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Cited by 111Antifungal resistance and susceptibilityFungal Infections and StudiesOcular Infections and Treatments

Treatment of Invasive Candidiasis: A Narrative Review

Open access
Ben-Ami, Ronen·2018·Journal of Fungi
DOI 10.3390/jof4030097PMC PMC6162658
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Abstract

Invasive candidiasis occurs frequently in hospitalized patients, and is associated with high mortality rates due to delays in recognition and initiation of appropriate antifungals. Management of invasive candidiasis must take into account multiple host, pathogen, and drug-related factors, including the site of infection, host immune status, severity of sepsis, resistance and tolerance to antifungal agents, biofilm formation, and pharmacokinetic/pharmacodynamic considerations. Recent treatment directives have been shaped by the widespread introduction of echinocandins, highly potent and safe antifungals, into clinical use, as well as important changes in drug susceptibility patterns and the emergence of known and novel drug-resistant Candida species. Advances in molecular diagnostics have the potential to guide early targeted treatment of high-risk patients.

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review summarizes the management of invasive candidiasis, emphasizing echinocandins as front-line therapy, species-specific resistance issues, source control, and emerging diagnostics/drugs. It highlights rising resistance in *C. glabrata* and *C. auris* and the need for early targeted treatment.

Key findings

  • Echinocandins are recommended as front-line agents for most invasive candidiasis; a patient-level meta-analysis of 7 trials with 1915 patients found echinocandin treatment associated with decreased mortality.
  • The Candida score (total parenteral nutrition, surgery, multifocal colonization = 1 point each; severe sepsis = 2 points) has 81% sensitivity and 74% specificity for invasive candidiasis at a score of ≥3, with a 7.7-fold greater risk.
  • Delayed antifungal treatment is associated with increased mortality; for candidemia with septic shock, initiation more than 24 h after shock onset is associated with a mortality rate of nearly 100%.
  • Central venous catheter removal is associated with higher treatment success and lower mortality, and T2Candida sensitivity was double that of conventional blood cultures when both were tested on follow-up blood samples.

Methods

  • Design: narrative review of treatment for invasive candidiasis, without a described systematic search strategy or meta-analysis.
  • Data: cited randomized controlled trials, observational studies, guidelines, in vitro studies, and animal models.
  • Main analysis: narrative synthesis of antifungal classes, susceptibility testing, resistance mechanisms, treatment strategies, source control, complications, and novel drugs.

Limitations

  • Stated in text: optimal drug treatment of *C. auris* has not yet been defined; there are no clinical data to support the CDC’s empiric echinocandin recommendation for *C. auris*; the clinical relevance of the paradoxical echinocandin effect is incompletely understood; and further work is needed to calculate the cost-benefit ratio of transesophageal echocardiography.
  • Evident from text: as a narrative review, it does not report systematic search criteria, risk-of-bias assessment, or quantitative pooling of evidence.
  • Evident from text: several recommendations rely on cited guidelines, observational data, or expert opinion rather than dedicated randomized trials, and some clinical questions remain unresolved.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/jof4030097

Cites

119 of 119 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 168 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    C. parapsilosis and C. guilliermondii are intrinsically less susceptible to echinocandins, reflecting naturally occurring polymorphisms in the FKS1 hotspot regions of these species.

    “C. parapsilosis and C. guilliermondii are intrinsically less susceptible to echinocandins, reflecting naturally occurring polymorphisms in the FKS1 hotspot regions of these species [19].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Katiyar, 2008, A naturally occurring proline-to-alanine amino acid change in Fks1p in Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis accounts for reduced echinocandin susceptibility, Antimicrob. Agents Chemother. source

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  • Premisecitation

    The superiority of anidulafungin over fluconazole was most significant for patients with C. albicans infection.

    “Interestingly, the superiority of anidulafungin was most significant for patients with C. albicans infection [22], indicating that drug susceptibility per-se could not account for the differences in treatment outcomes.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Reboli, 2007, Anidulafungin versus fluconazole for invasive candidiasis, N. Engl. J. Med. source

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  • Premisecitation

    The shift from C. albicans to species that are more frequently resistant or tolerant to fluconazole, such as C. glabrata and C. krusei, has impacted treatment recommendations.

    “The shift from C. albicans, which is overwhelmingly susceptible to all systemic antifungals, to species that are more frequently resistant or tolerant to fluconazole, such as C. glabrata and C. krusei, has impacted treatment recommendations [11,12,13].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [11] Cornely, 2012, ESCMID* guideline for the diagnosis and management of Candida diseases 2012: Non-neutropenic adult patients, Clin. Microbiol. Infect. source

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    • cites [12] Pappas, 2016, Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America, Clin. Infect. Dis. source

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    • cites [13] Ullmann, 2012, ESCMID* guideline for the diagnosis and management of Candida diseases 2012: Adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT), Clin. Microbiol. Infect. source

      Not checked in the free run.

  • Interpretationcitation

    Invasive candidiasis is associated with high mortality rates due to delays in recognition and initiation of appropriate antifungals.

