Fungal infections are getting harder to treat
The study focused on infections caused by Aspergillus fumigatus, a fungus that is ubiquitous in soil and decaying matter around the world. Aspergillus spores are inhaled all the time, usually without causing any problems. But in people who are immunocompromised or who have underlying lung conditions, Aspergillus can be dangerous.
The fungus is one of the World Health Organization's top concerns on its list of priority fungi, which notes that death rates for people with drug-resistant Aspergillus infections range from 47%-88%.
The new study found that the fungus' drug resistance is increasing. On top of that, patients are typically infected with multiple strains of the fungus, sometimes with different resistance genes.
'This presents treatment issues,' said the study's co-author, Jochem Buil, a microbiologist at Radboud University Medical Centre in the Netherlands.
Buil and his team analyzed more than 12,600 samples of Aspergillus fumigatus taken from the lungs of patients in Dutch hospitals over the last 30 years. Of them, about 2,000 harbored mutations associated with resistance to azoles, the class of antifungals used to treat the infections. Most of them had one of two well-known mutations, but 17% had variations of the mutations.
Nearly 60 people had invasive infections — meaning the fungi spread from the lungs to other parts of the body — 13 of which were azole-resistant. In those people, nearly 86% were infected with multiple strains of the fungi, making treatment even more complicated.
'It is an increasingly complicated story and physicians may have trouble identifying whether or not they are dealing with a drug-resistant fungal infection,' said Dr. Arturo Casadevall, chair of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, who wasn't involved with the research.
Before treating an Aspergillus fungal infection, doctors look for resistance genes that can give them clues about which drugs will work best. If someone is infected with multiple strains of the same type of fungus, this becomes much less clear-cut. Oftentimes, different strains will respond to different drugs.
'Azoles are the first line of treatment for azole-susceptible strains, but they do not work when a strain is resistant. For those, we need to use different drugs that don't work as well and have worse side effects,' Buil said, adding that some people will require treatment with multiple antifungal drugs at the same time.
The findings illustrate a larger trend of growing pressure on the few drugs available to treat fungal infections — there are only three major classes of antifungal drugs, including azoles, that treat invasive infections, compared with several dozen classes of antibiotics.
Resistance to such drugs is growing, and new ones are uniquely difficult to develop.
Humans and fungi share about half of their DNA, meaning we're much more closely related to fungi than we are to bacteria and viruses. Many of the proteins that are essential for fungi to survive are also essential for human cells, leaving fewer safe targets for antifungal drugs to attack.
'The big problem for all of these fungal species is that we don't have a lot of antifungals,' said Jarrod Fortwendel, a professor of clinical pharmacy at the University of Tennessee Health Science Center, who was not involved with the research. 'Typically the genetic mutations that cause resistance don't cause resistance to one of the drugs, it's all of them, so you lose the entire class of drugs.'
Further complicating matters, the vast majority of azole resistance in Aspergillus fumigatus stems from agriculture, which widely uses fungicides. The fungicides typically have the same molecular targets as antifungal drugs. Farmers spray them on crops, including wheat and barley in the U.S., to prevent or treat fungal disease. (The first instance of azole resistance was documented in the Netherlands, where antifungals are widely used on tulips.) Aspergillus fungi aren't the target, but exposure to the fungicides gives them a head start developing genes that are resistant to the targets, sometimes before an antifungal drug with the same target even hits the market.
This was the source of the vast majority of the drug resistance analyzed in the study.
Fortwendel noted that fungal resistance is increasingly found around the world. 'Basically everywhere we look for drug-resistant isotopes, we find them,' he said. 'We are seeing this azole drug-resistance happening throughout the U.S. Those rates will likely climb.'
Any individual person's risk of having an azole-resistant Aspergillus fumigatus is low, Casadevall said. Infections typically affect people who are immunocompromised and amount to around a few thousand cases per year in the U.S., Casadevall said. While relatively uncommon, the bigger risk is the broader trend of drug-resistant fungal infections.
