Invasive candidiasis (IC) in Latin America is undergoing a significant epidemiological shift, increasingly driven by non-albicans strains such as Candida tropicalis, Candida parapsilosis, and Candidozyma auris. These pathogens often exhibit multidrug resistance, which complicates treatment and increases mortality. Diagnostic limitations, particularly in rural and public hospitals, delay detection and hinder the provision of rapid care. Environmental pressures, such as climate change and the widespread use of azoles in agriculture, appear to favor the selection of resistant and thermotolerant strains. Migratory birds may also play a role in the environmental transmission of pathogenic fungi. These factors are amplified by socioeconomic inequalities that restrict access to diagnostics and first-line antifungals. To help mitigate this emerging challenge, a One Health-oriented framework combining integrated environmental surveillance, robust antifungal-stewardship programmers, broader diagnostic access, and coordinated cross-sector public health actions should be developed. Reinforcing these pillars could lessen the regional burden of IC and slow the advance of antifungal resistance.

Invasive candidiasis (IC) in Latin America is undergoing a significant epidemiological shift, increasingly driven by non-albicans strains such as Candida tropicalis, Candida parapsilosis, and Candidozyma auris. These pathogens often exhibit multidrug resistance, which complicates treatment and increases mortality. Diagnostic limitations, particularly in rural and public hospitals, delay detection and hinder the provision of rapid care. Environmental pressures, such as climate change and the widespread use of azoles in agriculture, appear to favor the selection of resistant and thermotolerant strains. Migratory birds may also play a role in the environmental transmission of pathogenic fungi. These factors are amplified by socioeconomic inequalities that restrict access to diagnostics and first-line antifungals. To address this growing threat, we propose a “One Health” approach that integrates environmental surveillance, antifungal management, equitable access to diagnostics, and coordinated public health strategies. Strengthening these areas is essential to reduce the burden of IC and limit the spread of antifungal resistance in the region.

Diagnostic failure in invasive fungal infections (IFIs) remains a relevant and underrecognized cause of mortality, morbidity, delayed therapy, unnecessary antifungal exposure, and pharmacological selective pressure. Although major advances have been achieved in biomarkers, rapid diagnostic tests, molecular methods, imaging studies, and microbiological identification, timely diagnosis continues to be influenced by the interaction among host factors, pathogen-related factors, diagnostic tools, and healthcare system–related factors. This narrative review analyzes diagnostic failure in IFIs as a dynamic process that includes delayed, incorrect, and incomplete diagnosis. It examines its determinants and consequences in high-risk populations—critically ill patients, patients with hematologic diseases or hematopoietic stem cell transplant recipients, and neonates—as well as in invasive candidiasis, aspergillosis, mucormycosis, cryptococcosis, endemic mycoses, and infections caused by rare or emerging fungi. It also reviews how delayed sampling, decontextualized interpretation of biomarkers, incomplete microbiological identification, absence of antifungal susceptibility testing when clinically relevant, and fragmentation between clinical and laboratory teams contribute to adverse outcomes. Finally, it proposes a diagnostic-centered antifungal stewardship framework (AFSP-Dx) based on syndromic bundles, population-specific diagnostic algorithms, 48–72 h reassessment, and auditable indicators intended to support earlier recognition, more precise therapeutic decisions, and rational antifungal use.

Invasive candidiasis (IC), characterized by the most common clinical manifestation of candidemia, is a fungal infection with a high mortality rate and a significant impact on global public health. It is estimated that each year there are between 227,000 and 250,000 hospitalizations related to IC, with more than 100,000 associated deaths. In Latin America and the Caribbean (LA&C), the absence of a standardized surveillance system has led to multicenter studies documenting incidences ranging from 0.74 to 6.0 cases per 1000 hospital admissions, equivalent to 50,000–60,000 hospitalizations annually, with mortality rates of up to 60% in certain high-risk groups. Armed conflicts and structural violence in LA&C cause forced displacement, the collapse of health systems, and poor living conditions—such as overcrowding, malnutrition, and lack of sanitation—which increase vulnerability to opportunistic infections, such as IC. Insufficient specialized laboratories, diagnostic technology, and trained personnel impede pathogen identification and delay timely initiation of antifungal therapy. Furthermore, the empirical use of broad-spectrum antibiotics and the limited availability of echinocandins and lipid formulations of amphotericin B have promoted the emergence of resistant non-albicans strains, such as Candida tropicalis, Candida parapsilosis, and, in recent outbreaks, Candidozyma auris.

Invasive fungal infections (IFIs) are associated with high morbidity and mortality, particularly in immunocompromised or critically ill patients and in those with complex comorbidities. Despite advances in mycological diagnosis and antifungal therapy, outcomes remain poor in a significant proportion of patients. In clinical practice, a poor response is often attributed to microbiological resistance. This interpretation may lead to empirical treatment escalation, combination therapy without a clear indication, increased toxicity, clinically relevant drug–drug interactions, and inefficient use of healthcare resources. However, therapeutic failure rarely results from a single mechanism. More often, it reflects the interaction among host vulnerability, pathogen characteristics, delayed, incomplete, or incorrect diagnosis, insufficient antifungal exposure, and inadequate source control. This narrative review presents a structured clinical approach to evaluating suboptimal responses in IFIs without attributing them solely to antifungal resistance. It examines cross-cutting determinants and specific patterns associated with invasive aspergillosis, invasive candidiasis and persistent candidemia, cryptococcal meningitis, mucormycosis, infections caused by rare filamentous fungi, and disseminated endemic mycoses. It also presents clinical algorithms, checklists, and potential quality indicators to distinguish true from apparent failure, identify modifiable factors, and support transparent clinical decision-making within antifungal stewardship programs. The proposed framework supports the assessment of non-response through systematic diagnostic and therapeutic reassessment, timely source control, and identification of modifiable gaps in care.

Invasive fungal diseases remain an important cause of severe illness and death worldwide, and timely recognition and effective treatment are still difficult to achieve