Fluconazole prophylaxis isn’t enough to prevent invasive fungal infections (IFD) in Australian children with acute myeloid leukaemia (AML), new findings show.

Led by Dr Daniel Yeoh of the Perth Children’s Hospital, the national study found IFD prevalence during primary AML therapy was 20.7% with most (38%) occurring during the first cycle of primary therapy.

Most patients (89.4%) were already on antifungal prophylaxis with 50% on fluconazole as recommended in 2014 national guidelines.

The study, published in Paediatric Blood & Cancer, found non-aspergillus moulds comprised 37.9% of invasive mould infection isolates with Lomentospora prolificans the most common species (63.6%).

All yeast infections were caused by Candida spp. but mostly non-albicans.

Most mould infections were in the lungs and most yeast infections in the blood.

The study found the median duration of antifungal treatment was 107 days. Voriconazole monotherapy or in combination with liposomal amphotericin B was the most common treatment for mould infections.

Liposomal amphotericin B followed by caspofungin or fluconazole were the most common treatments for yeast infections.

Five deaths were attributed to IFD – four of which were Lomentospora prolificans infections and one C. glabrata infection.

“Our findings of high prevalence of IFD in the period immediately following AML diagnosis suggest a broad systems based approach is required to identify patients at highest risk of IFD, implement prophylaxis from the start of treatment and facilitate timely diagnostic testing to minimise time to initiation of appropriate antifungal therapy,” the study said.

“Newer mould-active antifungal agents and formulations are now available, presenting a number of options for prophylaxis in children with AML; the body of data demonstrating safety and efficacy of these agents in children is growing.”

Need for change

Dr Yeoh, an infectious diseases specialist, told the limbic that clinicians recognised that patients were getting some nasty infections.

“Although the majority do survive there is significant suffering and also delays in chemotherapy … and they are not just like a runny nose or a cold, we are talking about weeks and months of treatment.”

“I think it highlighted to us that what we were doing wasn’t enough and that we needed to make a change.”

He said new guidelines from the ANZ Mycology Interest Group (in press) were recommending prophylaxis with drugs with mould activity such as posaconazole or micafungin.

“Really we need to use better agents and we need to start them early on in treatment and make sure we are using them universally in children with AML.”

“Here in Perth we have started using other agents like posoconazole or micafungin that have a broader activity than fluconazole. I guess what we don’t understand at this stage is whether using these agents with a broader spectrum reduce the incidence of fungal infection.”

He said a more recent study across three states was underway.

Dr Yeoh said management of these patients was often not straightforward due to competing priorities.

“On the one hand you are trying to kill the leukamia cells but at the same time you know that by doing that you are weakening their immune system. It’s often a difficult balance between carrying on with chemotherapy and ensuring that they don’t die of the fungal infection.”

He said Lomentospora prolificans spreads quite easily in immunosuppressed children and was unfortunately resistant to the vast majority of antifungal agents.

He noted that clinicians should have a low threshold for chest imaging in children with symptoms such as prolonged fever, cough or chest pain.