'The organisms that cause disease are getting more resistant to drugs,' he said. 'Even though it's not like Covid, we don't wake up to a fungal pandemic, this is a problem that is worse today than it was five, 10 or 20 years ago.'
This article was originally published on NBCNews.com
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Approach Description Relevance to Cervical Cancer Immune checkpoint inhibitors Block proteins (PD-1, PD-L1) that prevent immune cells from attacking cancer Reactivates exhausted T cells to fight cervical cancer cells Monoclonal antibodies Lab-made antibodies designed to target specific tumor markers Some bind PD-L1 or deliver cytotoxic agents directly to tumor cells Cancer vaccines Stimulate immune response to HPV or tumor-associated antigens Promote lasting T cell activation and memory Adoptive T cell therapy Infuse engineered T cells that can attack tumor cells Under investigation for recurrent cervical cancer The PD-1/PD-L1 Pathway PD-1 is a receptor on T cells that regulates immune response PD-L1 is often overexpressed on cervical cancer cells When PD-L1 binds to PD-1, it "switches off" the immune attack Checkpoint inhibitors block this interaction – reactivating T cells to destroy cancer cells Why It Matters Many cervical tumors exhibit high PD-L1 expression, making them ideal candidates for immunotherapy. 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Side Effect Type Description Frequency Colitis Inflammation of the colon causing diarrhea Moderate Thyroiditis/Hypothyroidism Immune attack on the thyroid Common Dermatitis or skin rash Immune-related skin inflammation Common Fatigue and joint pain General inflammatory response Mild to moderate Pneumonitis Lung inflammation (rare but serious) Rare Cleveland Clinic highlights that these side effects are often immune-related and differ from those of chemotherapy, which typically causes nausea, hair loss, and bone marrow suppression. Most immune-related reactions are manageable with corticosteroids or immunosuppressive agents when diagnosed early. Importance of Tumor Profiling and Biomarker Testing Before initiating immunotherapy, tumor profiling is crucial. Tests that assess PD-L1 expression, tumor mutational burden, and immune cell markers help determine whether a patient is a good candidate. 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Primary Reasons Patients Travel Abroad for Treatment Limited access at home: In some countries, immune checkpoint inhibitors and personalized immunotherapy are not yet standard care – or are cost-prohibitive without insurance support. Delays in diagnosis or therapy: Long waitlists for oncology consultations or biopsy testing can result in treatment delays that worsen outcomes. Patients who choose to treat cervical cancer abroad often report improved outcomes, better coordination, and more comprehensive care – especially when guided by experienced facilitators like Booking Health. From Research to Results: How Immunotherapy Extends Life Expectancy Recent clinical advances highlight the growing role of immunotherapy in improving life expectancy for patients with stage 4 cervical cancer. 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As immunotherapy research continues to expand, it represents a significant shift in the management of advanced cervical cancer, giving more women a realistic chance at extended survival and an improved quality of life. Key Takeaways: Immunotherapy's Impact on Advanced Cervical Cancer Immunotherapy offers hope for women with stage 4 cervical cancer, especially when other treatments have failed. It works by strengthening the immune system to recognize and eliminate cancer cells more effectively. Most effective in patients with PD-L1-positive, recurrent, metastatic, or invasive cervical cancer. Recent phase III clinical trials show longer survival and improved median progression-free survival compared to chemotherapy alone. Booking Health connects international patients with leading European hospitals that specialize in cervical cancer immunotherapy and personalized care. 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Choosing Booking Health means more than just acquiring access to innovative world-class therapy - it means saving valuable time knowing that every detail is handled by professionals. Headquartered in Bad Hönningen, Germany and officially registered in Düsseldorf under HRB 106466, Booking Health proudly consults patients from over 75 countries for over a decade, offering services in 11 languages. Press inquiries Booking Health Lena Hanten marketing@ Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
