The DOI matches its Crossref record, with a small difference in title or year; 57 of the 57 references it cites were found in a registry or an index; 4 of the 176 sources its claims cite were checked for support.
Echinocandin resistance: an emerging clinical problem?
Open accessAbstract
PURPOSE OF REVIEW: Echinocandin resistance in Candida is a great concern, as the echinocandin drugs are recommended as first-line therapy for patients with invasive candidiasis. Here, we review recent advances in our understanding of the epidemiology, underlying mechanisms, methods for detection and clinical implications. RECENT FINDINGS: Echinocandin resistance has emerged over the recent years. It has been found in most clinically relevant Candida spp., but is most common in C. glabrata with rates exceeding 10% at selected institutions. It is most commonly detected after 3-4 weeks of treatment and is associated with a dismal outcome. An extensive list of mutations in hot spot regions of the genes encoding the target has been characterized and associated with species and drug-specific loss of susceptibility. The updated antifungal susceptibility testing reference methods identify echinocandin-resistant isolates reliably, although the performance of commercial tests is somewhat more variable. Alternative technologies are being developed, including molecular detection and matrix-assisted laser desorption ionization-time of flight. SUMMARY: Echinocandin resistance is increasingly encountered and its occurrence makes susceptibility testing essential, particularly in patients with prior exposure. The further development of rapid and user-friendly commercially available susceptibility platforms is warranted. Antifungal stewardship is important in order to minimize unnecessary selection pressure.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Echinocandin resistance in Candida is emerging, especially in C. glabrata, and is associated with treatment failure after prolonged exposure. Reference susceptibility testing is reliable, but commercial and rapid molecular/MALDI-TOF platforms need further optimization, and antifungal stewardship is needed.
Key findings
- Acquired echinocandin resistance has been reported in most clinically relevant Candida species, but is most common in C. glabrata, with rates exceeding 10% at selected institutions; a 10-year Duke University hospital survey found resistance increased from 4.9% to 12.3% in 2001–10.
- Most cases are diagnosed after 3–4 weeks of therapy, and outcomes are poor: 80% and 78.5% of candidaemia patients with an echinocandin-resistant C. glabrata isolate failed therapy in two studies.
- Resistance is often linked to FKS hot-spot mutations, with the greatest MIC elevation involving the first and fifth amino acids (F and S) in hot spot 1 of FKS1 or FKS2; cross-resistance to all three echinocandins is common, but some alterations are compound-specific.
- Detection challenges remain: reference microbroth dilution methods are reliable, but the VITEK system misclassified 19.4% of mutant isolates as susceptible, and post-treatment oral mucosal isolates from candidaemic patients initially treated with an echinocandin showed resistance in as many as 10%.
Methods
- Narrative review of recent advances in the epidemiology, molecular mechanisms, detection methods, and clinical implications of echinocandin resistance in Candida.
- Synthesizes published case reports/series, surveillance surveys, susceptibility-method evaluations, and in vitro/in vivo fitness studies; one Danish surveillance observation is cited as unpublished.
- Main analysis is qualitative synthesis; no systematic review protocol, meta-analysis, or primary statistical pooling is described.
Limitations
- Stated: fungaemia surveillance may underestimate true resistance because only the initial blood isolate is included; commercial susceptibility tests show variable performance, and VITEK cannot discriminate intermediate from susceptible C. glabrata isolates because its caspofungin concentration does not encompass the breakpoint.
- Stated: molecular methods are not yet commercially available and require expertise and in-house validation; MALDI-TOF extension to other species with different growth kinetics and species-specific breakpoints remains to be investigated; the impact of intrinsic target polymorphisms on therapeutic response is unclear.
- Evident from the text: this is a narrative review without a described systematic search or quality appraisal, and some cited resistance data are unpublished observations.
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Claims the paper makes
66 Not checked yet · 9 Own interpretation · 1 Mixed support · 1 Couldn’t confirm · accuracy not yet measured
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“Thus, mutations at these hot spots have been linked to a) impaired enzyme capacity, b) altered cell wall composition, i.e. reduced glucan and increased chit in content, c) increased cell wall thickness and d) impaired filamentation properties, which contribute to a lower growth rate in vitro and in vivo in drosophila and mouse models (31–33).”
§ Echinocandin resistance: an emerging clinical problem? > Implication on fitness
What the sources say
- Partly supportedcites [31] Ben-Ami R Garcia-Effron G Lewis RE Fitness and Virulence Costs of Candida albicans FKS1 Hot Spot Mutations Associated With Echinocandin Resistance J Infect Dis 2011 8 204 4 626 35 21791665 PMC3144175 sourceExperimental — accuracy not yet measured
The “Growth Rate and Filamentation Are Impaired in fks1 Mutants” section reports lower in vitro growth rates for three of five homozygous mutants. The Discussion reports reduced virulence in Drosophila and reduced virulence and tissue fungal burdens in mice, but these outcomes do not establish a lower growth rate in both animal models; it also notes similar growth rates for the strains compared in competition experiments. (LLM, conf=0.88)
- Partly supportedcites [32] Singh-Babak SD Babak T Diezmann S Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata PLoS Pathog 2012 5 17 8 5 e1002718 22615574 PMC3355103 sourceExperimental — accuracy not yet measured
The Results section on the FKS2 S663P mutation reports significantly reduced fitness in vitro in the absence of drug. The murine-infection Results report a trend toward reduced kidney fungal burden with early resistance, later mitigated by further evolution. The paper does not report a Drosophila model or establish a lower in vivo growth rate across both animal models. (LLM, conf=0.88)
- Disputedcites [33] Lee KK MacCallum DM Jacobsen MD Elevated Cell Wall Chitin in Candida albicans Confers Echinocandin Resistance In Vivo Antimicrobial Agents and Chemotherapy 2012 1 1 56 1 208 17 21986821 PMC3256049 sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) says strains with an Fks1 Ser645 mutation showed very few differences in mouse virulence as measured by fungal burdens, and that further studies are needed to determine whether FKS1 mutations alter fitness in vivo. That runs contrary to the asserted lower growth rate in mice. Our copy also provides no Drosophila result or evidence of a lower in vitro growth rate. (LLM, conf=0.82)
Checked by a reasoning model — may be wrong.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Categorizations determined using MALDI-TOF MS-based AFST (ms-AFST) were consistent with the wild-type and mutant FKS1 genotypes and the AFST reference methodology.”
§ Echinocandin resistance: an emerging clinical problem? > Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF)
What the sources say
- Could not verifycites [53] sourceExperimental — accuracy not yet measured
The Materials and Methods section describes CLSI broth microdilution susceptibility testing and FKS sequence analysis, but does not describe MALDI-TOF MS-based AFST. The Results relate FKS mutations to echinocandin MICs; neither those passages nor searches for “ms-AFST” and “MALDI” establish the claimed agreement between ms-AFST categorizations, genotypes, and the reference method. No page numbers are available in our copy. (LLM, conf=0.76)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Could not verify
None of the sources cited for this claim have been checked yet.
