The unity of the global 2025 ECMM/ISHAM/ASM Candida guideline (global Candida 2025 guideline) means a practitioner can find all important topics in one document, whereas in 2012 one had to consult multiple papers for each subgroup. The global Candida 2025 guideline retains echinocandins as the first-line treatment for invasive candidiasis while incorporating new agents – such as rezafungin for once-weekly dosing and novel oral options for resistant infections – to offer more personalized, susceptibility-guided therapy. They also recommend an earlier intravenous-to-oral step-down in stable non-neutropenic patients, and emphasize the need for prompt source control. Additionally, there is a stronger focus on managing emerging resistance (notably with Candida auris and azole-resistant Candida parapsilosis) and tailoring prophylaxis and treatment strategies to local epidemiology and special patient populations. It provides detailed, evidence-graded recommendations using the GRADE system, with explicit sections on emerging pathogens, resistance, antifungal stewardship, and infection control. The global Candida 2025 guideline incorporates broader public health considerations and guidance on resource-limited settings.
La guía global 2025 de Candida de las sociedades ECMM, ISHAM y ASM (guía global de Candida 2025) hará posible que un profesional pueda encontrar todos aquellos temas importantes en un solo documento, cuando en la guía de 2012 se tenían que consultar múltiples artículos para cada subgrupo de pacientes. La guía global de Candida 2025 mantiene las equinocandinas como el tratamiento de primera línea para la candidiasis invasiva, mientras incorpora nuevos fármacos antifúngicos, como la rezafungina, con dosificación semanal, y nuevas opciones orales para el tratamiento de las infecciones resistentes, ofreciendo una terapia más personalizada y guiada basada en los datos de sensibilidad in vitro de los aislamientos clínicos. También se recomienda una transición más temprana del tratamiento intravenoso al tratamiento oral en pacientes estables y sin neutropenia, y se enfatiza la necesidad de un control rápido del origen de la infección. Además, hay un enfoque sólido sobre el manejo de la resistencia emergente (especialmente en Candida auris y Candida parapsilosis resistentes a los azoles) y en la adaptación de las estrategias de profilaxis y tratamiento a la epidemiología local, y a poblaciones de pacientes especiales. La guía proporciona recomendaciones detalladas y clasificadas según la evidencia utilizando el sistema GRADE, con secciones específicas sobre especies emergentes, resistencia, administración de fármacos antifúngicos y control de infecciones. La guía global de Candida 2025 incorpora también consideraciones más amplias de salud pública y orientación para entornos con recursos limitados.
The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 2012 recommendations for Candida infections were published as a series of documents in a supplement of Clinical Microbiology and Infection.1,3–7 Each part focused on a particular population or aspect: e.g., one part for non-neutropenic adults,1 another for neutropenic adults/hematopoietic stem-cell transplantation,7 another for pediatrics/neonates,4 and one covering diagnostic procedures.3 This segmented approach meant the guidance was somewhat siloed by patient group. The structure followed a traditional guideline format with recommendations graded and did not extensively cover superficial candidiasis like oropharyngeal or vulvovaginal candidiasis – those were considered outside the remit or covered briefly. It was largely a European initiative (ESCMID and its Fungal Infection Study Group, with the European Confederation of Medical Mycology – ECMM), though it included international experts. Evidence at that time was summarized in each section, but there was no single unified document – readers had to piece together the full story from multiple publications. Importantly, topics like antifungal stewardship or detailed infection control guidance were not prominent in 2012's structure.
