Weill Cornell Medical Center, NewYork-Presbyterian Queens and NewYork-Presbyterian Brooklyn Methodist Hospital. The study found no infections among 382 men randomised to undergo the transperineal procedure compared with six infections affecting 1.6% of the 370 men randomised to undergo the traditional transrectal biopsy procedure. The lower infection rate is particularly remarkable because the men in the transrectal biopsy group received a targeted course of antibiotics designed to help reduce their infection risk, and the men in the transperineal group received no antibiotics.
“Transperineal biopsy should be the new standard of care for prostate biopsy,” said Dr Jim Hu, Professor of Urologic Oncology at Weill Cornell Medicine. “It was as effective as the traditional transrectal biopsy approach at detecting cancer, but without the risk of infection or the need for antibiotics.”
Prostate biopsies are an essential tool for detecting prostate cancer, and about 3 million people worldwide undergo the procedure each year. Dr Hu noted that physicians collect about 90% of these biopsies in the United States via a transrectal procedure. Yet studies have found that 5% to 7% of patients develop infections after biopsy, and 1% to 3% require hospitalisation for these complications, he said. To help prevent infections, physicians typically prescribe a prophylactic course of antibiotics before the procedure.
Dr. Hu noted that the investigators used a personalised approach to prophylactic antibiotics in the patients undergoing the transrectal biopsy procedure. Rather than giving the men a broad-spectrum antibiotic or multiple antibiotics, they matched the antibiotics to cultures obtained from the patient’s rectum during prostate exams before the procedure. This targeted antibiotic approach reduced the infection rate in those undergoing the traditional transrectal procedure substantially compared with the national infection rate for the procedure. Yet, they achieved a statistically significant reduction in infections in the transperineal group by eliminating infections altogether.
“Transperineal prostate biopsy makes a common diagnostic procedure safer for men,” said Dr Hu, who is also a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. “It also eliminates the use of antibiotics, helping to reduce the emergence of antibiotic-resistant infections, a growing public health concern.”
Despite the promise of the new procedure, Dr. Hu acknowledged a few hurdles to making it more widely available to men in the United States. He explained that few physicians in the country have been trained in the perineal procedure. Additionally, he noted that US insurers pay the same amount for either procedure but the transperineal biopsy costs more and takes longer to perform, creating a financial disincentive for physicians to make the switch.
However, there is reason to think the status quo will change, Dr Hu said, noting the switch to transperineal prostate biopsies in Norway after a man died after a routine transrectal prostate biopsy. The change virtually eliminated biopsy-related infections and deaths in that country with the nationwide switch to transperineal biopsy, he said.
“There is a strong case to make the switch,” he said. “It will take time. But as more patients request the new procedure, we think it will become more widely available.”
Researchers at Umeå University and Tartu University have found that a history of repeated antibiotic use causes defects in the normally protective mucus barrier of the gut, due to antibiotic-driven alterations in the microbiota. In a further study in a different collaboration, the researchers found a bacteria-independent mechanism through which antibiotics can damage the mucus barrier directly.
“Together, these two studies suggest that antibiotics can damage the mucus layer through at least two independent mechanisms, and that they may have long-lasting effects through an altered gut bacteria. This further supports the notion that antibiotics should be administered in a responsible manner,” says Björn Schröder, Docent in Infection Biology in the Department of Molecular Biology at Umeå University.
Previous research has shown the consequences of short-term antibiotic treatments on the intestinal environment, but it is less clear how repeated antibiotic use in past years can affect our guts.
To address this question, Björn Schröder and his group at Umeå University teamed up with a research group at Tartu University in Estonia, who have built a deeply characterised cohort of individuals that provided stool samples and health records.
The researchers selected individuals who had taken at least five courses of antibiotics in the past, but not within six months before the stool collection, and compared their microbiota composition to individuals who had not taken any antibiotics within the last 10 years.
“The analysis revealed changes to the gut bacteria composition, even though the antibiotics were taken a long time ago. These results indicate that repeated antibiotic use has a lasting effect on gut bacteria composition that can persist at least months after the last treatment,” says Kertu-Liis Krigul, PhD student at Tartu University.
