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β-D-glucan surveillance with preemptive anidulafungin for invasive candidiasis in intensive care unit patients: a randomized pilot study.

Hanson KE, Pfeiffer CD, Lease ED, Balch AH, Zaas AK, Perfect JR, Alexander BD - PLoS ONE (2012)

Bottom Line: BDG levels were higher in subjects with proven/probable IC as compared to those without an IFI (117 pg/ml vs. 28 pg/ml; p<0.001).Receipt of preemptive antifungal treatment had a significant effect on BDG concentrations (p< 0.001).Preemptive anidulafungin was safe and generally well tolerated with excellent outcome.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Pathology, University of Utah, Salt Lake City, Utah, United States of America. kim.hanson@hsc.utah.edu

ABSTRACT

Background: Invasive candidiasis (IC) is a devastating disease. While prompt antifungal therapy improves outcomes, empiric treatment based on the presence of fever has little clinical impact. Β-D-Glucan (BDG) is a fungal cell wall component detectable in the serum of patients with early invasive fungal infection (IFI). We evaluated the utility of BDG surveillance as a guide for preemptive antifungal therapy in at-risk intensive care unit (ICU) patients.

Methods: Patients admitted to the ICU for ≥ 3 days and expected to require at least 2 additional days of intensive care were enrolled. Subjects were randomized in 3:1 fashion to receive twice weekly BDG surveillance with preemptive anidulafungin in response to a positive test or empiric antifungal treatment based on physician preference.

Results: Sixty-four subjects were enrolled, with 1 proven and 5 probable cases of IC identified over a 2.5 year period. BDG levels were higher in subjects with proven/probable IC as compared to those without an IFI (117 pg/ml vs. 28 pg/ml; p<0.001). Optimal assay performance required 2 sequential BDG determinations of ≥ 80 pg/ml to define a positive test (sensitivity 100%, specificity 75%, positive predictive value 30%, negative predictive value 100%). In all, 21 preemptive and 5 empiric subjects received systemic antifungal therapy. Receipt of preemptive antifungal treatment had a significant effect on BDG concentrations (p< 0.001). Preemptive anidulafungin was safe and generally well tolerated with excellent outcome.

Conclusions: BDG monitoring may be useful for identifying ICU patients at highest risk to develop an IFI as well as for monitoring treatment response. Preemptive strategies based on fungal biomarkers warrant further study.

Trial registration: Clinical Trials.gov NCT00672841.

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Related in: MedlinePlus

Study Subject Disposition.Abbreviations: RX = treatment; TX = transplant; LFTs = liver function tests; ULN = upper limit of the normal reference range; IC = invasive candidiasis; IFI = invasive fungal infection; IA = invasive aspergillosis; BDG = β-D-Glucan; medical vs. surgical = ICU location.*5 subjects in the preemptive group had a positive BDG test(s) but did not receive anidulafungin; 2 were BDG positive only at baseline/screening, 2 were transitioned to comfort care and 1 was treated empirically with antifungal therapy before development of a single positive test. All 5 subjects in the empiric therapy group that received systemic antifungal therapy had at least 1 positive BDG test around the time antifungal treatment.
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pone-0042282-g001: Study Subject Disposition.Abbreviations: RX = treatment; TX = transplant; LFTs = liver function tests; ULN = upper limit of the normal reference range; IC = invasive candidiasis; IFI = invasive fungal infection; IA = invasive aspergillosis; BDG = β-D-Glucan; medical vs. surgical = ICU location.*5 subjects in the preemptive group had a positive BDG test(s) but did not receive anidulafungin; 2 were BDG positive only at baseline/screening, 2 were transitioned to comfort care and 1 was treated empirically with antifungal therapy before development of a single positive test. All 5 subjects in the empiric therapy group that received systemic antifungal therapy had at least 1 positive BDG test around the time antifungal treatment.

Mentions: More than 1000 ICU admissions were screened over a 2.5 year period. The trial was stopped in January 2011, short of the targeted 100 subject sample size, due to slow accrual. Subject disposition is illustrated in Figure 1. In all, 345 patients met study inclusion criteria, 64 of these agreed to participate and 47 were randomized to receive active BDG surveillance. Two subjects in the preemptive group developed grossly icteric sera which precluded reliable glucan measurements; therefore, these subjects were excluded from the BDG analyses. Approximately one-half of potentially eligible subjects (51%, 177/345) could not give effective informed consent due to the severity of their illness and did not have a designated medical decision maker available to discuss study participation.


