Candida infections are among the most common fungal diseases globally, with candidemia posing a serious threat in hospitalized and immunocompromised patients. In Portugal, though Candida albicans is the predominant species identified, other species such as Candida parapsilosis and Nakaseomyces glabratus (formerly Candida glabrata) are increasingly detected, particularly in intensive care units and patients with invasive devices. Emerging multidrug-resistant strains, notably Candidozyma auris (formerly Candida auris), have raised significant concern, with the first Portuguese cases reported recently. Surveillance studies suggest that antifungal resistance rates are generally low, though fluconazole resistance in C. parapsilosis is a concern, since ERG11 mutations were recently detected in several isolates. Echinocandins are recommended as first-line therapy, yet availability is uneven across healthcare centers. Beyond candidemia, superficial infections like vulvovaginal candidiasis and onychomycosis remain highly frequent. Active research in Portugal on Candida biology, virulence, and novel therapies, have been conducting for different research groups. Strengthening surveillance, rapid diagnostics, molecular identification, and infection control measures, alongside mandatory notification of C. auris, are critical for effective management. Integrated strategies under a “One Health” framework are essential to mitigate morbidity, mortality, and resistance trends associated with Candida infections.
Las infecciones por Candida se encuentran entre las enfermedades fúngicas más comunes a nivel mundial, siendo la candidemia una amenaza grave en pacientes hospitalizados e inmunocomprometidos. En Portugal, aunque Candida albicans es la especie predominante, se detectan cada vez más otras especiesdel género, como Candida parapsilosis y Nakaseomyces glabratus (antes Candida glabrata), especialmente en unidades de cuidados intensivos y en pacientes con dispositivos invasivos. Las cepas multirresistentes emergentes, en particular Candidozyma auris (antes Candida auris), han generado gran preocupación, con los primeros casos portugueses reportados recientemente. Los estudios de vigilancia indican tasas generalmente bajas de resistencia a los antifúngicos, aunque la resistencia al fluconazol en C. parapsilosis es motivo de preocupación, dado que se han detectado mutaciones en el gen ERG11 en varios aislamientos. Se recomienda el uso de equinocandinas como terapia de primera línea, aunque su disponibilidad es desigual entre los centros sanitarios. Más allá de la candidemia, las infecciones superficiales como la candidiasis vulvovaginal y la onicomicosis siguen siendo muy frecuentes. En Portugal, diversos grupos de investigación desarrollan estudios sobre biología, virulencia y nuevas terapias contra Candida. Fortalecer la vigilancia, el diagnóstico rápido, la identificación molecular y las medidas de control, junto con la notificación obligatoria de C. auris, es fundamental para una gestión eficaz. Estrategias integradas bajo el marco “One Health” son esenciales para mitigar la morbilidad, mortalidad y tendencias de resistencia asociadas a las infecciones por Candida.
Candidemia remains a major cause of morbidity and mortality worldwide, posing significant challenges to healthcare systems. In Portugal, recent data reveal evolving epidemiological patterns and antifungal resistance trends that warrant closer attention. This article explores these developments and offers a critical perspective on their implications for public health and clinical practice in Portuguese settings.
Epidemiological insights on candidemiaCandida infections are among the most frequent causes of fungal infections worldwide,15 with candidemia representing a serious nosocomial infection associated with high morbidity and mortality, especially among the immunocompromised and those exposed to invasive medical procedures. Early epidemiological estimates suggested an incidence of candidemia of approximately 2.19 cases per 100,000 population in Portugal, equating to roughly 231 cases annually.45 Recent data from 16 Portuguese medical centers show that invasive fungal diseases are perceived as low-to-very low incidence, with Candida species identified as the most frequent pathogen.22 In all candidemia surveillance programs performed around the world, Candida albicans was the most frequent species found, but non-C. albicans species and multidrug-resistant strains are increasingly reported.37 This has been attributed to evolving patient populations (older, immunocompromised, more invasive procedures), antifungal selection pressures, and improved diagnostic methods.49 In Portuguese settings, C. albicans was historically the predominant species, while other species such as Candida parapsilosis emerged in intensive care units and among patients with invasive devices, as oncological patients. In fact, in the last decades, C. parapsilosis has been described as the second most frequent species found in blood cultures, both in general and specific populations, with a prevalence of around 20–25% .12,19,28,34,44 In recent years, several studies have reported an increasing prevalence of Nakaseomyces glabratus (previously known as Candida glabrata), as mentioned in a retrospective study conducted at Centro Hospitalar Universitário de São João,38 between 2016 and 2017, where 117 episodes of candidemia were diagnosed, or in a 5-year retrospective study (2015–2019) at the Cova da Beira University Hospital Center.46 In both cases, N. glabratus was the etiological agent isolated in 22% of cases.
