Fever keeps returning despite antibiotics? Could it be a fungal infection?

A fever that goes away and then keeps returning, even after a full course of antibiotics, can be a genuinely tricky clinical picture to work through. Usually, prolonged fever is most often traced back to tuberculosis, malaria, or enteric fever, given how common these conditions are. Because of this, fungal infections don't always come up early in the diagnostic process, even though they can present in very similar ways and deserve consideration, especially when the usual causes have been ruled out.

Why fungal infections are often missed

Fungal infections that cause fever tend to look a lot like more familiar illnesses, which is exactly why they get missed.

Histoplasmosis

Histoplasmosis is a fungal infection that can spread through the body, causing fever, weight loss, and an enlarged liver or spleen, symptoms that look almost identical to a form of tuberculosis affecting organs outside the lungs. Because TB is so common in India, doctors often start TB treatment first, which can delay the correct diagnosis by weeks.

Aspergillosis

Aspergillosis is a fungal lung infection that causes similar confusion. It typically shows up as fever with breathing difficulty, especially in people with a history of TB, chronic lung disease (COPD), or long-term steroid use, symptoms that are easily mistaken for an ordinary chest infection.

Candidemia

Candidemia is a bloodstream infection caused by Candida, a type of yeast, and is common in ICUs. It often shows up as a fever that won't settle, or one that briefly improves and then returns, even though the patient is already on antibiotics.

Mucormycosis
Mucormycosis (popularly known in India as “black fungus”) is a more aggressive fungal infection, often affecting the sinuses, face, or eyes. It is strongly linked to uncontrolled diabetes and recent steroid use or COVID-19, and became widely recognised during the COVID-19 pandemic. Facial or sinus pain, swelling around the eyes, or blackish discolouration inside the nose are warning signs that need urgent medical attention.

The warning sign: a fever that won't stay away

A fever that keeps returning despite a full, appropriate course of antibiotics — or one that briefly settles and then comes back — should prompt doctors to think beyond the usual bacterial causes.

This is especially true in people who are hospitalised, those with drips, catheters, or central lines in place, and those who have spent an extended time in intensive care.

Who is most at risk?

A few groups face a notably higher risk of fungal infections:

• Uncontrolled diabetes: High blood sugar weakens the immune cells that normally fight fungi, and also creates conditions where fungi thrive. This is one of the most important risk factors for serious fungal infections such as mucormycosis.
• Prolonged steroid use: Whether for COPD, an autoimmune disease, or recovery from COVID-19, steroids can suppress the immune response and create an opening for fungal infections.
• Weakened immunity: Including people with blood cancers, those undergoing chemotherapy, people living with HIV, or those who have had an organ transplant.
• ICU stay with tubes or lines: Central lines, urinary catheters, and ventilators can allow fungi such as Candida to get past the body's normal defences and form hard-to-treat films on these devices.
• Recent, prolonged antibiotic use: Broad-spectrum antibiotics tend to disturb the normal balance of bacteria in the body, leaving room for fungi to overgrow.

When should you suspect a fungal infection?

It's worth asking your doctor about a possible fungal cause when a fever:

• Doesn't respond to a full, appropriate course of antibiotics
• Occurs in someone with diabetes, recent steroid use, a hospital or ICU stay, or a weakened immune system
• Continues even though blood tests and TB tests come back negative
• Is accompanied by unexplained breathlessness, sinus or facial pain, or unusual changes in the skin or inside the nose/mouth

How is it diagnosed?

Once a fungal infection is suspected, there are a few ways to confirm the same. Blood tests for beta-D-glucan or galactomannan catch chemical markers the fungi shed, and they're usually faster than a standard culture — which can take days, sometimes weeks. CT scans of the chest or abdomen can flag patterns typical of certain infections. When that's still not enough, a biopsy with special fungal staining is what settles it.

Why early suspicion matters

Invasive fungal infections can be more serious than typical bacterial infections, and the risk increases the longer treatment is delayed. Starting the right antifungal medicine as early as possible, once the specific fungus is identified, offers the best chance of a good outcome. Because fungal infections are still under-recognised outside major hospitals in India, it is important for both patients and doctors to keep this possibility in mind when a fever simply “keeps coming back.”

-Dr. Vasif Mayan MC is Associate Consultant – Infectious Diseases at Aster Medcity, Kochi