Treatment practices for adults with candidemia at 9 active surveillance sites—United States, 2017–2018.
Open accessAbstract
Background: Candidemia is a common opportunistic infection causing substantial morbidity and mortality. Because of an increasing proportion of non-albicans Candida species and rising antifungal drug resistance, the Infectious Diseases Society of America (IDSA) changed treatment guidelines in 2016 to recommend echinocandins over fluconazole as first-line treatment for adults with candidemia. We describe candidemia treatment practices and adherence to the updated guidelines. Methods: During 2017–2018, the Emerging Infections Program conducted active population-based candidemia surveillance at 9 US sites using a standardized case definition. We assessed factors associated with initial antifungal treatment for the first candidemia case among adults using multivariable logistic regression models. To identify instances of potentially inappropriate treatment, we compared the first antifungal drug received with species and antifungal susceptibility testing (AFST) results from initial blood cultures. Results: Among 1835 patients who received antifungal treatment, 1258 (68.6%) received an echinocandin and 543 (29.6%) received fluconazole as initial treatment. Cirrhosis (adjusted odds ratio = 2.06; 95% confidence interval, 1.29–3.29) was the only underlying medical condition significantly associated with initial receipt of an echinocandin (versus fluconazole). More than one-half (n = 304, 56.0%) of patients initially treated with fluconazole grew a non-albicans species. Among 265 patients initially treated with fluconazole and with fluconazole AFST results, 28 (10.6%) had a fluconazole-resistant isolate. Conclusions: A substantial proportion of patients with candidemia were initially treated with fluconazole, resulting in potentially inappropriate treatment for those involving non-albicans or fluconazole-resistant species. Reasons for nonadherence to IDSA guidelines should be evaluated, and clinician education is needed.
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- Findingown data
Among patients with available in-hospital mortality data (n=1795, 99.7%), a higher percentage of those initially treated with an echinocandin died during hospitalization (28.3%) than those initially treated with fluconazole (16.1%) (P < .0001).
“Among patients with available in-hospital mortality data (n = 1795, 99.7%), a higher percentage of patients who received an echinocandin (n = 355, 28.3%) versus fluconazole (n = 87, 16.1%) as initial treatment died during their candidemia-associated hospitalization (P < .0001).”
Quote in the paperNot a substantial claim - Findingown data
Of the 2271 index cases, 1835 received an antifungal drug for candidemia treatment.
“For the index cases of these 2271 patients, 1835 received an antifungal drug for candidemia treatment.”
Quote in the paperSubstantial claim - Findingown data
In bivariate analysis, echinocandin recipients were less likely to have had a recent hospitalization within 90 days before candidemia than fluconazole recipients (53.5% vs 59.5%, P = .0190).
“Patients who received an echinocandin were less likely to have had a recent hospitalization (within 90 days before candidemia) than were patients who received fluconazole (n = 673, [53.5%] versus n = 323 [59.5%], P = .0190).”
Quote in the paperNot a substantial claim - Findingown data
In bivariate analysis, echinocandin recipients were more likely to have cirrhosis (110, 8.7%) than fluconazole recipients (23, 4.2%) (P = .0008).
“In bivariate analyses comparing initial antifungal treatment, patients who received an echinocandin were more likely to have cirrhosis (n = 110, 8.7%) than were patients who received fluconazole (n = 23, 4.2%) (P = .0008) (Table 1).”
Quote in the paperNot a substantial claim - Findingown data
In a multivariable logistic regression model adjusting for age, cirrhosis, recent hospitalization, and surveillance site were the only factors significantly associated with receipt of an echinocandin versus fluconazole.
“In a multivariable logistic regression model adjusting for age, cirrhosis, recent hospitalization, and surveillance site were the only factors significantly associated with receipt of an echinocandin versus fluconazole (Table 2).”
Quote in the paperSubstantial claim
- Findingown data
Median time from first positive blood culture collection to initial antifungal drug receipt was 2.0 days (mean 1.8, IQR 1.0-3.0).
