Management of Invasive Mould Infections

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Abstract:

Fungal diagnostics is an often overlooked field that has indirectly resulted in an increase in the number of antifungal-resistant pathogens. Fungal infections, such as candidosis and aspergillosis are the predominant types of fungal infections, and can be lethal to immunocompromised patients. At the recent Knowlex Infection Prevention and Control Conference held in London on February 23, 2016, Dr. Samir Agrawal addressed the current state of fungal infections in the United Kingdom, and the current problems associated with inappropriate diagnosis and treatment of suspected cases.

Main Article:

Fungal infections are sometimes life threatening illnesses.  Candida and Aspergillis are the most predominant causes of mould infections. Among these, Aspergillus makes up almost 70% of mould infections. Around the world, the number of life threatening infections due to mould is estimated to be over 2 million patients per year, and the mortality rate of these infections (depending on region) can range from 20% to 95% (Brown et al, 2012).

Antifungal strategies

Prophylaxis is the giving of a preventive drug to a population to control the spread of infectious diseases. Pre-emptive treatment can include screening, and is incredibly important for immunocompromised patient outcome. Delays as short as 12 hours in pre-emptive screening can greatly worsen outcomes. Mortality after the window for pre-emptive treatment can range from 40-90% for in-patients. Screening can be organism specific, and is typically prescribed based on clinical presentation of symptoms.  Both pre-screening and diagnostic driven studies can include blood tests for fungal markers, polymerase chain reaction (PCR) identification of microorganisms, and computed tomography (CT) exams of the chest for identifying chest infections (Agrawal et al, 2012).

Positive diagnosis is not always clear. If clinicians can prove the presence of host factors (microscopy of samples), positive tissue samples (clinical features) and fungal culture (mycology), this is considered a proven or probable case of mould infection.  Without mycology, the best that clinicians can conclude is a possible case of fungal infection; without obvious clinical presentation, no statement of mould infection can be concluded. In 2012, it was found that despite a lack of evidence of either probable or possible mould infection diagnoses, 44% of patients were still treated for mould infections (Tsitsikas et al, 2012).

There is an enormous cost associated with incorrect prescription of medication without probable cause.  In the United Kingdom, the cost of antifungal medications prescribed to patients without a possible fungal infection cost taxpayers over £1.35 million.  This represents nearly 85% of all antifungal drug costs (Tsitsikas et al, 2011).

Antifungal resistance

The use of antifungals, like echinocandin, has lead to an explosion in the prevalence of its resistance among fungi. Approximately 5.1% of fungi are resistant against azoles, a broad class of antifungals. Despite the lack of other resistance, the presence of azole resistance results in a much worse outcome for patients with infection by these resistant species (Van der Linden, 2015). The discovery of new drugs, like virconazole has greatly improved the number of mould infections that can be treated. However, nearly half (47.2%) of infections treated with virconazole were still ineffective, which shows that despite the discovery of new drugs, this is not necessarily enough for the growing number of resistant organisms (Herbrecht et al, 2002).  This evidence in echoed in studies of newer azoles, like isavuconazole.

Stewardship

The goal of antifungal stewardship is to promote the responsible use of antifungals to preserve their efficacy. This includes “prescribing the right antibiotic, for the right patient at the right dose and right route, causing the least harm to patients and future patients” (CDC, 2013). Education of doctors is the key tool in this, but is often met with complacency from experienced doctors.

Conclusion:

Invasive fungal disease is a life threatening infection for immunocompromised patients. Due to the severity of the illness, the prescription of antifungal agents is commonplace, but often unnecessary, leading to the development of antifungal resistance. There are a number of diagnostic tools available for detection of fungi, but prescription of these tests, as well as adherence to guidelines are necessary to curb the growing threat of highly resistant fungal infections.

About Knowlex:

Knowlex, shorthand for ‘Knowledge Exchange’, is a new organisation that has been set up with the ambition of disseminating information on research and innovative practice to help healthcare professionals in their working lives.

http://www.knowlex.co.uk/

Upcoming Conference:

Tuesday 6th September 2016 RNCM Manchester, UK
European City of Science 2016

In light of estimates that the total cost of AMR to healthcare systems within OECD countries will reach £1.9 trillion by 2050, on 8th September 2016, Knowlex will welcome more than 350 healthcare professionals to Manchester, European City of Science, for Infection Prevention & control 2016.

Conference Website: http://www.infectioncontrolmanchester2016.co.uk/

References:

Agrawal, S., Jones, B., Barnes, R., Kibbler, C., Millen, M., Ashcroft, M., … & Patel, M. (2012). A practical critique of antifungal treatment guidelines for haemato-oncologists. Critical reviews in microbiology, 38(3), 203-216.

Brown, G. D., Denning, D. W., Gow, N. A., Levitz, S. M., Netea, M. G., & White, T. C. (2012). Hidden killers: human fungal infections. Science translational medicine, 4(165), 165rv13-165rv13.

CDC (2013) Antibiotic Resistance Threates in the United States. Centre for Disease Control. Accessed Apr 1, 2016 http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf

Herbrecht, R., Denning, D. W., Patterson, T. F., Bennett, J. E., Greene, R. E., Oestmann, J. W., … & Sylvester, R. (2002). Invasive Fungal Infections Group of the European Organisation for Research and Treatment of Cancer and the Global Aspergillus Study Group. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med347(6), 408-15

Tsitsikas, D. A., Morin, A., Araf, S., Murtagh, B., Johnson, G., Vinnicombe, S., … & Agrawal, S. G. (2012). Impact of the revised (2008) EORTC/MSG definitions for invasive fungal disease on the rates of diagnosis of invasive aspergillosis. Medical mycology, 50(5), 538-542.

Tsitsikas, D. A., Morin, A., Araf, S., Murtagh, B., Johnson, G., Vinnicombe, S., … & Agrawal, S. G. (2011). Impact of the revised (2008) EORTC/MSG definitions for invasive fungal disease on the rates of diagnosis of invasive aspergillosis. Chemotherapy, 423, 71-9.

van der Linden, J. W. M., Arendrup, M. C., Warris, A., Lagrou, K., Pelloux, H., Hauser, P. M., … & Dannaoui, E. (2015). Prospective multicenter international surveillance of azole resistance in Aspergillus fumigatus. Emerging infectious diseases21(6), 1041.

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Andrew Duong
With over 7 years of research experience, Andrew joins InfectionControl.tips as a co-editor and contributing author. After obtaining his Bachelor of Science in Genetics, he earned a Master of Science in Microbiology from the Michael DeGroote Institute of Infectious Disease Research at McMaster University. As a previous Ontario Graduate Scholar, he has applied his accolades as a teaching assistant and has become a research associate in the department of surgery at Hamilton Health Sciences. Andrew has received numerous awards and scholarships including: the Ontario Graduate Scholarship, the William Henry Yates Travel Scholarship and the Institute of Infectious Disease Research Undergraduate Research Award. Andrew is an avid runner, and is said to dabble in the culinary arts, when he’s not spoiling his dog.

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