After transplantation of the human microbiota into mice and using specialised methods to analyse the mucus function in the gut, the researchers found that the function of the mucus layer was disrupted in mice transplanted with bacteria from humans with a history of repeated antibiotic use. Expansion of the mucus was reduced, and the mucus layer became penetrable, allowing bacteria to move closer to the intestinal lining.
“Looking at the bacteria present in the gut in more detail, we could see that bacteria known to feed on the mucus layer were present at higher levels in these mice. This further supports a role for the gut bacteria in determining how well the mucus barrier can function,” says Rachel Feeney, PhD student at the Department of Molecular Biology at Umeå University.
A separate study carried out in another international collaboration, further showed that antibiotics can also directly disrupt the mucus barrier in a gut bacteria-independent manner.
By giving the antibiotic vancomycin to normal and ‘bacteria-free’ mice, the researchers were able to show that this antibiotic can act directly on the mucus barrier, independent of the gut bacteria. Complementary experiments on intestinal tissue were carried out at Umeå University and showed that the antibiotic could disrupt the mucus expansion within a few minutes of application.
Gut Microbiome. Credit Darryl Leja National Human Genome Research Institute National Institutes Of Health
Researchers have developed a new antibiotic that reduced or eliminated drug-resistant bacterial infections in mouse models of acute pneumonia and sepsis while sparing healthy microbes in the mouse gut. The drug, called lolamicin, also warded off secondary infections with Clostridioides difficile, and was effective against more than 130 multidrug-resistant bacterial strains in cell culture.
“People are starting to realise that the antibiotics we’ve all been taking – that are fighting infection and, in some instances, saving our lives – also are having these deleterious effects on us,” said University of Illinois Urbana-Champaign chemistry professor Paul Hergenrother, who led the study with former doctoral student Kristen Muñoz. “They’re killing our good bacteria as they treat the infection. We wanted to start thinking about the next generation of antibiotics that could be developed to kill the pathogenic bacteria and not the beneficial ones.”
“Most clinically approved antibiotics only kill gram-positive bacteria or kill both gram-positive and gram-negative bacteria,” Muñoz said.
The few drugs available to fight gram-negative bacteria, which are protected by their double cell walls, also kill other potentially beneficial gram-negative bacteria. For example, colistin, one of the few gram-negative-only antibiotics approved for clinical use, can cause C. difficile-associated diarrhoea and pseudomembranous colitis, a potentially life-threatening complication. The drug also has toxic effects on the liver and kidney, and “thus colistin is typically utilised only as an antibiotic of last resort,” the researchers wrote.
To tackle the many problems associated with indiscriminately targeting gram-negative bacteria, the team focused on a suite of drugs developed by the pharmaceutical company AstraZeneca. These drugs inhibit the Lol system, a lipoprotein-transport system that is exclusive to gram-negative bacteria and genetically different in pathogenic and beneficial microbes. These drugs were not effective against gram-negative infections unless the researchers first undermined key bacterial defenses in the laboratory. But because these antibiotics appeared to discriminate between beneficial and pathogenic gram-negative bacteria in cell culture experiments, they were promising candidates for further exploration, Hergenrother said.
In a series of experiments, Muñoz designed structural variations of the Lol inhibitors and evaluated their potential to fight gram-negative and gram-positive bacteria in cell culture. One of the new compounds, lolamicin, selectively targeted some “laboratory strains of gram-negative pathogens including Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae,” the researchers found. Lolamicin had no detectable effect on gram-positive bacteria in cell culture. At higher doses, lolamicin killed up to 90% of multidrug-resistant E. coli, K. pneumoniae and E. cloacae clinical isolates.
When given orally to mice with drug-resistant septicemia or pneumonia, lolamicin rescued 100% of the mice with septicemia and 70% of the mice with pneumonia, the team reported.
Extensive work was done to determine the effect of lolamicin on the gut microbiome.