“The median time between first positive blood culture collection and initial antifungal drug receipt was 2.0 days (mean 1.8, interquartile range [1.0, 3.0]).”
Quote in the paperNot a substantial claim - Findingown data
During 2017-2018, 2415 candidemia cases occurred among 2271 adult patients in EIP surveillance areas.
“During 2017–2018, 2415 candidemia cases occurred among 2271 adult patients residing within EIP surveillance areas.”
Quote in the paperNot a substantial claim - Findingown data
AFST for both fluconazole and an echinocandin was performed for 701 patients (38.9%, range among sites 4.9%-95.1%).
“AFST for both fluconazole and an echinocandin was performed for 701 patients (38.9%, range among sites = 4.9%–95.1%).”
Quote in the paperNot a substantial claim - Findingown data
Nearly one-half of patients started initially on fluconazole were then switched to an echinocandin, usually within several days.
“We noted that nearly one-half of patients started initially on fluconazole were then switched to an echinocandin, usually within several days; although the motivation driving this switch is unknown, we suspect that these changes could be due to treatment failure, receipt of AFST results, identification of additional species that warranted a new treatment plan, specialist consultation, or clinical”
Quote in the paperNot a substantial claim - Findingown data
Patients with cirrhosis had over twice the odds of receiving an echinocandin versus fluconazole as initial candidemia treatment (adjusted odds ratio 2.06; 95% CI 1.29-3.29).
“Cirrhosis (adjusted odds ratio = 2.06; 95% confidence interval, 1.29–3.29) was the only underlying medical condition significantly associated with initial receipt of an echinocandin (versus fluconazole).”
- Also stated in: § Initial Antifungal Treatment · plain
“Patients with cirrhosis had over twice the odds of receiving an echinocandin versus fluconazole as initial candidemia treatment (adjusted odds ratio: 2.06, 95% confidence interval, 1.29–3.29).”
Quote in the paperSubstantial claim - Also stated in: § Initial Antifungal Treatment · plain
- Findingown data
In our analysis, 39.1% of patients were switched from an echinocandin to fluconazole without receiving fluconazole AFST.
“In our analysis, 39.1% of patients were switched from an echinocandin to fluconazole without receiving fluconazole AFST.”
Quote in the paperSubstantial claim - Findingown data
Eight of 525 (1.5%) patients initially treated with an echinocandin who received echinocandin AFST grew an echinocandin-resistant Candida species.
“Eight of 525 (1.5%) patients who were treated initially with an echinocandin and received echinocandin AFST grew an echinocandin-resistant Candida species.”
Quote in the paperNot a substantial claim - Findingown data
Recent hospitalization was associated with lower odds of receiving an echinocandin as first-line treatment (adjusted odds ratio 0.80; 95% CI 0.65-0.98).
“Recent hospitalization was associated with a lower odds of receiving an echinocandin as first-line treatment (adjusted odds ratio: 0.80; 95% confidence interval, 0.65–0.98).”
Quote in the paperSubstantial claim - Findingown data
One in four patients received an antifungal drug on or during the 14 days before the specimen collection day of their first positive blood culture.
“Furthermore, 1 in 4 patients received an antifungal drug on or during the 14 days before the specimen collection day of their first positive blood culture, suggesting that they may have received empiric therapy for suspected candidemia before Candida was detected.”
Quote in the paperNot a substantial claim - Findingown data
Approximately 25% of patients first received antifungal treatment ≥3 days after the date of their first positive blood culture collection.
“Approximately 25% of patients in our analysis first received antifungal treatment ≥3 days after the date of their first positive blood culture collection, which is consistent with previous research of candidemia treatment delays [26].”
Quote in the paperSubstantial claim - Interpretationreasoning
Treatment practices observed at EIP surveillance sites may not reflect those throughout the country.
“Although EIP candidemia surveillance encompassed a source population of approximately 17.1 million, treatment practices observed in EIP surveillance sites may not reflect those throughout the country.”
Quote in the paperSubstantial claim - Interpretationreasoning
It is difficult to definitively state whether the treatment decisions were inappropriate.
