Fighting the fungi

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You aren’t from a farming family unless you’ve had ringworm. The distinctive red circular pattern which inches up your arm, its characteristic red flaky skin coupled with a burning itch, was probably caught from some four-legged friend. Catching this fungal skin infection is a rite of passage.

If you’ve ever had ringworm you’ll know there are several remedies. Our old housekeeper’s was to paint your rings in clear nail varnish, a bizarre manicure which seals in the fungal spores so they are unable to reproduce and spread.  Medically the best way to eliminate ringworm or Tinea corporis, if affecting the body, is to treat it pharmaceutically with antifungals. Normally slathering the effected spot in a cream containing clotrimazole does the trick. (1)

If only all fungal infections were as easy to treat as ringworm. Everyone is aware of the growing threat of resistance to antibiotics, drugs which are used to treat bacterial infections. The fact there have been no ‘new’ classes of antibiotics since the 1980’s is extremely concerning. Yet antifungals seem to have been forgotten, although their plight is much graver. There are only five classes of molecules that are used clinically to treat every fungal infection, with only one new class in the last 30 years, and resistance to them is growing. (2,3)

Candida auris– an emerging pathogenic fungus

Take Candida auris, first identified in Japan, and cause of nosocomial outbreaks on 5 continents. (4) This globetrotting yeast has found its way into intensive care units up and down the UK, having been reported  in 2017 in over 20 NHS trusts. This particular strain is multi drug resistant. It has increasing resistance to the main fungi fighting drug of choice Fluconazole, from the azoles family, but also to drugs from the newer family of echinocandins.  

C. auris thrives in the most vulnerable members of society; those with compromised immune systems, the elderly and the young. It isn’t picky either; it will live in your ear, hence the name, but if it can gain an entry point through wounds, surgery or catheterisation, it will also cause wound bloodstream and invasive infections (such as in the brain).  It’s hard to diagnose, requiring special tests to distinguish it from more common types of Candida, and it’s harder to treat. (5)

There are some strains which have become resistant to four classes of antifungal drug. These nosocomial strains, meaning originating from a hospital, have established an infection in the blood stream with reported mortality above 30%. Though it’s worth bearing in mind those who have died with a C. auris infection have had other serious medical problems. The reliance on tubes, lines and catheters to keep patients alive, offers an easy route for invasive infections of all kinds. (6, 7)

Candida is a huge yeast family with species mostly commensal.  So has the resistance of C auris been caused by a case of misidentification? Notoriously hard to identify from its Candida cousins, the only true confirmation is by either using Matrix-assisted laser desorption ionization–time of flight mass spectrometry, simply(!)  MALDI-TOF MS, or molecular methods based on sequencing ribosomal DNA.  Yet, information in molecular identification databases regarding fungal pathogens is extremely limited.

It seems we have a fight on our hands to try and stop this superbug from becoming dominant on the wards of hospitals all over the world.

Antimicrobial stewardship

Recently the limelight has shifted slightly from resistance in bacteria to all infectious microbes. A study in 2017 asked whether the excessive use of antifungals in farming is contributing to resistance in human infections: the results showed that the same point mutations were found in both the environmental and clinical samples of the fungi Aspergillus fumigatus resistant to triazoles (8). The fungus initially responsible for primarily respiratory illnesses, such as Farmer’s lung, is now becoming invasive and increasingly fatal immunocompromised hosts.

Antimicrobial stewardship needs to be embraced by all, not just by governments and clinicians. As with antibiotics, we need to stop prescribing and using antifungal drugs like they are the cure to all, we need to step up hygiene levels especially when visiting relatives in healthcare settings, we need to think about the indiscriminate use of antimicrobial drugs in agriculture. Maybe we should reduce the number of over the counter antifungals available, and start looking at alternative treatments to mild fungal infections. There might be something in the nail varnish cure after all.

Global Health database has over 89,800 records on mycoses (fungal infection), with 7914 on antifungal resistance and 98 records focussed on Candida auris .

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References: 

  1. National Health Service (2015). Ringworm. [online] NHS direct Wales. Available at: https://www.nhsdirect.wales.nhs.uk/encyclopaedia/r/article/ringworm/ [Accessed 7 Dec. 2018].
  2.  Roemer, T. and Krysan, D. (2014). Antifungal Drug Development: Challenges, Unmet Clinical Needs, and New Approaches. Cold Spring Harbor Perspectives in Medicine, 4(5), pp.a019703-a019703.
  3.  Ahmad, A., Molepo, J. and Patel, M. (2016). Challenges in the Development of Antifungal Agents Against Candida: Scope of Phytochemical Research. Current Pharmaceutical Design, 22(27), pp.4135-4150.
  4.  Cdc.gov. (2018). Candida auris | Candida auris | Fungal Diseases | CDC. [online] Available at: https://www.cdc.gov/fungal/candida-auris/index.html [Accessed 7 Dec. 2018].
  5.  ECDC (2018). Candida auris in healthcare settings – Europe. [ebook] ECDC, pp.1-10 pp. Available at: https://ecdc.europa.eu/sites/portal/files/documents/RRA-Candida-auris-European-Union-countries.pdf [Accessed 10 Jan. 2019].
  6. Tsay, S., Kallen, A., Jackson, B., Chiller, T. and Vallabhaneni, S. (2017). Approach to the Investigation and Management of Patients With Candida auris, an Emerging Multidrug-Resistant Yeast. Clinical Infectious Diseases, 66(2), pp.306-311.
  7. Public Health England (2017). Guidance for the laboratory investigation, management and infection prevention and control for cases of Candida auris. London: PHE.
  8.  Berger, S., El Chazli, Y., Babu, A. and Coste, A. (2017). Azole Resistance in Aspergillus fumigatus: A Consequence of Antifungal Use in Agriculture?. Frontiers in Microbiology, 8.

2 thoughts on “Fighting the fungi

  1. Oliver Ellingham January 31, 2019 / 3:02 pm

    Fungi are not always the enemy, and often we have to work with the Fungi as well; for species conservation, human driven industries and medical discoveries the fungal queendom can provide many sustainable answers!

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