Each year, fungal infections kill the same number of people as tuberculosis. They are often caught in vulnerable people because of a weakened immune system caused by a major disease such as cancer or a viral infection such as HIV or COVID. Our new study shows that antibiotics can lead to immune system deficiencies that increase the risk of dangerous fungal infections.
Candida is a common cause of fungal infections in humans. Yeast infection is caused by thrush Candida. But it can also lead to a life-threatening blood-borne infection called invasive candidiasis.
One of the risk factors for invasive candidiasis is antibiotics. When we take antibiotics, we kill some of the bacteria in the gut. This can make room for intestinal fungi (e.g. Candida) to grow. And if your intestines are damaged by chemotherapy or surgery Candida Leaking from the intestines can lead to bloodstream infections.
However, the most common cause of invasive candidiasis in humans is the skin, not the intestines. Patients in intensive care with a catheter inserted into a vein may develop invasive candidiasis, especially if treated with antibiotics.
We wanted to know exactly why antibiotics are more likely to cause fungal infections, such as invasive candidiasis. For the study, we treated the mice with a broad-spectrum antibiotic cocktail and then infected them. Candida mushrooms. We compared them to a control group of mice infected with candidiasis but treated with a cocktail of antibiotics.
Antibiotic treatment has been reported in mice with fungal infections. In this fungal infection, the target of the kidney infection is often the mice that get sick because their kidneys fail. But this did not happen here. Although antibiotics made mice worse, they were able to control fungal infections of the kidneys, just as mice did not. So what is hurting them?
Antibiotics cause a defect in the immune response to the fungus, or more precisely, in the gut. The level of fungal infection in the intestines of mice treated with antibiotics was much higher than that of untreated mice. As a result, the bacteria in the gut then spread to the bloodstream. Mice treated with antibiotics now had to fight both bacterial and fungal infections. This made them more painful than mice without antibiotics.
To understand why this is happening, we analyzed the immune cells in the gut to find out how antibiotics triggered the immune response against the fungus. Immune cells in the gut produce tiny proteins called cytokines, which serve as messages to other cells. For example, cytokines called IL-17 and GM-CSF help immune cells fight fungal infections. We found that antibiotics reduced the levels of these cytokines in the gut, partly because mice treated with the antibiotic could not control the fungal infection in the gut or stop the release of bacteria.
Some of these cytokines can be given as immune-boosting drugs to help patients fight infection. To see if this could be an option for patients treated with antibiotics at risk for fungal infections, we injected some of these cytokines into our antibiotic-treated mice and found that we could make them less painful. Our findings suggest that we may have a way to help patients who need antibiotics and are at risk for fungal infections.
Next, we wanted to know if there was a specific antibiotic that increased the risk of fungal infection. We treated mice with a variety of antibiotics and found that vancomycin, a commonly used antibiotic in hospitals to treat C diff infections, made mice more painful after a fungal infection. Vancomycin kills immune-boosting bacteria from the intestinal microbiome, which is needed to instruct the immune system to make IL-17.
Does this study apply to anyone? Analysis of our patients’ records shows this. We looked at a large database of hospital records and found that similar bacterial / fungal infections can occur in humans after treatment with antibiotics.
Given the growing problem of antibiotic resistance, it is now more important than the careful use of antibiotics. Our research shows that antibiotics can provide an additional risk of dangerous fungal infections. However, antibiotics are a risk factor that we can control. Fungal infections remain an important problem for human health, but research like ours can help us understand how to deal with them.