“which makes it difficult to generalize about treatment practices across the nation or to definitively state whether the treatment decisions were inappropriate.”
Quote in the paperSubstantial claim - Study design and conductown data
The analysis was limited by lack of facility-level data, setting of care, and treating physician type, making it difficult to compare practices among facility types.
“our analysis was limited by the lack of facility-level data needed to compare practices among facility types (eg, tertiary, academic, community hospitals), as well as a lack of data on setting of care (eg, ward, intensive care unit) and treating physician type (eg, infectious disease specialist) at the time of antifungal drug treatment initiation.”
Quote in the paperSubstantial claim - Interpretationown data
Initial fluconazole treatment resulted in potentially inappropriate treatment for patients with non-albicans or fluconazole-resistant species.
“A substantial proportion of patients with candidemia were initially treated with fluconazole, resulting in potentially inappropriate treatment for those involving non-albicans or fluconazole-resistant species.”
- Also stated in: § DISCUSSION · plain
“However, a substantial proportion (29.6%) of patients initially received fluconazole, which resulted in potentially inappropriate treatment.”
- Also stated in: § DISCUSSION · plain
“Nonetheless, our analysis of data from a large, population-based, and multisite candidemia surveillance system identified instances in which patients received potentially inappropriate candidemia treatment.”
Quote in the paperSubstantial claim - Also stated in: § DISCUSSION · plain
- Study design and conductown data
The multivariable logistic regression model was adjusted for age, cirrhosis, recent hospitalization, and surveillance site.
“In a multivariable logistic regression model adjusting for age, cirrhosis, recent hospitalization, and surveillance site were the only factors significantly associated with receipt of an echinocandin versus fluconazole (Table 2).”
Quote in the paperSubstantial claim - Interpretationown data
Regional practices play a stronger role in initial candidemia therapy than patient-level factors.
“This finding suggests that regional practices play a stronger role in initial candidemia therapy than patient-level factors and that clinician education regarding risk factors for drug-resistant candidemia may be needed.”
Quote in the paperSubstantial claim - Interpretationcitation
The mortality difference between initial echinocandin and fluconazole groups is likely due to confounding because critically ill patients are more likely to be treated with an echinocandin.
“In our investigation, patients treated initially with an echinocandin were more likely to die during their candidemia-associated hospitalization than those treated with fluconazole. However, this finding is likely from confounding factors because critically ill patients are more likely to be treated with an echinocandin [33].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [33] Leroy, 2016, Systemic antifungal therapy for proven or suspected invasive candidiasis: the AmarCAND 2 study, Ann Intensive Care source
Not checked in the free run.
- Premisecitation
IDSA changed treatment guidelines in 2016 to strongly recommend echinocandins instead of fluconazole as initial treatment for candidemia in all adults.
“IDSA changed treatment guidelines in 2016 to strongly recommend echinocandins instead of fluconazole as the initial treatment of candidemia in all adults; the guidelines consider fluconazole to be an acceptable alternative to an echinocandin as initial therapy in noncritically ill patients and patients considered unlikely to have a fluconazole-resistant Candida species [13].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13] 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.
- Premisecitation
Critically ill patients are more likely to be treated with an echinocandin.
“However, this finding is likely from confounding factors because critically ill patients are more likely to be treated with an echinocandin [33].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [33] Leroy, 2016, Systemic antifungal therapy for proven or suspected invasive candidiasis: the AmarCAND 2 study, Ann Intensive Care source
Not checked in the free run.
- Premisecitation
The frequency of AFST performance and use in clinical decision-making might vary based on cost, lack of trained personnel, and reliance on off-site testing, which can delay results (about 3 days on-site vs 7 days off-site).
“Although the capacity of laboratories in the United States to perform AFST has increased in recent years, the frequency of AFST performance and use in clinical decision-making might vary based on several factors, including cost, a lack of personnel trained in mycology, and reliance on off-site testing, which can substantially delay results (from ~3 days with on-site testing versus ~7 days for off”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [14] Vallabhaneni, 2017, Antifungal susceptibility testing practices at acute care hospitals enrolled in the national healthcare safety network, United States, 2011–2015, Open Forum Infect Dis source
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- cites [32] Pai, 2003, Antifungal susceptibility testing in teaching hospitals, Ann Pharmacother source
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- Premisecitation
A recent analysis using National Healthcare Safety Network data found that reflexive AFST is lacking in approximately two-thirds of acute care hospitals.