    “Invasive candidiasis occurs frequently in hospitalized patients, and is associated with high mortality rates due to delays in recognition and initiation of appropriate antifungals.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [70] Morrell, 2005, Delaying the empiric treatment of candida bloodstream infection until positive blood culture results are obtained: A potential risk factor for hospital mortality, Antimicrob. Agents Chemother. source

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    • cites [71] Garey, 2006, Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: A multi-institutional study, Clin. Infect. Dis. source

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    • cites [72] Farmakiotis, 2015, Early initiation of appropriate treatment is associated with increased survival in cancer patients with Candida glabrata fungaemia: A potential benefit from infectious disease consultation, Clin. Microbiol. Infect. source

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  • Premisecitation

    Candida strains with acquired resistance to echinocandins, specifically C. glabrata, while still generally infrequent, are increasing in incidence in some hospitals.

    “Candida strains with acquired resistance to echinocandins, specifically C. glabrata, while still generally infrequent, are increasing in incidence in some hospitals [10,14].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [10] Cleveland, A.A., Harrison, L.H., Farley, M.M., Hollick, R., Stein, B., Chiller, T.M., Lockhart, S.R., and Park, B.J. (2015). Declining incidence of candidemia and the shifting epidemiology of Candida resistance in two US metropolitan areas, 2008–2013: Results from population-based surveillance. PLoS ONE, 10. source

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    • cites [14] Alexander, 2013, Increasing echinocandin resistance in Candida glabrata: Clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations, Clin. Infect. Dis. source

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  • May combine two claims. 43
  • Classified as probably not a substantial claim. 11
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    Premisecitation

    Anidulafungin is associated with a higher treatment success rate than fluconazole, but mortality rates are not significantly different.

    “Anidulafungin was associated with a higher treatment success rate than was fluconazole, but mortality rates were not significantly different [22].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Reboli, 2007, Anidulafungin versus fluconazole for invasive candidiasis, N. Engl. J. Med. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Candida species account for about 1 in 5 nosocomial bloodstream infections.

    “In point prevalence studies, Candida species account for about 1 in 5 nosocomial bloodstream infections [1,3].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Magill, 2014, Multistate point-prevalence survey of health care-associated infections, N. Engl. J. Med. source

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    • cites [3] Vincent, 2009, International study of the prevalence and outcomes of infection in intensive care units, JAMA source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Candida species are frequent colonizers of the human alimentary tract and skin that have emerged as important nosocomial pathogens.

    “Candida species are frequent colonizers of the human alimentary tract and skin that have emerged as important nosocomial pathogens, in tandem with advances in modern medical therapeutics [1,2].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Magill, 2014, Multistate point-prevalence survey of health care-associated infections, N. Engl. J. Med. source

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    • cites [2] Wisplinghoff, 2004, Nosocomial bloodstream infections in US hospitals: Analysis of 24,179 cases from a prospective nationwide surveillance study, Clin. Infect. Dis. source

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    Premisecitation

    Caspofungin and amphotericin B deoxycholate have similar efficacy in the intention to treat analysis but caspofungin is superior in the per-protocol analysis.

    “Prospective studies comparing echinocandins with amphotericin B for the treatment of candidiasis have shown similar efficacy of caspofungin and amphotericin B deoxycholate in the intention to treat analysis but superiority of caspofungin in the per-protocol analysis [20]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Betts, 2002, Comparison of caspofungin and amphotericin B for invasive candidiasis, N. Engl. J. Med. source

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    Premisecitation

    C. auris presents a serious challenge to healthcare systems due to its frequent resistance to multiple systemic antifungals and disinfectants and its capacity for rapid spread within healthcare facilities.

    “C. auris presents a serious challenge to healthcare systems due to its frequent resistance to multiple systemic antifungals and disinfectants and its capacity for rapid spread within healthcare facilities [15,16].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [15] Ku, 2018, Candida auris: Disinfectants and Implications for Infection Control, Front. Microbiol. source

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    • cites [16] Lockhart, 2016, Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses, Clin. Infect. Dis. source

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    Premisecitation

    C. glabrata has become an important pathogen in North America, Europe (with the exception of Spain), and Australia, whereas C. parapsilosis is the dominant non-albicans species in South America, Japan, and Spain.

    “Specifically, C. glabrata has become an important pathogen in North America, Europe (with the exception of Spain), and Australia, whereas C. parapsilosis is the dominant non-albicans species in South America, Japan, and Spain [8,9,10].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [8] Pfaller, 2010, Geographic variation in the frequency of isolation and fluconazole and voriconazole susceptibilities of Candida glabrata: An assessment from the ARTEMIS DISK Global Antifungal Surveillance Program, Diagn. Microbiol. Infect. Dis. source

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    • cites [9] Arendrup, 2010, Epidemiology of invasive candidiasis, Curr. Opin. Crit. Care source

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    • cites [10] Cleveland, A.A., Harrison, L.H., Farley, M.M., Hollick, R., Stein, B., Chiller, T.M., Lockhart, S.R., and Park, B.J. (2015). Declining incidence of candidemia and the shifting epidemiology of Candida resistance in two US metropolitan areas, 2008–2013: Results from population-based surveillance. PLoS ONE, 10. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Micafungin at both 100 mg and 150 mg daily is non-inferior to caspofungin, whereas median time to culture negativity was 1 day longer for micafungin 150 mg versus 100 mg.