In the paper
“It is most commonly detected after 3–4 weeks of treatment and is associated with a dismal outcome.”
§ Echinocandin resistance: an emerging clinical problem? > Abstract > Recent findings
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Echinocandin resistance has emerged over the recent years.”
§ Echinocandin resistance: an emerging clinical problem? > Abstract > Recent findings
What the sources say
- Not checked yetcites [9] Park S Kelly R Kahn JN Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates Antimicrob Agents Chemother 2005 8 49 8 3264 73 16048935 PMC1196231 source
- Not checked yetcites [10] Cleary JD Garcia-Effron G Chapman SW Perlin DS Reduced Candida glabrata susceptibility secondary to an FKS1 mutation developed during candidemia treatment Antimicrob Agents Chemother 2008 6 52 6 2263 5 18378714 PMC2415792 source
- Not checked yetcites [11] Desnos-Ollivier M Bretagne S Raoux D Mutations in the fks1 gene in Candida albicans, C. tropicalis and C. krusei correlate with elevated caspofungin MICs uncovered in AM3 medium using the EUCAST method Antimicrob Agents Chemother 2008 6 30 52 3092 8 18591282 PMC2533459 source
- Not checked yetcites [12] Jensen RH Johansen HK Arendrup MC Stepwise Development of a Homozygous S80P Substitution in Fks1p, Conferring Echinocandin Resistance in Candida tropicalis Antimicrobial Agents and Chemotherapy 2013 1 1 57 1 614 7 23089761 PMC3535961 source
- Not checked yetcites [13] Fekkar A Meyer I Brossas JY Rapid Emergence of Echinocandin Resistance during Candida kefyr Fungemia Treatment with Caspofungin Antimicrobial Agents and Chemotherapy 2013 5 1 57 5 2380 2 23439642 PMC3632960 source
- Not checked yetcites [14] Desnos-Ollivier M Moquet O Chouaki T Development of echinocandin resistance in Clavispora lusitaniae during caspofungin treatment J Clin Microbiol 2011 6 49 6 2304 6 21490186 PMC3122731 source
- Not checked yetcites [15] Arendrup MC Garcia-Effron G Lass-Florl C Echinocandin susceptibility testing of Candida species: comparison of EUCAST EDef 7.1, CLSI M27-A3, Etest, disk diffusion, and agar dilution methods with RPMI and isosensitest media Antimicrob Agents Chemother 2010 1 54 1 426 39 19884370 PMC2798528 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“It is most commonly detected after 3–4 weeks of treatment and is associated with a dismal outcome.”
§ Echinocandin resistance: an emerging clinical problem? > Abstract > Recent findings
What the sources say
- Not checked yetcites [12] Jensen RH Johansen HK Arendrup MC Stepwise Development of a Homozygous S80P Substitution in Fks1p, Conferring Echinocandin Resistance in Candida tropicalis Antimicrobial Agents and Chemotherapy 2013 1 1 57 1 614 7 23089761 PMC3535961 source
- Not checked yetcites [20] source
- Not checked yetcites [21] Dannaoui E Desnos-Ollivier M Garcia-Hermoso D Candida spp. with acquired echinocandin resistance, France, 2004–2010 Emerg Infect Dis 2012 1 18 1 86 90 22257484 PMC3310099 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“An extensive list of mutations in hot-spot regions of the genes encoding the target has been characterised and associated with species and drug specific loss of susceptibility.”
§ Echinocandin resistance: an emerging clinical problem? > Abstract > Recent findings
What the sources say
- Not checked yetcites [16] Perlin DS Resistance to echinocandin-class antifungal drugs Drug Resist Updat 2007 6 10 3 121 30 17569573 PMC2696280 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“It has been found in most clinically relevant Candida species, but is most common in C. glabrata with rates exceeding 10% at selected institutions.”
§ Echinocandin resistance: an emerging clinical problem? > Abstract > Recent findings
What the sources say
- Not checked yetcites [9] Park S Kelly R Kahn JN Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates Antimicrob Agents Chemother 2005 8 49 8 3264 73 16048935 PMC1196231 source
- Not checked yetcites [10] Cleary JD Garcia-Effron G Chapman SW Perlin DS Reduced Candida glabrata susceptibility secondary to an FKS1 mutation developed during candidemia treatment Antimicrob Agents Chemother 2008 6 52 6 2263 5 18378714 PMC2415792 source
- Not checked yetcites [11] Desnos-Ollivier M Bretagne S Raoux D Mutations in the fks1 gene in Candida albicans, C. tropicalis and C. krusei correlate with elevated caspofungin MICs uncovered in AM3 medium using the EUCAST method Antimicrob Agents Chemother 2008 6 30 52 3092 8 18591282 PMC2533459 source
- Not checked yetcites [12] Jensen RH Johansen HK Arendrup MC Stepwise Development of a Homozygous S80P Substitution in Fks1p, Conferring Echinocandin Resistance in Candida tropicalis Antimicrobial Agents and Chemotherapy 2013 1 1 57 1 614 7 23089761 PMC3535961 source
- Not checked yetcites [13] Fekkar A Meyer I Brossas JY Rapid Emergence of Echinocandin Resistance during Candida kefyr Fungemia Treatment with Caspofungin Antimicrobial Agents and Chemotherapy 2013 5 1 57 5 2380 2 23439642 PMC3632960 source
- Not checked yetcites [14] Desnos-Ollivier M Moquet O Chouaki T Development of echinocandin resistance in Clavispora lusitaniae during caspofungin treatment J Clin Microbiol 2011 6 49 6 2304 6 21490186 PMC3122731 source
- Not checked yetcites [15] Arendrup MC Garcia-Effron G Lass-Florl C Echinocandin susceptibility testing of Candida species: comparison of EUCAST EDef 7.1, CLSI M27-A3, Etest, disk diffusion, and agar dilution methods with RPMI and isosensitest media Antimicrob Agents Chemother 2010 1 54 1 426 39 19884370 PMC2798528 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“They display in vitro fungicidal activity against most Candida species, attractive tolerability and pharmacokinetic profiles, and have been recommended as first line agents for invasive candidiasis (1–6).”