In contrast, the global 2025 ECMM/ISHAM/ASM Candida guideline is a single, unified global document published in The Lancet Infectious Diseases.2 It was developed over four years by a team of 100+ experts from 35 countries, with input and endorsement from over 70 international organizations – truly a worldwide effort. The structure is expansive: it covers “prevention, diagnosis, and treatment of various forms of candidiasis – from superficial infections to life-threatening invasive infections.” This means the scope includes not just invasive candidemia and organ infections (as 2012 did), but also mucosal candidiasis (thrush, esophagitis, vulvovaginal candidiasis), chronic candidiasis, and even outlines for emerging scenarios.2 The 2025 document is likely organized by clinical syndrome: e.g. sections for candidemia, acute disseminated candidiasis, chronic disseminated (hepatosplenic) candidiasis, central nervous system (CNS) candidiasis, intra-abdominal candidiasis, urinary candidiasis, catheter-related, endocarditis, ocular, skin, etc., and special host groups (ICU, oncology, transplant, neonates). Each recommendation is accompanied by an evidence level, and an extensive evidence summary in an appendix is provided. The guideline also explicitly addresses emerging issues like antifungal resistance and new species.2 Additionally, topics such as antifungal stewardship and the call for excellence centers to manage tough cases appear in 2025, reflecting a broader scope that blends clinical guidance with system-level recommendations. In terms of format, the 2025 guideline uses the GRADE system and is a consensus “state-of-the-art” document (almost 200 pages if including appendices). In addition, an adaptation to resource-limited settings has been made. Allover, the 2025 guideline's structure makes it easier for practitioners to locate information for specific populations without cross-referencing multiple papers. The comprehensive nature of the new guideline, which even covers Candida infections in special sites (bones, joints, hardware) and adjunctive therapies, fills gaps that the 2012 guidelines had not explicitly discussed. In short, the 2025 guideline is a one-stop reference that reflects many years of progress and globalization of medical mycology.
Another development is taxonomic reclassification of Candida: the guideline notes that several medically important Candida species have been renamed or reclassified into new genera – for example, Candida glabrata is now officially Nakaseomyces glabratus and Candida krusei is Pichia kudriavzevii, etc. While this is more a scientific nuance, it can cause diagnostic confusion (labs might report unfamiliar names), so the guideline highlights it.
Epidemiology: urgent trendsOver 2012–2025, Candida epidemiology has shifted from a stable distribution to one with new challenges. The rise of Candida auris exemplifies this – unknown in 2012, by 2025 it is a global threat prompting CDC and WHO alerts. Guidelines needed to adapt, and the 2025 recommendations around identification, treatment, and infection control for C. auris are a direct response to its emergence.2 Similarly, Candida parapsilosis developing widespread azole resistance in some locales was unexpected in 2012; now, the guideline warns of it as an evolving situation. For clinicians, this means that they must be aware of local Candida species epidemiology – e.g., an ICU with predominantly N. glabratus will approach empiric therapy differently than one where C. parapsilosis prevails. The 2025 guideline, being global, encourages surveillance: it points out the value of identifying species for surveillance purposes, which in turn feeds epidemiologic knowledge.2 Another implication is infection prevention: knowing that C. auris can linger in environments, hospitals worldwide in the 2020s have had to implement screening and cleaning protocols (which was never an issue with Candida albicans). The mention of taxonomic changes also has a practical side – clinicians might see unfamiliar names in lab reports and should realize they are Candida species by another name. Overall, the 2025 guideline's take on epidemiology is more urgent and expansive: Candida infections are not only persistent causes of bloodstream infections, but now also agents of outbreaks (C. auris) and evolving resistance patterns, requiring a coordinated response. This contrasts with 2012, when epidemiology was relatively static – important, but not demanding radical shifts in infection control or treatment.
The global 2025 work also mentions emerging species threats – aside from C. auris, there's recognition of species like Candida lusitaniae, Candida kefyr, or Candida haemulonii complex causing sporadic outbreaks, though these are less prominent than C. auris. Another epidemiologic key point is the shift in ratio of C. albicans to other Candida species: in many tertiary centers by 2025, non-C. albicans Candida species (e.g. N. glabratus, C. parapsilosis, Candida tropicalis, C. auris) collectively exceed 50% of isolates. This is a change from a decade prior, when C. albicans was often the dominant species.