    “Micafungin at both doses was non-inferior to caspofungin, whereas the median time to culture negativity was 1 day longer for the micafungin 150-mg dose versus the micafungin 100-mg dose [23].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] Pappas, 2007, Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis, Clin. Infect. Dis. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Candida species were the fourth most frequent causes of bloodstream infection in hospitalized patients in the US, and were associated with the highest mortality rate among leading bloodstream isolates.

    “In an often cited nationwide survey, Candida species were found to be the fourth most frequent causes of bloodstream infection in hospitalized patients in the US, and were associated with the highest mortality rate among leading bloodstream isolates [2].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Wisplinghoff, 2004, Nosocomial bloodstream infections in US hospitals: Analysis of 24,179 cases from a prospective nationwide surveillance study, Clin. Infect. Dis. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Deep-seated candidiasis may affect a population as large as that of candidemia.

    “Deep-seated candidiasis, arising from direct inoculation or hematogenous dissemination of Candida into normally sterile body sites, is often difficult to diagnose and may affect a population as large as that of candidemia [4,5,6].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [4] Bongomin, F., Gago, S., Oladele, R.O., and Denning, D.W. (2017). Global and Multi-National Prevalence of Fungal Diseases-Estimate Precision. J. Fungi (Basel), 3. source

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    • cites [5] Cheng, 2014, Candida glabrata Intra-Abdominal Candidiasis Is Characterized by Persistence within the Peritoneal Cavity and Abscesses, Infect. Immun. source

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    • cites [6] Leroy, 2009, Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: A multicenter, prospective, observational study in France (2005–2006), Crit. Care Med. source

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  • May combine two claims.

    Premisecitation

    In randomized controlled trials of nonneutropenic patients with candidemia, outcomes were similar for fluconazole versus amphotericin B, but toxicity was more frequent with amphotericin B.

    “In randomized controlled clinical trials of nonneutropenic patients with candidemia, outcomes were similar for patients treated with fluconazole versus amphotericin B, but toxicity was more frequent with amphotericin B [26,27].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [26] Rex, 1994, A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. Candidemia Study Group and the National Institute, N. Engl. J. Med. source

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    • cites [27] Phillips, 1997, Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients. Canadian Candidemia Study Group, Eur. J. Clin. Microbiol. Infect. Dis. source

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  • May combine two claims.

    Premisecitation

    Drug efflux is the most frequent mechanism of acquired fluconazole resistance, and is mediated by transmembrane transporter molecules of either the ATP-binding cassette or major facilitator superfamilies.

    “Drug efflux is the most frequent mechanism, and is mediated by transmembrane transporter molecules of either the ATP-binding cassette (ABC) or major facilitator (MFS) superfamilies [48,49].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [48] Izumikawa, 2003, Function of Candida glabrata ABC transporter gene, PDH1, Yeast source

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    • cites [49] White, 1997, Increased mRNA levels of ERG16, CDR, and MDR1 correlate with increases in azole resistance in Candida albicans isolates from a patient infected with human immunodeficiency virus, Antimicrob. Agents Chemother. source

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  • May combine two claims.

    Premisecitation

    Breakpoints for C. albicans, C. tropicalis, and C. parapsilosis were lowered, so that MICs over 4 mg/L are considered resistant; for C. glabrata, an MIC greater than 32 mg/L is considered resistant, whereas an MIC of 32 mg/L or less is considered susceptible dose-dependent.

    “Breakpoints for C. albicans, C. tropicalis, and C. parapsilosis were lowered, so that MICs over 4 mg/L are considered resistant. For C. glabrata, an inherently fluconazole-tolerant species, an MIC greater than 32 mg/L is considered resistant, whereas an MIC of 32 mg/L or less is considered susceptible dose-dependent (S-DD), a term indicating that maximal drug dosage is required for optimal tre”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Pfaller, 2010, Wild-type MIC distributions, epidemiological cutoff values and species-specific clinical breakpoints for fluconazole and Candida: Time for harmonization of CLSI and EUCAST broth microdilution methods, Drug. Resist. Updat. source

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  • May combine two claims.

    Premisecitation

    Fluconazole combined with amphotericin B had a higher overall treatment success rate and a lower rate of failure to clear the bloodstream than fluconazole monotherapy.

    “A study comparing fluconazole monotherapy with fluconazole combined with amphotericin B found a higher overall treatment success rate and a lower rate of failure to clear the bloodstream with the combination regimen [28].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Rex, 2003, A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects, Clin. Infect. Dis. source

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    Premisecitation

    The paradoxical echinocandin effect is more pronounced with caspofungin than with other echinocandins, is unrelated to MIC, appears to be most common with C. albicans and C. dubliniensis, and is strikingly absent in C. glabrata.

    “This effect is more pronounced with caspofungin than with other echinocandins, is unrelated to MIC, appears to be most common with C. albicans and C. dubliniensis, and is strikingly absent in C. glabrata [37,38,39].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [37] Chamilos, 2007, Paradoxical effect of Echinocandins across Candida species in vitro: Evidence for echinocandin-specific and candida species-related differences, Antimicrob. Agents Chemother. source

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    • cites [38] Fleischhacker, 2008, Paradoxical growth effects of the echinocandins caspofungin and micafungin, but not of anidulafungin, on clinical isolates of Candida albicans and C. dubliniensis, Eur. J. Clin. Microbiol. Infect. Dis. source

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    • cites [39] Shields, 2011, Paradoxical effect of caspofungin against Candida bloodstream isolates is mediated by multiple pathways but eliminated in human serum, Antimicrob. Agents Chemother. source

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    Premisecitation

    Contrary to echinocandin resistance, fluconazole resistance does not incur a significant fitness cost, and may in fact be associated with enhanced virulence.

