22nd September 2021

According to the Global Action Fund for Fungal Infection, over 300 million people around the world are afflicted with a serious fungal infection every year and 25 million are at high risk of dying or losing their sight. Yet there is a persistent sense that fungal infections receive neither the attention nor the funding afforded to infectious diseases caused by viruses or bacteria. With this in mind, we invited Gavin Barlow, Senior Clinical Lecturer in Infection at Hull York Medical School and Hon. Physician in Infectious Diseases, Hull University Teaching Hospitals, to explain why we mustn’t forget fungal infection…

When I was appointed as an NHS consultant in infectious diseases in late 2004, the infection concerns of primacy in both my hospital and generally within the NHS, were methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile infections. Both were causing havoc, harm, and deaths and, not before time, the UK government and, as a result, NHS managers started to take note and action. At the time, relatively few infection doctors were talking or worried about resistance to antibiotics amongst Gram-negative bacteria, despite antibiotics being commonly prescribed for both uncomplicated and life-threatening Gram-negative infections. Gram-negative resistance was undoubtedly out there, increasing, and having a negative clinical impact. Jump sixteen years and now the predominant focus in the world of infection, other than COVID-19 over the last 18 months, has turned to Gram-negative resistance. The global impact is huge and costly with vulnerable patients commonly affected. Who would have thought it, hey?!

But I hear you thinking: “This blog was meant to be about fungal infections and I’m almost one-third in and not a mention”! You are correct but stick with me for a bit. Although humans are avid historians, we do not always learn from history. And let’s face it, learning from history isn’t easy when other urgencies get in the way. Predicting the future is even trickier – the financial crisis of 2008 and a coronavirus as the cause of the next major pandemic, despite the historical and ‘shot over the bow’ experiences of the great depression and SARS and MERS, amongst others, attest to that. Back in 2004, few were talking about fungal infections and resistance to therapy thereof, at least in my infection world. Antiretroviral therapy was well established in the management of HIV infection and the commonly associated fungal infections, such as candidiasis and Pneumocystis jirovecii, were less common than before.

During my infection training, fungal infections were, and indeed remain, somewhat of a mystery – mycology within the clinical and laboratory disciplines of infection, and those who do it, after all, have a similarly mysterious reputation and relationship to that of neurology within internal medicine and ophthalmology within the whole of medicine! I certainly claim no expertise here, and probably never will, despite my involvement in a successful antimicrobial stewardship programme within my own hospital between 2005 and 2019. Guidelines were and remain a godsend when it comes to fungal infections. A small number of new antifungal agents have gradually emerged, but the concept of antifungal stewardship largely remained a ‘Cinderella’ area of infection practice until recently. Although clinicians with an interest in fungal infections are probably more common now, clinical mycologists remain rare. When an academic haematology colleague suggested we apply for some research funding in antifungal stewardship early in the pandemic, at a time when I was exhausted, it was not only the exhaustion that made me hesitate!

But fungi, for life in general – read the book Entangled Life by Merlin Sheldrake – and in medicine, are undoubtedly critically important. Fungal infections are more common, and the associated costs higher, than we sometimes acknowledge – look at the array of topical therapies available at your local pharmacy and think oral and genital thrush, ringworm, and fungal nail infections to name but some. This, of course, will be no news to those working in primary care, some specialties in secondary care, or low-income countries. Commonly used over-the-counter antifungals, or within class relatives thereof, are also often used to prevent or treat life-threatening fungal infections in hospitalised patients. Severe fungal infections are also surprisingly common – in England, almost 2000 bloodstream infections were reported to be due to Candida species in 2020 via voluntary surveillance. These infections have a predilection for ecological niches and the vulnerable, such as those being treated for cancer or in intensive care or who have undergone transplantation – about 5 to 10% of acute leukaemia patients develop invasive aspergillosis during chemotherapy; have a higher mortality than many severe bacterial infections; are neglected diseases within low- and-middle-income environments; and are challenging to treat with even fewer classes, and agents within, of antifungal compared to antibacterial drugs. Fungal diagnostics are also underdeveloped, under-researched, under-available, and under-used. When non-culture tests for severe fungal infections are available and used, the time to result is often unacceptably long, even in the UK. Does all this sound familiar?!

We have had recent and ongoing warnings that we dispel at our potential peril. Candida auris is arguably an exemplar of a resistant fungal pathogen that can cause outbreaks within healthcare settings and establish itself within a local community. It is challenging to prevent, diagnose and treat, affects the most vulnerable, and is associated with resistance to some of our relatively limited arsenal of antifungal agents. Extensively-drug resistant isolates have been identified. Resistance amongst other important fungal pathogens, such as Aspergillus species, is also of concern.

So, we mustn’t forget fungal infections. All infection healthcare professionals, and those working within relevant clinical specialties and in the fields of antimicrobial resistance and diagnostics, have a responsibility to advocate, learn more, and remain vigilant. Whether you are interested in fungal infections or not, why not join us to learn more and have a chat at 4-30pm (BST) on Tuesday 5th October 2021 for the BSAC webinar on the Treatment of Systemic Fungal Infections as part of the Infection Clinical Dilemmas series. And for those who manage invasive fungal infections within haematology departments in the UK, consider getting involved in the NIHR funded BioDriveAFS trial, which is endeavouring to answer a key question within the antifungal stewardship field, starting March 2022.

Interested in exploring this topic further? Gavin Barlow is chairing our upcoming Infection Clinical Dilemmas webinar: Treatment of systemic fungal infections. Taking place 5 October 2021, 1630-1800hrs BST, this free event will feature clinical case presentations and lively panel discussion – absolutely not to be missed! Book your place here.

 

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