RARE DISEASE
Invasive candidiasis
Invasive candidiasis
Invasive candidiasis
Synonyms: Disseminated candidiasis, Systemic candidiasis
Synonyms: Disseminated candidiasis, Systemic candidiasis
Synonyms: Disseminated candidiasis, Systemic candidiasis
Drug discovery
13
drugs
With orphan designations
Overview
Invasive candidiasis is a life-threatening fungal infection caused by Candida species, primarily affecting immunocompromised individuals and hospitalized patients. It manifests as candidemia or deep-seated infections in sterile sites (e.g., abdomen, heart, brain). Diagnosis relies on blood cultures and non-cultural methods (e.g., β-D-glucan), while treatment involves systemic antifungals tailored to resistance patterns and host factors [1][2][11]. Mortality remains high despite advances in antifungal therapies.
Population
High-risk groups: ICU patients, those with central venous catheters, abdominal surgery recipients, immunocompromised individuals (e.g., hematologic malignancies, transplants), and neonates [1][5][12][17].
Emerging risk: Injection drug use contributors to rising candidemia cases in younger adults [12].
Burden
Incidence: ~25,000 annual U.S. cases (3–5 per 100,000 globally) [5][12].
Mortality: 25–55% in-hospital mortality (attributable mortality: 19–24%) [4][9][12].
Costs: U.S. direct medical costs exceed $1.2 billion annually; ICU stays increase by 3–13 days per case [4][12][17].
Resistance: Rising echinocandin resistance in C. glabrata (3%) and pan-resistant C. auris outbreaks [5][12].
Therapies
First-line: Echinocandins (caspofungin, micafungin) for critically ill patients or azole-resistant strains [2][8].
Alternatives: Fluconazole for stable patients with susceptible isolates; lipid-based amphotericin B for refractory cases [3][8].
Duration: Minimum 14 days post-negative blood cultures and symptom resolution; catheter removal strongly recommended [2][3].
Categories: rare infectious diseases
Research Papers
5,292 drug discovery papers about Invasive candidiasis, with 1 first-in-class and 12 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
5,292 drug discovery papers about Invasive candidiasis, with 1 first-in-class and 12 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-14 | Epigenetic repression of IL-1β by C1QBP restricts Dectin-1-mediated host defense against murine invasive candidiasis
Invasive candidiasis, predominantly caused by Candida albicans, threatens immunocompromised individuals with high mortality. Dendritic cell-derived interleukin-1β, orchestrated via Dectin-1-mediated β-glucan recognition, is central to antifungal defense. While the Dectin-1/Syk/CARD9 axis governing Il1b transcription is defined, the epigenetic regulatory mechanisms remain elusive. Here, we identify Complement C1q binding protein (C1QBP) as a critical negative regulator of Dectin-1-mediated interleukin-1β production. C1QBP sequesters phosphorylated protein kinase C δ in the cytoplasm, preventing its nuclear transport. Nuclear phosphorylated-PKCδ activates the RNF20/RNF40 ubiquitin ligase complex, which recruits the methyltransferase DOT1L to catalyze histone H3 lysine 79 trimethylation at the Il1b locus to promote its transcription. DC-specific C1QBP depletion enhances interleukin-1β secretion, amplifies protective T helper 17 cell responses, and improves host resistance to systemic C. albicans infection in mice. Collectively, our findings establish C1QBP as a key checkpoint in a PKCδ-dependent epigenetic pathway that constrains antifungal immunity, highlighting its therapeutic potential for invasive fungal diseases. Engagement of Dectin-1 on dendritic cells drives IL-1β production and is a critical component of the immune response to invasive candidiasis. Here the authors show epigenetic repression of IL-1β by a complement binding protein can restrain the dectin1 driven immune response in a murine model of invasive candidiasis.
2026-08-14 | First Reported Neonatal Invasive Candidozyma auris (Candida auris) Infection in Brazil: Successful Management, Evolving Amphotericin B Resistance, and Infection Containment.
To describe the first neonatal invasive Candida auris infection in Brazil and its successful clinical and infection control management. Retrospective description of the clinical course, microbiological findings, antifungal susceptibility evolution, and follow-up of an extremely preterm infant. A 25 + 4-week male neonate developed bloodstream and urinary C. auris infection during the first week of life. Progressive amphotericin B resistance in urine isolates required the addition of fluconazole. No secondary NICU cases occurred. Early diagnosis, serial susceptibility testing, and immediate containment measures enabled successful treatment and prevented nosocomial spread.
