Indian Study Finds 90% of Candida auris Isolates Resist Azoles, Exposing Gaps in Dosing Tests

The news

Hyderabad / Bengaluru. A study published in Nature Communications by Kaustuv Sanyal and his research associate Aswathy Narayanan of the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bengaluru, working with collaborators at the Indian Institute of Science Education and Research (IISER), Thiruvananthapuram, has characterised clinical isolates of Candida auris from across India, The Hindu’s science page reports in an article by Somdatta Karak, who heads science communication at CSIR-CCMB. C. auris is a yeast — a fungus that lives as single oval cells, unlike moulds, which grow in strands — that is emerging as a multidrug-resistant pathogen in intensive care units. It enters the bloodstream and causes severe infections, most of which cannot be treated with available antifungals; Shivaprakash Rudramurthy, Professor of medical mycology at PGIMER, Chandigarh, puts mortality at 30%-40%. The first report of the fungus was from Japan in 2009. The isolates came from PGIMER’s repository, begun some 25 years ago because most Indian hospitals cannot identify fungal pathogens, and which now holds 15,000 clinical fungal isolates; Professor Rudramurthy says roughly 20% of infections reported in hospitals are fungal. “More than 90% clinical isolates of C. auris are resistant to common azole-based antifungals, such as fluconazole,” Professor Sanyal said; some 30% resist the polyenes, and most still respond to the echinocandins. The mechanisms were found in the genome. Azoles and polyenes attack ergosterol, a fat in the cell membrane; the fungus responds to fluconazole by making extra copies of the Erg11 gene and producing more ergosterol. Echinocandins such as caspofungin attack the cell wall; mutations in the Fks1 gene let the fungus survive caspofungin at up to 16 µg/ml, while clinicians test susceptibility only up to 2 µg/mL, the limit defined by the U.S. Centers for Disease Control and Prevention and followed globally. Professor Sanyal suggests raising the test limit above 16 µg/ml. Even without mutations, the fungus survives exceptionally high caspofungin doses by producing extra chitin — a paradox called the Eagle effect, after U.S. pathologist Harry Eagle. Sriram Varahan of CSIR-CCMB links the rise of such fungi to the “fungal infection–mammalian selection hypothesis”: fungi grow best below 30°C, and global warming selects heat-tolerant strains able to survive the human body’s 37°C. He argues for targeting less critical pathways rather than an “arms race”. The syllabus link is antimicrobial resistance, public health capacity and biotechnology.

Static syllabus linkage

1. Antimicrobial resistance covers fungi, not only bacteria. Antimicrobial resistance (AMR) is the ability of bacteria, viruses, fungi and parasites to survive medicines designed to kill them, and the World Health Organization lists it among the top global public health threats. India adopted a National Action Plan on AMR in 2017 built on the One Health approach, which treats human, animal and environmental health as linked. The Indian Council of Medical Research runs an AMR Surveillance and Research Network of tertiary hospitals that monitors resistance trends. Fungal resistance is less tracked than bacterial resistance, partly because many hospitals cannot culture and identify fungi at all.
2. WHO’s first fungal priority list put Candida auris in the critical group. In October 2022 the WHO published its first Fungal Priority Pathogens List, grading 19 fungi into critical, high and medium priority to guide research and public health action. Candida auris was placed in the critical group, along with Cryptococcus neoformans, Aspergillus fumigatus and Candida albicans. The list was a response to the rise of invasive fungal infections among immunocompromised patients, including those in ICUs, cancer and transplant patients and people with HIV. India’s experience with mucormycosis during the COVID-19 second wave in 2021, when several States declared it a notifiable disease, showed how quickly a fungal threat can overwhelm hospitals.
3. Three drug classes, two targets: why the cell wall matters. Antifungals are few because fungal cells, like human cells, are eukaryotic, so drugs that harm the fungus often harm the patient. Azoles such as fluconazole block the making of ergosterol, the fungal counterpart of cholesterol in the cell membrane, while polyenes such as amphotericin B bind to ergosterol and punch holes in the membrane. Echinocandins such as caspofungin inhibit the enzyme that builds glucan in the fungal cell wall, a structure human cells do not have, which is why they are the last line of defence against resistant Candida. When a pathogen resists all three classes, clinicians have almost nothing left.
4. Breakpoints decide treatment, and the Eagle effect breaks the simple rule. A susceptibility test measures the minimum inhibitory concentration — the lowest drug concentration that stops a microbe’s growth — and compares it with a “breakpoint” that classifies the microbe as susceptible or resistant. If the tested range is too narrow, a resistant strain can be wrongly reported and a patient under-dosed. The Eagle effect, first observed with penicillin, is the paradox in which a microbe survives better at very high drug concentrations than at moderate ones. It means that simply raising the dose is not always the answer, which is why combination therapy is advocated.

