When resistance identified in a fungal infection rules out the use of a particular antifungal, the remaining choices may carry substantial limitations of their own. Toxicity can complicate treatment, drug interactions can interfere with other necessary medicines, and available formulations can restrict administration. The World Health Organization (WHO) identified these overlapping problems among the key priorities for antifungal development.1
At IDWeek 2026, presentations in the sessions “What is New in the Global Antimicrobial Resistance Landscape” and “New Antimicrobials in the Pipeline” brought these treatment constraints into focus. The global session examined problems involving Aspergillus fumigatus, Candida auris, Fusarium, and Trichophyton, highlighting distinct treatment and surveillance needs. In the pipeline session, presentations on SCY-247 and turletricin explored investigational approaches to expanding treatment options. Those discussions, alongside separately reported clinical findings for olorofim and ongoing development of fosmanogepix, reveal several approaches to addressing resistance and treatment limitations, with different levels of evidence supporting their potential benefits.
Different Fungi Require Different Responses
For A. fumigatus, resistant infection can originate outside the clinical setting. Researchers including a team at Imperial College London analyzed 218 clinical and environmental isolates from the United Kingdom and Ireland.2 Their genomic analysis identified closely related environmental and clinical isolates, including near-identical genotypes, supporting acquisition of resistant infections from the environment. Medical prescribing practices therefore address only part of the resistance problem.
C. auris combines resistance concerns with healthcare transmission. Echinocandins remain the Centers for Disease Control and Prevention’s (CDC) recommended initial treatment for adults and children older than two months, and most U.S. strains remain susceptible. Nevertheless, reports of echinocandin-resistant and pan-resistant infections are increasing. The Centers for Disease Control and Prevention (CDC) recommend susceptibility testing and careful monitoring during treatment, while emphasizing that colonization without signs or symptoms of infection does not warrant antifungal treatment.3
The CDC’s tracking page records 6,304 U.S. clinical cases in 2024.4 These are detections from specimens collected to investigate suspected infection, including invasive and noninvasive sites rather than a count limited to bloodstream infections. Screening detections constitute a separate category. Early detection, screening, and infection prevention remain central to controlling spread, including after treatment, because patients can remain colonized.5
In community care, T. indotineae can cause extensive, difficult-to-treat skin infections. Researchers from the UK Health Security Agency and collaborating institutions reported 363 reference-laboratory-confirmed cases between January 2017 and August 2025 in Eurosurveillance.7 Of these, 85% were identified from January 2023 onward. The investigators could not determine the relative contributions of international importation and domestic transmission. The findings document increasing detections within a referral system, rather than population prevalence.
The CDC’s October 2026 guidance identifies T. indotineae and terbinafine-resistant T. rubrum as public-health concerns.6 Specialized identification and susceptibility testing remain difficult to access, and U.S. reporting is not mandatory. Antifungal–corticosteroid combination products, inappropriate prescribing, misuse of topical treatments, and inadequate adherence may contribute to emergence and spread. These challenges extend resistance management into the settings where patients seek care for common skin infections.
The picture is less resolved for Fusarium and the related genus Neocosmospora. Researchers at Universidad de los Andes in Colombia and Nantes Université in France examined 52 human, animal, and environmental isolates.8 The minimum inhibitory concentration (MIC) is the lowest tested concentration that inhibits fungal growth. Several medical antifungals and agricultural fungicides produced high MICs in the study. The collection included archived isolates, and the authors discussed intrinsic resistance as a possible contributor. Shared susceptibility patterns across sources do not establish that agricultural exposure generated resistance or that resistant organisms transmitted to patients.
The invasive infections among these examples create a need for additional therapies, while resistant dermatophytes expose a separate community treatment and diagnostic challenge. The programs presented at IDWeek address selected parts of that broader need.
Expanding Options Against Resistant Invasive Infections
Resistance to echinocandins raises the question of whether another compound acting on the fungal cell wall can retain useful activity. In the IDWeek pipeline session, SCYNEXIS presented SCY-247, a triterpenoid antifungal under development in oral and intravenous (IV) formulations. It inhibits glucan synthase, an enzyme involved in producing a component of the fungal cell wall, using a different chemical class to act on an established target.
Researchers at the University of Texas Health Science Center at San Antonio evaluated SCY-247 against C. glabrata.9 The compound maintained laboratory activity against 24 of 29 echinocandin non-susceptible or resistant strains. In infected mice, treatment produced dose-dependent reductions in kidney and lung fungal burdens.
On October 22, SCYNEXIS reported completion of phase I studies of both formulations.10 The IV study enrolled 56 healthy participants. The company reported generally favorable tolerability, with infusion-site erythema and pain among the most common adverse reactions and no drug-related serious adverse events. Selected doses achieved exposures at or above a target derived from mouse models. Phase II development in 2027 remained subject to regulatory agreement; these studies had not established efficacy in infected patients.