The increasing prevalence of C. parapsilosis and N. glabratus may be attributed to species-specific characteristics: C. parapsilosis has the capacity to form biofilms and persist on surfaces for extended periods, while N. glabratus has intrinsic reduced susceptibility to fluconazole and genuine fluconazole resistance observed in varying rates,50 an antifungal agent that is widely used in prophylaxis regimens.
Recent surveillance studies indicate growing concern over the emergence of multidrug-resistant species,27,39 with emphasis on the growing prevalence of Candidozyma auris (previously known as Candida auris).17 In 2023, the first case of C. auris (Clade III) was reported in Portugal. The patient had been transferred from Angola to an ICU in a Lisbon hospital for liver transplantation after a SARS-CoV-2 infection.24 In this case, it was not possible to determine if C. auris was an agent of infection or colonization. Miranda et al. reported cases of C. auris (Clade I) candidemia occurred in the same year, comprising eight epidemiologically linked isolates from colonized and infected patients admitted to a major hospital in northern Portugal.29
Candida antifungal susceptibility profile and therapeutic approachAccording to the recently published 2025 ECMM/ISHAM/ASM global Candida guideline, echinocandins are strongly recommended as first-line treatment of candidemia.9 The paper enrolling data from 16 Portuguese medical centers states that antifungal therapy is widely available, yet only 85% of sites stock echinocandins.22
Candida susceptibility to antifungals in Portugal has been investigated in some multicentric studies and in surveillance reports, showing that antifungal resistance rates among most Candida species is low. Nationwide surveillance in 2011–201219 collected 97 C. albicans isolates from patients with candidemia across 10 hospitals. Resistance to fluconazole, voriconazole, and posaconazole was 2%, 4%, and 11%, respectively. Echinocandin resistance ranged from 8% for anidulafungin to 15% for micafungin, with all isolates remaining susceptible to amphotericin B. Cross-resistance among azoles was observed in eight isolates. The most recent multicenter analysis (2020–2022)31 evaluated 185 isolates from ICU patients and reported very low azole resistance (0.8% for fluconazole; 1.6% for voriconazole), including two isolates resistant to both antifungals. Anidulafungin resistance was slightly higher (3.8%), and amphotericin B resistance was not detected. In recent years, fluconazole resistance in C. parapsilosis has been emerging in different countries, being subject of significant interest and concern.13 Hospital transmission appears to be a major factor in spreading resistant strains, as the emergence of resistance is not solely attributable to the selective pressure resulting from the use of antifungals.16 In the previously mentioned multicentric study performed in 2011–2012,19 4% of fluconazole resistance was found among the 55 C. parapsilosis isolates tested. In a prospective ICU colonization study (2020–2022),31 two out of 89 C. parapsilosis isolates were resistant to fluconazole, which corresponds to ∼2.2% resistance rate.
A very recent study analyzed 145 C. parapsilosis isolates collected from different biological and environmental products in Portugal in 2003–2007 and 2017–2024: eight fluconazole-resistant isolates (8.5% frequency) from the latter period were found, which contrasts with the absence of fluconazole-resistant isolates collected before 2007.33 The dominant mechanism is a mutation in ERG11, the Y132F substitution, which markedly reduces fluconazole susceptibility.
