Fungal infections kill about the same number of people each year as tuberculosis. They mainly take hold in vulnerable people because they have a faulty immune system caused by an underlying disease, such as cancer, or a viral infection, such as HIV or COVID. Our new study shows that antibiotics can cause immune system abnormalities that increase the risk of dangerous fungal infections.
candidiasis is a fungus that is a common cause of fungal infections in humans. Thrush is caused by candidiasis. But it can also cause a life-threatening bacteremia called invasive candidiasis.
One of the risk factors for contracting invasive candidiasis is taking antibiotics. When we take antibiotics, we kill some of our gut bacteria. This can create space for intestinal fungi (like candidiasis) to grow. And if your intestines are damaged by chemotherapy or surgery, then the candidiasis can come out of the intestine and cause a blood infection.
Yet the most common way people contract invasive candidiasis is not from their gut, but from their skin. Patients in intensive care who are fitted with an intravenous catheter can contract invasive candidiasis, especially if they have been treated with antibiotics.
We wanted to know exactly why antibiotics make fungal infections such as invasive candidiasis more likely. To investigate, we treated mice with a broad-spectrum antibiotic cocktail and then infected them with candidiasis mushrooms. We compared them to a control group of mice that we infected with the Candida fungus, but did not treat with the cocktail of antibiotics.
We found that antibiotic treatment made mice sicker when infected with the fungus. In this fungal infection, it is normally the kidneys that become the target of infection and the mice become ill because their kidneys stop working. But that was not the case here. Although the antibiotics made the mice sicker, they controlled the fungal infection in the kidneys as well as the mice that did not receive the antibiotics. So what made them sick?
The antibiotics were found to cause a defect in the antifungal immune response, particularly in the gut. Mice treated with antibiotics had much higher levels of fungal infection in the intestines than untreated mice. The consequence was that the intestinal bacteria then escaped into the blood. The antibiotic-treated mice now had both a bacterial infection and a fungal infection to deal with. It made them much sicker than the mice that didn’t have antibiotics.
To understand why this was happening, we analyzed immune cells in the gut to understand how antibiotics caused a faulty antifungal immune response. Immune cells in the gut make small proteins called cytokines that act 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 amount of these cytokines in the gut, which we believe partly explains why mice treated with antibiotics couldn’t control fungal infections in the gut or prevent bacteria from escaping. .
Some of these cytokines can be given to patients as immune-boosting drugs to help fight infections. To see if this might be an option for antibiotic-treated patients at risk of fungal infections, we injected our antibiotic-treated mice with some of these cytokines and found that we could make them less sick. Our findings mean we may have a way to help patients who need antibiotics and are at risk of fungal infection.
Next, we wanted to know if there was a specific antibiotic that increased the risk of fungal infection. We treated mice with different antibiotics and found that vancomycin, an antibiotic commonly used to treat C diff infections in hospitals, made mice sicker after a fungal infection. Vancomycin eliminated immune-boosting bacteria from the gut microbiome that are needed to instruct the immune system to produce IL-17.
Are any of these searches relevant to people? Our analysis of patient records suggests so. We reviewed a large database of hospital records and found that similar bacterial/fungal co-infections could occur in humans after being treated with antibiotics.
With the growing problem of antibiotic resistance, it is now more important that antibiotics are used with care. Our research shows that antibiotics may pose an additional risk of dangerous fungal infections. However, antibiotics are a risk factor that we can control. Fungal infections remain a significant human health problem, but studies like ours help us understand how to combat them.