2026-08-12 | Candidalysin at the epithelial-systemic interface: mechanistic evidence, critical-care relevance, and translational opportunities in invasive candidiasis
Invasive candidiasis remains a stubborn source of morbidity and mortality in critically ill and immunocompromised patients. One reason progress has been slow is that the route from epithelial colonization to bloodstream or deep-organ infection is still described with more confidence than the evidence often allows. Candidalysin, a 31-amino-acid amphipathic peptide released from the Ece1 precursor by Candida albicans hyphae, is well established as a driver of epithelial damage and mucosal immune activation. Its contribution to invasive disease is far less certain. Recent work has broadened the molecular framework for candidalysin biology. Host-binding studies have identified sulfated glycosaminoglycans and other candidate partners. Biophysical studies have refined models of peptide polymerization, membrane insertion, and host membrane repair. Infection models have linked candidalysin to intestinal epithelial barrier failure, catheter persistence, macrophage escape, neutrophil remodeling, commensal fitness, and protective Th17 immunity. These observations sit at different distances from human invasive candidiasis: some are biochemical or cell-based, some are supported by organotypic or animal models, and only a small subset currently has human diagnostic or clinical correlation. In this review, we separate these evidence layers and argue that candidalysin should be treated as a candidate biomarker or adjunctive target for selected toxin-producing Candida albicans infections, not as a general explanation for invasive candidiasis.
2026-08-11 | Mitochondrial characteristics of echinocandin tolerance and resistance in Candida glabrata and Candida krusei.
Candidiasis, especially candidemia, is one of the most common invasive fungal infections. With the increase of risk factors such as tumors, its high incidence and high mortality rate pose a significant challenge to public health. Echinocandins, as first-line drugs for candidemia, have their clinical efficacy severely weakened by the emergence of tolerant or resistant strains such as Candida glabrata and Candida krusei. The study evaluated the changes in mitochondrial phenotype (intracellular ATP levels, mitochondrial membrane potential, mitochondrial superoxide levels, and intracellular ROS levels), proteomic, metabolomic, and genomic in C. glabrata and C. krusei. By analyzing strains with different susceptibility profiles, the study found that echinocandin tolerant or resistant strains displayed significant upregulation of ATP levels and unique metabolic adaptations. Quantitative proteomics identified differentially expressed proteins associated with mitochondrial function and energy metabolism. Metabolomic analysis further revealed distinct profiles linking resistance to alterations in purine metabolism and oxidative phosphorylation. Additionally, genomic sequencing of the resistant strains highlighted mutations in key genes involved in ATP binding. These findings highlight the mitochondrial characteristics in echinocandin tolerance and resistance in C. glabrata and C. krusei, providing valuable insights into potential pathways for future therapeutic interventions targeting resistant Candida species.
2026-08-10 | Slt2 kinase of the cell wall integrity pathway is required for Fks2-specific echinocandin resistance in Candida glabrata.
Candida glabrata is an opportunistic yeast that causes invasive infections in immunocompromised individuals. Echinocandin antifungals are first-line agents in the treatment of invasive candidiasis and act by inhibiting fungal cell wall synthesis by targeting β-1,3-glucan synthase. Echinocandin resistance is primarily associated with mutations in FKS1 or FKS2, which encode for the catalytic subunit (Fks1 or Fks2) of the targeted glucan synthase. The cell wall integrity (CWI) pathway, including Slt2 kinase, is known to mediate tolerance to antifungal drugs, but its role in resistance is not completely defined. Here, we observed that disruption of SLT2 abrogated echinocandin resistance due to FKS2, but not FKS1, mutation in C. glabrata. As expected, reintroduction of plasmid-borne SLT2 restored elevated MICs of fks2 mutants. RT-qPCR revealed that loss of SLT2 led to decreased FKS2 expression levels in wild-type and echinocandin-resistant strains following echinocandin exposure. In conclusion, the CWI pathway and Slt2 comprise a primary control mechanism for FKS2-mediated echinocandin resistance in C. glabrata.IMPORTANCEThe higher rates of acquired antifungal resistance exhibited by Candida glabrata merit further understanding of resistance mechanisms including fungal regulation of drug target genes and enzymes. Here, we focused on a fungal tolerance pathway, the cell wall integrity pathway, and its requirement in C. glabrata echinocandin antifungal resistance. Interestingly, we found that targeting the pathway through disruption of a key protein, Slt2, reversed echinocandin resistance within one subset of resistant strains (fks2 mutants) but not another (fks1 mutants). Gene expression studies demonstrated the requirement of SLT2 for full FKS2 gene expression following echinocandin treatment. Overall, we discovered that Slt2 is specifically required for Fks2-mediated echinocandin resistance through partial regulation of FKS2 expression. This study provides further insight into the regulation of drug target genes in C. glabrata and provides a possible therapeutic target for echinocandin-resistant infections caused by mutation of FKS2.