§ Echinocandin resistance: an emerging clinical problem? > Introduction
What the sources say
- Not checked yetcites [1] Andes DR Safdar N Baddley JW 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 2012 4 54 8 1110 22 22412055 source
- Not checked yetcites [2] Cuenca-Estrella M Verweij PE Arendrup MC ESCMID* Guideline for the Diagnosis and Management of Candida Diseases 2012: Diagnostic Procedures Clinical Microbiology and Infection 2012 18 Suppl 7 9 18 23137134 source
- Not checked yetcites [3] Cornely OA Bassetti M Calandra T ESCMID* Guideline for the Diagnosis and Management of Candida Diseases 2012: Non-Neutropenic Adult Patients Clinical Microbiology and Infection 2012 18 Suppl 7 19 37 23137135 source
- Not checked yetcites [4] Hope WW Castagnola E Groll AH ESCMID* Guideline for the Diagnosis and Management of Candida Diseases 2012: Prevention and Management of Invasive Infections in Neonates and Children Caused by Candida spp Clinical Microbiology and Infection 2012 18 Suppl 7 38 52 23137136 source
- Not checked yetcites [5] Ullmann AJ Akova M Herbrecht R ESCMID* Guideline for the Diagnosis and Management of Candida Diseases 2012: Adults with Haematological Malignancies and after Haematopoietic Stem Cell Transplantation (HCT) Clinical Microbiology and Infection 2012 18 Suppl 7 53 67 23137137 source
- Not checked yetcites [6] Pappas PG Kauffman CA Andes D Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America Clin Infect Dis 2009 3 1 48 5 503 35 19191635 PMC7294538 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“However, some Candida spp. are inherently less susceptible in vitro due to naturally occurring polymorphisms in the target protein (Table 1) (7).”
§ Echinocandin resistance: an emerging clinical problem? > Introduction
What the sources say
- Not checked yetcites [7] Garcia-Effron G Katiyar SK Park S 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 2008 7 52 7 2305 12 18443110 PMC2443908 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“For example, the echinocandin MIC is approx. 7-fold higher against C. parapsilosis, which has a naturally occurring alteration in the target gene (Table 1).”
§ Echinocandin resistance: an emerging clinical problem? > Introduction
What the sources say
- Not checked yetcites [7] Garcia-Effron G Katiyar SK Park S 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 2008 7 52 7 2305 12 18443110 PMC2443908 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 7
- It may state two separate claims as one. 25
None of the sources cited for this claim have been checked yet.
In the paper
“Alternative technologies are being developed including molecular detection and MALDI-TOF.”
§ Echinocandin resistance: an emerging clinical problem? > Abstract > Recent findings
What the sources say
- Not checked yetcites [50] source
- Not checked yetcites [51]
- Not checked yetcites [52] De Carolis E Vella A Florio AR Use of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry for Caspofungin Susceptibility Testing of Candida and Aspergillus Species Journal of Clinical Microbiology 2012 7 1 50 7 2479 83 22535984 PMC3405623
- Not checked yetcites [53] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“They display in vitro fungicidal activity against most Candida species, attractive tolerability and pharmacokinetic profiles, and have been recommended as first line agents for invasive candidiasis (1–6).”
§ Echinocandin resistance: an emerging clinical problem? > Introduction
What the sources say
- Not checked yetcites [1] Andes DR Safdar N Baddley JW 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 2012 4 54 8 1110 22 22412055 source
- Not checked yetcites [2] Cuenca-Estrella M Verweij PE Arendrup MC ESCMID* Guideline for the Diagnosis and Management of Candida Diseases 2012: Diagnostic Procedures Clinical Microbiology and Infection 2012 18 Suppl 7 9 18 23137134 source
- Not checked yetcites [3] Cornely OA Bassetti M Calandra T ESCMID* Guideline for the Diagnosis and Management of Candida Diseases 2012: Non-Neutropenic Adult Patients Clinical Microbiology and Infection 2012 18 Suppl 7 19 37 23137135 source
- Not checked yetcites [4] Hope WW Castagnola E Groll AH ESCMID* Guideline for the Diagnosis and Management of Candida Diseases 2012: Prevention and Management of Invasive Infections in Neonates and Children Caused by Candida spp Clinical Microbiology and Infection 2012 18 Suppl 7 38 52 23137136 source
- Not checked yetcites [5] Ullmann AJ Akova M Herbrecht R ESCMID* Guideline for the Diagnosis and Management of Candida Diseases 2012: Adults with Haematological Malignancies and after Haematopoietic Stem Cell Transplantation (HCT) Clinical Microbiology and Infection 2012 18 Suppl 7 53 67 23137137 source
- Not checked yetcites [6] Pappas PG Kauffman CA Andes D Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America Clin Infect Dis 2009 3 1 48 5 503 35 19191635 PMC7294538 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“It has been found in most clinically relevant Candida species, but is most common in C. glabrata with rates exceeding 10% at selected institutions.”
§ Echinocandin resistance: an emerging clinical problem? > Abstract > Recent findings
What the sources say
- Not checked yetcites [23]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Additionally, polymorphisms occur at codon I660 in hot spot 1 of FKS1 in C. krusei, for which the in vitro micafungin MIC is elevated approx. 2-fold and at codon V641 in FKS1 and V1374 in FKS2 in Saccharomyces cerevisiae, which is in general slightly less echinocandin susceptible than C. albicans and C. glabrata.”
§ Echinocandin resistance: an emerging clinical problem? > Mechanisms and impact of the MIC
What the sources say
- Not checked yetcites [7] Garcia-Effron G Katiyar SK Park S 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 2008 7 52 7 2305 12 18443110 PMC2443908 source
- Not checked yetcites [26] Jensen RH Arendrup MC Candida palmioleophila: characterization of a previously overlooked pathogen and its unique susceptibility profile in comparison with five related species J Clin Microbiol 2011 2 49 2 549 56 21147953 PMC3043495 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Here, no cases were found in 2004–7, whilst 0.9% of the C. glabrata blood stream infections involved resistant isolates in 2008–9, 1.2% in 2010–11 and 3.1% resistance in 2012–13 (Arendrup, unpublished observations).”
§ Echinocandin resistance: an emerging clinical problem? > Epidemiology
What the sources say
- Not checked yetcites Arendrup, unpublished observations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Most are case reports or case series, which collectively document the potential of resistance development in almost all species that are not intrinsically susceptible (9–15).”