“The mouse microbiome is a good tool for modeling human infections because human and mouse gut microbiomes are very similar,” Muñoz said. “Studies have shown that antibiotics that cause gut dysbiosis in mice have a similar effect in humans.”
Treatment with standard antibiotics amoxicillin and clindamycin caused dramatic shifts in the overall structure of bacterial populations in the mouse gut, diminishing the abundance several beneficial microbial groups, the team found.
“In contrast, lolamicin did not cause any drastic changes in taxonomic composition over the course of the three-day treatment or the following 28-day recovery,” the researchers wrote.
Many more years of research are needed to extend the findings, Hergenrother said. Lolamicin, or other similar compounds, must be tested against more bacterial strains and detailed toxicology studies must be conducted. Any new antibiotics also must be assessed to determine how quickly they induce drug resistance, a problem that arises sooner or later in bacteria treated with antibiotics.
The study is a proof-of-concept that antibiotics that kill a pathogenic microbe while sparing beneficial bacteria in the gut can be developed for gram-negative infections – some of the most challenging infections to treat, Hergenrother said.
According to a massive new medical insurance database study, the U.S. is going the wrong way with antibiotic stewardship, with 1 in 4 prescriptions going to patients who have conditions that the drugs simply won’t work on. In fact, the percentage of all antibiotic prescriptions given to treat conditions they’re useless against was even higher in December 2021 than it was before the pandemic began, the study shows – increasing the rate of antibiotic resistance development.
The percentage inappropriate prescriptions actually fell slightly in the early months of the pandemic, when far fewer people sought medical care for infectious or non-infectious reasons, the new research shows. But this trend was soon reversed.
The study, published in the journal Clinical Infectious Diseases by a team from the University of Michigan, Northwestern University and Boston Medical Center, is based on data from more than 37.5 million children and adults covered by private insurance or Medicare Advantage plans from 2017 to 2021. Patients received antibiotic prescriptions from both in-person and telehealth visits.
The team looked back at any new diagnosis given to each patient on the day they received a prescribed antibiotic or in the three days before getting the prescription. If none of these diagnoses justified the use of antibiotics, they classified the prescription as inappropriate.
Key findings:
In all, 60.6 million antibiotic prescriptions were dispensed in the five years of the study period from January 2017 to December 2021. The share that were inappropriate rose from 25.5% to 27.1% during this period.
The proportion of people getting inappropriate antibiotics was 1.7% in December 2019, dipped to 0.9% in April 2020 – largely because fewer people get antibiotics in general – and returned to 1.7% by December 2021.
Some groups of people were more likely to receive inappropriate antibiotics. At the end of 2021, 30% of antibiotics for older adults with Medicare Advantage coverage were inappropriate, compared with 26% of antibiotics for adults with private health insurance and 17% of antibiotics for children with private insurance.
Among the diagnoses listed for people who received antibiotics for inappropriate reasons, “contact with and suspected exposure to COVID-19” was one of top two most common reasons from March 2020 through December 2021. There is no evidence that taking antibiotics after an exposure can reduce risk of developing COVID-19.
Of all the inappropriately prescribed antibiotics dispensed in the last half of 2021, 15% were for a COVID-19 infection. And COVID-19 infections accounted for 2% of all antibiotic prescribing – regardless of appropriateness – from March 2020 through December 2021.
Telehealth appointments accounted for 9% of all inappropriate antibiotic prescriptions in the latter half of 2021, down somewhat from 2020. There were almost no telehealth-based antibiotic prescriptions before March 2020.
For 28% to 32% of the antibiotic prescriptions filled by patients in the study period, there was no diagnosis available to judge appropriateness, potentially because the patient received the prescription at an appointment that didn’t get billed to their insurance, or it was a refill of a past prescription. The percentage was especially high in the first months of the pandemic.
45% of all the patients in the study received antibiotics at least once in the five years, and 13% received them four or more times.
