Effect of direct infusion of antifungal agent on invasive pulmonary aspergillosis in a patient with acute leukemia

2002 ◽  
Vol 8 (1) ◽  
pp. 106-108 ◽  
Author(s):  
Kazunori Nakase ◽  
Akira Yazaki ◽  
Hiroshi Shiku ◽  
Sigehisa Tamaki ◽  
Motoaki Tanigawa ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Antifungal Agent ◽  
Invasive Pulmonary Aspergillosis ◽  
Direct Infusion ◽  
Pulmonary Aspergillosis

scholarly journals Activity of voriconazole (UK-109,496) against clinical isolates of Aspergillus species and its effectiveness in an experimental model of invasive pulmonary aspergillosis.

1997 ◽  
Vol 41 (3) ◽  
pp. 696-698 ◽  
Author(s):  
M Murphy ◽  
E M Bernard ◽  
T Ishimaru ◽  
D Armstrong
Keyword(s):  
Body Weight ◽  
Experimental Model ◽  
Antifungal Agent ◽  
Invasive Pulmonary Aspergillosis ◽  
Clinical Isolates ◽  
Aspergillus Species ◽  
Pulmonary Aspergillosis

Voriconazole, a new azole antifungal agent, showed potent activity against clinical isolates of Aspergillus spp. in vitro. For A. fumigatus, the MIC range was < 0.03 to 0.5 microgram/ml and the MIC at which 90% of isolates are inhibited was 0.25 microgram/ml. In an experimental model of invasive pulmonary aspergillosis which mimics infection in humans, oral voriconazole at dosages of 30 mg/kg of body weight per day significantly delayed or prevented mortality.

Comparison of Sensitivity of Low-Dose CT Scan and Serum Galactomannan in Patients with Hematologic Malignancies and Positive Bronchoalveolar Lavage for Invasive Pulmonary Aspergillosis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1490-1490 ◽  
Author(s):  
Sita Bhella ◽  
Narinder Paul ◽  
Shahid Husain ◽  
Joseph M. Brandwein
Keyword(s):  
Acute Leukemia ◽  
Ct Scan ◽  
Low Dose ◽  
Invasive Pulmonary Aspergillosis ◽  
Hematologic Malignancies ◽  
Ct Scans ◽  
Pulmonary Aspergillosis ◽  
Low Dose Ct ◽  
Radiologic Findings ◽  
Positive Serum

Abstract Abstract 1490 Background: Invasive pulmonary aspergillosis (IPA) is associated with considerable morbidity and mortality in patients with acute leukemia and those undergoing hematopoietic stem cell transplantation (HSCT). Timely diagnosis of IPA is crucial, but difficult. Strategies for early detection of IPA include serum galactomannan (GM), bronchoalveolar lavage (BAL) GM and characteristic radiologic abnormalities on CT scan; however, the relative sensitivity of these diagnostic tests is unclear. We sought to determine the utility of serum GM and characteristic CT radiologic abnormalities in diagnosing IPA in patients with hematologic malignancies who had a positive BAL for Aspergillus. Methods: We performed a single center retrospective cohort study from 2010 to 2012 to determine the sensitivity serum GM (OD > 0.5) and low dose CT scan in patients with hematologic malignancies. All positive BAL GM samples and Aspergillus isolates from BAL fluid cultures from patients with acute leukemia and those undergoing HSCT were reviewed; all patients had abnormal chest CT scans consistent with pulmonary infection. IPA was classified as proven, probable or possible according to EORTC/MSG criteria. Recent low dose CT scans correlating to the date of the positive BAL GM or Aspergillus isolation were reviewed and graded: halo signs, cavities, crescents and nodules were deemed to be consistent with IPA, while other changes (e.g. ground-glass changes, consolidation) were considered non-specific. Results: A total of 49 BAL samples were included; of these, 31 were considered probable IPA and 18 possible IPA (on the basis of non-specific radiologic findings). Most patients had either no prior or 1–2 days of mold-active antifungal agents. There were 43 cases with positive BAL GM and 11 cases of positive Aspergillus BAL isolates; 5 patients had both. Of the positive BAL GM cases, 27 (63%) were associated with radiologic findings consistent with IPA. The remaining cases were associated with non-specific radiologic findings. Of the patients with Aspergillus isolates on BAL, 55% (6/11) had radiologic features consistent with IPA, while the remaining cases had non-specific radiologic findings. We next evaluated the sensitivity of serum GM. Of 34 patients with BAL GM positivity who had concomitant serum GM testing, 4 (12%) had positive serum GM. Of 8 patients with Aspergillus species isolated on BAL who had serum GM performed, only 1 (12.5%) had positive serum GM. In contrast, 5/8 patients (63%) with Aspergillus isolates on BAL had a positive BAL GM. The combined sensitivity of serum GM was 12% (5/42). Conclusions: Although the majority of patients with positive BAL for Aspergillus (+GM and/or isolates) had characteristic radiologic findings on CT scan, the absence of such findings did not exclude this diagnosis, as over one third had only non-specific radiologic findings. Serum GM had very low sensitivity in this population and should not be used in isolation to diagnose IPA. Disclosures: No relevant conflicts of interest to declare.

