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Antimicrobial Resistance 2019

We are seeing an emergence of antifungal resistance

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Professor Maurizio Sanguinetti

President-Elect and Secretary General, European Society of Clinical Microbiology and Infectious Diseases (ESCMID)

It was only very recently that the World Health Organization’s global antimicrobial resistance surveillance system has considered emergence of resistance among fungal pathogens [1].

This settled lack of interest is primarily because fungal diseases are generally not transmissible among humans. Nevertheless, fungal pathogens such as Candida and Aspergillus represent a major cause of life-threatening invasive diseases, especially in patients with impaired immunity [2].

More people die from fungal infections each year than by malaria or tuberculosis. The emergence of resistance to the most commonly used classes of drugs — triazoles, echinocandins and polyenes, is a growing public health threat that greatly hampers the patient management [3].

Emergence of multidrug-resistant species

While the antifungal resistance to any one drug-class limits the therapy, due to paucity of therapeutic options, multidrug resistance can definitely eliminate these options.

Azole resistance among Candida and Aspergillus species has become a substantial cause for concern, followed by echinocandin and multidrug resistance among some Candida species.

Another important Candida species with a multidrug-resistant phenotype is Candida auris [4], which emerged in clonal outbreaks within Indian healthcare facilities some years ago.

Since then, this multidrug-resistant species has emerged worldwide as a healthcare-associated fungus causing invasive infections with high rates of clinical treatment failure.

Poor infection control may increase chances of transmission

A recent international study found that, overall, 41% of the isolates from 54 patients with C. auris infection were resistant to two antifungal classes (multidrug-resistant) and 4% were resistant to three classes (triazoles, echinocandins, and polyenes) [5].

Although the drivers of the C. auris emergence remain unknown, extensive empirical fluconazole usage and poor infection control may promote easy transmission of C. auris among patients.

The emergence of multidrug-resistant C. auris recalls the need for enhanced surveillance and novel therapeutic agents. These may include new antifungal agents, repurposed existing agents, analogues of existing antifungal agents, and combination therapies.

In this context, we must invest in the development and enhancement of diagnostic platforms that can rapidly detect resistant fungal diseases [6].

Stewardship should include diagnostics, drug monitoring and intervention

As effective antifungal stewardship is essential to control drug resistance, it should incorporate rapid fungal diagnostics, therapeutic drug monitoring, and clinical intervention teams to preserve drug effectiveness.

Looking ahead, microbiome research and whole-genome sequencing analysis will offer tools for enhancing our capacity to recognise drug resistance and providing effective antifungal stewardship in the next years [6].

Finally, if better provision of fungal diagnostic testing may be a means of curtailing antibacterial usage [7], it will be object of further investigation.

1. WHO. Meeting on global surveillance of AMR in invasive Candida infections, 24 April 2018, Madrid, Spain. http://who.int/glass/events/AMR-in-invasive-candida-infections-meeting/en/ (accessed Oct 31, 2018). | 2. Köhler JR, Hube B, Puccia R, Casadevall A, Perfect JR. Fungi that infect humans. Microbiol Spectr. 2017;5(3). | 3. Perlin DS, Rautemaa-Richardson R, Alastruey-Izquierdo A. The global problem of antifungal resistance: prevalence, mechanisms, and management. Lancet Infect Dis. 2017;17:e383-e392. | 4. Meis JF, Chowdhary A. Candida auris: a global fungal public health threat. Lancet Infect Dis. 2018 Oct 4. |5. Lockhart SR, Etienne KA, Vallabhaneni S, Farooqi J, Chowdhary A, Govender NP, Colombo AL, Calvo B, Cuomo CA, Desjardins CA, Berkow EL, Castanheira M, Magobo RE, Jabeen K, Asghar RJ, Meis JF, Jackson B, Chiller T, Litvintseva AP. Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses. Clin Infect Dis. 2017;64(2):134-140. |6. McCarthy MW, Denning DW, Walsh TJ. Future research priorities in fungal resistance. J Infect Dis. 2017;216:S484-S492. | 7. Denning DW, Perlin DS, Muldoon EG, Colombo AL, Chakrabarti A, Richardson MD, Sorrell TC. Delivering on antimicrobial resistance agenda not possible without improving fungal diagnostic capabilities. Emerg Infect Dis. 2017;23:177-183.

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