A US study found that, despite prescriptions for the antibiotic ciprofloxacin dropping by two-thirds between 2015 and 2021, the rates of ciprofloxacin-resistant E. coli bacteria circulating in the community did not decline.
In fact, a study of women over age 50 who had not taken any antibiotics for at least a year discovered that the incidence of gut-colonising ciprofloxacin-resistant E. coli actually increased. About 1 in 5 women in the study were affected.
Scientists at the University of Washington School of Medicine, Kaiser Permanente Washington Health Research Institute and Seattle Children’s Hospital conducted the study. Their findings appear in Communications Medicine.
Their results are consistent with theoretical models indicating that, once a drug-resistant form of E.coli emerges, it will continue to spread by taking up long-term residence in individuals’ gut microbiomes. E. coli is among an alarming number of disease-causing bacteria that have become resistant to several types of antibiotics. Resistance means that the antibiotics can’t kill the bacteria.
Pathogenic E. coli from the gut occasionally enters the urinary tract opening and causes infections. The female pelvic anatomy makes women more vulnerable to these mobile bacteria. Postmenopausal women are especially susceptible to severe, drug-resistant infection. Some drug-resistant E. coli infections are associated with considerable risk of hospitalization and death from sepsis.
Urinary tract infections from antibiotic-resistant E. coli can be frustrating to treat, even with third-generation cephalosporins, the newer types of antibiotics that are being prescribed more frequently for some populations of patients. Resistance to cephalosporins among ciprofloxacin-resistant E. coli also rose between 2015 and 2021.
Ciprofloxacin and similar drugs in its class were once the most prescribed antibiotic for urinary tract infections. In 2015, recommendations from the Centers for Disease Control and Prevention, Food and Drug Administration and Infectious Disease Society of America discouraged broad use of this class of drugs for uncomplicated urinary tract infections, partly due to rising resistance.
“However, it appears to be questionable whether a reduction in antibiotic use can be effective in reducing the rates of resistance in E. coli infections,” the research paper’s authors noted.
“Evidence from studies such as this one may be changing lots of paradigms on how to fight the rise in antibiotic resistance,” said physician scientist Dr. Evgeni V. Sokurenko, professor of microbiology at the University of Washington School of Medicine, who headed this latest research.
In the study, the scientists examined participants’ positive samples to determine which antibiotic-resistant strains of E. coli were present.
They found that the rate of a particularly virulent strain, ST1193, rose during the study period. Together with E. coli strain ST131-H30, these strains are the major causes of a global pandemic of multi-drug-resistant urinary tract infections among all women.
If ST1193 makes its home in more people’s guts, the situation could lead to more urinary tract infections with this more virulent strain, regardless of the curbing of fluoroquinolones prescriptions.
Another strain with a troubling increase in the participant samples was ST69, known to more frequently cause urinary tract infections in children.
tize discovering better ways to control drug-resistant E. coli’s ability to colonize the gut before it causes these infections, the authors wrote. They mentioned potential strategies of deploying probiotic bacteria and anti-bacterial viruses (bacteriophages).
The researchers added that these approaches might be offered to high-risk patients or deployed against the most clinically relevant strains. More investigation is needed on the epidemiology and ecology of antibiotic-resistant gut E. coli, they said, to help determine how these bacteria skillfully colonize human guts and how to target them most effectively to reduce antibiotic-resistant infections.
In children with suspected sinusitis, a nasal swab to test for three types of bacteria can tell whether antibiotics are likely to be effective or not, according to a new JAMAstudy by researchers at the University of Pittsburgh and UPMC. They also found that nasal discharge colour was no help in differentiating a viral or bacterial infection.
“Sinusitis is one of the most common diseases we see in children, but it’s difficult to diagnose because it’s based on the duration of symptoms: If the child has a runny nose or congestion for more than 10 days, we suspect sinusitis,” said said lead author Nader Shaikh, MD. “For an ear infection, we can look inside the ear; for pneumonia, we listen to the lungs. But for sinusitis, we have nothing to go on from a physical exam. That was very unsatisfying to me.”