    “Contrary to echinocandin resistance, fluconazole-resistance does not incur a significant fitness cost, and may in fact be associated with enhanced virulence [55].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [55] Ferrari, S., Ischer, F., Calabrese, D., Posteraro, B., Sanguinetti, M., Fadda, G., Rohde, B., Bauser, C., Bader, O., and Sanglard, D. (2009). Gain of function mutations in CgPDR1 of Candida glabrata not only mediate antifungal resistance but also enhance virulence. PLoS Pathog., 5. source

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  • May combine two claims.

    Premisereasoning

    Candida species carrying FKS hotspot mutations are almost invariably recovered from patients with extensive recent exposure to echinocandins, and usually after more than 3 weeks of treatment.

    “Perhaps related to their reduced fitness, Candida species carrying FKS hotspot mutations are almost invariably recovered from patients with extensive recent exposure to echinocandins, and usually after more than 3 weeks of treatment [45].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Dannaoui, 2012, Candida spp. with acquired echinocandin resistance, France, 2004-2010, Emerg. Infect. Dis. source

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    Premisecitation

    Acute kidney injury occurs in 30% of adults treated with amphotericin B, and is associated with significantly increased mortality rates, length of hospital stay, and costs.

    “Overall, acute kidney injury occurs in 30% of adults treated with amphotericin B, and is associated with significantly increased mortality rates, length of hospital stay, and costs [30].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [30] Bates, 2001, Mortality and costs of acute renal failure associated with amphotericin B therapy, Clin. Infect. Dis. source

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    Premisecitation

    Acquired echinocandin resistance has been described in all major Candida species, but is most frequently encountered in C. glabrata, where an association with echinocandin treatment failure has been described.

    “Acquired echinocandin resistance has been described in all major Candida species, but is most frequently encountered in C. glabrata, where an association with echinocandin treatment failure has been described [14,42].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [14] Alexander, 2013, Increasing echinocandin resistance in Candida glabrata: Clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations, Clin. Infect. Dis. source

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    • cites [42] Shields, 2013, Caspofungin MICs correlate with treatment outcomes among patients with Candida glabrata invasive candidiasis and prior echinocandin exposure, Antimicrob. Agents Chemother. source

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    Premisecitation

    The paradoxical effect is abolished by testing in 50% human serum and in the presence of the chitin synthase inhibitor nikkomycin Z and calcineurin inhibitors, suggesting that cell-wall stress response pathways are involved.

    “The paradoxical effect is abolished by testing in 50% human serum and in the presence of the chitin synthase inhibitor nikkomycin Z and calcineurin inhibitors, suggesting that cell-wall stress response pathways are involved [39].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] Shields, 2011, Paradoxical effect of caspofungin against Candida bloodstream isolates is mediated by multiple pathways but eliminated in human serum, Antimicrob. Agents Chemother. source

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    Premisecitation

    Of the major pathogenic Candida species, C. glabrata is the most prone to acquire fluconazole resistance, usually associated with upregulation of the ABC efflux pumps CDR1 and CDR2.

    “Of the major pathogenic Candida species, C. glabrata is the most prone to acquire fluconazole resistance, usually associated with upregulation of the ABC efflux pumps CDR1 and CDR2 [51,52].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [51] Sanglard, 1999, The ATP binding cassette transporter gene CgCDR1 from Candida glabrata is involved in the resistance of clinical isolates to azole antifungal agents, Antimicrob. Agents Chemother. source

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    • cites [52] Miyazaki, 1998, Fluconazole resistance associated with drug efflux and increased transcription of a drug transporter gene, PDH1, in Candida glabrata, Antimicrob. Agents Chemother. source

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  • The quote only partly states this claim.

    Premisecitation

    Treatment failure occurred most frequently with C. albicans in trials comparing fluconazole with amphotericin B.

    “Treatment failure occurred most frequently with C. albicans [26].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Rex, 1994, A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. Candidemia Study Group and the National Institute, N. Engl. J. Med. source

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    Premisecitation

    C. auris is intrinsically resistant to fluconazole, and cannot reliably be treated with other azoles.

    “C. auris is intrinsically resistant to fluconazole, and cannot reliably be treated with other azoles [16,58,59].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [16] Lockhart, 2016, Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses, Clin. Infect. Dis. source

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    • cites [58] Berman, 2017, Multidrug-Resistant Candida haemulonii and C. auris, Tel Aviv, Israel, Emerg. Infect. Dis.

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    • cites [59] Chowdhary, A., Sharma, C., and Meis, J.F. (2017). Candida auris: A rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally. PLoS Pathog., 13. source

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    Premisecitation

    Real-life use of the Candida score in the intensive care setting reveals a high negative predictive value (80% to 97%) but modest positive predictive value (57% to 70%).