Performance of IFIGC/MSG/EORTC Criteria for the Diagnosis of Invasive Pulmonary Aspergillosis in the Clinical Management of Unselected Patients with Acute Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4519-4519
Author(s):  
Erika Borlenghi ◽  
Maria Adele Capucci ◽  
Chiara Cattaneo ◽  
Nicoletta Petrella ◽  
Liana Signorini ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Diagnostic Criteria ◽  
Clinical Management ◽  
Invasive Pulmonary Aspergillosis ◽  
Pulmonary Infiltrate ◽  
Pulmonary Aspergillosis ◽  
Clinical Criteria ◽  
Pulmonary Infiltrates ◽  
Eortc Criteria ◽  
Microbiological Criterion

Abstract Invasive pulmonary aspergillosis (IPA) is a severe complication in patients (pts) treated for acute leukemia. Since its diagnosis is still difficult, sets of non-invasive diagnostic criteria were recently proposed by IFIGC/MSG/EORTC for study purposes. The performance of those criteria in the clinical management of unselected leukemic pts is still unknown. We have therefore applied IFIGC/MSG/EORTC criteria to the diagnosis of pulmonary infiltrates occurred in 83 consecutive pts, aged <65, with newly diagnosed acute leukemia (19 APL, 38 AML, 26 ALL) treated at a single Institution between 1/2000 and 12/2003. The frequency of the different categories of IPA as diagnosis of pulmonary infiltrates and the relative contribution of the specific sets of diagnostic criteria were analysed. Forty-one pulmonary infiltrates developed in 30/83 pts (36.1%), during 364 chemotherapy cycles. IPA was diagnosed in 22 pts (26.5%). “Proven” IPA occurred in 1 (1.2%), “probable” IPA in 7 (8.4%) and “possible” IPA in 14 pts (16.8%). IPA was significantly more frequent in AML (36,8%), than in APL (15,7%) or ALL (15,3%) (P=0.041), and during the first induction (21/83; 25.3%) than during subsequent cycles (20/281; 7.1%) (P< 0.001). Considering the episodes of pulmonary infiltrate, IPA criteria were met in 27/41 (65,8%) [1 “proven”, 7 “probable” (17%) and 19 “possible” (46,3%)]. Specifically, “host criteria” were met in 41/41 (100%), “microbiological criteria” in 8/41 (17%), and “clinical criteria” in 27/41 (65,8%). The presence of one “major clinical” criterion, i.e. a typical radiological image on chest Xray or CT, was significantly associated with the positivity of a “microbiological” criterion, hence with a diagnosis of “probable” IPA (P=0,012). On the other hand, since “host” criteria were not discriminant, being positive in 100% of cases, the presence of two aspecific “minor clinical” criteria (dyspnea, cough, pleural rub, chest pain, hemophtysis) was the sole responsible for the classification of any non-typical pulmonary infiltrate either as “possible” IPA (17/19 cases; 84.2 %) or as “no IPA”. The bacterial origin of the pulmonary infiltrate was documented on follow-up in 5/19 “possible” IPA, which responded to specific antibacterial treatment. All patients had received antifungal prophylaxis, in 88% with oral itraconazole. A clinical response to ampho/voriconazole was obtained in 6/8 (71,4%) “proven/probable” and 17/19 (89,4%) “possible” IPA. Four of 22 pts with IPA (2 “probable” and 2 “possible”) died early during aplasia (multiorgan failure (MOF) 3, cerebral hemorrhage 1) compared to 2/8 pts without IPA (MOF 1, leukemia 1). In conclusion, according to IFIGC/MSG/EORTC criteria, IPA was diagnosed in 26.5% of pts with acute leukemia and in 65,8% of pulmonary infiltrates. AML and the first induction cycle were significant risk factors. “Proven” IPA was rare. “Probable” IPA was more frequent (8,4% of pts), its diagnosis being strongly supported by the association of a “major” clinical criterion with one microbiological criterion. “Possible IPA” likely represents an overestimation (43,9% of pulmonary infiltrates) since its diagnosis derived in most cases from the combined presence of a “host” criterion with two “minor” aspecific clinical criteria. These data allow a critical analysis of IFIGC/MSG/EORTC criteria in the setting of acute leukemia.

