Changing Climate, Changing Candida: Environmental and Social Pressures on Invasive Candidiasis and Antifungal Resistance in Latin America

1. Introduction

Invasive candidiasis (IC) represents a growing threat in hospital settings, particularly in intensive care units (ICUs), where patient susceptibility facilitates the hematogenous spread of Candida spp. (1–3). Traditionally, Candida albicans has been the most frequently identified strains. However, in recent years, significant concern has emerged regarding non-albicans strains, such as Candida tropicalis, Candida parapsilosis, Nakaseomyces glabratus (formerly C. glabrata), and Candidozyma auris, which is a cause for great concern given their multidrug resistance to antifungal agents (1,3). These infections can manifest as candidemia or compromise deep organs such as the peritoneum, bones, or heart (4,5).

Its frequency has increased alarmingly in highly complex clinical settings, with a mortality rate that, in some series, exceeds 40%. It ranks between the fourth and fifth leading causes of healthcare-associated bloodstream infections, with the ICU being the place with the highest incidence of CI worldwide, with a rate of 5.5 to 7 cases per 1,000 admissions (2,6). In Europe, the incidence in the South of the continent was higher than in the North (5.29 vs. 3.77 per 100,000 inhabitants), which could be due to climatic variations, differences in the management of candidemia, and sociodemographic factors (7). In the United States, the rate of candidemia is 7 to 9 per 100,000 inhabitants, being higher in patients with risk factors such as age over 65, total parenteral nutrition (TPN), diabetes mellitus, diagnosis of hematological neoplastic diseases, or a history of recent hospitalization (8–10).

Various factors influence the epidemiology of this mycosis. Geographic region, environmental conditions, access to health services, and demographic characteristics of the population affect both the incidence and distribution of the strains involved, which could favor an increase in cases caused by non-albicans strains (11). In regions such as Asia and Latin America, infections by non-albicans species have a higher prevalence, with a predominance of C. tropicalis, C. auris, and C. parapsilosis, strains that are not only emerging more frequently but also have increasingly complex multi-drug resistance profiles (12,13). On the other hand, although historically most cases in high-income countries (Europe and North America) were attributed to C. albicans, recent data show an increase in infections caused by non-albicans strains, especially N. glabratus (7,13–16). This strain has been linked to elderly patients and sophisticated healthcare settings, suggesting that the transition to a more resistant candidiasis profile is a global phenomenon, not limited to resource-constrained environments (3,10,13).

2. Epidemiology of IC in Latin America

Although the epidemiology of CI in Europe and the United States is well documented, knowledge remains limited in Latin America; however, recent multicenter studies have begun to outline its regional scope. Between 2008 and 2010, a descriptive observational multicenter epidemiological surveillance study was conducted in 20 hospitals in seven Latin American countries, which reported an overall incidence of 1.18 cases per 1,000 hospital admissions (0.23 cases per 1,000 patient-days); the variation between countries was notable, with Argentina having the highest incidence (1.95 per 1,000 admissions) and Chile the lowest (0.33 per 1,000 admissions). Colombia, with data from a single center, recorded 1.96 cases per 1,000 admissions; Venezuela, 1.72 (range 1.04–2.90); Brazil, 1.38 (0.55–2.11); and both Ecuador and Honduras, 0.90 cases per 1,000 admissions (Ecuador: 0.30–1.10; Honduras: 0.88–0.98) (17,18).

Among the countries with the most robust data, Brazil stands out, where candidemia rates in ICUs have ranged from 1.2 to 2.49 cases per 1,000 admissions. In some specific series, alarming figures of up to 42.6 cases per 1,000 ICU admissions have been observed (19). Figure 1 shows the geographical distribution of the main Candida spp. isolated from patients in Latin America, highlighting the clear prevalence of C. albicans and regional variations in non-albicans strains. In terms of distribution by strain, more than 60% of cases correspond to non-albicans strains, with C. parapsilosis accounting for 20.5% and C. tropicalis for 15.3% of isolates, and some studies have reported mortality rates of up to 80% (19–21). Recently, Guinsburg et al. published a systematic review on candidemia in Brazil in 2024 that included 2,305 isolates from blood cultures, with C. albicans being the most frequent strain (37.2%), followed by C. parapsilosis (22.5%) and C. tropicalis (18,1 %) (22).