“A recent analysis using National Healthcare Safety Network data found that reflexive AFST is lacking in approximately two-thirds of acute care hospitals [14].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [14] Vallabhaneni, 2017, Antifungal susceptibility testing practices at acute care hospitals enrolled in the national healthcare safety network, United States, 2011–2015, Open Forum Infect Dis source
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- Premisecitation
A randomized controlled trial found superior outcomes for patients who received an echinocandin as primary treatment for invasive candidiasis.
“A randomized controlled trial, more robust for examining effects of treatment, found superior outcomes for patients who received an echinocandin as primary treatment for invasive candidiasis [12].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [12] Reboli, 2007, Anidulafungin versus fluconazole for invasive candidiasis, N Engl J Med source
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- Premisecitation
Early identification and treatment of candidemia with an appropriate antifungal drug improves morbidity and mortality.
“Early identification and treatment of candidemia with an appropriate antifungal drug improves morbidity and mortality [8, 9].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [8] 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
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- cites [9] Ostrosky-Zeichner, 2011, Early treatment of candidemia in adults: a review, Med Mycol source
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- Premisecitation
A large multicenter randomized controlled trial did not find a significant survival difference between empiric micafungin and placebo in nonneutropenic critically ill patients.
“a large, multicenter randomized control trial of empiric antifungal therapy in nonneutropenic critically ill patients did not find a significant difference in survival among patients treated empirically with micafungin versus placebo [29].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [29] Timsit, 2016, Empirical micafungin treatment and survival without invasive fungal infection in adults with ICU-acquired sepsis, Candida colonization, and multiple organ failure: the EMPIRICUS randomized clinical trial, JAMA source
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- Premisecitation
A common practice among clinicians is to initially treat candidemia with an echinocandin followed by deescalation to fluconazole after clinical improvement.
“A common practice among clinicians is to initially treat candidemia with an echinocandin followed by deescalation to fluconazole after the patient shows clinical improvement [13].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13] 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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- Premisecitation
Non-albicans Candida species tend to be more resistant to antifungal drugs than C albicans.
“Non-albicans Candida species tend to be more resistant to antifungal drugs than C albicans, and the emergence of drug-resistance among both albicans and non-albicans Candida, including C auris, constitutes a major public health threat [7].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7] Centers for Disease Control and Prevention., 2019 source
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- May combine two claims. 17
- Classified as probably not a substantial claim. 12
May combine two claims.
Findingown dataAmong 1835 treated patients, 1258 (68.6%) received an echinocandin and 543 (29.6%) received fluconazole as initial treatment.
“Among 1835 patients who received antifungal treatment, 1258 (68.6%) received an echinocandin and 543 (29.6%) received fluconazole as initial treatment.”
- Also stated in: § Initial Antifungal Treatment · plain
“Initial antifungal treatments included an echinocandin (n = 1258, 68.6%), fluconazole (n = 543, 29.6%), and other drugs (eg, amphotericin, non-fluconazole triazole) (n = 34, 1.9%); 436 patients received no antifungal treatment (Figure 1).”
- Also stated in: § DISCUSSION · plain
“Our analysis of candidemia treatment practices at 9 US surveillance sites found that most adult patients received an echinocandin rather than fluconazole as initial treatment for candidemia.”
Quote in the paperSubstantial claim- Also stated in: § Initial Antifungal Treatment · plain
May combine two claims.
Findingown dataThere were no significant differences between initial echinocandin and fluconazole groups in age group, sex, race/ethnicity, diabetes, transplant status, solid organ malignancy, neutropenia, history of fluconazole prophylaxis, or time in long-term acute care/long-term care facility.