2026-08-14 | Epigenetic repression of IL-1β by C1QBP restricts Dectin-1-mediated host defense against murine invasive candidiasis
Invasive candidiasis, predominantly caused by Candida albicans, threatens immunocompromised individuals with high mortality. Dendritic cell-derived interleukin-1β, orchestrated via Dectin-1-mediated β-glucan recognition, is central to antifungal defense. While the Dectin-1/Syk/CARD9 axis governing Il1b transcription is defined, the epigenetic regulatory mechanisms remain elusive. Here, we identify Complement C1q binding protein (C1QBP) as a critical negative regulator of Dectin-1-mediated interleukin-1β production. C1QBP sequesters phosphorylated protein kinase C δ in the cytoplasm, preventing its nuclear transport. Nuclear phosphorylated-PKCδ activates the RNF20/RNF40 ubiquitin ligase complex, which recruits the methyltransferase DOT1L to catalyze histone H3 lysine 79 trimethylation at the Il1b locus to promote its transcription. DC-specific C1QBP depletion enhances interleukin-1β secretion, amplifies protective T helper 17 cell responses, and improves host resistance to systemic C. albicans infection in mice. Collectively, our findings establish C1QBP as a key checkpoint in a PKCδ-dependent epigenetic pathway that constrains antifungal immunity, highlighting its therapeutic potential for invasive fungal diseases. Engagement of Dectin-1 on dendritic cells drives IL-1β production and is a critical component of the immune response to invasive candidiasis. Here the authors show epigenetic repression of IL-1β by a complement binding protein can restrain the dectin1 driven immune response in a murine model of invasive candidiasis.
2026-08-14 | First Reported Neonatal Invasive Candidozyma auris (Candida auris) Infection in Brazil: Successful Management, Evolving Amphotericin B Resistance, and Infection Containment.
To describe the first neonatal invasive Candida auris infection in Brazil and its successful clinical and infection control management. Retrospective description of the clinical course, microbiological findings, antifungal susceptibility evolution, and follow-up of an extremely preterm infant. A 25 + 4-week male neonate developed bloodstream and urinary C. auris infection during the first week of life. Progressive amphotericin B resistance in urine isolates required the addition of fluconazole. No secondary NICU cases occurred. Early diagnosis, serial susceptibility testing, and immediate containment measures enabled successful treatment and prevented nosocomial spread.
2026-08-12 | Candidalysin at the epithelial-systemic interface: mechanistic evidence, critical-care relevance, and translational opportunities in invasive candidiasis
Invasive candidiasis remains a stubborn source of morbidity and mortality in critically ill and immunocompromised patients. One reason progress has been slow is that the route from epithelial colonization to bloodstream or deep-organ infection is still described with more confidence than the evidence often allows. Candidalysin, a 31-amino-acid amphipathic peptide released from the Ece1 precursor by Candida albicans hyphae, is well established as a driver of epithelial damage and mucosal immune activation. Its contribution to invasive disease is far less certain. Recent work has broadened the molecular framework for candidalysin biology. Host-binding studies have identified sulfated glycosaminoglycans and other candidate partners. Biophysical studies have refined models of peptide polymerization, membrane insertion, and host membrane repair. Infection models have linked candidalysin to intestinal epithelial barrier failure, catheter persistence, macrophage escape, neutrophil remodeling, commensal fitness, and protective Th17 immunity. These observations sit at different distances from human invasive candidiasis: some are biochemical or cell-based, some are supported by organotypic or animal models, and only a small subset currently has human diagnostic or clinical correlation. In this review, we separate these evidence layers and argue that candidalysin should be treated as a candidate biomarker or adjunctive target for selected toxin-producing Candida albicans infections, not as a general explanation for invasive candidiasis.
2026-08-11 | Mitochondrial characteristics of echinocandin tolerance and resistance in Candida glabrata and Candida krusei.
