Faculty Opinions recommendation of Clinical issues regarding relapsing aspergillosis and the efficacy of secondary antifungal prophylaxis in patients with hematological malignancies.

Author(s):  
Ben de Pauw
2019 ◽  
Vol 57 (Supplement_3) ◽  
pp. S274-S286
Author(s):  
Marta Stanzani ◽  
Claudia Sassi ◽  
Giuseppe Battista ◽  
Russell E Lewis

Abstract CT imaging remains an essential diagnostic test for identification, staging and management of invasive mould infection (IMI) in patients with hematological malignancies. Yet the limited specificity of standard CT imaging can drive excessive antifungal use in patients, especially when more definitive diagnosis cannot be established through microbiology or invasive diagnostic procedures. CT pulmonary angiography (CTPA) is a complimentary, non-invasive approach to standard CT that allows for direct visualization of pulmonary arteries inside infiltrates for signs of angioinvasion, vessel destruction and vessel occlusion. Experience from several centers that are using CTPA as part of a standard diagnostic protocol for IMI suggests that a positive vessel occlusion sign (VOS) is the most sensitive and a specific sign of IMI in both neutropenic and non-neutropenic patients. CTPA is particularly useful in patients who develop suspected breakthrough IMI during antifungal prophylaxis because, unlike serum and/or BAL galactomannan and polymerase chain reaction (PCR) testing, the sensitivity is not reduced by antifungal therapy. A negative VOS may also largely rule-out the presence of IMI, supporting earlier discontinuation of empirical therapy. Future imaging protocols for IMI in patients with hematological malignancies will likely replace standard chest X-rays in favor of early low radiation dose CT exams for screening, with characterization of the lesions by CTPA and routine follow-up using functional/metabolic imaging such as 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (FDG-PET/CT) to assess treatment response. Hence, enhanced CT imaging techniques can improve the diagnostic-driven management of IMI management in high-risk patients with hematological malignancies.


2016 ◽  
Vol 8 ◽  
pp. e2016040 ◽  
Author(s):  
Lourdes Vazquez

Invasive fungal infections (IFIs) represent significant complications in patients with hematological malignancies. Chemoprevention of IFIs may be important in this setting, but most antifungal drugs have demonstrated poor efficacy, particularly in the prevention of invasive aspergillosis. Antifungal prophylaxis in hematological patients is currently regarded as the gold standard in situations with a high risk of infection, such as acute leukemia, myelodysplastic syndromes, and autologous or allogeneic hematopoietic stem cell transplantation. Over the years, various scientific societies have established a series of recommendations for antifungal prophylaxis based on prospective studies performed with different drugs. However, the prescription of each agent must be personalized, adapting its administration to the characteristics of individual patients and taking into account possible interactions with concomitant medication.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3334-3334
Author(s):  
Takamichi Shintani ◽  
Osamu Imataki ◽  
Hiroaki Ohnishi ◽  
Akira Kitanaka ◽  
Yoshitsugu Kubota ◽  
...  