With the goal of developing a better tool to diagnose bacterial sinusitis, Shaikh and his team enrolled about 500 children with sinusitis symptoms from six centres across the US and randomly assigned them to receive either a course of antibiotics or placebo. The researchers also took nasal swabs from each child and tested for the three main types of bacteria involved in sinusitis.
Children who tested positive for the bacteria had better resolution of symptoms with antibiotic treatment compared to those who did not have bacteria. These findings suggest that testing for bacteria could be a simple and effective way to detect children who are likely to benefit from antibiotics and avoid prescribing antibiotics to those who wouldn’t.
“If antibiotics aren’t necessary, then why use them?” said Shaikh. “These medications can have side effects, such as diarrhoea, and alter the microbiome, which we still don’t understand the long-term implications of. Overuse of antibiotics can also encourage antibiotic resistance, which is an important public health threat.”
According to Shaikh, a common belief among parents and doctors is that yellow or green snot signals a bacterial infection. Although several small studies have suggested that nasal discharge colour is not meaningful, Shaikh and his team formally tested this idea by asking parents to identify the hue of their child’s snot on a colour card.
“If kids with green or yellow discharge benefitted more from antibiotics than those with clear-coloured discharge, we would know that colour is relevant for bacterial infection,” explained Shaikh. “But we found no difference, which means that colour should not be used to guide medical decisions.”
The researchers are now looking at how to best roll out nasal testing in the clinic. A major challenge is that bacterial culture-based tests used in the study are not easy for most family doctors to order and can take several days to get results. A more practical approach could be commercially available molecular testing, which could return results overnight, said Shaikh.
Another possibility could be development of rapid antigen tests that work like COVID-19 at-home testing kits. The researchers also plan to delve deeper into the data from this study to see whether there could be another type of biomarker in nasal discharge indicating the presence of bacteria that would be easier to test for.
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.
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.”
Globally, infections by antimicrobial-resistant (AMR) bacteria caused more than 1.2 million deaths worldwide in 2019, according to a study published in The Lancet. It is the largest and most comprehensive one to date of this critical issue.
Lower-income countries are worst affected but antimicrobial resistance remains a global threat, the researchers wrote.
The researchers emphasised that investment in new drugs is urgently needed, as well as vaccination and better antimicrobial stewardship.
The estimate of global deaths from AMR, is based on the researchers’ analysis of 204 countries, assuming the counterfactual that the bacteria responsible would be antibiotic-susceptible.
Of the 4.95 million deaths in which AMR played a role, 1.27 million were directly attributable to it. In 2019, 860 000 deaths were estimated from HIV and 640 000 from malaria.
Most of the AMR-related deaths resulted from lower respiratory infections, such as pneumonia, and bloodstream infections, which can lead to sepsis.
Deaths from AMR were estimated to be highest in sub-Saharan Africa at 23.7 deaths per 100 000, and lowest in North Africa and the Middle East at 11.2 per 100 000. Young children are at most risk, with about one in five deaths linked to AMR being among the under-fives.
The researchers also noted that “resistance is high for multiple classes of essential agents, including beta-lactams and fluoroquinolones.”
MRSA (methicillin-resistant Staphylococcus aureus) was particularly deadly, while E. coli, K. pneumoniae, S. pneumoniae, A. baumannii, and P. aeruginosa were associated with high levels of resistance. The researchers wrote that “each of these leading pathogens is a major global health threat that warrants more attention, funding, capacity building, research and development, and pathogen-specific priority setting from the broader global health community.”
They also recommend that immunity to these pathogens be built up by vaccination, and since currently only S. pneumoniae has a vaccine readily available, these will need to be developed and deployed as a matter of urgency. They noted several limitations to their study, the first being the sparsity of data drawn from low- and middle-income countries, which may in fact lead to an underestimate of the prevalence of AMR. Secondly, there is the possibility of multiple sources of bias inherent in combining datasets from different providers. Finally, there may be bias in surveillance, eg if cultures are drawn only if a patient is unresponsive to antibiotics, leading to an overestimate.
