Index to Predict Invasive Mold Infection in High-Risk Neutropenic Patients Based on the Area Over the Neutrophil Curve

Portugal, Rodrigo de Souza; Garnica, Márcia; Nucci, Márcio

doi:10.1200/jco.2008.21.0856

Cited by 107 publications

(114 citation statements)

References 18 publications

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“…Risk factors for pulmonary hemorrhage due to S. maltophilia were HCT recipient, prolonged days of neutropenia, high C-reactive protein level at BSI onset and complication by pneumonia. In addition to the duration of neutropenia, the D-and cumulative D-index 23 were also considered to be factors that predicted pulmonary hemorrhage, whereas a high PITT score at the onset of BSI was not associated with pulmonary hemorrhage.…”

Section: Discussionmentioning

confidence: 99%

“…13,20 The severity of illness was assessed by the bacteremia score according to the University of Pittsburgh (PITT score). 21,22 The D-index and cumulative D-index, which were calculated as the area over the neutrophil curve that is based on a graph plotting the absolute neutrophil counts during neutropenia, 23 were also investigated to evaluate the impact of both duration and severity of neutropenia on S. maltophilia infection.…”

Section: Definitionsmentioning

confidence: 99%

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Stenotrophomonas maltophilia infection in hematopoietic SCT recipients: high mortality due to pulmonary hemorrhage

Tada¹,

Kurosawa²,

Hiramoto³

et al. 2012

Bone Marrow Transplant

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To clarify the clinical features and outcome of Stenotrophomonas maltophilia infection among hematopoietic SCT (HCT) recipients, we retrospectively reviewed the records of 1085 consecutive HCT recipients and identified 42 episodes in 31 HCT recipients with S. maltophilia infection. We compared these recipients with 30 non-HCT patients with S. maltophilia infection. The mortality rate in HCT recipients was significantly higher than that in non-HCT patients (relative risk 5.7, P ¼ 0.04), and we identified seven patients with pulmonary hemorrhage due to S. maltophilia, exclusively in the HCT cohort. Six of these latter seven patients died within 1 day from the onset of hemorrhage and the isolate was identified after death in most cases; one patient, who received empiric therapy for S. maltophilia and granulocyte transfusion, survived for more than 2 weeks. The patients with pulmonary hemorrhage had a more severe and longer duration of neutropenia, persistent fever despite of the use of broad-spectrum antibiotics, complication by pneumonia and higher C-reactive protein levels than those without pulmonary hemorrhage. In conclusion, S. maltophilia was associated with fulminant and fatal pulmonary hemorrhage in HCT recipients. Empiric therapy with antibiotics before the onset of pulmonary hemorrhage may be effective in HCT recipients who carry the conditions identified.

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Section: Discussionmentioning

confidence: 99%

Section: Definitionsmentioning

confidence: 99%

Stenotrophomonas maltophilia infection in hematopoietic SCT recipients: high mortality due to pulmonary hemorrhage

Tada¹,

Kurosawa²,

Hiramoto³

et al. 2012

Bone Marrow Transplant

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“…Rapid attainment of effective posaconazole concentrations during the neutropenic phase may be of paramount importance, considering that this is the most vulnerable period for mold infections in hematological patients (4). Unfortunately, the currently available oral formulation of posaconazole has an unpredictable pharmacokinetic behavior, and therapeutic drug monitoring (TDM) of trough plasma concentrations (C min ) is being increasingly advocated for guidance of appropriate drug exposure with posaconazole over time (5)(6)(7).…”

mentioning

confidence: 99%

Antifungal Prophylaxis with Posaconazole in Patients with Acute Myeloid Leukemia: Dose Intensification Coupled with Avoidance of Proton Pump Inhibitors Is Beneficial in Shortening Time to Effective Concentrations

Cojutti

Candoni

Simeone

et al. 2013

Antimicrob Agents Chemother

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Posaconazole is a second-generation triazole antifungal agent with a broad spectrum (1) that is currently licensed for prophylaxis in hematological patients at high risk of invasive fungal infections (2, 3).Rapid attainment of effective posaconazole concentrations during the neutropenic phase may be of paramount importance, considering that this is the most vulnerable period for mold infections in hematological patients (4). Unfortunately, the currently available oral formulation of posaconazole has an unpredictable pharmacokinetic behavior, and therapeutic drug monitoring (TDM) of trough plasma concentrations (C min ) is being increasingly advocated for guidance of appropriate drug exposure with posaconazole over time (5-7).As far as the therapeutic range for posaconazole is concerned, some authors suggest a C min of Ͼ500 ng/ml as a target threshold (8), whereas others found evidence to support a more conservative C min of Ͼ700 ng/ml (9), although a definitive threshold is still to be defined. Achievement of the desired threshold with the current posaconazole formulation is quite challenging, considering that several factors were shown to affect its absorption rate (10).Various strategies have been suggested in order to improve its oral bioavailability, among which avoidance of drugs altering gastric acidic pH, taking posaconazole with a high-fat meal, and increase of dose frequency are considered the most clinically relevant (11). Of note, these approaches are not always simultaneously feasible for the same patient, and what remains to be answered is the role that these approaches may have in shortening the time to therapeutically relevant concentrations in daily clinical practice.The aim of this study was to assess the relative influence that dose frequency and the presence or absence of cotreatment with proton pump inhibitors (PPIs) had on the time to a target C min of Ͼ700 ng/ml in a population of hematological patients who received posaconazole prophylaxis after induction chemotherapy for acute myeloid leukemia. MATERIALS AND METHODSStudy design. This was an observational study which involved adult patients with acute myeloid leukemia who underwent antifungal prophylaxis with posaconazole in the period between August 2009 and November 2010 after receiving induction chemotherapy at the hematologic clinic of our university teaching hospital. During this period, posaconazole prophylaxis was carried out with 2 dosing regimens at the physician's discretion, namely, 200 mg every 8 h (q8h) or 200 mg q6h, with the latter regimen usually being preferred in cases of very severe neutropenia. Concomitant use of PPIs was discouraged as much as possible.Only patients who had at least three subsequent C min assessments during the first 8 days of treatment according to our routine TDM program were considered feasible for this study. Blood samples for TDM were collected immediately before the morning administration and after centrifuged plasma samples were analyzed by means of a validated liquid chromatography-tandem mass ...

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“…induced by intensive chemotherapy. Th e risk for fungal infections is highest in patients with persistent, [38,39] profound neutropenia. Patients undergoing intensive induction chemotherapy for acute leukaemia are at risk for candida and aspergillus infections [40].…”

Section: Prophylaxis With Anti-infective Agentsmentioning

confidence: 99%

Prevention and treatment of febrile neutropenia

Weißinger

Heinz

2012

memo

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Index to Predict Invasive Mold Infection in High-Risk Neutropenic Patients Based on the Area Over the Neutrophil Curve

Abstract: The high negative predictive value of the c-D-index may be of help in defining different risks for IMI in febrile neutropenic patients.

Cited by 107 publications

References 18 publications

Stenotrophomonas maltophilia infection in hematopoietic SCT recipients: high mortality due to pulmonary hemorrhage

Stenotrophomonas maltophilia infection in hematopoietic SCT recipients: high mortality due to pulmonary hemorrhage

Antifungal Prophylaxis with Posaconazole in Patients with Acute Myeloid Leukemia: Dose Intensification Coupled with Avoidance of Proton Pump Inhibitors Is Beneficial in Shortening Time to Effective Concentrations

Prevention and treatment of febrile neutropenia

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