galactomannan and Febrile-Neutropenia

We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462).

Topics: 14-alpha Demethylase Inhibitors; Adolescent; Adult; Aged; Antifungal Agents; Aspergillosis; Candidiasis; Coccidioidomycosis; Febrile Neutropenia; Female; Galactose; Hematologic Neoplasms; Humans; Itraconazole; Male; Mannans; Middle Aged; Prospective Studies; Treatment Outcome; Young Adult

An open-label, prospective, multicenter study was conducted between October 2006 and March 2010 to assess the efficacy and safety of intravenous voriconazole (VRCZ) as empirical therapy for antibiotic-refractory febrile neutropenia in Japanese patients with hematological disorders. In addition, to find the patient groups that may benefit from antifungal therapy, the definition of invasive fungal infection proposed by EORTC/MSG (2002) was assessed in this study. Plasma (1-3)-β-D-glucan and Aspergillus PCR in blood were also measured to improve the diagnostic accuracy. A total of 103 patients (median age, 59 years), including 25 undergoing induction chemotherapies and 19 allogeneic hematopoietic cell transplants, were evaluable. Sixty-nine percent of the patients achieved resolution of clinical symptoms and 31% achieved treatment success, defined as fulfilling the previously described five-part composite endpoint. Although VRCZ was discontinued in 9.7% of the patients because of adverse effects, all the patients recovered soon after discontinuation of VRCZ. The treatment success rate of VRCZ appeared to be higher in patients categorized as "not classified" compared with "possible invasive fungal disease" according to the EORTC/MSG criteria. Moreover, six "not classified" patients were positive for either plasma (1-3)-β-D-glucan (n = 5) or Aspergillus PCR in blood (n = 2). The present study demonstrates that empirical VRCZ therapy is safe and effective in Japanese patients. Additionally, (1-3)-β-D-glucan and Aspergillus PCR tests were expected to provide additional information on the diagnosis of invasive fungal infections.

Topics: Adolescent; Adult; Aged; Antibiotic Prophylaxis; Antifungal Agents; Antigens, Fungal; Febrile Neutropenia; Female; Galactose; Hematologic Neoplasms; Humans; Male; Mannans; Middle Aged; Mycoses; Prospective Studies; Pyrimidines; Triazoles; Voriconazole; Young Adult

To investigate the value of serum galactomannan antigen (GM) testing combined with chest computed tomography (CT) as a noninvasive method for early diagnosis of invasive pulmonary aspergillosis (IPA) in patients with hematological malignancies with febrile neutropenia after antifungal drug treatment.. We retrospectively analyzed the data of 376 patients with febrile neutropenia from January 2015 to August 2017. All patients were given broad-spectrum antibiotics and divided into the control group (effective antibiotic treatment, no antifungal drugs given) and the observational group (ineffective antibiotic treatment, antifungal drugs given). The serum GM testing, chest CT, and microbiological examination findings were compared between the two groups.. The false-positive rates of GM testing for IPA in the control and observational groups were 4.04% and 8.65%, respectively, and the false-negative rates in the two groups were 1.10% and 9.62%, respectively. Sixty-five patients in the observational group and 11 in the control group had typical features of CT imaging.. Clinical weekly screening of serum GM and chest CT may be an effective combined approach to the early diagnosis of IPA in patients with febrile neutropenia, even if they have undergone antifungal treatment.

Topics: Adolescent; Adult; Aged; Antifungal Agents; Aspergillus; Early Diagnosis; Febrile Neutropenia; Female; Follow-Up Studies; Galactose; Hematologic Neoplasms; Humans; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Prognosis; Retrospective Studies; Tomography, X-Ray Computed; Young Adult