“There were no significant differences in the proportion of patients who received an echinocandin versus fluconazole by age group, sex, race/ethnicity, diabetes, transplant status, solid organ malignancy, neutropenia, history of fluconazole prophylaxis (within 14 days before candidemia), and time spent at a long-term acute care hospital or long-term care facility within 90 days before candidemia”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataAmong adult candidemia patients at EIP sites in 2017-2018, 436 received no antifungal treatment and 34 received other drugs as initial treatment.
“Initial antifungal treatments included an echinocandin (n = 1258, 68.6%), fluconazole (n = 543, 29.6%), and other drugs (eg, amphotericin, non-fluconazole triazole) (n = 34, 1.9%); 436 patients received no antifungal treatment (Figure 1).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataFewer than half of patients (720, 40.0%) received echinocandin AFST, with site-specific percentages ranging from 5.3% to 95.1%.
“Fewer than half of patients (n = 720 [40.0%]) received echinocandin AFST, with site-specific percentages ranging from 5.3% to 95.1%.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataOf 543 patients initially treated with fluconazole, 304 (56.0%) grew a non-albicans species, including 145 with C glabrata, 76 with C parapsilosis, and 9 with C krusei.
“More than one-half (n = 304, 56.0%) of patients initially treated with fluconazole grew a non-albicans species.”
- Also stated in: § Antifungal Drug Choice by Species and Antifungal Susceptibility · plain
“Of 543 patients treated initially with fluconazole, 304 (56.0%) grew a non-albicans species, including 145 patients with C glabrata, 76 with C parapsilosis, and nine with C krusei (Table 3).”
Quote in the paperNot a substantial claim- Also stated in: § Antifungal Drug Choice by Species and Antifungal Susceptibility · plain
May combine two claims.
Findingown dataAmong 265 patients initially treated with fluconazole who received fluconazole AFST, 28 (10.6%) had fluconazole-resistant isolates; of these 28, 19 were switched to echinocandin, 3 to another drug class, and 6 were not switched.
“Among 265 patients initially treated with fluconazole and with fluconazole AFST results, 28 (10.6%) had a fluconazole-resistant isolate.”
- Also stated in: § Antifungal Drug Choice by Species and Antifungal Susceptibility · plain
“Among 265 patients initially treated with fluconazole and that received fluconazole AFST, 28 (10.6%) were ultimately found to have fluconazole-resistant isolates; of these 28 patients, 19 were switched to echinocandin, three were switched to another drug class, and six were not switched.”
Quote in the paperSubstantial claim- Also stated in: § Antifungal Drug Choice by Species and Antifungal Susceptibility · plain
May combine two claims.
Findingown dataEchinocandin AFST was performed for 226 (42.6%) of 530 patients with C glabrata and for 103 (43.5%) of 237 patients with C parapsilosis.
“Echinocandin AFST was performed for 226 (42.6%) of 530 patients with C glabrata and for 103 (43.5%) of 237 patients with C parapsilosis.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataAmong 1801 patients treated with either an echinocandin or fluconazole, 968 (53.7%) received fluconazole AFST, with site-specific proportions ranging from 11.5% to 95.1%.
“Among the 1801 patients treated with either an echinocandin or fluconazole, 968 (53.7%) received fluconazole AFST, and this proportion ranged substantially across surveillance sites from 11.5% to 95.1% (Figure 2).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataOf 226 patients switched from fluconazole to an echinocandin, 157 (69.5%) grew a non-albicans Candida species and 110 (48.7%) had fluconazole AFST performed.
“Of the 226 patients who were switched from fluconazole to an echinocandin, 157 (69.5%) grew a non-albicans Candida species and 110 (48.7%) had fluconazole AFST preformed.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataAmong 539 patients switched from an echinocandin to fluconazole, 263 (48.8%) grew a non-albicans Candida species and 328 (60.9%) had fluconazole AFST performed.
“Among 539 patients who were switched from an echinocandin to fluconazole, 263 (48.8%) grew a non-albicans Candida species and 328 (60.9%) had fluconazole AFST performed.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe odds of receiving an echinocandin versus fluconazole as initial treatment varied significantly by surveillance site (P < .0001), with patients from certain sites having over twice the odds compared with others.