§ Echinocandin resistance: an emerging clinical problem? > Epidemiology
What the sources say
- Not checked yetcites [9] Park S Kelly R Kahn JN Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates Antimicrob Agents Chemother 2005 8 49 8 3264 73 16048935 PMC1196231 source
- Not checked yetcites [10] Cleary JD Garcia-Effron G Chapman SW Perlin DS Reduced Candida glabrata susceptibility secondary to an FKS1 mutation developed during candidemia treatment Antimicrob Agents Chemother 2008 6 52 6 2263 5 18378714 PMC2415792 source
- Not checked yetcites [11] Desnos-Ollivier M Bretagne S Raoux D Mutations in the fks1 gene in Candida albicans, C. tropicalis and C. krusei correlate with elevated caspofungin MICs uncovered in AM3 medium using the EUCAST method Antimicrob Agents Chemother 2008 6 30 52 3092 8 18591282 PMC2533459 source
- Not checked yetcites [12] Jensen RH Johansen HK Arendrup MC Stepwise Development of a Homozygous S80P Substitution in Fks1p, Conferring Echinocandin Resistance in Candida tropicalis Antimicrobial Agents and Chemotherapy 2013 1 1 57 1 614 7 23089761 PMC3535961 source
- Not checked yetcites [13] Fekkar A Meyer I Brossas JY Rapid Emergence of Echinocandin Resistance during Candida kefyr Fungemia Treatment with Caspofungin Antimicrobial Agents and Chemotherapy 2013 5 1 57 5 2380 2 23439642 PMC3632960 source
- Not checked yetcites [14] Desnos-Ollivier M Moquet O Chouaki T Development of echinocandin resistance in Clavispora lusitaniae during caspofungin treatment J Clin Microbiol 2011 6 49 6 2304 6 21490186 PMC3122731 source
- Not checked yetcites [15] Arendrup MC Garcia-Effron G Lass-Florl C Echinocandin susceptibility testing of Candida species: comparison of EUCAST EDef 7.1, CLSI M27-A3, Etest, disk diffusion, and agar dilution methods with RPMI and isosensitest media Antimicrob Agents Chemother 2010 1 54 1 426 39 19884370 PMC2798528 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Although some cases are reported after short-term use (a week)(13;19), most cases are diagnosed after 3–4 weeks of therapy or even later (12;20;21).”
§ Echinocandin resistance: an emerging clinical problem? > Epidemiology
What the sources say
- Not checked yetcites [12] Jensen RH Johansen HK Arendrup MC Stepwise Development of a Homozygous S80P Substitution in Fks1p, Conferring Echinocandin Resistance in Candida tropicalis Antimicrobial Agents and Chemotherapy 2013 1 1 57 1 614 7 23089761 PMC3535961 source
- Not matchedcites [20]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked yetcites [21] Dannaoui E Desnos-Ollivier M Garcia-Hermoso D Candida spp. with acquired echinocandin resistance, France, 2004–2010 Emerg Infect Dis 2012 1 18 1 86 90 22257484 PMC3310099 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Acquired FKS alterations are most commonly substitutions, but deletions and stop codons have also been reported in C. glabrata (Table 1) (16;21).”
§ Echinocandin resistance: an emerging clinical problem? > Mechanisms and impact of the MIC
What the sources say
- Not checked yetcites [16] Perlin DS Resistance to echinocandin-class antifungal drugs Drug Resist Updat 2007 6 10 3 121 30 17569573 PMC2696280 source
- Not checked yetcites [21] Dannaoui E Desnos-Ollivier M Garcia-Hermoso D Candida spp. with acquired echinocandin resistance, France, 2004–2010 Emerg Infect Dis 2012 1 18 1 86 90 22257484 PMC3310099 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, some alterations cause more moderate MIC elevations and not always for all three compounds (Table 2).”
§ Echinocandin resistance: an emerging clinical problem? > Mechanisms and impact of the MIC
What the sources say
- Not checked yetcites [16] Perlin DS Resistance to echinocandin-class antifungal drugs Drug Resist Updat 2007 6 10 3 121 30 17569573 PMC2696280
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Resistance is more often found in C. glabrata, although this species is less frequent than C. albicans as a cause of invasive infections and has been reported on both sides of the Atlantic ocean (Fig 1) (21;22).”
§ Echinocandin resistance: an emerging clinical problem? > Epidemiology
What the sources say
- Not checked yetcites [21] Dannaoui E Desnos-Ollivier M Garcia-Hermoso D Candida spp. with acquired echinocandin resistance, France, 2004–2010 Emerg Infect Dis 2012 1 18 1 86 90 22257484 PMC3310099 source
- Not checked yetcites [22] Matsumoto E Boyken L Tendolkar S Candidemia surveillance in Iowa: emergence of echinocandin resistance Diagnostic Microbiology and Infectious Disease 2014 6 79 2 205 8 24666704 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Recently, EUCAST breakpoints were developed for anidulafungin and micafungin and the former CLSI breakpoints were revised providing species specific breakpoints for all three echinocandins and their value confirmed (28;39–42).”
§ Echinocandin resistance: an emerging clinical problem? > Microdilution Reference testing and commercial phenotypic susceptibility tests
What the sources say
- Not checked yetcites [28] source
- Not checked yetcites [39] Marcos-Zambrano LJ Escribano P Sanchez C Antifungal Resistance to Fluconazole and Echinocandins Is Not Emerging in Yeast Isolates Causing Fungemia in a Spanish Tertiary Care Center Antimicrobial Agents and Chemotherapy 2014 8 1 58 8 4565 72 24867979 PMC4136060 source
- Not matchedcites [40]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [41] Clinical and Laboratory Standards Institute (CLSI) Reference method for broth dilution antifungal susceptibility testing of yeasts; Fourth informational Supplement CLSI document M27-S4 2012 Clinical and laboratory Standards Institute Pennsylvania, USA
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [42]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Thus, almost 20% of C. glabrata isolates and more than a third of the C. krusei isolates were anidulafungin and micafungin susceptible but caspofungin non-susceptible (44;45).”
§ Echinocandin resistance: an emerging clinical problem? > Microdilution Reference testing and commercial phenotypic susceptibility tests
What the sources say
- Not checked yetcites [44] Arendrup MC Pfaller MA Caspofungin Etest susceptibility testing of Candida species: risk of misclassification of susceptible isolates of C. glabrata and C. krusei when adopting the revised CLSI caspofungin breakpoints Antimicrob Agents Chemother 2012 7 56 7 3965 8 22564836 PMC3393381
- Not checked yetcites [45]
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Besides being the reference method commercial susceptibility tests are standardised against, these reference methods have proven reliable and useful in mycology reference laboratories for the detection of resistance in referred clinical isolates.”
§ Echinocandin resistance: an emerging clinical problem? > Microdilution Reference testing and commercial phenotypic susceptibility tests
What the sources say
- Not checked yetcites [36] Clinical and Laboratory Standards Institute (CLSI) Reference method for broth dilution antifungal susceptibility testing of yeasts; Approved standard - Third edition CLSI document M27-A3 2008 Clinical and laboratory Standards Institute Pennsylvania, USA
- Not checked yetcites [37] Arendrup MC Cuenca-Estrella M Lass-Florl C Hope W EUCAST technical note on the EUCAST definitive document EDef 7.2: method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for yeasts EDef 7.2 (EUCAST-AFST) Clin Microbiol Infect 2012 7 18 7 E246 E247 22563750
- Not checked yetcites [38] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Consequently, anidulafungin and micafungin have been evaluated as markers for caspofungin susceptibility and found appropriate for this purpose and is recommended also by EUCAST (40;47;48).”
