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(1, 3)-?-D-glucan assay for diagnosing invasive fungal infections in critically ill patients with hematological malignancies.

ABSTRACT: Invasive fungal infections (IFIs) are life-threatening complications of hematological malignancies that must be diagnosed early to allow effective treatment. Few data are available on the performance of serum (1-3)-?-D-glucan (BG) assays for diagnosing IFI in patients with hematological malignancies admitted to the intensive care unit (ICU). In this study, 737 consecutive patients with hematological malignancies admitted to 17 ICUs routinely underwent a BG assay at ICU admission. IFIs were diagnosed using standard criteria applied by three independent specialists. Among the 737 patients, 439 (60%) required mechanical ventilation and 273 (37%) died before hospital discharge. Factors known to alter BG concentrations were identified in most patients. IFIs were documented in 78 (10.6%) patients (invasive pulmonary aspergillosis, n = 54; Pneumocystis jirovecii pneumonia, n = 13; candidemia, n = 13; and fusarium infections, n = 3). BG concentrations (pg/mL) were higher in patients with than without IFI (144 (77-510) vs. 50 (30-125), < 0.0001). With 80 pg/mL as the cutoff, sensitivity was 72%, specificity 65%, and area-under-the-curve 0.74 (0.68-0.79). Assuming a prevalence of 10%, the negative and positive predictive values were 94% and 21%. By multivariable analysis, factors independently associated with BG > 80 pg/mL were IFI, admission SOFA score, autologous bone-marrow or hematopoietic stem-cell transplantation, and microbiologically documented bacterial infection. In conclusion, in unselected critically ill hematology patients with factors known to affect serum BG, this biomarker showed only moderate diagnostic performance and rarely detected IFI. However, the negative predictive value was high. Studies are needed to assess whether a negative BG test indicates that antifungal de-escalation is safe.

SUBMITTER: Azoulay E

PROVIDER: S-EPMC5008300 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Project description:Echinocandins, such as anidulafungin, are the first-line treatment for candidemia or invasive candidiasis in critically ill patients. There are conflicting data on the pharmacokinetic properties of anidulafungin in intensive care unit (ICU) patients. Adult ICU patients (from 3 hospitals) receiving anidulafungin for suspected or proven fungal infections were included in the present study. Patients were considered evaluable if a pharmacokinetic curve for day 3 could be completed. Twenty-three of 36 patients (7 female and 16 male) were evaluable. The median (range) age and body weight were 66 (28 to 88) years and 76 (50 to 115) kg, respectively. Pharmacokinetic sampling on day 3 (n = 23) resulted in a median anidulafungin area under the concentration-time curve from 0 to 24 h (AUC0-24) of 72.1 (interquartile range [IQR], 61.3 to 94.0) mg · h · liter-1, a median daily trough concentration (C24) of 2.2 (IQR, 1.9 to 2.9) mg/liter, a median maximum concentration of drug in serum (Cmax) of 5.3 (IQR, 4.1 to 6.0) mg/liter, a median volume of distribution (V) of 46.0 (IQR, 32.2 to 60.2) liters, and a median clearance (CL) of 1.4 (IQR, 1.1 to 1.6) liters · h-1 Pharmacokinetic sampling on day 7 (n = 13) resulted in a median AUC0-24 of 82.7 (IQR, 73.0 to 129.5) mg · h · liter-1, a median minimum concentration of drug in serum (Cmin) of 2.8 (IQR, 2.2 to 4.2) mg/liter, a median Cmax of 5.9 (IQR, 4.6 to 8.0) mg/liter, a median V of 39.7 (IQR, 32.2 to 54.4) liters, and a median CL of 1.2 (IQR, 0.8 to 1.4) liters · h-1 The geometric mean ratio for the AUCday7/AUCday3 term was 1.13 (90% confidence interval [CI], 1.03 to 1.25). The exposure in the ICU patient population was in accordance with previous reports on anidulafungin pharmacokinetics in ICU patients but was lower than that for healthy volunteers or other patient populations. Larger cohorts of patients or pooled data analyses are necessary to retrieve relevant covariates. (This study has been registered at ClinicalTrials.gov under identifier NCT01438216.).

Project description:BackgroundPosaconazole is confirmed to be more effective for preventing invasive fungal infections (IFIs) than first-generation triazoles (fluconazole and itraconazole), but its economic value has not been comprehensively evaluated in China. This study compared the cost-effectiveness of these two antifungal prophylaxis regimens in hematological-malignancy patients at high risk for IFIs from the Chinese healthcare perspective.MethodsA hybrid decision tree and Markov model were built using published data to estimate the total costs and quality-adjusted life-years (QALYs) of antifungal prophylaxis with posaconazole oral suspension and first-generation triazoles. Regimens with an incremental cost-effectiveness ratio (ICER) lower than the threshold of willingness to pay (WTP) were considered cost-effective. One-way and probabilistic sensitivity analyses were performed to assess model robustness. The regional imbalance of economic development and the tablet formulation of posaconazole were considered in the scenario analyses.ResultsIn the base-case analysis, posaconazole oral suspension provided an additional 0.109 QALYs at an incremental cost of $954.7, yielding an ICER of $8,784.4/QALY, below the national WTP threshold of $31,315/QALY. One-way and probabilistic sensitivity analyses showed that the results were robust. Scenario analyses showed that the base-case ICER was consistently below the WTP thresholds of all 31 Chinese provinces, with the likelihood of posaconazole being cost-effectiveness ranging from 78.1 to 99.0%. When the posaconazole oral suspension was replaced by the tablet formulation, the ICER increased to $29,214.1/QALY, still below the national WTP threshold and WTP thresholds of 12 provinces.ConclusionsPosaconazole oral suspension is a highly cost-effective regimen for preventing IFI in high-risk hematological-malignancy patients from the Chinese healthcare perspective. Posaconazole tablets may also be considered in some high-income regions of China.

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(1, 3)-?-D-glucan assay for diagnosing invasive fungal infections in critically ill patients with hematological malignancies.

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