“The odds of receiving an echinocandin versus fluconazole as initial treatment varied significantly by surveillance site (P < .0001), with patients from certain sites having over twice the odds of receiving an echinocandin compared with others.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThe study used standardized case report forms to collect demographic and clinical data.
“Surveillance personnel used standardized case report forms to collect demographic and clinical data from medical and laboratory records.”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductnone givenEIP surveillance data lack information on why patients were switched between drug classes, how clinicians use site-specific antibiograms or local species data, and timing of species/AFST results.
“Further, EIP surveillance data lack information regarding why patients were switched from one drug class to another, how clinicians might use site-specific antibiograms or local candidemia species data, and information regarding the timing of when clinicians receive results of species testing and AFST.”
Quote in the paperSubstantial claimMay combine two claims.
Study design and conductown dataThe study used active population-based candidemia surveillance at 9 US sites with a standardized case definition.
“During 2017–2018, the Emerging Infections Program conducted active population-based candidemia surveillance at 9 US sites using a standardized case definition.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductcitationAFST results were interpreted using species-specific CLSI breakpoints.
“AFST results were interpreted based on species-specific Clinical and Laboratory Standards Institute breakpoints [19], and isolates were classified as resistant, not resistant, or no interpretation if a species with no Clinical and Laboratory Standards Institute–defined breakpoint was tested.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [19] Clinical and Laboratory Standards Institute., 2020
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Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).
PremisecitationThe appropriate role for empiric antifungal therapy for suspected candidemia remains controversial.
“The appropriate role for empiric antifungal therapy for suspected candidemia remains controversial, and further investigation of this topic is needed [29].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [29] Timsit, 2016, Empirical micafungin treatment and survival without invasive fungal infection in adults with ICU-acquired sepsis, Candida colonization, and multiple organ failure: the EMPIRICUS randomized clinical trial, JAMA source
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Classified as probably not a substantial claim.
PremisecitationEchinocandin AFST is not recommended for all bloodstream Candida isolates.
“Compared with fluconazole AFST, echinocandin AFST was performed less frequently, which is expected because echinocandin AFST is not recommended for all bloodstream isolates [13].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13] 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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May combine two claims.
InterpretationcitationTreatment delays likely occurred because of non-specific clinical presentation, low sensitivity of blood cultures, and time needed to detect Candida in blood cultures.
“These possible treatment delays likely occurred because of the non-specific clinical presentation of candidemia, low sensitivity of blood cultures for candidemia detection, and the time needed to detect Candida in blood cultures [15, 27].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [15] Clancy, 2013, Finding the “missing 50%” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care, Clin Infect Dis source
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- cites [27] Guery, 2009, Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: part I. Epidemiology and diagnosis, Intensive Care Med source
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Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIDSA guidelines strongly recommend performing fluconazole AFST on all bloodstream Candida isolates.
“IDSA guidelines also strongly recommend performing fluconazole antifungal susceptibility testing (AFST) on all bloodstream Candida isolates because of the emergence of fluconazole resistance.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [13] 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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Classified as probably not a substantial claim.
PremisecitationIDSA guidelines consider fluconazole an acceptable alternative to an echinocandin as initial therapy in noncritically ill patients and patients unlikely to have a fluconazole-resistant Candida species.
“IDSA changed treatment guidelines in 2016 to strongly recommend echinocandins instead of fluconazole as the initial treatment of candidemia in all adults; the guidelines consider fluconazole to be an acceptable alternative to an echinocandin as initial therapy in noncritically ill patients and patients considered unlikely to have a fluconazole-resistant Candida species [13].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13] 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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Probably not a substantial claim: may not pass S2 (checkable).
PremisecitationAFST results can be an important adjunct in clinical decision-making.
“Our findings also suggest an opportunity for increased use of AFST because AFST results can be an important adjunct in clinical decision-making [30].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [30] Sanguinetti, 2018, Susceptibility testing of fungi to antifungal drugs, J Fungi source
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Classified as probably not a substantial claim.
