Breakthroughs Blog: Antimicrobial resistance

A team of chemists from the University of Warwick and Monash University has identified a promising, potent new antibiotic that seems to be much more effective than existing drugs against deadly superbugs like MRSA and shows no signs of resistance so far, encouraging news as the global threat of antimicrobial resistance continues to grow and the pipeline of new antibiotics continues to fall short. The molecule had been overlooked for decades as an intermediate chemical in the natural process to produce another known antibiotic, methylenomycin A, which was discovered 50 years ago, and despite having been synthesized multiple times, the synthetic intermediates have seemingly not been tested before for antimicrobial activity. The new antibiotic is much more potent than methylenomycin A itself—100 times more active against a range of serious bacteria. It could not only be a powerful new tool against rising drug resistance, but this work could also pave the way for new approaches to antibiotic discovery. A team of researchers has developed an antivenom using antibodies from a llama and an alpaca that can neutralize venom from some of the world’s most venomous snakes. Snakebites are a neglected public health issue that kill around 20,000 people in sub-Saharan Africa yearly. Current antivenom treatments are usually specific to a single snake species, and it can be difficult to identify which of the many types of venomous snakes is behind a bite, making timely, effective treatment difficult to achieve. The researchers exposed an alpaca and a llama to venoms from 18 of the most dangerous snake species in sub-Saharan Africa, isolated the antibodies that the animals produced against the venom, and then combined some of those antibodies in a single cocktail. In mice, the treatment protected against toxins from 17 African snake species and reduced skin damage. Many scientists previously thought that developing a broad-spectrum antivenom would require too many antibodies to be practical because some venom can contain up to 100 toxins, but this study shows that a combination of just a handful of antibodies can neutralize the venom of many snake species, paving the way for the development of similar broad-spectrum antivenoms for other areas where snakebites are a common public health challenge. Last week, Cepheid announced that its Xpert MTB/XDR test for tuberculosis (TB) drug resistance has been prequalified by the World Health Organization (WHO), enabling procurement through international agencies and greater access in areas with a high TB burden. The test is designed to detect resistance to multiple first- and second-line TB drugs from patient samples. It also delivers results quickly, within 90 minutes, allowing health care providers to make quicker, more reliable treatment decisions and have a better understanding of drug resistance, especially in regions with a high TB burden where timing and accuracy are critically important. 

Last week, the World Health Organization (WHO) published its latest reports on the new antibacterial agents and diagnostics in the pipeline, seeking to encourage research and development (R&D) to invigorate the sparse pipeline of tools to address the growing global threat of antibiotic resistance. The report highlights a lack of innovation in the antibacterial pipeline and major gaps in antibacterials targeting the most critical bacterial threats and addressing needs like pediatric formulations and oral treatments for outpatient use. There are similar persistent gaps for diagnostics, including a lack of new tests that are affordable, robust, and easy to use in low-resource settings. A new study, led by Imperial College London and supported by the Coalition for Epidemic Preparedness Innovations (CEPI) found that vaccines designed to protect against a wide range of coronaviruses, including a novel sarbecovirus, the type of coronavirus that includes the viruses that caused SARS and COVID-19, could be a gamechanger in a future global coronavirus pandemic, dramatically reducing deaths and disruption. A broad vaccine like this could be manufactured and stockpiled before an outbreak arises and quickly rolled out when a new outbreak is identified, providing protection to high-risk populations 60 years and older. This immediate protection could be a powerful stopgap while a new vaccine targeting the specific virus behind the outbreak is developed. An international research team has developed a simple, affordable HPV test that delivers results in less than an hour outside of a specialized laboratory, which could be a breakthrough for improving access to cervical cancer screening for women in low-resource settings. Cervical cancer continues to cause more than 350,000 deaths every year, particularly in low- and middle-income countries with limited regular access to cervical cancer screening. The test uses a swab sample and a battery-operated portable device, projected to cost less than $8 each, and it was found to be highly accurate compared to the reference standard. 

A Phase 1 clinical trial testing an experimental monoclonal antibody for malaria found that the highest dose of the treatment studied was highly effective in preventing malaria. Researchers from the University of Maryland, Sanaria, the Vital Narrative consultancy, and the Gates Medical Research Institute tested the monoclonal antibody, MAM01, in 37 adults who had never been exposed to malaria, who received either a single dose of varying sizes or a placebo, and then were infected by the bites of infected mosquitoes. None of the three recipients who received the highest dose had malaria parasites in their blood after infection. The monoclonal antibody could prove to be an important treatment option that provides immediate, high-level, and long-lasting protection with just one doseA Japanese research team has isolated natural compounds from marine sponges that demonstrate an ability to kill parasites that cause leishmaniasis, which affects approximately 12 million people around the world. Current treatments are highly toxic, cause serious side effects, and can be prohibitively expensive, leaving patients, particularly in low-income communities, which face a disproportionate burden of leishmaniasis, unable to access or complete treatment. Drug resistance is also complicating leishmaniasis treatment efforts. These findings could guide research into new treatment approaches and could potentially also be applied to other protozoan diseases like Chagas disease and African sleeping sickness. A new CRISPR-based RNA test could help track the parasites that spread Human African trypanosomiasis, or sleeping sickness, which affects around 500 people per year and many more livestock animals. The test can identify parasite species living in an animal’s blood, helping public health workers carry out targeted treatment of infected animals and prevent transmission to humans. This One Health approach to zoonotic or parasitic diseases could also be rolled out to address other diseases, such as Chagas disease or leishmaniasis.  

An international research team led by the University of Liverpool has discovered an exciting new class of antibiotics with the potential to target some of the world’s most dangerous multidrug-resistant bacteria, including MRSA and Enterococcus faecium, as experts continue to warn of the growing global threat of antimicrobial resistance. The new class, Novltex, targets a key component of bacterial cell walls that does not mutate, meaning that, unlike traditional antibiotics, it could offer long-lasting protection against antibiotic-resistant strains of bacteria. Novltex is a synthetically designed platform, making it cheaper to produce and easier to scale up for global use than common antibiotics that utilize complex, expensive natural molecules. In studies so far, researchers found Novltex to be potent and fast-acting, even at low doses, and safe. A research team led by investigators at Weill Cornell Medicine has been awarded a five-year, $20.8 million grant from the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health to further the preclinical development of a promising experimental HIV vaccine for pediatric populations. Experts agree that a preventive vaccine for HIV could help turn the tide of the pandemic. Previous studies of the experimental vaccine found that it was safe and may be effective in infants, although it seems to only work in young immune systems, not in adults. The new funding will support optimization of the vaccine in preparation for clinical trials in infants in parts of the world with a high burden of HIV. Researchers at Tulane University have designed an optimized CRISPR-based tuberculosis (TB) test that uses a simple tongue swab, which, if it continues to demonstrate promise, could be a breakthrough for TB testing. Current TB tests often rely on sputum, which can be difficult to collect and which not everyone can produce, and require sophisticated laboratory equipment and skilled health care workers, leading to gaps in diagnosis, particularly in low-resource settings. The researchers built on a previous CRISPR-based TB test, developing an assay that they found to be highly effective using tongue swabs and also highly sensitive in detecting TB in respiratory, pediatric stool, and spinal fluid samples. This painless and low-resource method could improve access to TB testing, particularly at the point of care in remote and low-resource communities.