Galactomannan (GM) assay is commonly used as an early diagnostic tool for invasive fungal infection (IFI) in high-risk hematology patients. False positivity is frequently observed in GM with the use of piperacillin/tazobactam. The usage of generic drugs over the original brand has a significant cost advantage. The aim of this study was to assess the performance of GM test among patients receiving original and generic piperacillin/tazobactam formulations. The study included 85 adult patients; 62.4% were male with hematological malignancy currently receiving piperacillin/tazobactam. The study group was divided into two groups: patients receiving original and generic piperacillin/tazobactam. Serum GM index was positive in one of 35 patients receiving original piperacillin/tazobactam, whereas it was positive in 46 out of 50 patients receiving generic piperacillin/tazobactam (P < .001). However, the patients receiving generic piperacillin/tazobactam underwent computed tomography (CT) scans more frequently than those receiving original piperacillin/tazobactam (P = .047). In addition, in vitro analysis of GM was performed in two generics and one original piperacillin/tazobactam vials. One generic piperacillin/tazobactam vial included high GM level. False positivity of serum GM with generic formulations of piperacillin/tazobactam is still an ongoing issue in hematology patients. A high rate of serum GM index false positivity may unexpectedly lead to a higher rate of CT scan. Selected piperacillin/tazobactam vials in each batch should be checked for GM to identify a false positivity of GM before purchase.

Topics: Anti-Bacterial Agents; Antigens, Fungal; False Positive Reactions; Febrile Neutropenia; Female; Galactose; Humans; Invasive Pulmonary Aspergillosis; Male; Mannans; Microbiological Techniques; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

The incidence of invasive aspergillosis (IA) has increased over the last years, especially in immuncompromised patients with high mortality rates. Because of difficulties about the diagnosis; serological methods [galactomannan (GM) antigen test] and polymerase chain reaction (PCR) developed in recent years. MycAssay Aspergillus PCR performance in the diagnosis of IA was evaluated and compared with the GM and in-house PCR. This study was conducted with 358 serum samples obtained from 99 patient with febrile neutropenic episodes who were followed in haematology and bone marrow transplantation units. Patients were classified by the European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria, 18 of them is proven and probable IA. GM antigen test and two different real-time PCR; one of them is fist commercial PCR for IA; Mycassay Aspergillus and the other one is in-house real-time PCR performed. Sensitivity values were Mycassay Aspergillus PCR, in-house PCR, and GM 65.38%, 11.53% and 23.07%, respectively. The high sensitivity obtained from Mycassay Aspergillus PCR and sensitivity is increased by using a combination of diagnostic methods. GM antigen test and real-time PCR could be beneficial for early diagnosis and treatment of IA. For routine usage of PCR as diagnostic assay more studies needed in future.

Topics: Adult; Aspergillus; DNA, Fungal; Febrile Neutropenia; Female; Galactose; Humans; Invasive Pulmonary Aspergillosis; Male; Mannans; Middle Aged; Molecular Diagnostic Techniques; Polymerase Chain Reaction; Sensitivity and Specificity; Serologic Tests; Young Adult

Patients with persistent or recurrent neutropenic fevers at risk of invasive fungal disease (IFD) are treated empirically with antifungal therapy (AFT). Early treatment using a diagnostic-driven (DD) strategy may reduce clinical and economic burdens. We compared costs and outcomes of both strategies from a UK perspective.. An empirical strategy with conventional amphotericin B deoxycholate (C-AmB), liposomal amphotericin B (L-AmB), or caspofungin was compared with a DD strategy (initiated based on positive ELISA results for galactomannan antigen) and/or positive results for Aspergillus species on polymerase chain reaction assay) using C-AmB, voriconazole, or L-AmB in a decision-analytic model. Rates of IFD incidence, overall mortality, and IFD-related mortality in adults expected to be neutropenic for ≥10 days were obtained. The empirical strategy was assumed to identify 30% of IFD and targeted AFT to improve survival by a hazard ratio of 0.589. AFT-specific adverse events were obtained from a summary of product characteristics. Resource use was obtained, and costs were estimated by using standard UK costing sources. All costs are presented in 2012 British pounds sterling.. Total costs were 32% lower for the DD strategy (£1561.29) versus the empirical strategy (£2301.93) due to a reduced incidence of adverse events and decreased use of AFT. Administration of AFT was reduced by 41% (DD strategy, 74 of 1000; empirical strategy, 125 of 1000), with similar survival rates.. This study suggests that a DD strategy is likely to be cost-saving versus empirical treatment for immunocompromised patients with persistent or recurrent neutropenic fevers.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Caspofungin; Cost Savings; Decision Trees; Deoxycholic Acid; Drug Combinations; Echinocandins; Febrile Neutropenia; Galactose; Health Care Costs; Health Resources; Humans; Immunocompromised Host; Lipopeptides; Mannans; Survival Rate; Voriconazole