Antifungal and Antiviral Resistance
Antifungal and antiviral resistance is the loss of susceptibility of fungi and viruses to the drugs used to treat them. It is the non-bacterial face of antimicrobial resistance: as antifungal and antiviral agents are used more widely in medicine and, for some compounds, in agriculture, fungal and viral populations evolve mechanisms that blunt or abolish drug activity, narrowing the already limited treatment options for invasive fungal disease and chronic viral infection.
Definition
Antifungal and antiviral resistance refers to genetically or phenotypically determined reductions in the susceptibility of fungal or viral organisms to antifungal or antiviral agents, such that drug concentrations achievable in the host no longer reliably inhibit the pathogen.
Scope
This area orients the reader to resistance in two distinct microbial worlds that share a conceptual frame with bacterial resistance but differ biologically. It covers azole-resistant Candida and the molecular mechanisms of antifungal resistance on the fungal side, and resistance to antiviral drugs in influenza and HIV on the viral side. It treats the subject as a reference field within antimicrobial resistance and microbiology, not as a guide to selecting or dosing therapy.
Sub-topics
Core questions
- How do antifungal and antiviral resistance resemble, and differ from, bacterial antimicrobial resistance?
- What selective pressures - clinical and, for fungi, agricultural - drive the emergence of resistance?
- Why do limited drug classes and shared molecular targets make resistance especially consequential for fungal and viral infections?
Key concepts
- Drug-target alteration
- Drug efflux
- Target overexpression
- Selective pressure from antimicrobial use
- Cross-resistance within a drug class
- Minimum inhibitory concentration and clinical breakpoints
- Genotypic resistance testing for viruses
- Limited antifungal and antiviral armamentarium
Mechanisms
Resistance arises by the same broad strategies across microbial kingdoms but through kingdom-specific biology. In fungi, the dominant routes are alteration or overexpression of the drug target (for azoles, the ergosterol-biosynthesis enzyme Erg11/Cyp51) and increased drug efflux through membrane transporters; echinocandin resistance follows from mutations in the FKS genes encoding the glucan-synthase target (Fisher 2018; Perlin 2017). In viruses, error-prone replication generates diverse quasispecies, and drug pressure selects for variants carrying resistance mutations in the targeted enzyme or protein - for example neuraminidase or polymerase changes in influenza and reverse-transcriptase, protease, or integrase changes in HIV (De Clercq 2016). Because antifungal and antiviral agents act on a small number of conserved targets, resistance to one member of a class often confers cross-resistance to others.
Clinical relevance
Resistance in fungi and viruses matters because the treatment options are narrow to begin with: only a handful of antifungal classes exist, and several chronic viral infections depend on lifelong suppressive therapy. When resistance emerges, clinicians may be left with more toxic, less effective, or no alternative agents. This area describes how such resistance arises and is detected; it characterises the problem at a population and mechanistic level and is not a source of diagnostic or treatment recommendations for individual patients.
Epidemiology
Invasive fungal infections such as candidaemia carry high mortality, and the rise of azole-resistant and intrinsically resistant species has reshaped their epidemiology (Kullberg 2015; Perlin 2017). Antifungal resistance is increasingly recognised as a One Health problem, with environmental azole exposure in agriculture implicated in resistant Aspergillus (Fisher 2018). On the viral side, transmitted and acquired drug resistance shapes the global response to HIV and the surveillance of influenza antivirals (De Clercq 2016).
History
Antiviral and antifungal chemotherapy matured later than antibacterial therapy, and resistance was documented soon after each new class entered wide use. The expansion of triazole antifungals from the 1990s, the introduction of echinocandins in the 2000s, and the successive waves of antiviral drugs over the past half century each brought their own resistance phenotypes, prompting the consolidation of antifungal and antiviral resistance as recognised components of the broader antimicrobial-resistance agenda (De Clercq 2016; Fisher 2018).
Debates
- How much does agricultural azole use drive clinical antifungal resistance?
- Environmental exposure to agricultural azole fungicides is implicated in the emergence of azole-resistant fungi that then infect humans, but quantifying that contribution relative to clinical drug use remains an active question framed within a One Health perspective.
Key figures
- David S. Perlin
- Matthew C. Fisher
- Erik De Clercq
- Bart Jan Kullberg
Related topics
Seminal works
- fisher-2018
- perlin-2017
- declercq-2016
- kullberg-2015
Frequently asked questions
- How is antifungal and antiviral resistance different from antibiotic resistance?
- The concept is the same - loss of drug susceptibility under selective pressure - but the biology differs. Fungi are eukaryotes with their own drug targets such as ergosterol synthesis and glucan synthase, while viruses depend on host cells and evolve rapidly as quasispecies, so the resistance mechanisms and the diagnostic tools differ from those used for bacteria.
- Why is non-bacterial resistance considered especially serious?
- Because the number of antifungal and antiviral drug classes is small and several conditions require prolonged or lifelong therapy, the loss of even one option can substantially narrow the choices available to manage invasive fungal disease or chronic viral infection.