Fungal infections are becoming more difficult to treat as they become more resistant to available drugs, according to research published Wednesday in Lancet Microbe.
The study focused on infections caused by Aspergillus fumigatus, A fungus that is omnipresent in the soil and the decaying matter in the world. Aspergillus spores are inhaled all the time, generally without causing problems. But in immunocompromised people or who have underlying pulmonary conditions, Aspergillus can be dangerous.
The fungus is one of the main concerns of the World Health Organization on its list of priority mushrooms, which notes that mortality rates for people with aspergillus drug infections vary from 47% to 88%.
The new study revealed that the resistance to fungi drugs increases. In addition to this, patients are generally infected with several mushroom strains, sometimes with different resistance genes.
“This presents treatment problems,” said the study co-author, Jochem Buil, microbiologist at the Radboud University Medical Center in the Netherlands.
Buil and his team have analyzed more than 12,600 samples of Aspergillus Fumigatus taken from the lungs of Dutch hospitals over the past 30 years. Among them, around 2,000 accommodated mutations associated with the Azol resistance, the antifungal class used to treat infections. Most of them had one of the two well -known changes, but 17% had changes in changes.
Nearly 60 people had invasive infections – which means that mushrooms spread from lungs to other parts of the body – including 13 resistant to Azols. In these people, almost 86% were infected with multiple mushroom strains, making treatment even more complicated.
“It is an increasingly complicated story and doctors may find it difficult to identify whether or not they are a fungal infection resistant to drugs,” said Dr. Arturo Casadevall, president of microbiology and public health immunology by John Hopkins Bloomberg, which was not involved in research.
Before treating an Aspergillus fungal infection, doctors are looking for resistance genes that can give them clues to the drugs that will work best. If someone is infected with several strains of the same type of fungus, it becomes much less clear. Often different stumps will respond to different drugs.
“Azols are the first line of treatment for strains sensitive to Azols, but they do not work when a strain is resistant. For these, we must use different drugs that do not work as well and have worse side effects,” said Buil, adding that some people will need treatment with multiple antifungal drugs at the same time.
The results illustrate a greater trend in increasing pressure on the few drugs available to treat fungal infections – there are only three major classes of antifungal drugs, including Azols, which treat invasive infections, compared to several dozen antibiotic classes.
Resistance to these drugs increases and new ones are particularly difficult to develop.
Humans and mushrooms share about half of their DNA, which means that we are much more closely linked to mushrooms than to bacteria and viruses. Many proteins that are essential to the survival of fungi are also essential for human cells, leaving less secure targets for antifungal drugs to attack.
“The big problem for all these fungal species is that we do not have many antifungals,” said Jarrod Fortwendel, a clinical pharmacy teacher at the University of Tennessee Health Science Center, who was not involved in research. “As a rule, the genetic mutations that cause resistance do not cause resistance to one of the drugs, these are all, so you lose the whole class of medication.”
To complicate the questions, the vast majority of the Azol resistance at Aspergillus Fumigatus comes from agriculture, which largely uses fungicides. Fungicides generally have the same molecular targets as antifungal drugs. Farmers spray them on crops, including wheat and barley in the United States, to prevent or treat fungal diseases. (The first instance of Azols resistance was documented in the Netherlands, where antifungals are widely used on tulips.) Aspergillus mushrooms are not the target, but exposure to fungicides gives them one step ahead of genes which are resistant to targets, sometimes in front of an antifungal drug with the same target, even the market.
It was the source of the vast majority of drug resistance analyzed in the study.
Fortwendel noted that mushroom resistance is increasingly found in the world. “Basically, wherever we are looking for drug-resistant isotopes, we find them,” he said. “We see this resistance to Azole drugs occurring in the United States, these rates will probably climb.”
The risk of any individual to have an Aspergillus fumigatus resistant to azole is low, said Casadevall. Infections generally affect immunocompromised people and amount to around a few thousand cases a year in the United States, Casadevall said. Although relatively rare, the larger risk is the broader trend of fungal infections resistant to drugs.
“Organizations that cause a disease become more resistant to medication,” he said. “Even if it is not as if you do not wake up with a fungal pandemic, it is a worse problem today that five, 10 or 20 years ago.”
