Antifungal Resistance

Antifungal Resistance is another class of the emerging AMR threat. Read here to learn more about it.

The US Centers for Disease Control and Prevention (CDC) observed the 10th Annual Fungal Disease Awareness Week (FDAW), with antifungal resistance as one of its central themes.

The CDC has highlighted the growing difficulty of treating fungal infections, particularly those caused by multidrug-resistant organisms such as Candida auris.

The issue is important because, unlike antibacterial therapy, the antifungal arsenal is limited, while fungal pathogens share several biological features with human cells, making selective drug targeting difficult.

What are Fungi?

Fungi are eukaryotic, heterotrophic organisms that include yeasts, moulds and mushrooms.

Unlike plants, fungi:

• Lack chlorophyll and do not perform photosynthesis.
• Obtain nutrients through extracellular digestion and absorption.
• Possess a nucleus and membrane-bound organelles.
• Have cell walls primarily containing chitin and other polysaccharides.
• Reproduce through spores, budding or fragmentation, depending on the species.

Ecological and economic significance

Fungi perform essential ecological functions as decomposers, recycling carbon and nutrients.

They are also important in:

• Bread and alcohol fermentation.
• Production of antibiotics such as penicillin.
• Food processing.
• Enzyme and organic-acid production.
• Biotechnology and pharmaceutical industries.

However, pathogenic fungi can cause mycoses, ranging from superficial infections such as ringworm and nail infections to potentially fatal systemic infections.

Why is Antifungal Resistance a Concern?

Antifungal resistance occurs when fungi develop the ability to survive exposure to medicines that previously inhibited or killed them.

• The problem is particularly significant because the therapeutic arsenal is considerably smaller than that available for bacterial infections.
• WHO has identified 19 fungal pathogens as priority pathogens and has emphasised the need for stronger surveillance, laboratory capacity and research into new antifungal therapies.
• WHO’s 2026 Blueprint for strengthening responses to fungal disease and antifungal resistance further identifies antifungal resistance as an integral component of the broader AMR challenge.

Candida auris: A Major Emerging Threat

Candida auris is a yeast first described in 2009 that has emerged as an important healthcare-associated pathogen.

It is particularly concerning because it:

• Can cause bloodstream and other invasive infections.
• Spreads readily in healthcare environments.
• Can persist on environmental surfaces.
• Is frequently resistant to antifungal medicines.
• Can be difficult to identify using conventional laboratory methods.
• Has caused hospital outbreaks in several countries.

WHO classifies C. auris among its critical-priority fungal pathogens.

Indian evidence

A multicentre Indian study of 350 C. auris isolates from 10 hospitals found that approximately 90% were resistant to fluconazole.

• The study also identified associations between azole resistance and mutations in the ERG11 gene, while an FKS1 mutation was associated with echinocandin resistance.
• Importantly, these figures come from a particular Indian study population and period and should not be interpreted as a current national prevalence estimate.

How Does Antifungal Resistance Develop?

1. Target modification

• Many azole drugs interfere with ergosterol biosynthesis, an essential component of the fungal cell membrane.
• Changes in genes involved in this pathway can reduce drug effectiveness.

2. Increased target production

• Changes in gene regulation or copy number can increase production of components of the ergosterol pathway, reducing the relative effect of the drug.

3. Drug efflux

• Fungi can increase efflux pump activity or expression, removing antifungal molecules from the cell.

4. Cell-wall adaptation

• Echinocandins inhibit β-1,3-glucan synthesis, an important component of the fungal cell wall.
• Mutations in the FKS1 gene can alter the drug target and produce echinocandin resistance. Such resistance is particularly concerning because echinocandins are an important treatment option for invasive auris infections.

5. Compensatory cellular responses

• Fungi can sometimes remodel their cell wall or activate alternative pathways under antifungal stress.
• The phenomenon sometimes called the Eagle effect refers to paradoxical growth observed at certain high concentrations of antifungal agents.
• It is associated with cellular compensatory responses, including changes in cell-wall composition.
• However, it should not be treated as a universal mechanism of antifungal resistance.

Major Classes of Antifungal Drugs

Drug class	Principal target/mechanism	Examples
Azoles	Inhibit ergosterol biosynthesis	Fluconazole, voriconazole
Polyenes	Bind ergosterol and disrupt fungal membranes	Amphotericin B
Echinocandins	Inhibit β-1,3-glucan synthesis in cell wall	Caspofungin, micafungin
Flucytosine	Interferes with fungal nucleic-acid/protein synthesis	Flucytosine

WHO notes that C. auris can show high resistance to fluconazole, while resistance to amphotericin B and echinocandins varies across isolates and regions.

Climate Change and Emergence of Fungal Pathogens

An important scientific hypothesis links rising environmental temperatures with the emergence and adaptation of certain fungal pathogens.

