Invasive Fungal Infections In Pediatric Patients Research Articles

Invasive Fungal Diseases in Children with Acute Leukemia and Severe Aplastic Anemia.

Although the outcomes of childhood leukemia and severe aplastic anemia (SAA) have improved, infectious complications are still the major concern. Particularly worrisome are invasive fungal diseases (IFDs), one of the most common causes of infectious-related deaths in patients with prolonged neutropenia. A retrospective study was conducted of IFDs in pediatric patients with newly diagnosed or relapsed acute leukemia, or with SAA, at Siriraj Hospital, Mahidol University, Thailand. There were 241 patients: 150 with acute lymphoblastic leukemia (ALL), 35 with acute myeloid leukemia (AML), 31 with relapsed leukemia, and 25 with SAA. Their median age was 5.4 years (range, 0.3–16.0 years). The overall IFD prevalence was 10.7%, with a breakdown in the ALL, AML, relapsed leukemia, and SAA patients of 8%, 11.4%, 19.3%, and 16%, respectively. Pulmonary IFD caused by invasive aspergillosis was the most common, accounting for 38.5% of all infection sites. Candidemia was present in 34.6% of the IFD patients; Candida tropicalis was the most common organism. The overall case-fatality rate was 38.5%, with the highest rate found in relapsed leukemia (75%). The incidences of IFDs in patients with relapsed leukemia and SAA who received fungal prophylaxis were significantly lower than in those who did not (P = N/A and 0.04, respectively). IFDs in Thai children with hematological diseases appeared to be prevalent, with a high fatality rate. The usage of antifungal prophylaxes should be considered for patients with SAA to prevent IFDs.

Invasive fungal infections in a pediatric hematology-oncology department: A 16-year retrospective study

Background and Purpose: Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in immunocompromised children. The purpose of our study was to evaluate the incidence of IFIs in pediatric patients with underlying hematologic malignancies and determine the patient characteristics, predisposing factors, diagnosis, treatment efficacy, and outcome of IFIs.Materials and Methods: For the purpose of the study, a retrospective analysis was performed on cases with proven and probable fungal infections from January 2001 to December 2016 (16 years)Results: During this period, 297 children with hematologic malignancies were admitted to the 2nd Pediatric Department of Aristotle University of Thessaloniki, Greece, and 24 cases of IFIs were registered. The most common underlying diseases were acute lymphoblastic leukemia (ALL; n=19,79%), followed by acute myeloid leukemia (AML; n=4, 17%) and non-Hodgkin lymphoma (NHL; n=1,4%). The crude incidence rates of IFIs in ALL, AML, and NHL were 10.5%, 18.2%, and 2.8% respectively. Based on the results, 25% (n=6) and 75% (n=18) of the patients were diagnosed as proven and probable IFI cases, respectively. The lung was the most common site of involvement in 16 (66.7%) cases. Furthermore, Aspergillus and Candida species represented 58.3% and 29.1% of the identified species, respectively. Regarding antifungal treatment, liposomal amphotericin B was the most commonly prescribed therapeutic agent (n=21), followed by voriconazole (n=9), caspofungin (n=3), posaconazole (n=3), micafungin (n=1), and fluconazole (n=1). In addition, 12 children received combined antifungal treatment. The crude mortality rate was obtained as 33.3%.Conclusion: As the findings of the present study indicated, despite the progress in the diagnosis and treatment of IFIs with the use of new antifungal agents, the mortality rate of these infections still remains high.

Voriconazole plus caspofungin for treatment of invasive fungal infection in children with acute leukemia.

BackgroundInvasive fungal infections (IFIs) are a life-threatening problem in immunocompromised patients. Despite timely diagnosis and appropriate antifungal therapy, clinical outcomes of IFIs remain unsatisfactory, necessitating treatment with a combination of antifungal agents. Therefore, childhood leukemic patients treated with voriconazole plus caspofungin were evaluated for the safety and efficacy of the combination antifungal therapy to treat IFIs.MethodsIn this retrospective study, medical records were retrieved for patients admitted to the Pediatric Department of Yeungnam University Hospital, Daegu, South Korea, between April 2009 and May 2013. Medical records of 22 patients were analyzed.ResultsOf the 22 patients studied, nine (41%) had been diagnosed with probable IFI, and 13 (59%) with possible IFI. All patients, except one, were already receiving antifungal monotherapy for the treatment of neutropenic fever. After a diagnosis of IFI was confirmed, antifungal monotherapy was replaced with combination therapy. The study's overall response rate was 90.9%, with complete responses in 86.3% of the patients. Two patients experienced a side effect of a small increase in liver enzyme levels.ConclusionVoriconazole plus caspofungin combination therapy is an effective and safe treatment for serious IFI in pediatric patients with acute leukemia.