§ Echinocandin resistance: an emerging clinical problem? > Microdilution Reference testing and commercial phenotypic susceptibility tests
What the sources say
- Not checked yetcites [40]
- Not checked yetcites [47]
- Not checked yetcites [48]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Thus, the echinocandin MICs were elevated at least 5-foldabove the breakpoints for C. krusei harbouring the D662Y compared to 1-foldabove the breakpoint for C. albicans and an MIC below the breakpoint for C. glabrata harbouring the corresponding alterations (D648Y in C. albicans and D666Y in the Fks2p protein for C. glabrata)(20;28).”
§ Echinocandin resistance: an emerging clinical problem? > Mechanisms and impact of the MIC
What the sources say
- Not checked yetcites [20]
- Not checked yetcites [28] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Overall a good inter laboratory agreement was achieved and the resistance rates reported for anidulafungin and micafungin was within the expected range (4.3 and 4.4% for anidulafungin and micafungin, respectively) (45).”
§ Echinocandin resistance: an emerging clinical problem? > Microdilution Reference testing and commercial phenotypic susceptibility tests
What the sources say
- Not checked yetcites [45]
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Thus, mutations at these hot spots have been linked to a) impaired enzyme capacity, b) altered cell wall composition, i.e. reduced glucan and increased chit in content, c) increased cell wall thickness and d) impaired filamentation properties, which contribute to a lower growth rate in vitro and in vivo in drosophila and mouse models (31–33).”
§ Echinocandin resistance: an emerging clinical problem? > Implication on fitness
What the sources say
- Not checked yetcites [31] Ben-Ami R Garcia-Effron G Lewis RE Fitness and Virulence Costs of Candida albicans FKS1 Hot Spot Mutations Associated With Echinocandin Resistance J Infect Dis 2011 8 204 4 626 35 21791665 PMC3144175 source
- Not checked yetcites [32] Singh-Babak SD Babak T Diezmann S Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata PLoS Pathog 2012 5 17 8 5 e1002718 22615574 PMC3355103 source
- Not checked yetcites [33] Lee KK MacCallum DM Jacobsen MD Elevated Cell Wall Chitin in Candida albicans Confers Echinocandin Resistance In Vivo Antimicrobial Agents and Chemotherapy 2012 1 1 56 1 208 17 21986821 PMC3256049 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This finding coupled with the fact that the system could not discriminate intermediate from susceptible C. glabrata isolates because the caspofungin concentration used in the system does not encompass the breakpoint, renders it less useful in its current form despite being very user friendly.”
§ Echinocandin resistance: an emerging clinical problem? > Microdilution Reference testing and commercial phenotypic susceptibility tests
What the sources say
- Not checked yetcites [49]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The two organisations EUCAST and CLSI both have established reproducible and reliable microbroth dilution susceptibility tests for Candida and echinocandins (36–38).”
§ Echinocandin resistance: an emerging clinical problem? > Microdilution Reference testing and commercial phenotypic susceptibility tests
What the sources say
- Not checked yetcites [36] Clinical and Laboratory Standards Institute (CLSI) Reference method for broth dilution antifungal susceptibility testing of yeasts; Approved standard - Third edition CLSI document M27-A3 2008 Clinical and laboratory Standards Institute Pennsylvania, USA
- Not checked yetcites [37] Arendrup MC Cuenca-Estrella M Lass-Florl C Hope W EUCAST technical note on the EUCAST definitive document EDef 7.2: method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for yeasts EDef 7.2 (EUCAST-AFST) Clin Microbiol Infect 2012 7 18 7 E246 E247 22563750
- Not checked yetcites [38] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“For example, the F659-DEL in C. glabrata confers resistance to all three echinocandins, whereas the F659S substitution at the same codon gives rise to anidulafungin and caspofungin resistance, whereas the micafungin MIC and in vivo efficacy in a murine animal model remains unchanged (23;25;27–30).”
§ Echinocandin resistance: an emerging clinical problem? > Mechanisms and impact of the MIC
What the sources say
- Not checked yetcites [23]
- Not checked yetcites [25]
- Not checked yetcites [27] Arendrup MC Perlin DS Jensen RH Differential In vivo activity of Anidulafungin, Caspofungin and Micafungin against C. glabrata with and without FKS resistance mutations Antimicrob Agents Chemother 2012 2 21 PMC3346593 22354305
- Not checked yetcites [28] source
- Not checked yetcites [29]
- Not checked yetcites [30] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Target gene sequencing has become increasingly available and appropriate primers designed and published for the most common species (9–15).”
§ Echinocandin resistance: an emerging clinical problem? > Molecular approaches
What the sources say
- Not checked yetcites [9] Park S Kelly R Kahn JN Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates Antimicrob Agents Chemother 2005 8 49 8 3264 73 16048935 PMC1196231 source
- Not checked yetcites [10] Cleary JD Garcia-Effron G Chapman SW Perlin DS Reduced Candida glabrata susceptibility secondary to an FKS1 mutation developed during candidemia treatment Antimicrob Agents Chemother 2008 6 52 6 2263 5 18378714 PMC2415792 source
- Not checked yetcites [11] Desnos-Ollivier M Bretagne S Raoux D Mutations in the fks1 gene in Candida albicans, C. tropicalis and C. krusei correlate with elevated caspofungin MICs uncovered in AM3 medium using the EUCAST method Antimicrob Agents Chemother 2008 6 30 52 3092 8 18591282 PMC2533459 source
- Not checked yetcites [12] Jensen RH Johansen HK Arendrup MC Stepwise Development of a Homozygous S80P Substitution in Fks1p, Conferring Echinocandin Resistance in Candida tropicalis Antimicrobial Agents and Chemotherapy 2013 1 1 57 1 614 7 23089761 PMC3535961 source
- Not checked yetcites [13] Fekkar A Meyer I Brossas JY Rapid Emergence of Echinocandin Resistance during Candida kefyr Fungemia Treatment with Caspofungin Antimicrobial Agents and Chemotherapy 2013 5 1 57 5 2380 2 23439642 PMC3632960 source
- Not checked yetcites [14] Desnos-Ollivier M Moquet O Chouaki T Development of echinocandin resistance in Clavispora lusitaniae during caspofungin treatment J Clin Microbiol 2011 6 49 6 2304 6 21490186 PMC3122731 source
- Not checked yetcites [15] Arendrup MC Garcia-Effron G Lass-Florl C Echinocandin susceptibility testing of Candida species: comparison of EUCAST EDef 7.1, CLSI M27-A3, Etest, disk diffusion, and agar dilution methods with RPMI and isosensitest media Antimicrob Agents Chemother 2010 1 54 1 426 39 19884370 PMC2798528 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Antifungal stewardship is an important tool reducing unnecessary use and the treatment duration whenever clinically indicated may help reducing the selection pressure and thus reverting the rise in resistance.”