    “Real-life use of this prediction rule in the intensive care setting reveals a high negative predictive value (80% to 97%) but modest positive predictive value (57% to 70%) [77,78].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [77] Bruyere, R., Quenot, J.P., Prin, S., Dalle, F., Vigneron, C., Aho, S., Leon, C., and Charles, P.E. (2014). Empirical antifungal therapy with an echinocandin in critically-ill patients: Prospective evaluation of a pragmatic Candida score-based strategy in one medical ICU. BMC Infect. Dis., 14. source

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    • cites [78] Posteraro, 2011, Early diagnosis of candidemia in intensive care unit patients with sepsis: A prospective comparison of (1-->3)-beta-d-glucan assay, Candida score, and colonization index, Crit. Care source

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    Premisecitation

    Lipid formulations of amphotericin B are associated with similar rates of treatment success as echinocandins but higher rates of nephrotoxicity.

    “Lipid formulations of amphotericin B are associated with similar rates of treatment success as echinocandins but higher rates of nephrotoxicity [21].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] Kuse, 2007, Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: A phase III randomised double-blind trial, Lancet source

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    Premisecitation

    Treatment failure and the emergence of fluconazole-resistant strains occur frequently during treatment of initially susceptible C. glabrata isolates.

    “Not only does C. glabrata have higher median MICs of fluconazole compared with other common Candida species, but treatment failure and the emergence of fluconazole-resistant strains occur frequently during treatment of initially susceptible isolates [52].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [52] Miyazaki, 1998, Fluconazole resistance associated with drug efflux and increased transcription of a drug transporter gene, PDH1, in Candida glabrata, Antimicrob. Agents Chemother. source

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    Premisecitation

    Median time to blood culture positivity is 2-3 days, and may be as long as 8 days; median time to detection is longer for C. glabrata versus other species.

    “Moreover, the median time to blood culture positivity is 2–3 days, and may be as long as 8 days. Again, median time to detection is longer for C. glabrata versus other species [75].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [75] Pfeiffer, 2011, Quantitation of Candida CFU in initial positive blood cultures, J. Clin. Microbiol. source

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    Premisecitation

    Heteroresistance to fluconazole is highly frequent among clinical C. glabrata strains, and is associated with failure of fluconazole to clear C. glabrata from tissues of experimentally infected immunocompetent mice.

    “Heteroresistance, specifically to fluconazole, was also shown to be highly frequent among clinical C. glabrata strains, and is associated with failure of fluconazole to clear C. glabrata from tissues of experimentally infected immunocompetent mice [68].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] Zimmerman, 2016, Heteroresistance to Fluconazole Is a Continuously Distributed Phenotype among Candida glabrata Clinical Strains Associated with In Vivo Persistence, mBio source

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    Premisecitation

    PCR assays that detect Candida DNA in full blood or serum are both sensitive and specific.

    “Finally, PCR assays that detect Candida DNA in full blood or serum are both sensitive and specific [82].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [82] Avni, 2011, PCR diagnosis of invasive candidiasis: Systematic review and meta-analysis, J. Clin. Microbiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Candida strains resistant to amphotericin B were found to harbor mutations in ERG2, ERG3, ERG5, and ERG11, and were co-resistant to fluconazole.

    “Candida strains resistant to amphotericin B were found to harbor mutations in ERG2, ERG3, ERG5, and ERG11, and were co-resistant to fluconazole [63,64,65,66].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [63] Martel, 2010, Identification and characterization of four azole-resistant erg3 mutants of Candida albicans, Antimicrob. Agents Chemother. source

      Not checked in the free run.

    • cites [64] Martel, 2010, A clinical isolate of Candida albicans with mutations in ERG11 (encoding sterol 14alpha-demethylase) and ERG5 (encoding C22 desaturase) is cross resistant to azoles and amphotericin B, Antimicrob. Agents Chemother. source

      Not checked in the free run.

    • cites [65] Sanglard, 2003, Candida albicans mutations in the ergosterol biosynthetic pathway and resistance to several antifungal agents, Antimicrob. Agents Chemother. source

      Not checked in the free run.

    • cites [66] Jensen, 2015, Stepwise emergence of azole, echinocandin and amphotericin B multidrug resistance in vivo in Candida albicans orchestrated by multiple genetic alterations, J. Antimicrob. Chemother. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Specific mutations in the DNA mismatch repair gene MSH2 lead to a hyper-mutable phenotype and were found to be highly prevalent in clinical C. glabrata isolates.

    “Specific mutations in the DNA mismatch repair gene MSH2 lead to a hyper-mutable phenotype and were found to be highly prevalent in clinical C. glabrata isolates [67].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] Healey, 2016, Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance, Nat. Commun. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Acquired resistance to amphotericin B is rare, and involves reduced ergosterol biosynthesis and the production of alternative sterols to which amphotericin B has low affinity.

    “Acquired resistance is also rare, and involves reduced ergosterol biosynthesis and the production of alternative sterols to which amphotericin B has low affinity.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [63] Martel, 2010, Identification and characterization of four azole-resistant erg3 mutants of Candida albicans, Antimicrob. Agents Chemother. source

      Not checked in the free run.

    • cites [64] Martel, 2010, A clinical isolate of Candida albicans with mutations in ERG11 (encoding sterol 14alpha-demethylase) and ERG5 (encoding C22 desaturase) is cross resistant to azoles and amphotericin B, Antimicrob. Agents Chemother. source

      Not checked in the free run.