Micafungin As Antifungal Prophylaxis during Induction Phase of Chemotherapy in Pediatric Acute Lymphoblastic Leukemia

Background:Invasive fungal infection (IFI) comprises a major cause of infection related morbidity and mortality in neutropenic patients receiving chemotherapy or hematopoietic stem cell transplantation (HSCT). Micafungin exhibits broad antifungal activity against both Aspergillus and Candida species.Objective:We performed a prospective study to determine the efficacy, safety, and tolerability of prophylactic micafungin against IFI in pediatric neutropenic patients during induction chemotherapy for acute lymphoblastic leukemia (ALL). Patients and methods:The study included 70 patients randomized in to two groups: Intervention group: 35 patients were given micafungin daily at a dose of (1 mg/kg/day) with maximum of 50mg/day from day one to the end of induction with close follow up for toxicity, tolerability, and efficacy. In case of failure of prophylaxis (defined as development of proven, probable, or possible fungal infection according to revised definitions of EORTC/MSG consensus group), we shifted to either voriconazole or liposomal ampho-B. Control group: 35 patients were treated according to empirical antifungal approach. Follow up of patients by clinical examination, routine work up, serum galactomannan, blood cultures, and CT chest together with paranasal sinuses. Results:Treatment success rate, defined as absence of proven, probable, or possible IFIs was 75%; in the control group 8/35 (22.8%) developed IFIs, while in the intervention group 2/35 (5.7%). No adverse events were observed that could be related to micafungin prophylaxis. Conclusions:These results suggest that prophylactic micafungin is well tolerated and may prevent IFIs in pediatric patients with neutropenia receiving chemotherapy.Keywords:Pediatric, ALL, induction chemotherapy, IFI, micafungin prophylaxis. DisclosuresNo relevant conflicts of interest to declare.

Non-Invasive Methods to Diagnose Fungal Infections in Pediatric Patients with Hematologic Disorders.

BackgroundInvasive fungal infection (IFIs) is a major infectious complication in immunocompromised patients. Early diagnosis and initiation of antifungal therapy is important to achieve the best outcome.ObjectivesThe current study aimed to investigate the incidence of IFIs and evaluate the diagnostic performance of non-invasive laboratory tests: serologic (β-D-glucan, galactomannan) and molecular (nested polymerase chain reaction) tests to diagnose fungal infections in hematologic pediatric patients.Patients and MethodsIn a cross-sectional study from October 2014 to January 2015, 321 blood samples of 62 pediatric patients with hematologic disorders and at high risk for fungal infections were analyzed. Non-invasive tests including the Platelia Aspergillus enzyme immunoassay (EIA) to detect galactomannan antigen, Glucatell for β–D–glucan and nested PCR to detect Candida and Aspergillus species-specific DNA were used in a weekly screening strategy.ResultsTwenty six patients (42%) were considered as proven and probable IFIs, including 3 (5%) proven and 23 (37%) probable cases. Eighteen patients (29%) were considered as possible cases. The sensitivity, specificity, positive and negative predictive values for galactomannan test in 26 patients with proven and probable fungal infections were 94.4%, 100%, 100% and 94.7%; for β-D-glucan test 92.3%, 77.7%, 85%, 87.5% and for nested-PCR were 84.6%, 88.8%, 91.7% and 80%, respectively.ConclusionsThe rate of IFIs in pediatric patients with hematologic disorders is high, and sample collection from the sterile sites cannot be performed in immunocompromised patients. Detection of circulating fungal cell wall components and DNA in the blood using non-invasive methods can offer diagnostic help in patients with suspected IFIs. Their results should be interpreted in combination with clinical, radiological and microbiological findings.

Detection of β-D-glucan for the diagnosis of invasive fungal infection in children with hematological malignancy

The ß-D-glucan assay (BDG) has been added to the EORTC/MSG criteria for the diagnosis of invasive fungal infections (IFI), but data from pediatric populations is scarce. The aim of this study was to evaluate performance of BDG in a cohort of hemato-oncological children with hematological malignancy at risk for IFI. 113 patients were included through an 18-month period. In addition to routine IFI screening, BDG was assayed once a week. IFIs were classified using EORTC/MSG criteria without including the BDG results. Performances were assessed after a ROC analysis for optimization and multivariate analysis to detect the causes of false positivity. 8 proven and 4 probable IFIs, and 7 possible IFIs were diagnosed in 9 and 7 patients, respectively. Sensitivity and specificity increased from 75% and 56% to 100% and 91.1%, respectively when considering the whole population and patients not having received any antifungals prior to the test. Multivariate analysis revealed that being younger than 7, severe colitis/mucositis, recent administration of polyvalent immunoglobulins and digestive colonization with Enterococcus sp were independent risk factors for false positivity. BDG is a valuable test to detect IFI in pediatric patients not previously treated with antifungals and to detect the occurrence of chronic infection.