§ Echinocandin resistance: an emerging clinical problem? > Conclusion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds. It may state two separate claims as one.
- Rests on an assumption: Antifungal stewardship reduces unnecessary use and selection pressure.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This may suggest that early de-escalation is a reasonable approach at least in this category of patients.”
§ Echinocandin resistance: an emerging clinical problem? > Clinical implications
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“New modalities including molecular and MALDI-TOF detection are under development and appear promising for future implementation in clinical microbiology laboratories.”
§ Echinocandin resistance: an emerging clinical problem? > Conclusion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Resistant isolates can be detected in the oral flora post candidaemia treatment at a rate of approx. 10% often in co-existence with susceptible isolates but is detected at a lower rate and apparently typically later (3–4 weeks) among blood isolates (12;21;24).”
§ Echinocandin resistance: an emerging clinical problem? > Clinical implications
What the sources say
- Not checked yetcites [12] Jensen RH Johansen HK Arendrup MC Stepwise Development of a Homozygous S80P Substitution in Fks1p, Conferring Echinocandin Resistance in Candida tropicalis Antimicrobial Agents and Chemotherapy 2013 1 1 57 1 614 7 23089761 PMC3535961 source
- Not checked yetcites [21] Dannaoui E Desnos-Ollivier M Garcia-Hermoso D Candida spp. with acquired echinocandin resistance, France, 2004–2010 Emerg Infect Dis 2012 1 18 1 86 90 22257484 PMC3310099 source
- Not matchedcites [24]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This is particularly true for the emergence of echinocandin resistance in C. glabrata, an organism that is commonly resistant to azole drugs and for which amphotericin B is therefore the only therapeutic alternative.”
§ Echinocandin resistance: an emerging clinical problem? > Clinical implications
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Recently, the potential of using MALDI-TOF detection of proteome changes after a 15-h exposure of fungal cells to serial drug concentrations was described for the determination of antifungal susceptibility (52).”
§ Echinocandin resistance: an emerging clinical problem? > Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF)
What the sources say
- Not checked yetcites [52] De Carolis E Vella A Florio AR Use of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry for Caspofungin Susceptibility Testing of Candida and Aspergillus Species Journal of Clinical Microbiology 2012 7 1 50 7 2479 83 22535984 PMC3405623
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Echinocandin resistance is emerging in population based candidaemia surveys and particularly in severely ill patients receiving longer-term therapy.”
§ Echinocandin resistance: an emerging clinical problem? > Conclusion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
In the paper
“Based upon the data from initial controlled trial, ESCMID recommended de-escalation after 10 days, as data was not available supporting any earlier time-point (54).”
§ Echinocandin resistance: an emerging clinical problem? > Clinical implications
What the sources say
- Not checked yetcites [54] Reboli AC Rotstein C Pappas PG Anidulafungin versus fluconazole for invasive candidiasis N Engl J Med 2007 6 14 356 24 2472 82 17568028
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper relies on this without support.
Echinocandins inhibit glucan synthase encoded by FKS1, FKS2 and FKS3.
“The echinocandins exhibit their antifungal activity via inhibition of the enzyme glucan synthase encoded by three related genes (FKS1, FKS2 and FKS3).”
The paper relies on this without support.
Echinocandin use for prophylaxis and treatment has grown substantially following regulatory approval.
“Following regulatory approval, the use of the echinocandins for prophylaxis and treatment has grown substantially.”
The paper relies on this without support.
None of the molecular methods for echinocandin resistance detection is yet commercially available.
“Finally, none of these methods is yet commercially available and therefore implementation requires molecular biology expertise and in house validation.”
The paper relies on this without support.
Echinocandins are not used in the primary health care sector or for plant and material protection.
“Unlike the azoles, echinocandins are not used in the primary health care sector or for plant and material protection.”
The paper relies on this without support.
Antifungal stewardship reduces unnecessary use and selection pressure.
“Antifungal stewardship is important in order to minimise unnecessary selection pressure.”
The paper relies on this without support.
The clinical situation may mandate longer treatment and voriconazole or high dose fluconazole may not be attractive alternatives in severely ill patients with C. glabrata candidaemia.
“It is well recognised, that the clinical situation may mandate longer treatment and that voriconazole or high dose fluconazole may not be attractive alternatives in severely ill patients with C. glabrata candidaemia.”
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?
In the citing paper
“Among the species more tolerant to echinocandins, besides C. parapsilosis, we can find C. orthopsilosis, C. metapsilosis, C. guillerimondii, C. lipolytica, and C. fermentati [33,34,35].”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [34]
In the citing paper
“Candida can evade the activity of echinocandins by mutations in particular regions (called hotspots) in the FKS1 gene and in the case of C. glabrata, as well in FKS2 (Table 4) [34].”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [34]
In the citing paper
“Notably, many of these resistance-causing sequence variations are constitutive in species showing a higher intrinsic tolerance towards echinocandins (e.g., C. parapsilosis, C. orthopsilosis, C. metapsilosis, C. guillerimondii, and C. lipolytica) [34,35].”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [34]
In the citing paper
“What is more, the degree of susceptibility towards echinocandins depends on the position and specificity of the mutation [34].”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [34]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Echinocandin resistance: an emerging clinical problem? > Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF)
“discrimination of susceptible and resistant isolates of C. albicans after only 3 hours of incubation”
§ Echinocandin resistance: an emerging clinical problem? > References
“First same-day susceptibility screening test for echinocandin resistance in C. glabrata using MALDI-TOF is described.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Echinocandin resistance: an emerging clinical problem? > Mechanisms and impact of the MIC
“C. krusei harbouring the D662Y”
§ Echinocandin resistance: an emerging clinical problem? > References
“First description of the D660Y alteration in C. krusei”
Citations
Cites
Pappas, P. G., Kauffman, C. A., Andes, D., Benjamin, D. K., Calandra, T. F., Edwards, J. E., Filler, S. G., Fisher, J. F., Kullberg, B.-J., Zeichner, L. O., et al. (2009) · Clinical Infectious Diseases · doi:10.1086/596757 · Cited by 3,191
Cornely, O. A., Bassetti, M., Calandra, T., Garbino, J., Kullberg, B. J., Lortholary, O., Meersseman, W., Akova, M., Arendrup, M. C., Arikan-Akdagli, S., et al. (2012) · Clinical Microbiology and Infection · doi:10.1111/1469-0691.12039 · Cited by 1,217
Self-citationAnidulafungin versus Fluconazole for Invasive Candidiasis
Reboli, A. C., Rotstein, C., Pappas, P. G., Chapman, S. W., Kett, D. H., Kumar, D., Betts, R., Wible, M., Goldstein, B. P., Schranz, J., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa066906 · Cited by 894
Andes, D. R., Safdar, N., Baddley, J. W., Playford, G., Reboli, A. C., Rex, J. H., Sobel, J. D., Pappas, P. G., Kullberg, B. J., & for the Mycoses Study Group (2012) · Clinical Infectious Diseases · doi:10.1093/cid/cis021 · Cited by 793
Alexander, B. D., Johnson, M. D., Pfeiffer, C. D., Jiménez-Ortigosa, C., Catania, J., Booker, R., Castanheira, M., Messer, S. A., Perlin, D. S., & Pfaller, M. A. (2013) · Clinical Infectious Diseases · doi:10.1093/cid/cit136 · Cited by 778
Self-citationParczewska, O. K., Posaconazol, przeciwgrzybicze, L., Anidulafungina, Micafungina, & wrażliwość, O. (2009) · Cited by 656
Resistance to echinocandin-class antifungal drugs.