In Colombia, the incidence in ICUs was reported at 2.3 cases per 1,000 admissions (23). A retrospective descriptive observational cohort study conducted at a high-complexity hospital in Bogotá showed a significant increase in infections caused by non-albicans strains, which rose from 44% to 51% in a short period (24). The distribution of isolates in the country varies depending on the hospital. However, C. tropicalis usually ranks second in frequency, ranging from 17% to 23%, followed by C. parapsilosis, whose percentages range from 13% to 23% (23). A notable finding in Salinas' study (2022) was the increase in the isolation of N. glabratus, a strain typically associated with developed countries. This variation could be attributed to changes in comorbidities and demographic characteristics of the patients evaluated. However, the author does not propose additional hypotheses to explain this unusual behavior (24). In a multicenter observational and retrospective cohort study, C. auris was reported to be the second most isolated strain (26.1%), surpassed only by C. albicans (36.5%). This suggests a significant change in the epidemiological profile. However, the authors emphasize that, in the studied Colombian context, C. auris candidemia does not have a worse prognosis than that caused by other isolates, provided that adequate antifungal management and rigorous control of septic shock are ensured (25).

In Argentina, according to epidemiological estimation studies, the incidence varied between 1.15 and 2.25 cases per 1,000 hospital admissions, with a progressive mortality rate of between 40% and 50%; non-albicans strains predominate, accounting for 59.1% of infections, with C. parapsilosis (21.7%) and C. tropicalis (15.5%) being the most relevant (26,27). Peru reports an incidence of 2.04 cases per 1,000 hospital admissions and a mortality rate of 40%, similar to the regional average, and 70% of isolates correspond to non-albicans strains, with C. parapsilosis (25.3%) and C. tropicalis (24.7%) (17,28). In Venezuela, although published information is limited, hospital rates of 1.72 cases per 1,000 admissions have been reported, with a high proportion of infections caused by non-albicans strains (73.2%), predominantly C. tropicalis and C. parapsilosis; mortality has varied, ranging from 3% to 76% (17,20,29). Paraguay has one of the lowest incidences in the region, with 0.74 cases per 1,000 hospital admissions and an approximate mortality rate of 30%; the most common isolates are C. albicans (34.4%), C. parapsilosis (30.4%), and C. tropicalis (25.4%) (30). In Uruguay, although the available data are less complete, a study in a hospital in Montevideo found that candidemia accounted for 2.83% of all positive blood cultures, with the predominant isolates being N. glabratus (32.74%), C. albicans (27.43%), and C. parapsilosis (23,01 %), which contrasts with the patterns observed in other countries in the region (31,32). In Mexico, there is an incidence of 1.93 cases per 1,000 hospital admissions; the distribution of isolates indicates a predominance of C. albicans (60%), followed by C. tropicalis (26%) and N. glabratus (13.5%); 30-day mortality has been estimated at 40% (33–35) In Central America and the Caribbean, information is scarce; in Trinidad and Tobago, for example, approximately 70 cases of candidemia are reported each year, although detailed data on the strains involved and clinical outcomes are not available (36).

3. Risk factors for IC in Latin America

This type of mycosis includes both candidemia (infection of the bloodstream) and deep infections in organs or tissues that are normally sterile, such as peritoneal fluid, the central nervous system, or heart valves (1,4,5). The risk factors for developing IC in Latin America largely coincide with those described worldwide. In general, they consist of conditions that weaken the immune system or alter anatomical barriers, facilitating the entry and proliferation of Candida spp. (3,4,6). The main risk factors include prolonged stay in the ICU, use of TPN, exposure to broad-spectrum antibiotics, gastrointestinal surgery with intestinal opening, and prolonged immunosuppression (1,3,6,42,43).

A multicenter case-control study conducted in non-neutropenic critically ill patients from seven intensive care units (ICUs) at three university hospitals in Colombia identified the following independent risk factors associated with the development of candidemia: a hospital stay ≥ 25 days (OR 5.33; 95% CI 2.6–10.9), previous use of meropenem (OR 3.75; 95% CI 1.86–7.5), previous abdominal surgery (OR 2.9; 95% CI 1.39–6.06), and hemodialysis treatment (OR 3.35; 95% CI 1.5–7.7) (44).