β-D-glucan surveillance with preemptive anidulafungin for invasive candidiasis in intensive care unit patients: a randomized pilot study.

Hanson KE, Pfeiffer CD, Lease ED, Balch AH, Zaas AK, Perfect JR, Alexander BD - PLoS ONE (2012)

Study Subject Disposition.Abbreviations: RX = treatment; TX = transplant; LFTs = liver function tests; ULN = upper limit of the normal reference range; IC = invasive candidiasis; IFI = invasive fungal infection; IA = invasive aspergillosis; BDG = β-D-Glucan; medical vs. surgical = ICU location.*5 subjects in the preemptive group had a positive BDG test(s) but did not receive anidulafungin; 2 were BDG positive only at baseline/screening, 2 were transitioned to comfort care and 1 was treated empirically with antifungal therapy before development of a single positive test. All 5 subjects in the empiric therapy group that received systemic antifungal therapy had at least 1 positive BDG test around the time antifungal treatment.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3412848&req=5

pone-0042282-g001: Study Subject Disposition.Abbreviations: RX = treatment; TX = transplant; LFTs = liver function tests; ULN = upper limit of the normal reference range; IC = invasive candidiasis; IFI = invasive fungal infection; IA = invasive aspergillosis; BDG = β-D-Glucan; medical vs. surgical = ICU location.*5 subjects in the preemptive group had a positive BDG test(s) but did not receive anidulafungin; 2 were BDG positive only at baseline/screening, 2 were transitioned to comfort care and 1 was treated empirically with antifungal therapy before development of a single positive test. All 5 subjects in the empiric therapy group that received systemic antifungal therapy had at least 1 positive BDG test around the time antifungal treatment.
Mentions: More than 1000 ICU admissions were screened over a 2.5 year period. The trial was stopped in January 2011, short of the targeted 100 subject sample size, due to slow accrual. Subject disposition is illustrated in Figure 1. In all, 345 patients met study inclusion criteria, 64 of these agreed to participate and 47 were randomized to receive active BDG surveillance. Two subjects in the preemptive group developed grossly icteric sera which precluded reliable glucan measurements; therefore, these subjects were excluded from the BDG analyses. Approximately one-half of potentially eligible subjects (51%, 177/345) could not give effective informed consent due to the severity of their illness and did not have a designated medical decision maker available to discuss study participation.

Bottom Line: BDG levels were higher in subjects with proven/probable IC as compared to those without an IFI (117 pg/ml vs. 28 pg/ml; p<0.001).Receipt of preemptive antifungal treatment had a significant effect on BDG concentrations (p< 0.001).Preemptive anidulafungin was safe and generally well tolerated with excellent outcome.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Pathology, University of Utah, Salt Lake City, Utah, United States of America. kim.hanson@hsc.utah.edu

ABSTRACT

Background: Invasive candidiasis (IC) is a devastating disease. While prompt antifungal therapy improves outcomes, empiric treatment based on the presence of fever has little clinical impact. Β-D-Glucan (BDG) is a fungal cell wall component detectable in the serum of patients with early invasive fungal infection (IFI). We evaluated the utility of BDG surveillance as a guide for preemptive antifungal therapy in at-risk intensive care unit (ICU) patients.

Methods: Patients admitted to the ICU for ≥ 3 days and expected to require at least 2 additional days of intensive care were enrolled. Subjects were randomized in 3:1 fashion to receive twice weekly BDG surveillance with preemptive anidulafungin in response to a positive test or empiric antifungal treatment based on physician preference.

Results: Sixty-four subjects were enrolled, with 1 proven and 5 probable cases of IC identified over a 2.5 year period. BDG levels were higher in subjects with proven/probable IC as compared to those without an IFI (117 pg/ml vs. 28 pg/ml; p<0.001). Optimal assay performance required 2 sequential BDG determinations of ≥ 80 pg/ml to define a positive test (sensitivity 100%, specificity 75%, positive predictive value 30%, negative predictive value 100%). In all, 21 preemptive and 5 empiric subjects received systemic antifungal therapy. Receipt of preemptive antifungal treatment had a significant effect on BDG concentrations (p< 0.001). Preemptive anidulafungin was safe and generally well tolerated with excellent outcome.

Conclusions: BDG monitoring may be useful for identifying ICU patients at highest risk to develop an IFI as well as for monitoring treatment response. Preemptive strategies based on fungal biomarkers warrant further study.

Trial registration: Clinical Trials.gov NCT00672841.

Show MeSH
Related in: MedlinePlus