Perlin, D. S. (2007) · Drug Resistance Updates · doi:10.1016/j.drup.2007.04.002 · Cited by 512
Self-citationArendrup, M. C., Cuenca-Estrella, M., Lass-Flörl, C., & Hope, W. (2012) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.2012.03880.x · Cited by 451
Self-citationPark, S., Kelly, R., Kahn, J. N., Robles, J., Hsu, M.-J., Register, E., Li, W., Vyas, V., Fan, H., Abruzzo, G., et al. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.8.3264-3273.2005 · Cited by 434
Self-citationESCMID guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures.
Cuenca-Estrella, M., Verweij, P. E., Arendrup, M. C., Arikan-Akdagli, S., Bille, J., Donnelly, J. P., Jensen, H. E., Lass-Flörl, C., Richardson, M. D., Akova, M., et al. (2012) · Clinical Microbiology and Infection · doi:10.1111/1469-0691.12038 · Cited by 386
Self-citation
Cited by
Sorted by citations
Pappas, P. G., Lionakis, M. S., Arendrup, M. C., Ostrosky-Zeichner, L., & Kullberg, B. J. (2018) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2018.26 · Cited by 1,636
Self-citationKullberg, B. J., & Arendrup, M. C. (2015) · New England Journal of Medicine · doi:10.1056/nejmra1315399 · Cited by 1,315
Self-citationThe global problem of antifungal resistance: prevalence, mechanisms, and management
Perlin, D. S., Rautemaa-Richardson, R., & Alastruey-Izquierdo, A. (2017) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(17)30316-x · Cited by 1,055
Self-citationOral Candidiasis: A Disease of Opportunity
Vila, T., Sultan, A. S., Montelongo-Jauregui, D., & Jabra-Rizk, M. A. (2020) · Journal of Fungi · doi:10.3390/jof6010015 · Cited by 537
Molecular Evolution of Antifungal Drug Resistance
Robbins, N., Caplan, T., & Cowen, L. E. (2017) · Annual Review of Microbiology · doi:10.1146/annurev-micro-030117-020345 · Cited by 441
Echinocandin resistance in Candida.
Perlin, D. S. (2015) · Clinical Infectious Diseases · doi:10.1093/cid/civ791 · Cited by 374
Self-citationMechanisms of echinocandin antifungal drug resistance
Perlin, D. S. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12831 · Cited by 313
Self-citationEvolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens
Ksiezopolska, E., & Gabaldón, T. (2018) · Genes · doi:10.3390/genes9090461 · Cited by 230
Shaw, K. J., & Ibrahim, A. S. (2020) · Journal of Fungi · doi:10.3390/jof6040239 · Cited by 229
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Self-citationTargeting Candida albicans filamentation for antifungal drug development
Vila, T., Romo, J. A., Pierce, C. G., McHardy, S. F., Saville, S. P., & Lopez-Ribot, J. L. (2017) · Virulence · doi:10.1080/21505594.2016.1197444 · Cited by 174
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Holmes, A. R., Cardno, T. S., Strouse, J. J., Ivnitski-Steele, I., Keniya, M. V., Lackovic, K., Monk, B. C., Sklar, L. A., & Cannon, R. D. (2016) · Future Medicinal Chemistry · doi:10.4155/fmc-2016-0050 · Cited by 156
Changing epidemiology of candidaemia in Australia
Chapman, B., Slavin, M., Marriott, D., Halliday, C., Kidd, S., Arthur, I., Bak, N., Heath, C. H., Kennedy, K., Morrissey, C. O., et al. (2016) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkw422 · Cited by 163
The Quiet and Underappreciated Rise of Drug-Resistant Invasive Fungal Pathogens
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Self-citationThammahong, A., Puttikamonkul, S., Perfect, J. R., Brennan, R. G., & Cramer, R. A. (2017) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00053-16 · Cited by 125
Defining the frontiers between antifungal resistance, tolerance and the concept of persistence
Delarze, E., & Sanglard, D. (2015) · Drug Resistance Updates · doi:10.1016/j.drup.2015.10.001 · Cited by 118
Molecular basis of antifungal drug resistance in yeasts
Morio, F., Jensen, R. H., Le Pape, P., & Arendrup, M. C. (2017) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2017.05.012 · Cited by 114
Self-citationThe current treatment landscape: Candidiasis
Bassetti, M., Peghin, M., & Timsit, J.-F. (2016) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkw392 · Cited by 99
Vitenshtein, A., Charpak-Amikam, Y., Yamin, R., Bauman, Y., Isaacson, B., Stein, N., Berhani, O., Dassa, L., Gamliel, M., Gur, C., et al. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.09.008 · Cited by 96
Jensen, R. H., Astvad, K. M. T., Silva, L. V., Sanglard, D., Jørgensen, R., Nielsen, K. F., Mathiasen, E. G., Doroudian, G., Perlin, D. S., & Arendrup, M. C. (2015) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkv140 · Cited by 95
Self-citationYang, F., Zhang, L., Wakabayashi, H., Myers, J., Jiang, Y., Cao, Y., Jimenez-Ortigosa, C., Perlin, D. S., & Rustchenko, E. (2017) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00071-17 · Cited by 81
Self-citationPfaller, M. A., Messer, S. A., Rhomberg, P. R., Borroto-Esoda, K., & Castanheira, M. (2017) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00161-17 · Cited by 84
Acquired multidrug antifungal resistance in Candida lusitaniae during therapy
Asner, S. A., Giulieri, S., Diezi, M., Marchetti, O., & Sanglard, D. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02204-15 · Cited by 82
CD101: a novel long-acting echinocandin
Zhao, Y., Perez, W. B., Jiménez‐Ortigosa, C., Hough, G., Locke, J. B., Ong, V., Bartizal, K., & Perlin, D. S. (2016) · Cellular Microbiology · doi:10.1111/cmi.12640 · Cited by 81
