Current evidence of antifungal prophylaxis and therapy in pediatric patients

Invasive fungal infections (IFI) are an important complication in pediatric haematological and oncological patients who undergo intensive chemotherapy for leukemia, solid tumour at advanced stage or relapsed, and hematopoietic stem cell transplantation. The incidence of IFI is lower than bacterial infection but mortality rate remains high. This review is designed to help paediatric oncologists in choosing the appropriate anti-fungal strategy and agents for prophylaxis, empirical, pre-emptive and specific therapy on the basis of published evidence

Preventing transmission of infectious agents in the pediatric in-patients hematology-oncology setting: what is the role for non-pharmacological prophylaxis?

The most intensive chemotherapy regimens were used in the past for leukemia patients who were the main focus of trials on infections; today there are increasing numbers of children with solid cancer and considerable risk of infection who do receive intensive standard-dose chemotherapy. Despite a continuous will to protect the immune-compromised child from infections, evidence-based indications for intervention by non-pharmacological tools is still lacking in the pediatric hematology-oncology literature. Guidelines on standard precautions as well as precautions to avoid transmission of specific infectious agents are available. As a result of a consensus discussion, the Italian Association for Pediatric Hematology-Oncology (AIEOP) Cooperative Group centers agree that for children treated with chemotherapy both of these approaches should be implemented and vigorously enforced, while additional policies, including strict environmental isolation, should be restricted to patients with selected clinical conditions or complications. We present here a study by the working group on infectious diseases of AIEOP

Occurrence of adenovirus infection and clinical impact in paediatric stem cell transplant recipients

In this study, the occurrence and clinical impact of adenovirus (AdV) infection was investigated in paediatric hematopoietic stem cell transplantation (HSCT) recipients. A number of 603 specimens (including whole blood, respiratory and other samples) from 181 patients were tested by real-time polymerase chain reaction; clinical outcome was investigated. Overall, 118/603 (19.6%) specimens from 21/181 (11.6%) patients resulted positive to AdV (including 17.3, 29.9, 17.6, and 15.8% of total number of whole blood, respiratory, urine and other specimens, respectively). On whole blood specimens, viral loads ranged from <600 (limit of detection) to >5×106 copies/mL, with a median value 2×104. Multiple specimens were positive in patients in which viral load on whole blood was high. Adenoviral positivity on whole blood was associated to poor prognosis, as death occurred in three of ten (30%) patients with persistent positivity on whole blood specimens, also despite the administration of an antiviral agent (cidofovir). Adenovirus infection can account for systemic and/or organ-specific signs/symptoms in approximately 10% of paediatric HSCT recipients. At moment, there is no indication for routine monitor of AdV in these patients, although AdV aetiology of infectious transplant complications should be taken in account

Empirical treatment of fever in neutropenic children: the role of the carbapenems. International Antimicrobial Therapy Cooperative Group of the European Organisation for Research and Treatment of Cancer and the Gimema Infection Program.

Journal ArticleReviewinfo:eu-repo/semantics/publishe

Aspergillus Galactomannan Enzyme-Linked Immunosorbent Assay Cross-Reactivity Caused by Invasive Geotrichum capitatum

We report three cases of invasive Geotrichum capitatum infection in patients with acute leukemia for which an enzyme-linked immunosorbent assay (ELISA) for Aspergillus galactomannan was positive, with no evidence of aspergillosis. Supernatants obtained from suspensions of 17 G. capitatum strains gave positive reactions with the Aspergillus galactomannan ELISA. These clinical and laboratory data seem to suggest that G. capitatum produces a soluble antigen that is cross-reactive with Aspergillus galactomannan

Safety and efficacy of a caspofungin-based combination therapy for treatment of proven or probable aspergillosis in pediatric hematological patients

Background: Fungal infections are diagnosed increasingly often in patients affected by hematological diseases and their mortality has remained high. The recent development of new antifungal drugs gives the clinician the possibility to assess the combination of antifungal drugs with in-vitro or in animal-model synergistic effect. Methods: We analyzed retrospectively the safety and efficacy of caspofungin-based combination therapy in 40 children and adolescents, most of them were being treated for a malignant disease, who developed invasive aspergillosis (IA) between November 2002 and November 2005. Results: Thirteen (32.5%) patients developed IA after hematopoietic stem cell transplantation (HSCT), 13 after primary diagnosis, usually during remission-induction chemotherapy, and 14 after relapse of disease. Severe neutropenia was present in 31 (78%) out of the 40 patients. IA was classified as probable in 20 (50%) and documented in 20 (50%) patients, respectively. A favorable response to antifungal therapy was obtained in 21 patients (53%) and the probability of 100-day survival was 70%. Different, though not significant, 100-day survival was observed according to the timing of diagnosis of IA: 51.9% after HSCT; 71.4% after relapse; and 84.6% after diagnosis of underlying disease, p 0.2. After a median follow-up of 0.7 years, 20 patients are alive (50%). Overall, the combination therapy was well tolerated. In multivariate analysis, the factors that were significantly associated to a better overall survival were favorable response to antifungal therapy, p 0.003, and the timing of IA in the patient course of underlying disease, p 0.04. Conclusion: This study showed that caspofungin-based combination antifungal therapy is an effective therapeutic option also for pediatric patients with IA. These data need to be confirmed by prospective, controlled studie

Safety and efficacy of a caspofungin-based combination therapy for treatment of proven or probable aspergillosis in pediatric hematological patients

Background: Fungal infections are diagnosed increasingly often in patients affected by hematological diseases and their mortality has remained high. The recent development of new antifungal drugs gives the clinician the possibility to assess the combination of antifungal drugs with in-vitro or in animal-model synergistic effect. Methods: We analyzed retrospectively the safety and efficacy of caspofungin-based combination therapy in 40 children and adolescents, most of them were being treated for a malignant disease, who developed invasive aspergillosis (IA) between November 2002 and November 2005. Results: Thirteen (32.5%) patients developed IA after hematopoietic stem cell transplantation (HSCT), 13 after primary diagnosis, usually during remission-induction chemotherapy, and 14 after relapse of disease. Severe neutropenia was present in 31 (78%) out of the 40 patients. IA was classified as probable in 20 (50%) and documented in 20 (50%) patients, respectively. A favorable response to antifungal therapy was obtained in 21 patients (53%) and the probability of 100-day survival was 70%. Different, though not significant, 100-day survival was observed according to the timing of diagnosis of IA: 51.9% after HSCT; 71.4% after relapse; and 84.6% after diagnosis of underlying disease, p 0.2. After a median follow-up of 0.7 years, 20 patients are alive (50%). Overall, the combination therapy was well tolerated. In multivariate analysis, the factors that were significantly associated to a better overall survival were favorable response to antifungal therapy, p 0.003, and the timing of IA in the patient course of underlying disease, p 0.04. Conclusion: This study showed that caspofungin-based combination antifungal therapy is an effective therapeutic option also for pediatric patients with IA. These data need to be confirmed by prospective, controlled studie