Diagnostics: key updatesSince 2012, diagnostic practice has evolved to incorporate rapid identification and molecular detection – the 2025 recommendations reflect the maturation of these tools.2 Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF, largely unavailable or new in 2012) is now a routine method in many centers, allowing earlier species determination and, thus, appropriate therapy (e.g. ruling out N. glabratus or P. kudriavzevii before using fluconazole). Likewise, PCR assays (cleared mid-2010s) are recognized, though with caution due to limited species coverage. The core message remains that culture is still essential (for susceptibility testing and epidemiology), but 2025 places greater emphasis on combining traditional and novel diagnostics. This shift enables faster, targeted treatment (improving outcomes by days), yet warns clinicians not to over-rely on any single non-culture test, to avoid false positives or negatives leading to mismanagement. Overall, the 2025 guideline's diagnostic section is more detailed and expansive, mirroring advancements in the field and the need to diagnose Candida infections earlier in high-risk patients.
2025 global guideline still strongly endorses blood cultures (with recommendations to increase volume and number of sets to improve yield), but integrates new technologies for quicker, targeted diagnosis.2 PCR-based tests (commercial assays) from blood or sterile sites are moderately recommended as an adjunct (able to detect only certain Candida species). Beta-d-glucan (BDG) detection and combined mannan/anti-mannan assays are also moderately recommended as complementary tools – useful for their high negative predictive value – but should never be used alone to diagnose candidemia. Importantly, the 2025 guideline notes there is insufficient evidence to start pre-emptive antifungals solely on biomarkers or PCR results without other clinical clues.
Treatment: novel approachesThe core first-line therapy – echinocandins – is consistent between 2012 and 2025, but the therapeutic arsenal in 2025 is broader.2 The inclusion of rezafungin is a major update (added to guidelines in 2025 shortly after its approval, marking the first new echinocandin in over a decade). This offers clinicians a long-acting option that can facilitate outpatient intravenous (IV) therapy and improve compliance, a significant practical change from 2012 when daily IV dosing was required. The 2025 guideline also acknowledges new oral agents for Candida that were not available in 2012, addressing unmet needs like azole-resistant vaginal yeast infections (oteseconazole can be used for azole-resistant C. albicans in recurrent vulvovaginal candidiasis) and invasive candidiasis where long-term oral step-down is needed but fluconazole cannot be used (ibrexafungerp may fill that role). Another subtle shift is stronger emphasis on susceptibility-guided therapy: 2025 explicitly recommends performing antifungal susceptibility testing on all invasive isolates to direct therapy, whereas in 2012 this was implied but not always done routinely.2 Clinically, these updates mean more personalized and flexible treatment – patients have more options (including oral step-downs and once-weekly IV therapy), and therapy can be better aligned to the Candida species and resistance profile, improving outcomes especially in resistant infections. The reaffirmation of source control and adequate treatment duration in 2025 continues the 2012 principles, underscoring that despite new drugs, basics like removing infected catheters and treating for ≥2 weeks after bloodstream clearance remain critical for cure.
The 2025 global guideline reinforces many principles but incorporates new agents and evidence.2 Echinocandins remain first-line for invasive candidiasis (including candidemia) in almost all adult patient scenarios. Rezafungin's once-weekly dosing is highlighted for convenience in candidemia requiring prolonged therapy. Liposomal amphotericin B (L-AmB) is still recommended as a second-line or salvage therapy for candidemia/invasive disease – for instance, if echinocandins cannot be used due to intolerance or resistance. Fluconazole remains an important agent and displays an option for step-down therapy once the patient is stable and the isolate is confirmed susceptible; it continues to be first-line for less severe mucosal candidiasis. Notably, 2025 also introduces ibrexafungerp (a novel oral glucan synthase inhibitor) and oteseconazole (a novel azole for recurrent vulvovaginal candidiasis) as expanded options for mucocutaneous candidiasis, reflecting their recent approvals (ibrexafungerp in 2021, oteseconazole in 2022). Additionally, treatment is now more tailored by infection site: for Candida CNS infection, 2025 guideline recommends L-AmB (often with flucytosine) as initial therapy. The updated 2025 global guideline allows an earlier step-down (∼5 days of IV therapy) in candidemia, but only if the following strict criteria are met: the patient is hemodynamically stable, repeat blood cultures are negative (documented clearance of Candida from the bloodstream), the infection source is controlled, the isolate's susceptibility is confirmed, the patient can tolerate oral therapy, and the patient is non-neutropenic.2 In other words, ongoing neutropenia is an exclusion – neutropenic patients are not switched to oral therapy at the 5-day mark. Step-down is deferred until neutropenia has resolved, aligning with the principle that adequate immune recovery is needed before transitioning off IV therapy in this population. This is a notable update: the timeframe for considering oral step-down is shorter (5 days vs. 10 days in 2012 for stable cases), but with a clear stipulation that the patient must not be neutropenic at the time of switch.2