Candidiasis, especially candidemia, is one of the most common invasive fungal infections. With the increase of risk factors such as tumors, its high incidence and high mortality rate pose a significant challenge to public health. Echinocandins, as first-line drugs for candidemia, have their clinical efficacy severely weakened by the emergence of tolerant or resistant strains such as Candida glabrata and Candida krusei. The study evaluated the changes in mitochondrial phenotype (intracellular ATP levels, mitochondrial membrane potential, mitochondrial superoxide levels, and intracellular ROS levels), proteomic, metabolomic, and genomic in C. glabrata and C. krusei. By analyzing strains with different susceptibility profiles, the study found that echinocandin tolerant or resistant strains displayed significant upregulation of ATP levels and unique metabolic adaptations. Quantitative proteomics identified differentially expressed proteins associated with mitochondrial function and energy metabolism. Metabolomic analysis further revealed distinct profiles linking resistance to alterations in purine metabolism and oxidative phosphorylation. Additionally, genomic sequencing of the resistant strains highlighted mutations in key genes involved in ATP binding. These findings highlight the mitochondrial characteristics in echinocandin tolerance and resistance in C. glabrata and C. krusei, providing valuable insights into potential pathways for future therapeutic interventions targeting resistant Candida species.
2026-08-10 | Slt2 kinase of the cell wall integrity pathway is required for Fks2-specific echinocandin resistance in Candida glabrata.
Candida glabrata is an opportunistic yeast that causes invasive infections in immunocompromised individuals. Echinocandin antifungals are first-line agents in the treatment of invasive candidiasis and act by inhibiting fungal cell wall synthesis by targeting β-1,3-glucan synthase. Echinocandin resistance is primarily associated with mutations in FKS1 or FKS2, which encode for the catalytic subunit (Fks1 or Fks2) of the targeted glucan synthase. The cell wall integrity (CWI) pathway, including Slt2 kinase, is known to mediate tolerance to antifungal drugs, but its role in resistance is not completely defined. Here, we observed that disruption of SLT2 abrogated echinocandin resistance due to FKS2, but not FKS1, mutation in C. glabrata. As expected, reintroduction of plasmid-borne SLT2 restored elevated MICs of fks2 mutants. RT-qPCR revealed that loss of SLT2 led to decreased FKS2 expression levels in wild-type and echinocandin-resistant strains following echinocandin exposure. In conclusion, the CWI pathway and Slt2 comprise a primary control mechanism for FKS2-mediated echinocandin resistance in C. glabrata.IMPORTANCEThe higher rates of acquired antifungal resistance exhibited by Candida glabrata merit further understanding of resistance mechanisms including fungal regulation of drug target genes and enzymes. Here, we focused on a fungal tolerance pathway, the cell wall integrity pathway, and its requirement in C. glabrata echinocandin antifungal resistance. Interestingly, we found that targeting the pathway through disruption of a key protein, Slt2, reversed echinocandin resistance within one subset of resistant strains (fks2 mutants) but not another (fks1 mutants). Gene expression studies demonstrated the requirement of SLT2 for full FKS2 gene expression following echinocandin treatment. Overall, we discovered that Slt2 is specifically required for Fks2-mediated echinocandin resistance through partial regulation of FKS2 expression. This study provides further insight into the regulation of drug target genes in C. glabrata and provides a possible therapeutic target for echinocandin-resistant infections caused by mutation of FKS2.
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Drug Discovery Landscape
13 orphan drug designations for Invasive candidiasis, including 3 approved therapies.
13 orphan drug designations for Invasive candidiasis, including 3 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
triterpenoid antifungal | small molecules | FDA | 2026-03-15 | — | SCYNEXIS, Inc. |
Fosmanogepix | small molecules | EMA | 2022-07-18 | — | Basilea Pharmaceutica Deutschland GmbH |
Ibrexafungerp | small molecules | EMA | 2021-11-12 | — | GlaxoSmithKline Trading Services Limited |
Miltefosine | small molecules | FDA | 2021-11-01 | — | Profounda, lnc. |
Rezafungin acetate [Rezzayo] | small molecules | EMA | 2021-01-06 | 2023-12-22 | Mundipharma GmbH |
fosmanogepix | small molecules | FDA | 2016-10-19 | — | Basilea Pharmaceutica Ltd, Allschwil |
ibrexafungerp | small molecules | FDA | 2016-05-10 | — | GlaxoSmithKline LLC |
rezafungin [Rezzayo] | small molecules | FDA | 2016-02-08 | 2023-03-22 | Mundipharma GmbH |
isavuconazonium sulfate | small molecules | FDA | 2014-10-20 | — | Astellas Pharma Global Development, Inc. |
recombinant human monoclonal antibody to hsp90 | antibodies | FDA | 2002-09-16 | — | Novartis Pharmaceuticals Corp. |
Liposomal nystatin | small molecules | FDA | 2000-06-13 | — | The University of Texas |
Amphotericin B lipid complex | other | FDA | 1996-06-27 | — | The Liposome Company, Inc. |
Amphotericin B lipid complex [Abelcet] | small molecules | FDA | 1991-12-05 | 1996-10-18 | Liposome Company, Inc. |
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