Immunosuppression, whether secondary to underlying diseases (cancer, organ transplantation, or chronic renal failure) or immunosuppressive treatments (chemotherapy, corticosteroids, or biological drugs), is a key factor. In addition, the presence of multiple comorbidities in the same patient significantly increases the risk of invasive infection by Candida spp. (45,46). A systematic review with meta-analysis that evaluated the determinants for invasive Candida infection in critically ill patients showed that, apart from the classic factors, the use of broad-spectrum antibiotics (OR 5.6; 95% CI 3.6–8.8), blood transfusions (OR 4.9; 95% CI 1.5–16.3), Candida colonization (OR 4.7; 95% CI 1.6–14.3), the presence of a central venous catheter (OR 4.7; 95% CI 2.7–8.1), and TPN (OR 4.6; 95% CI 3.3–6.3) were independently associated with an elevated risk, while demographic factors lacked statistical significance, highlighting that ICU interventions and underlying comorbidities are the main drivers of this type of infection (47). Therapeutic management in Latin America faces growing challenges due to the increase in infections caused by non-albicans strains, many of which are resistant to commonly used antifungal agents. For this reason, international and regional guidelines agree in recommending the initiation of treatment with echinocandins as first-line therapy while the identification of the agent and its susceptibility profile is completed (48,49). In addition, it is essential to assess the potential involvement of target organs, given that controlling the source of infection, whether through catheter removal, abscess drainage, or surgical debridement, is key to achieving complete resolution of the clinical picture (3,6,45).

4. Diagnosis of IC in Resource-Limited Settings

The timely diagnosis of IC represents one of the main clinical challenges, especially in resource-limited settings such as those found in many Latin American countries (50). Although isolation of the fungus in blood cultures or cultures from sterile sites and histopathological identification of yeasts in tissue constitute the reference method, this method has variable sensitivity (20%–70%) and prolonged detection times, usually 3 to 5 days (51,52). These delays limit the early initiation of targeted treatment, resulting in poorer clinical outcomes. To overcome these diagnostic limitations, complementary tests have been incorporated that improve sensitivity and shorten waiting times; among them, mass spectrometry (MALDI-TOF) stands out for accurately identifying Candida spp. in a matter of minutes from cultures, in contrast to conventional methods such as VITEK®2 or API, which require an additional 24 to 48 hours after growth and can exhibit up to 72% identification errors in rare strains (51,53,54). Table 1 presents a comparison of the diagnostic methods available for IC, detailing their main advantages, limitations, and availability in Latin America.

Other useful tools include immunological tests, such as (1,3)-β-D-glucan (BDG), a pan-fungal marker that has shown 92% sensitivity, although its specificity is limited, as it can give positive results in infections caused by other fungi (46,51,55). In general, it is recommended to use it as a complementary tool to support diagnosis or to discontinue empirical antifungal treatments when clinical suspicion decreases (56). On the other hand, the use of molecular tests such as quantitative PCR in blood has shown good diagnostic performance, with sensitivity and specificity greater than 90% (57). In 2019, the MICAFEM study, conducted in 27 Spanish ICUs, was published. It compared multiplex PCR with blood cultures and abdominal fluid cultures in 176 critically ill patients at high risk of Candida infection. The PCR detected 9.1% of cases, compared to 8.0% for blood cultures and 65.3% for abdominal cultures. Only a Candida risk score ≥ 3 was significantly associated with combined positive results (OR 4.15; p = 0.03). In this group of patients, this test did not improve diagnostic performance (58).

The T2Candida panel is a relatively new technology that uses magnetic resonance imaging to directly detect Candida DNA in blood samples, without the need for prior culture. This test provides results in 3–5 hours, with a sensitivity of 91% and a specificity of 99%. Its main limitation is that it only detects five common strains and does not include C. auris (59–61). In research, the T2Cauris panel detects C. auris in inguinal swabs with a limit of 5 CFU/mL and provides 89% sensitivity and 98% specificity. However, data on its performance in whole blood have not yet been published (62,63). Other serological methods, such as detection of mannan antigen and anti-mannan antibodies, offer a combined sensitivity of 83% and specificity of 86% for C. albicans; however, they are less effective when evaluating other Candida strains (51,64).