PremisecitationSpecies and drug-resistance patterns vary substantially by geography, facility, and even among units within the same facility.
“Species and drug- resistance patterns are known to vary substantially by geography, facility, and even among units within the same facility [24, 25].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [24] Pfaller, 2011, Candida bloodstream infections: comparison of species distribution and resistance to echinocandin and azole antifungal agents in intensive care unit (ICU) and non-ICU settings in the SENTRY antimicrobial surveillance program (2008–2009), Int J Antimicrob Agents source
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- cites [25] Pfaller, 2011, Candida bloodstream infections: comparison of species distributions and antifungal resistance patterns in community-onset and nosocomial isolates in the SENTRY antimicrobial surveillance program, 2008–2009, Antimicrob Agents Chemother source
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Classified as probably not a substantial claim.
PremisecitationIDSA guidelines recommend echinocandin AFST for C glabrata and C parapsilosis bloodstream isolates.
“The guidelines further recommend echinocandin AFST for C glabrata and C parapsilosis bloodstream isolates because of emerging resistance in these species [13].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13] 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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Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe proportion of infections caused by non-albicans species has increased in recent decades.
“In the United States, Candida albicans is the most common species causing candidemia, but the proportion of infections caused by non-albicans species has increased in recent decades [5, 6].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [5] Lockhart, 2012, Species identification and antifungal susceptibility testing of Candida bloodstream isolates from population-based surveillance studies in two U.S. cities from 2008 to 2011, J Clin Microbiol source
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- cites [6] Toda, 2019, Population-based active surveillance for culture-confirmed candidemia—four sites, United States, 2012–2016, MMWR Surveill Summ source
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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationAFST results, if available, may be used to guide step-down treatment decisions and identify instances where treatment may be ineffective.
“AFST results, if available, may also be used to guide step-down treatment decisions and identify instances where treatment may be ineffective [17].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [17] Shah, 2011, Evaluation of antifungal therapy in patients with candidaemia based on susceptibility testing results: implications for antimicrobial stewardship programmes, J Antimicrob Chemother source
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PremisecitationBecause it generally takes at least 2-4 days after blood culture collection to detect and identify Candida species, and because access to AFST may be limited or delayed, clinicians usually select initial antifungal treatment based on local species epidemiology, antifungal resistance patterns, and individual patient factors.
“Because it generally takes at least 2–4 days after blood culture collection to detect and identify Candida species, and because access to AFST may be limited or delayed, clinicians usually select initial antifungal treatment based on local species epidemiology, antifungal resistance patterns, and individual patient factors [13–16].”
Quote in the paperNot a substantial claim0 of 4 sources checked- cites [13] 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 [14] Vallabhaneni, 2017, Antifungal susceptibility testing practices at acute care hospitals enrolled in the national healthcare safety network, United States, 2011–2015, Open Forum Infect Dis source
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- cites [15] Clancy, 2013, Finding the “missing 50%” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care, Clin Infect Dis source
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- cites [16] Safavieh, 2017, Advances in Candida detection platforms for clinical and point-of-care applications, Crit Rev Biotechnol source
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Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationRetrospective studies have suggested that empiric antifungal therapy might improve survival for select high-risk patients.
“Although retrospective studies have suggested that empiric antifungal therapy might improve survival for select high-risk patients [28]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [28] Parkins, 2007, Adequacy of empirical antifungal therapy and effect on outcome among patients with invasive Candida species infections, J Antimicrob Chemother source
Not checked in the free run.
May combine two claims.
PremisecitationEchinocandin use for candidemia treatment was increasing and fluconazole use decreasing during 2012-2016, even before the 2016 IDSA guidelines changed.
“Even before the IDSA guidelines changed in 2016, echinocandin use for candidemia treatment was increasing, whereas fluconazole use was decreasing during 2012–2016 [6].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6] Toda, 2019, Population-based active surveillance for culture-confirmed candidemia—four sites, United States, 2012–2016, MMWR Surveill Summ source
Not checked in the free run.
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?