Prophylaxis of Invasive Pulmonary Aspergillosis with Nebulized Lipid Complex Amphotericin B Is Feasible, Well Tolerated and Safe in Children with Acute Leukemia. Results of a Phase II Open Trial

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1409-1409
Author(s):  
Maria Trabazo ◽  
Albert Catala ◽  
Ruben Berrueco ◽  
Gabriela Corbalan ◽  
Anna Ruiz ◽  
...  
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Acute Leukemia ◽  
Drug Interactions ◽  
Amphotericin B ◽  
Pediatric Patients ◽  
Invasive Pulmonary Aspergillosis ◽  
Intensive Chemotherapy ◽  
Pulmonary Aspergillosis ◽  
Lipid Complex

Abstract BACKGROUND: Acute leukemia is the most frequent cancer in childhood. The use of dose-intensive chemotherapy regimens has significantly increased the overall survival of acute leukemia during the last years. As a result of more dose-intensive myelosuppressive and immunosuppressive therapies there is a higher risk of systemic fungal infections. Invasive pulmonary aspergillosis (IPA) represents a significant source of morbidity and mortality (>50%), and therefore measures that effectively prevent IPA are needed. Prophylaxis of IPA with anti-mold azoles is effective, but has adverse systemic effects and important drug interactions with some chemotherapeutic agents (i.e. vincristine). Currently there is no optimal prophylaxis for IPA in pediatric patients so new strategies are needed. Because IPA originates from the inhalation of conidia, a prophylactic approach is the topical administration of antifungals inside the lungs. Aerosolized lipid formulations of amphotericin B could prevent IPA and avoid systemic adverse events and drug interactions. There are no published studies reporting feasibility and safety of inhaled lipidic amphotericins in the pediatric population. PATIENTS AND METHODS: The safety, feasibility and tolerance of nebulized lipid complex amphotericin B (ABCL) was evaluated in a phase II open label single arm trial on the use in pediatric patients (3 to 18 year-old) with acute leukemia during intensive chemotherapy. Nebulized therapy was administered by a PARI eFlow®rapid nebulizer system twice weekly, at 50 mg the first week and then 25 mg during intensive chemotherapy until recovery of neutropenia (3 consecutive absolute neutrophil count (ANC) ≥1x109/L or one ANC ≥1.5x109/L). Treatment was resumed during neutropenic episodes following subsequent chemotherapy cycles. Serum galactomannan assay was performed twice weekly during neutropenia. High-resolution chest computed tomography was done when there was a clinical suspicion of IPA. Fluconazole was allowed but antifungal drugs with anti-mold activity were not permitted. The trial is registered at www.clinicaltrials.gov as NCT01615809. RESULTS: Thirty-two patients were included, 19 were male (59.4%), median age was of 5.5 years (range 3-16). Twenty-nine patients were diagnosed with acute lymphoblastic leukemia (ALL), 3 with acute myeloid leukemia. Among the patients with ALL, 24 had a de novo ALL and 5 a relapsed ALL. A total of 389 administrations of nebulized ABCL were performed, with a median per patient of 13 (range 1-19). All patients tolerated the drug and no patient had to discontinue it due to intolerance or an adverse event. No patient presented a severe adverse event in relation to ABCL. Five patients suffered from mild adverse events (cough, eye discomfort). Nine patients were withdrawn from the study, 2 were referred to another institution to undergo bone marrow transplantation and 7 due to systemic administration of an antifungal agent with anti-mold activity. Three of these patients developed a possible or probable IPA. There were no other cases of IPA. CONCLUSIONS: Prophylactic nebulizations with ABCL were well tolerated, safe and feasible in children aged 3-18 years diagnosed with acute leukemia. There is a need to perform further studies with a higher number of patients to evaluate the efficacy of this approach. Disclosures Rives: Teva Pharma: Other. Off Label Use: Nebulized Amphotericin-B lipid complex is not approved for prophylaxis of invasive fungal infection in pediatric patients with acute leukemia.

Invasive pulmonary aspergillosis in adult acute leukemia: clinical clues to its diagnosis.