Situation in Latin America: Challenges, Barriers, and Obstacles

In the Latin American context, there are significant challenges to implementing these advanced methods. The study by Falci et al. found that, by 2019, only 9% of the laboratories surveyed in the region met the minimum standards of excellence in clinical mycology (65). The availability of BDG is very limited, reaching only 17% of diagnostic centers. Molecular diagnostic techniques are accessible in 20%–26% of laboratories, and MALDI-TOF is only installed in 20%, mainly in large cities. Meanwhile, the T2Candida panel is not yet widely available in the region (50,65,66).

In most Latin American hospitals, blood cultures remain the main diagnostic tool, despite their low sensitivity and the long time required to obtain results. This limitation can delay the initiation of appropriate antifungal treatment and often lead to prolonged and inappropriate empirical use of antifungals, which promotes the development of resistance (50,65). In addition, there are institutional barriers, deficiencies in public policies, and limitations in the allocation of state budgets, as the best-equipped laboratories are concentrated in major urban centers, leaving hospitals in intermediate or rural areas without access to advanced diagnostic techniques (50,65,66). The shortage of personnel trained in clinical mycology and the lack of up-to-date epidemiological data are significant limitations, given that most of the information comes from Brazil, Colombia, Argentina, Mexico, and Chile, while in the Caribbean, Central America, and other Andean areas, no recent studies are available, underscoring the need to strengthen regional surveillance and diagnostic capabilities (17,18,27,31,35,36,67,68).

In Latin America, the identification of the emerging yeast C. auris continues to be problematic, as automated biochemical methods often confuse it with Candida haemulonii, Rhodotorula glutinis, or Saccharomyces cerevisiae. Even advanced commercial systems, such as the VITEK®2 system, show limitations in their accuracy, and although there are more affordable selective media, such as CHROMagar Candida Plus, which could facilitate its detection, their implementation is not yet widespread (69–71). It has been observed that, in the region, countries such as Colombia have established national reference centers that allow for detailed registration and confirmation of strains identification using proteomic or molecular methods (MALDI-TOF or genetic sequencing), in an effort to strengthen epidemiological surveillance and optimize the health response (70,72).

6. Impact of Climate Change on Fungal Infections (Invasive Candidiasis)

Climate change is a global phenomenon that is significantly transforming public health patterns, including the emergence and spread of fungal infections such as IC. The sustained increase in atmospheric and ocean temperatures, together with changes in humidity levels and the growing frequency of extreme weather events, is altering the ecological behavior of fungi, favoring the adaptation and emergence of thermotolerant and resistant pathogenic strains (105,106). From an environmental perspective, global warming has altered the distribution and survival of fungi in habitats that were previously hostile to their development. This transformation not only affects fungal diversity and the nutrient cycle, but more worryingly, it has created conditions favorable for the natural selection of strains capable of surviving increasingly high temperatures (107).

One of the most relevant hypotheses to explain the emergence of C. auris suggests climate change as a key evolutionary driver. In 2019, Casadevall and colleagues proposed the “thermal selection hypothesis,” according to which progressive environmental warming has favored the adaptation of certain environmental fungi to higher temperatures, allowing them to overcome the thermal barrier that historically limited their ability to infect humans. This phenomenon is not exclusive to C. auris, as other emerging strains, such as Cryptococcus deuterogattii, have also shown similar patterns of adaptation (108,109).

In addition to climate change, other environmental and anthropogenic factors have been associated with the emergence of Candidozyma auris and other resistant fungi. The indiscriminate use of antifungals in agriculture, especially azoles, has exerted selective pressure on environmental microorganisms. Sharma and Kadosh (2023) found that these compounds, widely used in fruit and vegetable cultivation, may have contributed to the emergence of resistant strains in the environment, which subsequently migrate to the hospital environment (110). This hypothesis of thermal selection has been proposed in other emerging fungi (111,112).