High-dose caspofungin (e.g., 150mg/day in severe cases), or other echinocandins are considered alternative options for severe or resistant cases of invasive candidiasis, particularly in patients who do not respond well to standard doses or first-line therapies, or in deep-seated infections, where achieving adequate tissue concentrations is crucial.7
Resistance management: key changesThe past decade saw Candida resistance go from a minor footnote to a central concern. The 2025 guideline responds by incorporating strategies beyond just drug selection – notably, infection control for C. auris (something entirely absent in 2012 guidelines).2 For example, where 2012 would simply switch to amphotericin B for a fluconazole-resistant isolate, 2025 proactively identifies risk scenarios (prior azole use, local resistance patterns) and recommends using echinocandins or newer agents upfront in those cases.
The mention of fluconazole-resistant C. parapsilosis reflects real-world shifts – this genotype was described in outbreaks in the late 2010s; accordingly, the new guideline warns institutions to adjust prophylaxis/treatment if this is an issue. The emphasis on susceptibility testing for every invasive case is a change from 2012, driven by increased incidence of echinocandin resistance (FKS mutations) and cross-resistance patterns that were not common before. Clinically, this means 2025 expects clinicians to obtain species identification and antifungal minimum inhibitory concentrations early, and to be aware of local Candida epidemiology. In summary, the 2025 guideline adopts a much more vigilant stance: Candida infection management now includes a strong public health component, with guidance on preventing spread of tough strains, whereas the 2012 guideline was focused on individual patient treatment and had not foreseen the need for outbreak management of Candida in hospitals.
If C. auris is echinocandin-resistant (due to FKS mutations), 2025 recommendations advise using alternative or combination therapy (e.g. high-dose L-AmB, sometimes combined with flucytosine or azoles, per available data – though specifics may be in the appendix, the need for expert guidance is emphasized). Similarly, azole-resistant C. parapsilosis is highlighted in 2025 as an emerging problem in some regions.
In fact, for prophylaxis scenarios in such settings, 2025 even suggests using an echinocandin prophylactically (instead of fluconazole) if patients have recently been exposed to azoles or the unit has high rates of azole-resistant Candida.2 The guideline also defers to EUCAST/CLSI standards for antifungal testing to harmonize lab practices. Overall, the 2025 approach to resistance is both clinical (choosing the right drug) and preventive (containment of resistant strains).
Prophylaxis: novel considerationsProphylaxis recommendations in 2025 are incrementally changed rather than overhauled.2 The main additions are the consideration of echinocandin prophylaxis in azole-exposed or high-resistance settings, and an emphasis on using mold-active agents for prophylaxis in high-risk neutropenia (shifting away from fluconazole monotherapy in those patients). These changes were driven by emerging resistance; e.g. an ICU that has seen clusters of C. auris or N. glabratus might choose micafungin prophylaxis to prevent an infection that fluconazole might not prevent. The clinical implication is a more tailored prophylaxis approach – one must know their hospital unit's Candida microbiota and resistance patterns before simply giving fluconazole to everyone. Otherwise, many principles remain the same: do not give prophylaxis to low-risk patients (to avoid unnecessary drug use), do give it to those with highest risk (certain neonatal intensive care unit (NICU) babies, complicated gastrointestinal surgery cases, and neutropenic/transplant patients) because it saves lives. The global 2025 guideline also integrates prophylaxis into an overall stewardship mindset, implying that prophylaxis should be part of a strategy that balances prevention of disease with avoidance of fostering resistance – a balance that was only lightly touched upon in 2012. For critically ill surgical patients with recurrent gastrointestinal leaks, fluconazole prophylaxis (loading dose 12mg/kg, then 6mg/kg daily) is again explicitly recommended.