1985 ◽  
Vol 3 (8) ◽  
pp. 1109-1116 ◽  
Author(s):  
S L Gerson ◽  
G H Talbot ◽  
E Lusk ◽  
S Hurwitz ◽  
B L Strom ◽  
...  
Keyword(s):  
Chest Pain ◽  
Acute Leukemia ◽  
Invasive Pulmonary Aspergillosis ◽  
Signs And Symptoms ◽  
Nasal Discharge ◽  
Pleuritic Chest Pain ◽  
Pulmonary Aspergillosis ◽  
Prolonged Duration ◽  
Clinical Description ◽  
Febrile Episodes

Invasive pulmonary aspergillosis, a leading cause of morbidity and mortality in patients with acute leukemia, is difficult to diagnose antemortem because its signs and symptoms are ill-defined. To refine the clinical description of this infection, we reviewed our experience with 15 pathologically documented cases of invasive pulmonary aspergillosis in a population of 60 patients treated for acute leukemia. Findings occurring significantly more often (P less than or equal to .001) among cases than controls included pleuritic chest pain; acute sinus tenderness, and nasal discharge, epistaxis and eschar; rales; development of multilobar infiltrates after the 14th hospital day; and presence of nodular or cavitary infiltrates. In addition, patients with invasive pulmonary aspergillosis had a significantly prolonged duration of granulocytopenia, more febrile days and febrile episodes without a fever diagnosis and more febrile days on antibiotics (P less than or equal to .001 in all). This complex of findings should improve the clinician's ability to diagnose invasive pulmonary aspergillosis in patients with acute leukemia.

Discriminant scorecard for diagnosis of invasive pulmonary aspergillosis in patients with acute leukemia

1985 ◽  
Vol 79 (1) ◽  
pp. 57-64 ◽  
Author(s):  
Stanton L. Gerson ◽  
George H. Talbot ◽  
Shelley Hurwitz ◽  
Edward J. Lusk ◽  
Brian L. Strom ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Invasive Pulmonary Aspergillosis ◽  
Pulmonary Aspergillosis

Invasive Pulmonary Aspergillosis in Acute Leukemia

CHEST Journal ◽  
1987 ◽  
Vol 92 (1) ◽  
pp. 95-99 ◽  
Author(s):  
Janet E. Kuhlman ◽  
Elliot K. Fishman ◽  
Patrick A Burch ◽  
Judith E. Karp ◽  
Elias A Zerhouni ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Invasive Pulmonary Aspergillosis ◽  
Pulmonary Aspergillosis

scholarly journals COVID-19-Associated Pulmonary Aspergillosis in Patients with Acute Leukemia: A Single-Center Study

2021 ◽  
Vol 7 (11) ◽  
pp. 890
Author(s):  
Jovan Rajic ◽  
Ivana Gmizic ◽  
Tara Gunjak ◽  
Violeta Milosevic ◽  
Nikola Pantic ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Respiratory Infections ◽  
Invasive Pulmonary Aspergillosis ◽  
Single Center ◽  
Positive Serology ◽  
Pulmonary Aspergillosis ◽  
Clinical Center ◽  
Single Center Study ◽  
Microbiological Criteria ◽  
Center Study

Patients with coronavirus disease 19 (COVID-19) have increased susceptibility to secondary respiratory infections including invasive pulmonary aspergillosis (IPA). COVID-19-associated pulmonary aspergillosis (CAPA) is difficult to diagnose and can be associated with increased mortality especially in severe immunodeficiency such as hematological malignancies. Our study evaluates IPA in COVID-19 patients defined as COVID-19-CAPA among patients with acute leukemia (AL). A retrospective single-center study analyzed 46 patients with COVID-19 infection and acute leukemia, admitted to the Clinic for Haematology, Clinical Center of Serbia, Belgrade between the 2 April 2020 and 15 May 2021. During hospitalization, all participants were diagnosed with probable IPA according to the previous consensus definitions. Positive serology and galactomannan (GM) detection values in bronchoalveolar lavage (BAL) and serum were used as microbiological criteria. COVID-19 associated probable IPA was found in 22% (9/41) tested patients, where serum GM and IgM anti-Aspergillus antibodies were positive in 12% (5/41) and 10% (4/41) had positive serology for aspergillosis. One patient died while eight recovered during follow-up. Our study showed that COVID-19 might be a risk factor for IPA development in patients with AL. Early diagnosis and prompt treatment are required as reported mortality rates are high.

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