• Most fungi cannot efficiently grow at human body temperature. Increased environmental temperatures could exert thermal selection pressure, potentially favouring heat-tolerant fungi.
• Researchers have proposed this as one possible factor in the emergence of auris.
• However, the precise contribution of climate change to the emergence of auris remains an area of scientific investigation.
• The CDC similarly notes that rising temperatures may allow environmental fungi to expand into previously unsuitable areas and may contribute to fungal adaptation.

This provides an important One Health dimension to antifungal resistance.

Fungal AMR and the One Health Approach

Antifungal resistance cannot be viewed exclusively as a hospital problem.

• Resistance can emerge under antifungal selection pressure across interconnected environments: Human health-Animal health-Agriculture-Environment
• For example, WHO has highlighted concerns regarding the relationship between agricultural azole use and the emergence of azole-resistant Aspergillus fumigatus.

Therefore, antifungal stewardship should extend beyond clinical medicine.

Fungi vs Bacteria vs Viruses

Feature	Fungi	Bacteria	Viruses
Cellular organisation	Eukaryotic	Prokaryotic	Acellular
Nucleus	Present	Absent	Absent
Genetic material	Mainly DNA	DNA	DNA or RNA
Size	Generally larger than bacteria	Generally smaller than fungi	Usually smallest
Cell wall	Often contains chitin	Usually peptidoglycan	No cellular wall
Nutrition	Absorptive heterotrophy	Diverse	No independent metabolism
Replication	Spores, budding, fragmentation etc.	Mainly binary fission	Replicate within host cells
Examples	Candida, Aspergillus, Penicillium	E. coli, M. tuberculosis	SARS-CoV-2, influenza virus, HIV
Major diseases	Candidiasis, ringworm, aspergillosis	TB, cholera, typhoid	COVID-19, influenza, dengue

Why Fungal Infections Are Difficult to Diagnose

A major challenge is diagnostic delay.

• Fungal infections can resemble bacterial or viral diseases, while conventional laboratory methods may have limited sensitivity or require considerable time.
• For auris specifically, conventional identification methods can misidentify the organism, creating problems for both treatment and infection control.
• WHO consequently identifies strengthening laboratory capacity and surveillance as a major priority.

Why India Needs Greater Attention

India faces several challenges:

1. Diagnostic capacity: Many healthcare facilities lack advanced fungal identification and susceptibility-testing capabilities.
2. Inadequate surveillance: The true burden of fungal infections and antifungal resistance is difficult to estimate without systematic surveillance.
3. Limited therapeutic options: Resistance to one class can substantially narrow treatment options because the antifungal arsenal is relatively small.
4. Healthcare-associated transmission: Crowded healthcare settings and vulnerable patients can facilitate transmission of organisms such as C. auris.
5. Environmental and agricultural selection pressure: The One Health relationship between environmental antifungal exposure and resistance requires greater surveillance.

What Can Be Done?

1. Strengthen fungal diagnostics

Develop and expand:

• Culture facilities.
• MALDI-TOF-based identification.
• Molecular diagnostics.
• Antifungal susceptibility testing.
• Genomic surveillance.

2. Establish stronger surveillance

India can integrate fungal resistance surveillance with existing AMR surveillance systems.

3. Antifungal stewardship

Hospitals should promote:

• Correct diagnosis before treatment where feasible.
• Appropriate drug selection.
• Dose optimisation.
• Avoidance of unnecessary antifungal exposure.
• Susceptibility-guided therapy.

4. Strengthen infection prevention

For healthcare-associated C. auris:

• Screening of high-risk patients.
• Contact precautions.
• Environmental cleaning.
• Appropriate disinfection.
• Rapid identification of outbreaks.

5. Promote R&D

Research should focus on:

• New antifungal targets.
• Novel drug classes.
• Combination therapies.
• Host-directed approaches.
• Rapid diagnostic technologies.
• Vaccines and preventive strategies.

WHO’s recent assessment of the antifungal pipeline highlights the continuing need to address major gaps in the development of new antifungal medicines.

6. Adopt a One Health framework

• Antifungal stewardship should encompass hospitals, agriculture, the veterinary sector, the environment, pharmaceutical industry

Way Forward

The response to antifungal resistance should move from a treatment-centric approach to a surveillance-diagnosis–prevention framework.

• Early detection
• Rapid species identification
• Antifungal susceptibility testing
• Targeted therapy
• Infection-control measures
• Resistance surveillance
• Research and development of new therapeutics

The WHO’s 2026 Blueprint for strengthening responses to fungal disease and antifungal resistance provides an operational framework centred on strengthening diagnosis, surveillance, treatment, research, workforce capacity and coordinated public-health action.

Conclusion

Antifungal resistance represents a less visible but increasingly important component of the global AMR crisis. The emergence of multidrug-resistant fungi such as Candida auris demonstrates that antimicrobial resistance is not restricted to bacteria.

For India, the challenge extends beyond discovering new drugs. It requires better fungal diagnostics, systematic surveillance, rational antifungal use, hospital infection control, environmental monitoring and sustained research investment.

The emerging threat also reinforces the importance of the One Health approach, since fungal evolution and resistance are influenced by interactions among humans, animals, agriculture and the environment.