Why UPSC loves this

1. AMR and biotechnology sit in both GS2 and GS3. GS2 covers issues relating to the development and management of health, and GS3 covers science and technology developments and their applications in everyday life. UPSC has asked about the causes of antibiotic resistance and the role of over-the-counter sales, and Prelims has tested which microbes cause which diseases and how drugs act. A fungal pathogen question is the natural next step as the WHO’s fungal list gains prominence.
2. Climate–health linkages are a rising theme. The examiner increasingly asks how climate change affects disease — vector ranges, heat stress and new pathogens. The fungal–mammalian selection hypothesis is a precise, citable example that turns a vague claim about “climate and health” into an argument with a mechanism.

Analysis

1. The most dangerous finding is about the test, not the fungus. That C. auris resists azoles was already known worldwide; what the Indian study adds is evidence that the global susceptibility test may be reporting some strains as treatable when they are not. If laboratories stop testing at 2 µg/mL while Fks1 mutants survive 16 µg/ml, a patient can be given the right drug at the wrong dose, and the drug is then blamed for failing. This is a quiet form of harm because it looks like good practice. The policy lesson is that India cannot simply import breakpoints set for other populations; it needs the capacity to validate them against its own isolates.
2. A 25-year freezer is national infrastructure. The study was possible only because PGIMER began storing fungal isolates a quarter-century ago and now shares 15,000 of them free of cost. Such biorepositories rarely appear in budget speeches, yet they are what allow Indian science to answer Indian questions instead of extrapolating from foreign data. The counter-view is that repositories are expensive to maintain and their pay-off is uncertain. But the pay-off here is exactly the kind no private actor would fund: evidence that changes public treatment protocols.
3. Diagnosis is the real bottleneck in Indian hospitals. Professor Rudramurthy’s statement that most hospitals cannot identify fungal pathogens explains why resistance spreads unseen: a clinician who cannot name the fungus prescribes the cheapest broad antifungal, usually an azole, and so selects for the resistance the study found. The fix is not only new drugs but district-level mycology capacity, referral links to reference laboratories and inclusion of fungi in AMR surveillance. This is an argument for public laboratories, not for more prescriptions.
4. Dr. Varahan’s “gentler” strategy is scientifically attractive but commercially hard. Targeting pathways that make a fungus harmful without killing it — an approach known in bacteria as anti-virulence therapy — reduces the pressure that selects for resistance. The difficulty is that such drugs are harder to prove effective in trials and earn less money, because they do not produce the dramatic cure regulators and companies prefer. Without public or philanthropic funding, the arms race Dr. Varahan criticises will continue by default. Professor Sanyal’s combination-therapy approach is the more immediately usable of the two ideas.
5. The climate hypothesis should be treated as a hypothesis. The article is careful to say the cause of the rise of pathogenic fungi “remains unresolved”. The fungal–mammalian selection idea is plausible and widely discussed, but an answer that presents it as settled overstates the evidence. Hospital practices — broad-spectrum antibiotic use, invasive devices, long ICU stays — are at least as important and more directly controllable. A good answer names both and gives priority to what policy can change now.

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