Another emerging hypothesis suggests the possible role of wild fauna as a passive vector in the spread of resistant fungi. From a One Health perspective, García-Bustos and colleagues proposed that migratory birds could act as carriers of C. auris, facilitating its transit from natural environments to rural or urban areas, where the fungus could establish itself and eventually enter the hospital environment. This integrative approach, which links human, animal, and environmental health, is essential for understanding the complex web underlying emerging mycoses (33,113,114).

Forced migration, overcrowding, shortages of drinking water, and limited access to healthcare in refugee camps significantly increase the vulnerability of these populations to invasive fungal infections. Added to this is the threat to food security, exacerbated by climate change, which can lead to malnutrition and, with it, a marked increase in the incidence of infectious diseases, including fungal infections. In addition, extreme weather events such as floods create humid environments conducive to the germination and spread of fungal spores. These conditions favor accelerated fungal growth, facilitating the large-scale dispersion of spores and mycotoxins (102,107–109,115–117).

Overall, it is recognized that various factors contribute to the emergence of invasive mycoses such as C. auris. These include the indiscriminate use of antifungals in agriculture, water contamination, inadequate hospital practices, and forced population displacement. Added to this are the interactions between degraded ecosystems, wild fauna, and the growth of vulnerable human populations, creating a scenario favorable to the emergence and spread of resistant pathogenic fungi (97,102,110,114,118,119).

7. Access to Health Services and Inequalities in the Region

Socioeconomic inequalities and differences in access to healthcare services in Latin America have a direct and significant impact on the management of fungal infections, including IC. The gap between public and private healthcare systems, as well as between urban and rural areas, and between countries with different levels of development, leads to profoundly unequal clinical scenarios. In many cases, the patient's prognosis depends more on their geographical location or socioeconomic status than on the natural course of the disease (27,31,34,35,66). In Brazil, for example, studies have shown that the incidence of candidemia in public hospitals is more than double that in private institutions, with rates of 2.42 versus 0.91 cases per 1,000 ICU admissions, respectively. In addition, the distribution of strains differs depending on the type of institution: while C. parapsilosis predominates in public hospitals, N. glabrata is more common in private hospitals (24,66,120).

Access to antifungal treatments in Latin America also presents marked inequalities. In many countries in the region, FCZ and AmB deoxycholate are the only widely available antifungals, even though they are not always the most appropriate therapeutic option. First-line drugs, such as echinocandins or lipid formulations of AmB, have limited availability, particularly in public hospitals and rural areas. Meanwhile, 5-flucytosine—essential for the treatment of certain serious fungal infections—is available in only 20% of the hospitals evaluated (50). The prices of antifungal drugs also vary considerably between countries in the region, with costs ranging from $1 to $31 per unit of FCZ. This variation can be a significant obstacle for many patients, especially when healthcare systems do not provide comprehensive coverage for antifungal treatment (121). In Colombia, for example, the healthcare system largely covers the costs of antifungal treatments. However, the availability of medications remains uneven. While cities such as Bogotá and Medellín have a more adequate supply, many rural regions face critical shortages, limiting timely access to effective therapies (122).

In the context of an IC, a key factor is the continuing education of healthcare personnel. In centers with greater resources, access to specialized training in fungal infections is more common, which translates into more appropriate clinical management by professionals. In contrast, in settings with less access to training, significant knowledge gaps persist. In this scenario, virtual education strategies (e-learning) become highly relevant for expanding access to training. However, there are barriers that can limit its effective implementation, such as poor internet connectivity, limited proficiency in other languages, and lack of knowledge or low familiarity with technological tools by some healthcare professionals (123–126).

In response to this situation, various regional initiatives have been launched to reduce existing gaps. The Pan American Health Organization (PAHO) and the Global Action Fund for Fungal Infections (GAFFI) have established strategic alliances to improve access to essential antifungals, standardizing clinical protocols, and strengthening the diagnostic capabilities of health systems in the region (127). The use of telemedicine and virtual education is also promoted as key tools for training healthcare personnel in remote areas. However, these efforts face various challenges, including poor connectivity, language barriers, and unequal access to digital technologies, which limits their effective implementation in some regions (126,128).

Reducing mortality from IC in the region requires much more than strengthening treatment options. It involves adopting a comprehensive approach that addresses structural barriers in the health system, improves resource distribution, and ensures equitable access to diagnosis and antifungal treatment at all levels of care.