Bacteremia during neutropenia is a predictive factor for invasive fungal infection in children

Invasive fungal infection (IFI) is a critical complication in the management of hematologic and malignant disease. Given that there is a tendency for IFI to occur after bacteremia following febrile episodes during neutropenia, the aim of this study was to determine if bacteremia was a predictive factor for IFI in pediatric patients with hematologic and malignant disease. Sixty-two patients (32 boys, 30 girls; median age, 4 years) with hematologic or malignant disease who had received chemotherapy, immunosuppressive therapy, and/or hematopoietic stem cell transplantation, and experienced febrile episodes during neutropenia were enrolled. In patient-based analysis, clinical features of 62 patients were compared between those with and without IFI. Meanwhile, in febrile episode-based analysis, clinical features were analyzed for 268 febrile episodes occurring during neutropenia in the 62 patients. Patient-based analysis showed that relapse of original disease and acute myeloid leukemia were risk factors for IFI. Meanwhile, febrile episode-based analysis identified bacteremia following febrile episodes during neutropenia as a potential risk factor for IFI. This is the first report to identify bacteremia following febrile episodes during neutropenia as a predictive factor for IFI in pediatric patients with hematologic or malignant disease. When bacteremia is detected in such patients, sufficient preventive measures against IFI, including intensive use of antifungal agents, are warranted.

Invasive Fungal Infections in Pediatric Patients With Hematologic Malignancies Receiving Oral Amphotericin B Solution and Early Intravenous Administration of Fluconazole

This study aimed to determine the frequency of invasive fungal infection (IFI) in pediatric patients with hematologic malignancy who received amphotericin B oral suspension and early intravenous fluconazole during the neutropenic phase as prophylaxis for IFI. Records of 743 neutropenic episodes induced by cytotoxic chemotherapy between 1997 and 2008 were retrospectively reviewed to determine risk factors for and frequency of IFI. The overall frequency of IFI was 0.8% (n=6) and frequencies of proven, probable, and possible infections were 0.3% (n=2), 0.4% (n=3), and 0.1% (n=1), respectively. During 351 episodes of profound neutropenia (neutrophil count <500/μL for ≥ 14 d), overall incidence of IFI was 1.71% (n=6). Pulmonary aspergillosis was the most common causative agent, and no patients showed candidemia, or hepatosplenic candidiasis. Cytotoxic chemotherapy regimens for acute myelogenous leukemia and profound neutropenia were significantly associated with IFI (P=0.004 and P=0.009, respectively). No IFI-attributable deaths or breakthrough fungal infections occurred. Our results indicate that amphotericin B oral solution and early intravenous fluconazole may be effective in reducing the incidence and mortality of IFI in pediatric patients with hematologic malignancies.

Antifungal prophylaxis with micafungin in patients treated for childhood cancer

Invasive fungal infections (IFIs) remain a major cause of infectious morality in neutropenic patients receiving chemotherapy or hematopoietic stem cell transplantation (HSCT). Micafungin exhibits broad antifungal activity against both Aspergillus and Candida species. We performed a retrospective study to determine the efficacy and safety of prophylactic micafungin against IFI in pediatric neutropenic patients during chemotherapy or HSCT. Forty patients were given micafungin (3 mg/kg/day) intravenously for neutropenia: 131 patient-cycles (39 patients) after chemotherapy and 15 patient-cycles (14 patients) after HSCT. Median duration of neutropenia and micafungin prophylaxis was 13 and 23 days after chemotherapy and HSCT, respectively. Treatment success rate, defined as absence of proven, probable, possible, or suspected IFIs, was 93.9% (121/131) and 80.0% (12/15) for chemotherapy and HSCT, respectively. Proven or probable IFI was documented in only one patient after HSCT. No adverse events were observed that could be related to micafungin prophylaxis. These results suggest that prophylactic micafungin is well tolerated and may prevent IFIs in pediatric patients with neutropenia receiving chemotherapy or HSCT.

Risks and outcomes of invasive fungal infections in pediatric patients undergoing allogeneic hematopoietic cell transplantation

Invasive fungal infections (IFI) are the leading cause of infectious mortality in adult patients undergoing hematopoietic cell transplantation (HCT) after myeloablative conditioning, but the extent of this problem in the pediatric population is unclear. We retrospectively examined risk factors for IFI among 120 consecutive pediatric patients undergoing allogeneic HCT at a single center. The incidence of proven or probable IFI in pediatric patients during the first year after allogeneic HCT was 13%, comparable to the rate reported in adult patients; however, unlike IFI in adult patients, the majority of IFI in children occurred within the first month after transplantation. The primary risk factors for IFI were duration of neutropenia, age greater than 10 years, transplant for severe aplastic anemia or Fanconi anemia, and high-dose corticosteroid administration for 10 days or longer. IFI were more likely to be successfully treated (42%, 5/12 patients) in pediatric HCT recipients when compared to previous reports of adult recipients. Nonrelapse mortality was estimated at 17% (20/120 patients) after allogeneic HCT, of which 35% (seven patients) were directly attributed to IFI. Thus, IFI is a significant cause of nonrelapse mortality in children undergoing allogeneic HCT and more effective strategies are needed to prevent and treat IFI.