Abstract Purpose Invasive fungal infection (IFI) is one of the leading causes of mortality and morbidity in neutropenic patients with hematological malignancies (HM). Randomized studies and followed by metanalysis suggest the prophylactic effects of antifungal agents for chemotherapy-induced neutropenia. The purpose of this study is to estimate the medical costs on each antifungal agent for prophylaxis of antifungal infection in neutropenic patients in Japan. Method PubMed was searched for articles, which reported antifungal prophylaxis in neutropenic patients with HM, published after 1999, using 3 keywords; ’prophylaxis ’, ’hematological malignancy’ and ’fungal infection’. Fifteen articles that met the criteria were selected; randomized controlled trial, more than 100 cases overall, prospective study, and single agent used in each study arm. Antifungal agents were limited to the 4 drugs; fluconazole (FLCZ) capsules or tablets, itraconazole (ITCZ) capsules or oral solution, micafungin (MCFG), and liposomal amphotericin B (L-AMB). We assumed 3-week-prophylaxis after chemotherapy and 2-week-target therapy for the occurrence of the breakthrough infection, and designed the decision tree models in which a breakthrough fungal infection occurred in certain incidence of proven and probable IFI. The incidences of IFI from the 15 studies were applied to our model. MCFG, voriconazole (VRCZ) and L-AMB were applied as target therapies to the assumed Candida spp., Aspergillus spp., and other fungal infections, respectively. An average expected cost for prophylaxis on each antifungal agent was calculated and compared. Sensitive analysis was performed for the parameter of the incidence of breakthrough IFI. Results In each prophylaxis agent, the collected study population was 1061 cases in FLCZ, 1510 in ITCZ, 425 in MCFG, and 219 in L-AMB. The incidence of proven and probable IFI was 4.3% (46/1061) in FLCZ, 2.7% (41/1510) in ITCZ, 1.6% (7/425) in MCFG, and 3.7% (8/219) in L-AMB. Causative fungi were revealed in table 1 below. The mean duration to the breakthrough fungal infection was 20 days (95CI, 13–26) after chemotherapy. The average expected cost for prophylaxis in each drug was $1,098 for FLCZ, $532 for ITCZ, $1,313 for MCFG, and $2297 for L-AMB. Conclusion In our review, the prophylactic failure seems be comparable in the 4 antifungal agents. However, cost-effectiveness was the superior in the prophylaxis by ITCZ than the other agents in neutropenic patients with HM in Japan. The incidence of proven and probable IFI and its causes. Agents for prophylaxis Proven and probable IFI Prophylactic success (%) (95% CI) Candida spp. (%) Aspergillus spp. (%) Other fungus (%) Number of the causative fungus is indicated as the proportion among prophylactic failure cases. FLCZ 4.3% (46/1061) 95.7 (94.3–96.7) 23.7 63.2 13.2 ITCZ 2.7% (41/1510) 97.3 (96.3–98.0) 23.5 58.8 17.6 MCFG 1.6% (7/425) 98.4 (96.6–99.2) 57.1 14.3 28.6 L-AMB 3.7% (8/219) 96.3 (93.0–98.1) 75.0 25.0 0.0


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4839-4839
Author(s):  
Mariana Bastos Oreiro ◽  
Miguel Canales ◽  
Julio García Rodríguez ◽  
Raquel de Paz ◽  
Ana Lopez de la Guia ◽  
...  

Abstract Introduction: Candidemia is a serious condition with a high mortality rate in patients with hematological malignancies. It is thus important to understand the associated risk factors, as well as the need to establish adequate prophylaxis and early, effective therapy. The objective of this study was to determine the incidence of candidemia in hospital patients with hematological malignancies; to describe its clinical features and the risk factors associated with infection and with a poor outcome. Materials and methods: An electronic database was used to identify cases with a positive blood culture for Candida spp in patients with hematological malignancies admitted to the Hematology Ward of Hospital Universitario La Paz between January 2000 to March 2008. The clinical history of each identified case was reviewed. SPSS 15.0 was used for the statistical analysis. Univariant analysis was carried out using χ2. Results: Forty seven patients were identified, with an annual incidence of 1%. The species identified were Candida parapsilopsis in 46% of cases (n = 22) and Candida albicans in 21.3% (n = 10); the remainder was distributed amongst C. guillermondi, C. tropicalis and C. krusei. The underlying hemalogic malignancies were non-Hodgkin lymphoma (34%, n = 16), multiple myeloma (19%, n = 9) and acute myeloid leukemia (17%, n = 8). 48.9% of patients underwent stem cell transplantation (45.3% allogeneic and 54.7% autologous). No significant association was found between the underlying hemalogic malignancy and the species of Candida that was isolated. The antifungals used in treatment were liposomal amphotericin in 48.9% of cases, fluconazole in 12.7%, caspofungin in 4.2% and voriconazole in 4.2%, with combined therapy in 30% of patients. MIC50 and MIC90 for fluconazole against C. parapsilopsis were 4 and 32, respectively, and 0.03 and 8, respectively against C. albicans. MIC90 against the other species was 0.03. MIC50 and MIC90 for amphotericin were 0.03 and 1, respectively, against C. albicans, C. parapsilopsis and C. krusei. Voriconazole, itraconazole and caspofungin were found to have an MIC90 of 0.03 against all species of Candida. Thirty seven point eight percet of patients were already receiving antifungal prophylaxis at the time of diagnosis of candidemia, although 90% of cases of C. albicans candidemia were not on prophylaxis (p<0.05). In terms of risk factors, 76.6% of patients had a central venous catheter, 78.8% were undergoing chemotherapy, 95.6% were receiving concomitant, broad-spectrum antibiotics, 21.7% were diabetic, 46.8% were receiving parenteral nutrition of which more than half (59.1%) were associated with C. parapsilopsis, 26.7% had a serious associated mucositis, 60.5% had less than 0.2 ×109/L neutrophils and 98% had less than 1.5 × 109/L neutrophils, 37% had kidney failure. Eight patients (17%) died as a result of candidemia: 4 from C. albicans, 2 from C. parapsilopsis, 1 from C. glabrata and 1 from C. krusei. Of the patients with C. albicans, 33% died, compared to 11.8% of those with other species of Candida (p<0.05). Conclusion: Candida parapsilopsis was found to be the main causative species of candidemia in our centre, with a markedly high MIC50 and MIC90 for fluconazole, probably related to fluconazole prophylaxis. These findings highlight the importance of understanding the epidemiology of each centre when planning treatment and establishing an effective scheme of prophylaxis in high-risk patients to avoid the mortality associated with this type of infectious complication