Special populations: new highlightsThe recommendations for immunocompromised patients in global 2025 guideline are more or less continuous with 2012 in terms of treatment; prophylaxis has shifted to broader antifungals and there is a greater stress on customizing therapy to pathogen and patient status. A patient with hematopoietic stem cell transplantation and graft-versus-host-disease might need long-term suppressive therapy, a circumstance the new guideline would cover as part of management.2 One subtle difference is the fact that the global 2025 guideline strongly recommends consulting susceptibility tests even for mucosal Candida in immunocompromised hosts not responding to empiric therapy, highlighting that these patients often have infections with resistant non-C. albicans Candida species and may need therapy adjustment.
By 2025, evidence have shown mixed results for empiric therapy in ICU. The new guideline likely advises an approach of “watchful waiting with diagnostics” for ICU patients: use scores (Candida colonization index or Candida score) and non-culture tests to decide on early therapy, rather than blind empiric treatment for every ICU fever – and, indeed, it cautions that biomarkers alone should not trigger treatment without other signs. Prophylaxis in ICU patients with specific surgical risk (as discussed above) is reaffirmed in 2025, but routine prophylaxis in all ICU patients is not recommended (to avoid resistance), consistent with 2012. Both 2012 and 2025 guidelines stress prompt removal of central lines in ICU patients with candidemia, and thorough search for metastatic infection (eyes, heart) in ICU candidemia cases. The 2025 guideline might put additional emphasis on source control in ICU – e.g. drainage of abscesses, removing infected devices – which was implied in 2012, but perhaps it is more highlighted now, given outcomes data.2
By 2025, there have been changes: micafungin is FDA- and EMA-approved for neonates and has become commonly used, especially for C. albicans and C. parapsilosis neonatal candidemia. If CNS involvement is present in a neonate, 2025 guideline would still recommend an amphotericin B-based regimen because of superior brain penetration. For pediatric patients (beyond neonates), 2025 recommendations are more aligned with adult recommendations: echinocandins as first-line for invasive candidiasis, fluconazole or L-AmB as alternatives depending on species. One change is dosing and approval of newer azoles in children – e.g. isavuconazole is not really for Candida, but posaconazole oral formulations and echinocandins have pediatric indications now, which the guideline would incorporate.2
Special populations also include pregnant patients – 2012 noted fluconazole is teratogenic in high doses, so L-AmB is preferred for invasive candidiasis in pregnancy. The 2025 guideline recommends L-AmB as standard treatment for invasive candidiasis in pregnancy.
Another special group is end-stage renal disease or ICU patients on dialysis: in 2012, dosing and choice (e.g. use fluconazole, which is renally cleared, vs. echinocandin, which is hepatic) were considered, and 2025 might provide more clarity (like avoiding cyclodextrin formulation of IV voriconazole in renally impaired, etc., although that is a minor detail).
Therapeutic drug monitoring: at a glanceThe guideline's section on therapeutic drug monitoring (TDM) concludes that while TDM is the most direct method for ensuring that antifungal drug exposures are both safe and effective, its routine use in invasive candidiasis is not universally supported by robust clinical outcome data.2 In practice, TDM-guided dosing is particularly valuable for antifungals with unpredictable pharmacokinetics (such as posaconazole suspension and voriconazole) and in patient groups where large variations in drug exposure are expected – like premature neonates, critically ill patients with altered volume of distribution, or those on extracorporeal support. Conversely, for some newer agents (for example, the new echinocandin rezafungin), there is no current evidence supporting routine TDM, though further evaluation in specific clinical settings is warranted. In summary, TDM should be considered for patients at risk of very low or high drug exposures rather than being implemented as a blanket recommendation for all antifungal treatments in invasive candidiasis.7
ConclusionThe global 2025 Candida guideline for the diagnosis and management of candidiasis covers both superficial and invasive forms of the infection, emphasizing that Candida species are major fungal pathogens affecting diverse patient populations. Key recommendations include detailed diagnostic strategies that combine traditional methods, such as direct microscopy and culture, with newer approaches, like biomarkers and molecular techniques. There is a strong preference for first-line treatment with echinocandins (including the novel agent rezafungin) for invasive candidiasis, while also discussing alternative treatments such as liposomal amphotericin B and fluconazole, with careful attention to antifungal resistance. The 2025 guideline underlines the importance of antifungal stewardship, source control (such as prompt catheter removal in candidaemia), and tailored treatment approaches based on patient-specific risk factors and local epidemiological data; discuss the challenges posed by emerging pathogens like C. auris; and provide evidence-based, multidisciplinary recommendations that can be adapted to both high-resource and low-resource settings.