    • cites [65] Sanglard, 2003, Candida albicans mutations in the ergosterol biosynthetic pathway and resistance to several antifungal agents, Antimicrob. Agents Chemother. source

      Not checked in the free run.

    • cites [66] Jensen, 2015, Stepwise emergence of azole, echinocandin and amphotericin B multidrug resistance in vivo in Candida albicans orchestrated by multiple genetic alterations, J. Antimicrob. Chemother. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Heteroresistance to fluconazole is associated with up-regulation of ABC-type drug transporters, and may be detected and quantified using population analysis profiling.

    “Heteroresistance to fluconazole is associated with up-regulation of ABC-type drug transporters, and may be detected and quantified using population analysis profiling [68], a method not routinely used by clinical microbiological laboratories.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] Zimmerman, 2016, Heteroresistance to Fluconazole Is a Continuously Distributed Phenotype among Candida glabrata Clinical Strains Associated with In Vivo Persistence, mBio source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A Candida score of 3 or more has 81% sensitivity and 74% specificity for the diagnosis of invasive candidiasis, and a 7.7-fold greater risk of candidiasis.

    “A total score of 3 or more has 81% sensitivity and 74% specificity for the diagnosis of invasive candidiasis, and a 7.7-fold greater risk of candidiasis [76].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [76] Leon, 2006, A bedside scoring system (“Candida score”) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization, Crit. Care Med. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A differential time to positivity of greater than 2 h is associated with Candida CVC infection, but is not useful in cases of C. glabrata bloodstream infection.

    “A differential time to positivity of greater than 2 h is associated with Candida CVC infection, but is not useful in cases of C. glabrata bloodstream infection [99].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [99] Park, 2014, Diagnostic usefulness of differential time to positivity for catheter-related candidemia, J. Clin. Microbiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Clinical trials have shown numerically more cases of treatment failure for C. parapsilosis with anidulafungin versus fluconazole and with caspofungin versus amphotericin B, although these differences were not statistically significant.

    “Clinical trials have shown numerically more cases of treatment failure for C. parapsilosis with anidulafungin versus fluconazole [22] and with caspofungin versus amphotericin B [20], although these differences were not statistically significant.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [22] Reboli, 2007, Anidulafungin versus fluconazole for invasive candidiasis, N. Engl. J. Med. source

      Not checked in the free run.

    • cites [20] Betts, 2002, Comparison of caspofungin and amphotericin B for invasive candidiasis, N. Engl. J. Med. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Exposure to echinocandins was consistently found to be a risk factor for infection with C. auris, and breakthrough infection on echinocandins has been noted.

    “Exposure to echinocandins was consistently found to be a risk factor for infection with C. auris, and breakthrough infection on echinocandins has been noted [16,90,91].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [16] Lockhart, 2016, Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses, Clin. Infect. Dis. source

      Not checked in the free run.

    • cites [90] Ruiz-Gaitan, A., Moret, A.M., Tasias-Pitarch, M., Aleixandre-Lopez, A.I., Martinez-Morel, H., Calabuig, E., Salavert-Lleti, M., Ramirez, P., Lopez-Hontangas, J.L., and Hagen, F. (2018). An outbreak due to Candida auris with prolonged colonization and candidemia in a tertiary care European hospital. Mycoses. source

      Not checked in the free run.

    • cites [91] Rudramurthy, 2017, Candida auris candidaemia in Indian ICUs: Analysis of risk factors, J. Antimicrob. Chemother. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Peripheral blood time to positivity greater than 30 h is associated with a significantly lower likelihood of CVC infection; for the slow growing C. glabrata, a breakpoint of 48 h may be used.

    “Peripheral blood time to positivity alone may also be of value, as a value greater than 30 h is associated with a significantly lower likelihood of CVC infection [100]. For the slow growing C. glabrata, a breakpoint of 48 h may be used [101].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [100] Weinberger, 2008, Time to blood culture positivity as a marker for catheter-related candidemia, J. Clin. Microbiol. source

      Not checked in the free run.

    • cites [101] Stempel, 2016, Time-to-reporting of blood culture positivity and central venous catheter-associated Candida glabrata fungemia in cancer patients, Diagn Microbiol. Infect. Dis. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    De-escalation to oral fluconazole may reduce exposure to echinocandins, limit the emergence of resistance to this important drug class, shorten hospital stays, and limit costs.

    “De-escalation to oral fluconazole may reduce exposure to echinocandins, limit the emergence of resistance to this important drug class, shorten hospital stays, and limit costs.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [94] Vazquez, J., Reboli, A.C., Pappas, P.G., Patterson, T.F., Reinhardt, J., Chin-Hong, P., Tobin, E., Kett, D.H., Biswas, P., and Swanson, R. (2014). Evaluation of an early step-down strategy from intravenous anidulafungin to oral azole therapy for the treatment of candidemia and other forms of invasive candidiasis: Results from an open-label trial. BMC Infect. Dis., 14. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Because subclinical vitritis may be present, treatment with antifungals that achieve therapeutic concentrations within the vitreous is preferred.

    “However, because subclinical vitritis may be present, treatment with antifungals that achieve therapeutic concentrations within the vitreous is preferred.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Subclinical vitritis may be present in patients with ocular candidiasis.

  • May combine two claims.

    Premisecitation

    There are no clinical data to support the recommendation of echinocandins as empiric treatment of C. auris infections, and there is evidence that C. auris is tolerant to echinocandins.