Fosmanogepix, an investigational antifungal prodrug being developed by Basilea in oral and IV formulations for invasive fungal infection, has published patient experience involving C. auris. Researchers from Augusta University, the University of Alabama at Birmingham, South African hospitals, and industry collaborators reported an open-label, single-arm phase II study in Antimicrobial Agents and Chemotherapy. Nine ICU patients in South Africa received IV treatment.11 Treatment success at the end of study treatment and survival at day 30 were each reported in eight patients, without a comparator group.
Its active phase III candidemia and invasive candidiasis study compares IV fosmanogepix, with optional oral transition, against IV caspofungin followed by optional fluconazole.12 The trial will assess a regimen that can continue with the investigational agent after the IV phase, rather than switching to a different antifungal. In its October 27 update, Basilea projected phase 3 readouts for its invasive yeast and mold programs in mid-2028.13
Reducing the Toxicity That Constrains Polyene Use
Amphotericin B offers broad antifungal activity, but toxicity can limit its use. In the IDWeek pipeline session, Elion Therapeutics chief medical officer Taylor Sandison presented turletricin, known as EL219 and formerly SF001, as an effort to retain useful polyene activity while reducing those treatment limitations.
Researchers at the Medical University of Innsbruck compared SF001 with amphotericin B against 56 Candida and 41 Aspergillus isolates.14 Overall activity against Candida was comparable, with differences among species. Against the tested Aspergillus isolates, SF001 generally produced lower MICs. Some isolates with elevated amphotericin B MICs had substantially lower values when tested against SF001.
The investigators cautioned that SF001-specific clinical breakpoints and epidemiological cutoff values had not been established. Its measured MICs therefore describe laboratory activity without providing a validated threshold for predicting treatment response.
Elion’s clinical program has begun examining the proposed tolerability advantage. In its IDWeek announcement, the company reported favorable findings across three phase I studies, including evaluation in participants with moderate or severe renal impairment, without signs of worsening renal impairment. It also reported that a phase II study in HIV-related cryptococcal meningitis met a predefined early fungicidal-activity threshold based on cerebrospinal fluid fungal clearance.
The clinical question is whether turletricin can control infection with less treatment-limiting toxicity than existing options. The early renal observations and fungal-clearance findings address parts of that question, but comparative patient outcomes remain to be established.
An Oral Alternative Reaches Comparative Evaluation
At a separate IDWeek 2026 late-breaking presentation, F2G chief medical officer John H. Rex presented findings from olorofim’s phase III OASIS trial.15 The study addressed invasive aspergillosis in patients for whom mold-active azoles were inappropriate or ineffective.
OASIS randomized 225 adults to oral olorofim or liposomal amphotericin B followed by standard of care. Eligibility included known or suspected resistance, azole intolerance, drug interactions, breakthrough infection, or prior treatment failure. The trial therefore addressed several reasons patients might need an alternative to azole therapy.
Day 42 mortality was 23.8% with olorofim and 24.3% with the comparator. The reported difference was −0.5 percentage points, with a 95% confidence interval from −13.1 to 10.8, meeting the prespecified noninferiority margin of 20 percentage points. Olorofim met the trial’s threshold for noninferiority, but the findings did not establish lower mortality. Drug-related adverse events were less frequent with olorofim, particularly renal events, while drug-induced liver injury remained a safety consideration. Olorofim remained investigational in the announcement.
Making Resistance Visible Enough to Act On
Emerging treatments also face resistance risks beyond clinical prescribing. A 2024 study in Nature Microbiology showed that laboratory selection for resistance to the agricultural fungicide ipflufenoquin could produce A. fumigatus strains cross-resistant to olorofim.16 The experiment identifies a potential resistance pathway; it does not demonstrate that agricultural use has caused olorofim treatment failures in patients.
Experimental research can identify such pathways, while surveillance establishes which organisms and susceptibility patterns occur in sampled populations and settings. Both are needed to clarify resistance risks. For dermatophytes, limited testing and reporting leave the burden uncertain. For Fusarium, shared laboratory profiles across sources leave important questions about resistance origins and transmission unresolved.6,8
WHO’s June 2026 blueprint connects treatment access and innovation with laboratory capacity, surveillance, stewardship, and outbreak preparedness. Its implementation priorities address the capabilities needed to detect fungal disease, recognize resistance, and support treatment decisions.
More accessible identification and susceptibility testing, better community surveillance, and effective healthcare containment can support the use of existing treatments while clinical trials establish where emerging therapies add benefit. The goal is to give patients effective, tolerable treatment options and clinicians the information needed to choose among them.
