Case 2 Revisited: When to stop empirical antifungals – Part 2

The ICU team hear back from the Infection Specialist. In the context of his current clinical condition, and the results now available, advice is to stop the intravenous echinocandin. No fluconazole prophylaxis is recommended. With some initial hesitation, the ICU team stop all antifungal treatment. Antibiotic treatment for his UTI continues for the full course.

Over the next 48 hours, Mr Wilson has a further feverish episode. This resolves with administration of intravenous paracetamol and he remains otherwise stable. His clinical recovery continues and he goes on to be discharged from the ICU. Mr Wilson is now comfortable on a medical ward and his recovery continues.

His case raises a difficult clinical question – when can empirical antifungal treatments be stopped?

When to stop empirical antifungals

Empirical antifungals are usually commenced in vulnerable or critically ill patients. The reluctance to withdraw these treatments once started is understandable – invasive fungal infections like candidaemia have high mortality even with effective treatment.

However, antifungal stewardship aims to reduce unnecessary antifungal treatments. Prolonged treatment with antifungals can promote resistance and cause adverse effects in the patient.

Some tests, such as blood cultures, have low sensitivity. They can miss true cases of candidaemia as only 50 – 75% of blood cultures are positive when the patient has the disease (providing 60ml of blood is collected).

However, β-1-3-D-glucan is a highly sensitive test. If negative, candidaemia is very unlikely. The accuracy of this test can be above 95% in the right setting. Antifungal Stewardship Teams can use these tests, in conjunction with local incidence rates, to construct an effective guideline. These guidelines can inform when antifungals should be started on the ICU and when they can safely be stopped.

Have a look at the guideline below. Empirical antifungals are not delayed if the patient satisfies the criteria for “Suspected Invasive Candidosis”. Timely samples for culture and β-1-3-D-glucan are essential. If these are negative, the guidance is clear – STOP antifungal treatment.

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Antifungal prophylaxis

The ICU team considered continuing the patient on antifungal prophylaxis. The Infection Specialist advised against.

Inappropriate use of fluconazole prophylaxis is a cause for concern in the ICU setting. Widespread azole use promotes antifungal resistance. Fluconazole interacts with many medications and may cause unnecessary harm to some patients.

There are some indications for fluconazole prophylaxis on the ICU. This protects highly vulnerable patients from acquiring candidaemia, especially following procedures like GI surgery. The evidence only supports use of this prophylaxis in a restricted group of patients, or in ICUs with high incidence of the disease. Fluconazole use outside of this is inappropriate.

Guidelines on the use of fluconazole prophylaxis can be found here: ESCMID 2012, IDSA 2016

Candida in the sputum

Some may be wondering about the yeasts isolated in Mr Wilson’s sputum. Does this require antifungal treatment? The answer here is no.

Candida is a commensal organism within the mouth and throat. It lives in balance with bacteria in this area. Contamination of sputum samples with this Candida is commonplace, particularly in patients on broad-spectrum antibiotics. It should not be confused for infection as lung infections caused by Candida are incredibly rare.

Educating clinicians on the meaning of microbiological results is another valid approach to Antifungal Stewardship.