    “However, there are no clinical data to support this recommendation, and there is evidence that C. auris is tolerant to echinocandins.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [89] Centers for Disease Control (2018, May 23). Recommendations for Treatment of Candida auris, Available online: https://www.cdc.gov/fungal/candida-auris/c-auris-treatment.html.

      Not checked in the free run.

    • cites [16] Lockhart, 2016, Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses, Clin. Infect. Dis. source

      Not checked in the free run.

    • cites [90] Ruiz-Gaitan, A., Moret, A.M., Tasias-Pitarch, M., Aleixandre-Lopez, A.I., Martinez-Morel, H., Calabuig, E., Salavert-Lleti, M., Ramirez, P., Lopez-Hontangas, J.L., and Hagen, F. (2018). An outbreak due to Candida auris with prolonged colonization and candidemia in a tertiary care European hospital. Mycoses. source

      Not checked in the free run.

    • cites [91] Rudramurthy, 2017, Candida auris candidaemia in Indian ICUs: Analysis of risk factors, J. Antimicrob. Chemother. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There is compelling evidence that CVC removal is associated with higher rates of treatment success and lower mortality rates as compared with CVC retention.

    “There is compelling evidence that CVC removal is associated with higher rates of treatment success and lower mortality rates as compared with CVC retention [73,84,88,96,97].”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [73] Kollef, 2012, Septic shock attributed to Candida infection: Importance of empiric therapy and source control, Clin. Infect. Dis. source

      Not checked in the free run.

    • cites [84] Andes, 2012, Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: A patient-level quantitative review of randomized trials, Clin. Infect. Dis. source

      Not checked in the free run.

    • cites [88] Aguado, 2014, Initial use of echinocandins does not negatively influence outcome in Candida parapsilosis bloodstream infection: A propensity score analysis, Clin. Infect. Dis. source

      Not checked in the free run.

    • cites [96] Liu, 2009, Candidemia in cancer patients: Impact of early removal of non-tunneled central venous catheters on outcome, J. Infect. source

      Not checked in the free run.

    • cites [97] Nguyen, 1995, Therapeutic approaches in patients with candidemia. Evaluation in a multicenter, prospective, observational study, Arch. Intern. Med. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Intra-abdominal candidiasis tends to progress to abscesses that are persistent and recalcitrant, and if undrained may predispose for the development of drug-resistance.

    “Intra-abdominal candidiasis tends to progress to abscesses that are persistent and recalcitrant, and if undrained may predispose for the development of drug-resistance [5,104].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [5] Cheng, 2014, Candida glabrata Intra-Abdominal Candidiasis Is Characterized by Persistence within the Peritoneal Cavity and Abscesses, Infect. Immun. source

      Not checked in the free run.

    • cites [104] Shields, 2014, Abdominal candidiasis is a hidden reservoir of echinocandin resistance, Antimicrob. Agents Chemother. source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Other groups have reported much lower incidence rates of endocarditis, suggesting that a more selective strategy may be reasonable.

    “However, other groups have reported much lower incidence rates of endocarditis, suggesting that a more selective strategy may be reasonable [12].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] Pappas, 2016, Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America, Clin. Infect. Dis. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    C. parapsilosis is particularly frequent as a cause of CVC infection, and neutropenic patients are relatively more likely than non-neutropenic patients to have Candida bloodstream infection that originates in the gut.

    “C. parapsilosis is particularly frequent as a cause of CVC infection, and neutropenic patients are relatively more likely than non-neutropenic patients to have Candida bloodstream infection that originates in the gut [88].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [88] Aguado, 2014, Initial use of echinocandins does not negatively influence outcome in Candida parapsilosis bloodstream infection: A propensity score analysis, Clin. Infect. Dis. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Endocarditis was clinically unsuspected in a third of the cases, prompting a recommendation for TEE in all patients with candidemia.

    “Importantly, endocarditis was clinically unsuspected in a third of the cases, prompting a recommendation for TEE in all patients with candidemia [11].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] Cornely, 2012, ESCMID* guideline for the diagnosis and management of Candida diseases 2012: Non-neutropenic adult patients, Clin. Microbiol. Infect. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Treatment options for drug-resistant C. glabrata and C. auris are poorly defined.

    “Treatment options for drug-resistant C. glabrata and C. auris are poorly defined”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Treatment of invasive candidiasis is changing.

    “Treatment of invasive candidiasis is changing.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Ibrexafungerp is a first-in-class oral glucan synthase inhibitor that has shown fungicidal activity against a wide range of Candida species in in vitro assays and animal models.

    “Ibrexafungerp (SCY-078, Scynexis, Jersey City, NJ, USA) is a first-in-class oral glucan synthase inhibitor that has shown fungicidal activity against a wide range of Candida species in in vitro assays and animal models [111].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [111] Schell, W.A., Jones, A.M., Borroto-Esoda, K., and Alexander, B.D. (2017). Antifungal Activity of SCY-078 and Standard Antifungal Agents against 178 Clinical Isolates of Resistant and Susceptible Candida Species. Antimicrob. Agents Chemother., 61. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Sensitive molecular diagnostics have the potential to shift treatment strategies from current, risk-based empirical therapy to early targeted treatments.