A prospective multicenter ICU study (three ICUs in Portugal) collected Candida isolates from 675 patients and tested them against fluconazole, voriconazole, amphotericin B, and anidulafungin. The overall rate of resistance to fluconazole was 2.7%, with three out of 133 C. albicans, two out of 89 C. parapsilosis and two out of 24 N. glabratus isolates identified as resistant. Only one C. albicans isolate was resistant to voriconazole, while three isolates from three species (C. albicans, C. tropicalis, and C. parapsilosis) were resistant to anidulafungin.31
The first documented case of C. auris isolated in Portugal showed that this isolate had resistance to fluconazole, itraconazole and voriconazole.24 In contrast, cases of C. auris candidemia reported in 2025 showed that all isolates were resistant to fluconazole, amphotericin B, and echinocandins.29
Superficial Candida infectionsNot only candidemia encompasses clinically relevant Candida infections in our country, but superficial infections also have an important role as well. In an 11-year retrospective study on vulvovaginal candidiasis (VVC) at the Centro Hospitalar Universitário Cova da Beira, covering 2011–2021,35 the prevalence of Candida in symptomatic women was ∼20.5%, while asymptomatic colonization was ∼16.1%. In that cohort, C. albicans was predominant (90.5% in symptomatic, 68.8% in colonized women), followed by N. glabratus (8.1%) and C. parapsilosis (3.4%) as the next most frequent non-C. albicans species. In a study focusing on VVC published in Portugal in 2022 that included 470 symptomatic and asymptomatic women,20 the incidence of VVC among women with vulvovaginitis was 74.4%. Furthermore, 63.7% of asymptomatic women were colonized with Candida species. In the study, C. albicans was the most common species identified (59%), followed by N. glabratus (27%). Eight distinct species were identified among the isolated Candida, with a similar distribution among colonized and infected participants. Of note, various isolates, especially of the most common species, showed low susceptibility towards fluconazole. Importantly, women with history of recurrent vaginal infections, those who use over-the-counter antifungals, oral contraceptive pills and non-cotton underwear were found to be at significantly higher risk of developing VVC frequently.20 In Portugal, recurrent vaginal candidiasis (rVVC) remains highly prevalent and recurrent in women of reproductive age. This clinical condition is defined as experiencing at least four distinct episodes of vaginal candidiasis within a 12-month period. Epidemiological estimates suggested an incidence of approximately 2854 cases per 100,000 females.45 Hence, accurate species identification, susceptibility testing and changes in specific behaviors may improve therapeutic outcomes and decrease recurrence episodes.
Regarding nail infections, and according to a multicentric study performed by the Portuguese Society of Dermatology and Venerology, comprising the years 2014–2016, from the 2375 fungal agents isolated, 13% were yeasts, being C. albicans and C. parapsilosis the most frequently isolated species, with 38.5% and 22% frequency, respectively.41
Research and development versus gaps and challengesIn addition to clinical investigations, several Portuguese groups have been engaged in diverse research areas related to Candida, from fundamental biology to applied innovation targeting a better knowledge of the pathogen itself, strategies for prevention of Candida colonization and/or infection and therapeutic approaches. Their work encompasses, for example, studies on biofilm structure,1,26,47 genomics,4,10,31,42 identification of new virulence factors,6,14,18,23,30,47 pathogenesis,2,25 application and development of new compounds with antifungal properties on Candida,7,8,21,32,40 and new therapeutical strategies,11,36 among others. The increasing number of groups working on Candida enhances its importance as pathogen and emphasizes how the Portuguese scientific community is committed in reducing, directly or indirectly, the mortality and morbidity associated to Candida infections. However, Portugal still has limited national data sets on candidiasis incidence, species-specific trends and resistance profiles, highlighting the urgent need for surveillance even for containment measures in healthcare settings. The non-mandatory notification of fungal infections and heterogeneous reporting hamper comprehensive epidemiology of this fungal agent. More data is needed to map species shifts, emerging resistance, and outcomes, particularly considering the changes in patient demographics and healthcare practices.
As advised by the Portuguese Association of Medical Mycology (ASPOMM), surveillance, prevention and innovation need to be integrated in a robust strategy, to build a comprehensive and sustainable response to fungal infections.43 Hence, from my perspective, the future management of Candida infections in Portugal will depend on the implementation of integrated strategies, as: (1) Rapid diagnostic methods and species identification using rapid tests with high sensitivity and specificity; (2) Molecular identification of the etiological agent by sequencing, especially from deep infections; (3) Enhanced and continuous surveillance with more frequent use of whole-genome sequencing for species identification, resistance profiling and detection of virulence traits; (4) Empirical therapy guided by local susceptibility data to both minimize resistance selection and provide timely antifungal therapy; (5) Interdisciplinary collaboration, addressing environmental and healthcare-related fungal threats, given the “One Health” context of these infections; (6) Implementation of robust infection control protocols, essential to improve patient outcomes and prevent outbreaks; (7) Mandatory notification of C. auris, given its potential to cause antifungal resistant outbreaks.
Recognizing Candida infection as a dynamic and evolving challenge, and strengthening surveillance and research, accordingly, may contribute to improved patient care and the development of evidence-based health policies and more effective healthcare planning.
FundingThis work was supported under the frame of iMed.ULisboa funding (UID/04138/2025) (https://doi.org/10.54499/UID/04138/2025).
Conflict of interestThe author declares no conflict of interest.
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