8. Impact of Housing and Environment on IC in Latin America

Although IC has been extensively studied in hospital settings, its relationship with environmental factors and living conditions in Latin America remains poorly explored. Unlike other invasive mycoses, such as histoplasmosis or cryptococcosis, in which the link with the natural environment is well documented, candidiasis has traditionally been considered a nosocomial infection. However, recent data suggest that the physical environment and living conditions may also influence the vulnerability of certain population groups to this infection (129,130). Although Candida is not a typical environmental fungus like Aspergillus or Cryptococcus, its presence has been documented in ecological niches outside the human environment. For example, strains such as C. albicans have been isolated in soil and vegetables, C. tropicalis in rivers and agricultural areas, and P. kudriavzevii in animals. In the particular case of C. auris, its detection in freshwater and marine bodies in coastal areas of Colombia reinforces the hypothesis that certain environmental settings could act as reservoirs or points of contact with humans, especially in populations with limited sanitary conditions (131,132).

One of the most important aspects from a social and environmental point of view is the quality of housing. In many urban areas of Latin America, informal settlements and marginalized neighborhoods lack basic services such as drinking water, adequate ventilation, and sanitation. These conditions favor the proliferation of opportunistic microorganisms and can facilitate colonization by yeasts, especially in humid or contaminated environments. Although the direct relationship between these conditions and IC has not yet been fully demonstrated, overcrowding and poor housing conditions have been associated with an increased risk of superficial infections, such as oral and vulvovaginal candidiasis. In addition, the high prevalence of chronic noncommunicable diseases in contexts of poverty—such as diabetes mellitus and chronic kidney disease—significantly increases the risk of invasive Candida infections (131,132).

Other Invasive Mycoses

The influence of the environment on invasive aspergillosis is closely related to exposure to spores present in the air, especially in contexts where construction work is being carried out or where ventilation systems are inadequate. These factors have been implicated in hospital outbreaks, as they facilitate the spread of Aspergillus conidia in clinical areas (18,35). In addition, there are isolated studies on other mycoses that support this perspective. In Brazil, for example, Cryptococcus gattii has been isolated from household dust in wooden houses located in the Amazon region, demonstrating that indoor spaces can also act as reservoirs for pathogenic fungi. Although such a direct link has not been established in the case of Candida, moisture accumulation and environmental contamination could play a role in its spread or in increasing the host's vulnerability (133).

Gaps in the literature and emerging hypotheses: in general, there are few studies exploring the link between housing conditions and IC, as most publications focus exclusively on hospital settings. However, in Argentina, there has been evidence of variation in the distribution of Candida strains causing invasive infections, associated with socioeconomic factors such as income level in dollars and type of healthcare institution (public or private) (66).

9. Conclusions

IC has become a significant threat to public health in Latin America. Its increasing incidence, especially in ICUs, and the high mortality rate associated with it highlight a clinical urgency that cannot be ignored. Although historically attributed to C. albicans, there is currently an epidemiological shift toward non-albicans strains, many of which are resistant to the most commonly used antifungal agents.

The emergence of C. auris, characterized by its remarkable ability to spread, resistance to multiple antifungals, and persistence in the environment, has highlighted the structural weaknesses of health systems in the region. Gaps in diagnosis, limited availability of effective therapies, and unequal access to medical care have left many populations in a vulnerable situation, especially in public health systems, rural areas, or impoverished communities.

In addition to these clinical and technical issues, social and environmental factors amplify the impact of fungal infections. Climate change, the indiscriminate use of antifungals in agriculture, poor housing conditions, and structural inequalities in healthcare systems create an environment favorable for the emergence of resistant pathogens and the spread of serious fungal infections.

To address this challenge, it is essential to adopt a comprehensive and coordinated approach that transcends the strictly hospital setting. It is necessary to strengthen mycological surveillance systems, ensure equitable access to advanced diagnostic tests and state-of-the-art antifungals, and train health personnel at all levels of care.

Regional research must be intensified, especially in countries where information on IC is limited, to obtain a more accurate picture of its actual burden and local characteristics. Only on this basis will it be possible to design effective, contextualized, and evidence-based public policies. It is time to look beyond the microscope and move toward solutions that integrate science, public health, and social justice.