    “Sensitive molecular diagnostics have the potential to shift treatment strategies from current, risk-based empirical therapy to early targeted treatments.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    VT-1161 has fewer off-target effects and drug-drug interactions compared with other azoles.

    “and has fewer off-target effects and drug-drug interactions compared with other azoles.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Oteseconazole has improved specific affinity towards fungal versus mammalian CYP51 compared with other azoles.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Widespread use of echinocandins is leading to rising rates of resistance in Candida isolates at some hospitals.

    “their widespread use is leading to rising rates of resistance in Candida isolates at some hospitals.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Echinocandins have transformed the care of patients with invasive candidiasis.

    “Echinocandins have transformed the care of patients with invasive candidiasis”
    Quote in the paperNot a substantial claim
52 of 52

  • The paper relies on this without support.

    Echinocandins may achieve subinhibitory concentrations within abdominal abscesses.

    “Echinocandins in particular may achieve subinhibitory concentrations within abdominal abscesses, underscoring the importance of surgical drainage and debridement.”

  • The paper relies on this without support.

    The chorioretinal layer is highly vascular.

    “Because the chorioretinal layer is highly vascular, treatment of chorioretinitis with any of the systemic antifungal drugs should be effective.”

  • The paper relies on this without support.

    Subclinical vitritis may be present in patients with ocular candidiasis.

    “However, because subclinical vitritis may be present, treatment with antifungals that achieve therapeutic concentrations within the vitreous is preferred.”

  • The paper relies on this without support.

    Oteseconazole has improved specific affinity towards fungal versus mammalian CYP51 compared with other azoles.

    “Oteseconazole (VT-1161, Viamet Pharmaceuticals, San Francisco, CA, USA) is a next-generation azole (tetrazole) with improved specific affinity towards fungal versus mammalian CYP51.”

  • The paper relies on this without support.

    APX001 inactivates the fungal enzyme Gwt1.

    “APX001 (Amplyx Pharmaceuticals, San Diego, CA, USA), another first-in-class drug, is a small molecule that inactivates the fungal enzyme Gwt1.”

  • The paper relies on this without support.

    APX001 prevents post-translational modification of GPI and disrupts anchoring of mannoproteins to the fungal cell wall.

    “This prevents post-translational modification of glycosylphosphatidylinositol (GPI) and disrupts the anchoring of mannoproteins to the fungal cell wall”

  • The paper relies on this without support.

    APX001 causes cell wall damage and impaired growth and biofilm formation.

    “causing cell wall damage and impaired growth and biofilm formation.”

  • The paper relies on this without support.

    MAT2203 is a novel encochleated amphotericin B formulation that allows oral administration.

    “MAT2203 (Matinas Biopharma, Bedminster, NJ, USA) is a novel encochleated amphotericin B formulation that allows oral administration.”
8 of 8

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • There is an increasing incidence of azole resistance particularly among non-albicans Candida species.

    “The most recent Infectious Disease Society of America (IDSA)125 and European guidelines126,127 recommend echinocandins as first-line initial treatment for most invasive candidiasis in both neutropenic and non-neutropenic patients prior to identification to the species level due to their broad spectrum of activity, favorable side effect profile, mortality benefit, and the increasing incidence of az”

    From Epidemiology of Invasive Candidiasis (2024) · cites this paper as [129]

    The Background section (page unavailable) says non-albicans Candida accounts for an increasing proportion of invasive cases and that species such as C. glabrata and C. krusei are more often resistant or tolerant to fluconazole. It does not establish an increasing incidence of azole resistance itself, as distinct from an increasing share of species more likely to resist fluconazole. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Echinocandins have a broad spectrum of activity, favorable side effect profile, and mortality benefit in invasive candidiasis.

    “The most recent Infectious Disease Society of America (IDSA)125 and European guidelines126,127 recommend echinocandins as first-line initial treatment for most invasive candidiasis in both neutropenic and non-neutropenic patients prior to identification to the species level due to their broad spectrum of activity, favorable side effect profile, mortality benefit, and the increasing incidence of az”

    From Epidemiology of Invasive Candidiasis (2024) · cites this paper as [129]

  • Acquisition of resistance can occur during long hospitalization periods and prolonged treatments.

    “This can occur during long hospitalization periods and prolonged treatments [66].”

    From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [66]

Cites

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Authors
Ben-Ami, R.
Affiliations
Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 64239, Israel
Venue
Journal of Fungi
Publisher
MDPI AG
Published
2018-08-16
Volume
4
Issue
3
Pages
97
ISSN
2309-608X (ISSN-L)
DOI
10.3390/jof4030097
PMC
PMC6162658
OpenAlex
W2886123035
Semantic Scholar
9e14838359705dd984dc34b1c1aabff55136e4ab
Cited by
111
References
119
Citations by year
2026: 5 · 2025: 11 · 2024: 14 · 2023: 14 · 2022: 11 · 2021: 15 · 2020: 24 · 2019: 13 · 2018: 4
FWCI
2.05
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Fungi (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
  • Health Sciences › Medicine › Ophthalmology › Ocular Infections and Treatments
Keywords
invasive candidiasis, antifungal therapy, echinocandins, antifungal resistance, Candida species, biofilm formation, pharmacokinetics/pharmacodynamics, sepsis, molecular diagnosis, host immune status

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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