Conclusions at a glance.
| Epidemiology |
| ○ Recognizes Candida as a leading cause of invasive fungal infections with a significant global burden. |
| ○ Highlights the emergence and spread of C. auris and increased rates of fluconazole-resistant non-C. albicans Candida species. |
| ○ Notes taxonomic reclassification of certain Candida species, adding complexity to diagnostics and surveillance. |
| ○ Stresses the importance of local epidemiologic data and infection control in managing outbreaks. |
| Diagnostics |
| ○ Blood cultures remain essential, with recommendations to increase volume and number for improved yield. |
| ○ Rapid species-level identification via MALDI-TOF is now strongly endorsed. |
| ○ PCR-based tests and chromogenic agar are moderately recommended as adjuncts, but none should be used alone for diagnosis. |
| ○ DNA sequencing is advised in specialized labs when definitive identification is needed. |
| ○ Emphasizes combining traditional culture methods with rapid, targeted diagnostics to improve treatment timing. |
| Treatment |
| ○ Echinocandins continue as first-line, with the addition of rezafungin – a long-acting, once-weekly echinocandin approved in 2023. |
| ○ Liposomal amphotericin B, optional combined with 5-flucytosine, is recommended as therapy in CNS infections. |
| ○ New oral agents (ibrexafungerp and oteseconazole) are introduced for mucocutaneous candidiasis and resistant cases. |
| ○ Therapy is more tailored to infection site with detailed, site-specific recommendations. |
| ○ Earlier step-down (around 5 days) may be considered if strict criteria are met: hemodynamic stability, negative repeat blood cultures, controlled infection source, confirmed susceptibility, and the patient's ability to tolerate oral therapy. |
| ○ Neutropenic patients are excluded from early step-down until immune recovery. |
| Resistance management |
| ○ Explicit strategies to address the global rise of resistant strains, notably C. auris. |
| ○ Aggressive infection control measures (rapid identification, contact precautions, environmental disinfection) are recommended for C. auris. |
| ○ Emphasizes routine susceptibility testing and using local resistance patterns to guide therapy choices. |
| Prophylaxis |
| ○ Continues prophylaxis in defined high-risk groups, with adjustments based on local resistance patterns. |
| ○ In settings with high azole resistance, echinocandin prophylaxis is considered. |
| ○ For neutropenic patients with prolonged risk, mold-active agents (like posaconazole) are recommended over fluconazole. |
| Therapeutic drug monitoring (TDM) |
| ○ TDM is considered for patients at risk of very low or high drug exposures rather than being implemented for all antifungal treatments in invasive candidiasis. |
| Special populations |
| • Immunocompromised patients |
| ○ Maintains echinocandins as first-line but tailors prophylaxis (e.g., posaconazole for acute leukemia) and stresses susceptibility-guided therapy. |
| • ICU/critically ill patients |
| ○ Advocates a “watchful waiting” approach using diagnostic scores and non-culture tests (like BDG) to guide targeted therapy; emphasizes aggressive source control. |
| • Neonates and pediatrics |
| ○ Echinocandins (especially micafungin) are now approved and commonly used in neonates, while maintaining amphotericin B for CNS involvement; pediatric dosing aligns more closely with adult guidelines. |
During the preparation of this work the author used GTP-4 (OpenAI©) in order to improve readability, and in addition to prepare Table 1.
FundingNo funding obtained for this review.
Conflict of interestsThe author has no conflicts of interest to declare.