The low percentage of echinocandin treatment likely occurred because certain patients died before treating providers knew about the candidemia diagnosis or because of low awareness of echinocandins as preferred first-line therapy.
“However, similar to surveillance findings during 2012–2016 (3), only 49.8% of candidemia cases involved echinocandin treatment, likely because certain patients died before treating health care providers knew about the candidemia diagnosis or because of low awareness of echinocandins as the preferred first-line therapy for most candidemia patients (26).”
From Population-Based Active Surveillance for Culture-Confirmed Candidemia — 10 Sites, United States, 2017–2021 (2025) · cites this paper as [26]
The paper states that 2016 guidelines recommend echinocandins as initial treatment for most adults with candidemia (guideline discussion; page unavailable). Its Results report patients who received no antifungal treatment, and its Discussion addresses diagnostic delays, but neither passage attributes low echinocandin use to patients dying before providers learned the diagnosis or to low awareness of the recommendation. (LLM, conf=0.82)
Experimental — accuracy not yet measured
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“Because it generally takes at least 2–4 days after blood culture collection to detect and identify Candida species, and because access to AFST may be limited or delayed, clinicians usually select initial antifungal treatment based on local species epidemiology, antifungal resistance patterns, and individual patient fa…”
BackgroundFluconazole resistance in <em>Candida</em> species: a current perspective
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Self-citationEstimation of Direct Healthcare Costs of Fungal Diseases in the United States
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Self-citationThe global burden of fungal diseases
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“EIP candidemia surveillance methods have been previously described [6].”
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Flagged first, then by citations
Research works printed but not linked: 1
- Clinical and Laboratory Standards Institute., 2020, M60 performance standards for antifungal susceptibility testing of yeasts
Cited by
Sorted by citations
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Jenkins, E. N., Gold, J. A. W., Benedict, K., Lockhart, S. R., Berkow, E. L., Dixon, T., Shack, S. L., Witt, L. S., Harrison, L. H., Seopaul, S., et al. (2025) · MMWR. Surveillance Summaries · doi:10.15585/mmwr.ss7404a1 · Cited by 43 · see citing works
Self-citation
- Authors
- Gold, J. A. W., Seagle, E. E., Nadle, J., Barter, D. M., Czaja, C. A., Johnston, H., Farley, M. M., Thomas, S., Harrison, L. H., Fischer, J., Pattee, B., Mody, R. K., Phipps, E. C., Davis, S. S., Tesini, B. L., Zhang, A. Y., Markus, T. M., Schaffner, W., Lockhart, S. R., Vallabhaneni, S., Jackson, B. R., & Lyman, M.
- Affiliations
- Centers for Disease Control and Prevention (US)
- California Emerging Infections Program, Oakland, California, USA
- Colorado Department of Public Health and Environment (US)
- Emory University (US)
- Johns Hopkins University (US)
- Minnesota Department of Health (US)
- New Mexico Emerging Infections Program, Albuquerque, New Mexico, USA
- University of Rochester Medicine (US)
- Oregon Health Authority (US)
- Vanderbilt University Medical Center (US)
- Corresponding author
- Gold, Jeremy A W
- ORCID
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2021-06-03
- Volume
- 73
- Issue
- 9
- Pages
- 1609-1616
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- PMC
- PMC8609664
- OpenAlex
- W3165035450
- Cited by
- 20
- References
- 31
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 2 · 2023: 6 · 2022: 4
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Infectious Diseases (publishedVersion, public-domain)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Centers for Disease Control and Prevention (CDC-RFA-CK17-1701)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Health Sciences › Medicine › Epidemiology › Infective Endocarditis Diagnosis and Management
- Keywords
- candidemia, echinocandins, fluconazole, non-albicans Candida, fluconazole resistance, antifungal susceptibility testing, guideline adherence, liver cirrhosis, opportunistic fungal infection
- MeSH terms
- Adult, Antifungal Agents, Candida, Humans, Microbial Sensitivity Tests, United States, Fluconazole, Echinocandins, Watchful Waiting, Candidemia
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 2026-10-05.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-05.
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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