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4107-4107
Author(s):  
Xiaowen Tang ◽  
Haoyue Huang ◽  
Shenghua Zhan ◽  
Xingwei Sun ◽  
Xiaolan Shi ◽  
...  

Abstract Abstract 4107 Objectives To determine the pulmonary pathological changes in patients of hematological malignancies with pulmonary complications using surgical or thoracoscopic technologie. Methods 17 hematological malignant patients who underwent surgical treatment were evaluated retrospectively in our study. Pulmonary infection was presented in 14 cases following chemotherapy, and lesions can not be completely absorbed after a broad-spectrum anti-bacterial and anti-fungal treatment. Furthermore, computerized tomographic scanning showed that there remained several kinds of localized lesions. Subsequently, all the 17 patients underwent open lung or thoracoscopic biopsies (lobar, partial, or wedge resection). The pathological changes of all the surgical specimens were examined postoperatively by standard hematoxylin and eosin staining. Results Pathological examination confirmed: Aspergillus infection in 9 patients, sub-acute inflammation (fibrosis and hematoma formation) in 3 patients, pulmonary infarction with granulomatous tissue in the periphery in 1 patient, granulomatous inflammation with calcified tubercle in 1 patient, alveolar dilation and hemorrhage, interstitial fibrosis and focal vasculitis in 1 patient, intercostal neurilemmoma in 1 patient, and moderate-differentiated adenocarcinoma accompanied by intrapulmonary metastasis in 1 patient. And several operative complications (1 case of fungal implantation, 3 cases of pleural effusion and adhesions and 2 cases of pulmonary hematoma) were occurred. The coincidence rate of pre- and post-operative diagnosis was 9/14 (64.3%). After surgery, 8 patients were received hematopoietic stem cell transplantation (HSCT, allo-gene or autologous), in which 7 cases were succeeded. Following the effective secondary antifungal prophylaxis,4 of 5 patients of aspergillosis were succeeded in transplantation free from mycotic relapse,just one patient was dead from fungal relapse. Conclusion Hematological malignancies with certain pulmonary complications, that is, persistent and/or medical-management-resistant pulmonary infection, hemoptysis, or lung diseases of diagnosis unknown, should be treated in time by surgical resection to effectively eliminate the residual disease and to achieve definitive diagnosis, so as to create a prerequisite condition for the following treatments. Moreover, the secondary antifungal prophylaxis could provide positive roles in protecting patients scheduled for chemotherapy and/or HSCT. Keywords hematological malignancies; immunocompromise; pulmonary aspergillosis; pulmonary resection; histopathology ; secondary antifungal prophylaxis Disclosures: No relevant conflicts of interest to declare.


2010 ◽  
Vol 19 (10) ◽  
pp. 1657-1665 ◽  
Author(s):  
Osamu Imataki ◽  
Yoshitsugu Kubota ◽  
Hiroaki Ohnishi ◽  
Akira Kitanaka ◽  
Toshihiko Ishida ◽  
...  

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