Multi-State Model of Invasive Aspergillosis and Antifungal Therapy in Febrile, Neutropenic Patients with Acute Myeloid Leukemia.

<p>Multi-State Model of Invasive Aspergillosis and Antifungal Therapy in Febrile, Neutropenic Patients with Acute Myeloid Leukemia.</p

Performance of β-glucan and qPCR, overall and according to two restrictive approaches of invasive aspergillosis diagnosis with selection of serum samples.

<p>Abbreviations: IA: Invasive Aspergillosis; GM: Aspergillus galactomannan antigenemia; ß-glucan: (1,3)-b-D glucan antigenemia; qPCR: PCR assay targeting Aspergillus fumigatus mitochondrial DNA.</p>a<p>Youden index is calculated as follows: Sensitivity+Specificity-1; and varies from 0 (no diagnostic accuracy) to 1 (perfect diagnostic accuracy).</p>b<p>Selection of serum samples after neutropenia/fever onset, and before antifungal therapy, invasive fungal infection, or neutropenia recovery.</p>c<p>Selection of serum samples collected on the same sample or the consecutive sample of a GM positive result as defined by a GM index ≥0.5 according to the manufacturer’s specifications.</p

Characteristics of 185 febrile, neutropenic patients treated for acute myeloid leukemia and by invasive aspergillosis.

<p>Abbreviations: IA: invasive aspergillosis; IQR: interquartile range; HEPA: High-Efficiency Particulate Air.</p>a<p>Of 11 IA, the independent blinded adjudication committee of the trial defined 2 proven IA and 9 probable IA according to international consensus definitions of 2002.</p>b<p>By chi-square test or exact Fisher test for binary variables; by Wilcoxon sum-rank test for continuous variables.</p>c<p>Prophylaxis included oral amphotericin B (n = 54), fluconazole (n = 23), and/or itraconazole (n = 10).</p>d<p>Of 11 IA, 7 IA were documented by procedures before or within 24 h after the first dose of antifungal therapy, and 4 breakthrough IA occurred after antifungal therapy was started.</p>e<p>Causes of death included 2 IA, 4 bacterial sepsis, 1 cardiogenic shock, and 1 coma of unknown origin. Follow-up was censored at 14 days after neutropenia recovery or at 60 days of neutropenia.</p

Galactomannan optical density index (GM-ODI) results of the reproducibility study upon the four tests (Test#1-#4) of the serum samples performed at Day 0, the four tests (Test#5-#8) performed at Day 1, and the GM-ODI after 8 month storage at -20°C (Test#9).

<p>^aDay 1 tests performed after 72h at 4°C.</p><p>The samples were classified as confirmed negative [all tests with GM optical density index (GM-ODI) <0.5], confirmed positive (all tests with GM-ODI ≥0.5), extraction unreproducible positive (Test#1 and Test#2 ODIs ≥0.5, and Test#3 and Test#4 GM-ODIs <0.5, or conversely), and ELISA unreproducible positive (only one test with GM-ODI ≥0.5). The same rules were applied at Day 1.</p><p>Galactomannan optical density index (GM-ODI) results of the reproducibility study upon the four tests (Test#1-#4) of the serum samples performed at Day 0, the four tests (Test#5-#8) performed at Day 1, and the GM-ODI after 8 month storage at -20°C (Test#9).</p

Graph plotting initial Test#1 against Test#5 (see Fig 1) performed after serum storage ≤72h at +4°C.

<p>A linear trend line was observed for confirmed positive and unreproducible positive results as in Fig 2.</p

Distribution of the different alleles in the 106 samples tested for the intronic (A), exonic (B) and intergenic (C) markers.

<p>Distribution of the different alleles in the 106 samples tested for the intronic (A), exonic (B) and intergenic (C) markers.</p

Characteristics of the STR markers and primers used in this study.

<p>Characteristics of the STR markers and primers used in this study.</p

Transmission map of the 10 patients in whom the <i>P</i>. <i>jirovecii</i> genotype 21 was detected.

<p>The date corresponds to the time at which the patient was present in the hospital and is delineated as a circle. Colored circles show <i>P</i>. <i>jirovecii</i> exposure of a given patient on a given day. Color coding distinguishes the different groups of patients (purple for patients 01–03, blue for patients 04–06 and turquoise for patients 07–10). The red bar corresponds to transmission between two groups of patients. Colored bars show the transmission routes.</p

Summary of genotype categories for <i>P</i>. <i>jirovecii</i> samples.

<p>Summary of genotype categories for <i>P</i>. <i>jirovecii</i> samples.</p

Discriminatory power of the assay for genotyping <i>P</i>. <i>jirovecii</i>.

<p>Discriminatory power of the assay for genotyping <i>P</i>. <i>jirovecii</i>.</p