Self-citationRogers, T. R., Verweij, P. E., Castanheira, M., Dannaoui, E., White, P. L., Arendrup, M. C., Subcommittee on Antifungal Susceptibility Testing (AFST) of the ESCMID European Committee for Antimicrobial Susceptibility Testing (EUCAST), Arendrup, M. C., Arikan-Akdagli, S., Barchiesi, F., et al. (2022) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkac161 · Cited by 82
Self-citationJensen, R. H., Johansen, H. K., Søes, L. M., Lemming, L. E., Rosenvinge, F. S., Nielsen, L., Olesen, B., Kristensen, L., Dzajic, E., Astvad, K. M. T., et al. (2016) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01763-15 · Cited by 77
Self-citationComparative Genomics for the Elucidation of Multidrug Resistance in Candida lusitaniae
Kannan, A., Asner, S. A., Trachsel, E., Kelly, S., Parker, J., & Sanglard, D. (2019) · mBio · doi:10.1128/mbio.02512-19 · Cited by 63
Rapid Detection of FKS -Associated Echinocandin Resistance in Candida glabrata
Zhao, Y., Nagasaki, Y., Kordalewska, M., Press, E. G., Shields, R. K., Nguyen, M. H., Clancy, C. J., & Perlin, D. S. (2016) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01574-16 · Cited by 61
Self-citationComparative Genomics of Two Sequential Candida glabrata Clinical Isolates
Vale-Silva, L., Beaudoing, E., Tran, V. D. T., & Sanglard, D. (2017) · G3 Genes|Genomes|Genetics · doi:10.1534/g3.117.042887 · Cited by 61
Rueda, C., Puig-Asensio, M., Guinea, J., Almirante, B., Cuenca-Estrella, M., Zaragoza, O., Padilla, B., Muñoz, P., Guinea, J., Paño Pardo, J. R., et al. (2017) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2016.09.016 · Cited by 58
Carreté, L., Ksiezopolska, E., Gómez-Molero, E., Angoulvant, A., Bader, O., Fairhead, C., & Gabaldón, T. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.00112 · Cited by 58
Rate of FKS Mutations among Consecutive Candida Isolates Causing Bloodstream Infection
Shields, R. K., Nguyen, M. H., Press, E. G., Cumbie, R., Driscoll, E., Pasculle, A. W., & Clancy, C. J. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01973-15 · Cited by 55
Fungal resistance to echinocandins and the MDR phenomenon in Candida glabrata
Healey, K., & Perlin, D. S. (2018) · doi:10.20944/preprints201808.0306.v1 · Cited by 194
Self-citationVale-Silva, L. A., Moeckli, B., Torelli, R., Posteraro, B., Sanguinetti, M., & Sanglard, D. (2016) · mSphere · doi:10.1128/msphere.00065-15 · Cited by 51
Marcos-Zambrano, L. J., Gómez-Perosanz, M., Escribano, P., Bouza, E., & Guinea, J. (2017) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkx010 · Cited by 44
Biswas, C., Chen, S. C.-A., Halliday, C., Kennedy, K., Playford, E. G., Marriott, D. J., Slavin, M. A., Sorrell, T. C., & Sintchenko, V. (2017) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2017.03.014 · Cited by 36
Garcia-Rubio, R., Hernandez, R. Y., Clear, A., Healey, K. R., Shor, E., & Perlin, D. S. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.702779 · Cited by 35
Self-citationHealey, K. R., Challa, K. K., Edlind, T. D., & Katiyar, S. K. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.04667-14 · Cited by 23
Rapid emergence of FKS mutations in Candida glabrata isolates in a peritoneal candidiasis
Sasso, M., Roger, C., & Lachaud, L. (2017) · Medical Mycology Case Reports · doi:10.1016/j.mmcr.2017.04.004 · Cited by 20
Yeoh, S. F., Lee, T. J., Chew, K. L., Lin, S., Yeo, D., & Setia, S. (2018) · Infection and Drug Resistance · doi:10.2147/idr.s165676 · Cited by 20
Schikora-Tamarit, M. À., Marcet-Houben, M., Nosek, J., & Gabaldón, T. (2021) · Open Biology · doi:10.1098/rsob.200362 · Cited by 16
Desnos-Ollivier, M., Bretagne, S., Lortholary, O., Dromer, F., & the French Mycoses Study Group N. Brieu CH Aix, T. C. (2022) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01725-21 · Cited by 13
Post-transcriptional control of antifungal resistance in human fungal pathogens
Sharma, C., & Kadosh, D. (2023) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2022.2080527 · Cited by 6
Metadata
- Authors
- Arendrup, M. C., & Perlin, D. S.
- Affiliations
- Statens Serum Institut (DK)
- Rutgers New Jersey Medical School (US)
- Corresponding author
- Arendrup, Maiken C.
- Venue
- Current Opinion in Infectious Diseases
- Published
- 2014-12
- Volume
- 27
- Issue
- 6
- Pages
- 484-492
- ISSN
- 0951-7375 (ISSN-L)
- PMC
- PMC4221099
- OpenAlex
- W1968846907
- Semantic Scholar
- 3c588a729e69401df53b1410d93567e60382b362
- Cited by
- 299
- References
- 57
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 15 · 2023: 17 · 2022: 18 · 2021: 24 · 2020: 30 · 2019: 29 · 2018: 29 · 2017: 44 · 2016: 35 · 2015: 26 · 2014: 1
- FWCI
- 4.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Pfizer
- Gilead Sciences
- Astellas Pharma
- National Institutes of Health (2r01ai109025-11)
- National Institute of Allergy and Infectious Diseases (R01AI069397, R01AI-109025)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Fungal Plant Pathogen Control
- Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
- Keywords
- echinocandin resistance, Candida glabrata, invasive candidiasis, antifungal susceptibility testing, antifungal stewardship, molecular detection of resistance, MALDI-TOF mass spectrometry, epidemiology of resistance, clinical outcomes
- MeSH terms
- Antifungal Agents, Candidiasis, DNA Mutational Analysis, Fungal Proteins, Humans, Microbial Sensitivity Tests, Mutation, Treatment Outcome, Genetic Predisposition to Disease, Drug Resistance, Fungal, Candida glabrata, Echinocandins, Molecular Targeted Therapy
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