Fungal infections kill the same number of people each year as tuberculosis. It often takes hold in people who are at risk 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 defects in the immune system that increase the risk of serious fungal infections.
Candida is a fungus that is a common cause of fungal infections in humans. Fungal yeast infection is caused by Candida. But it can also cause a life-threatening infection of the bloodstream called invasive candidiasis.
Antibiotics are a risk factor for invasive candidiasis. When we take antibiotics, we kill some of our gut bacteria. This can create space for the growth of gut fungi (such as Candida). And if your gut has been damaged by chemotherapy or surgery, the candida can pass out of the gut and cause an infection in the bloodstream.
However, the most common way of infection with invasive candidiasis is not from the intestine, but from the skin. Patients in the intensive care unit who have been fitted with an intravenous catheter can develop invasive candidiasis, especially if they are treated with antibiotics.
We wanted to know exactly why antibiotics make fungal infections like invasive candidiasis more likely. To investigate, we treated mice with a broad-spectrum antibiotic cocktail and then infected them with Candida fungi. We compared them to a control group of mice that we infected with Candida fungus, but did not treat with a combination of antibiotics.
We found that the antibiotic treatment made the mice sicker when they were infected with the fungus. In this fungal infection, the kidneys usually become the target of the infection and the mice get sick because the kidneys stop working. But this was not the case here. Although the antibiotics made the mice sicker, they controlled the fungal infection in the kidneys just as well as the mice that didn’t receive the antibiotics. So what made them get sick?
It turns out that the antibiotics disrupted the antifungal immune response, specifically in the gut. The antibiotic-treated mice had significantly higher levels of fungal infection in the gut than the untreated mice. As a result, gut bacteria escaped into the blood. The antibiotic-treated mice now have bacterial and fungal infections to deal with. This was making them sicker than mice without antibiotics.
To find out why this happens, we analyzed immune cells in the gut to see how the antibiotics triggered a defective immune response against the fungus. The immune cells in the intestine 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 is part of the reason why antibiotic-treated mice were unable to control fungal infections in the gut or prevent bacteria from escaping.
Candida fungi can cause life-threatening bloodstream infections. Science Photo Library / Alamy Stock Photo Possible solution
Some of these cytokines can be given to patients as immune-boosting medications to help fight infection. To see if this might be an option for antibiotic-treated patients at risk for fungal infections, we injected 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 developing a fungal infection.
Next, we wanted to find out if a particular antibiotic increases the risk of a fungal infection. We treated mice with different antibiotics and discovered that vancomycin, an antibiotic commonly used to treat C diff infections in hospitals, made mice sicker after a fungal infection. Vancomycin removed immune-boosting bacteria from the gut microbiome needed to direct the immune system to produce IL-17.
Is any of this research suitable for people? Our analysis of patient records suggests that it is. We looked at a large database of hospital records and found that similar bacterial/fungal infections may occur in humans after being treated with antibiotics.
With the growing problem of antibiotic resistance, it is now more important than using antibiotics with care. Our research shows that antibiotics may provide an additional risk of serious fungal infections. However, antibiotics are a risk factor that we can control. Fungal infections remain an important human health problem, but studies like ours help us understand how to combat them.
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