A Prospective, International Cohort Study of Invasive Mold Infections in Children

Wattier, Rachel L.; Dvorak, Christopher C.; Hoffman, Jill A.; Brozovich, Ava; Bin-Hussain, Ibrahim; Groll, Andreas H.; Castagnola, Elio; Knapp, Katherine M.; Zaoutis, Theoklis E.; Gustafsson, Britt; Sung, Lillian; Berman, David M.; Halasa, Natasha; Abzug, Mark J.; Velegraki, Aristea; Sharma, Tanvi; Fisher, Brian T.; Steinbach, William J.

doi:10.1093/jpids/piu074

Cited by 97 publications

(113 citation statements)

References 29 publications

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“…This was particularly true for adenovirus (42% mortality) and herpes viruses such as CMV (32% mortality) and may relate to antiviral resistance or high rates of T-cell immune incompetence secondary to the intensity of the conditioning, use of serotherapy, underlying disease, and processing, such as T-cell depletion (43). Consistent with the literature, fungal infections had a strong association with mortality, although our finding of 33.7% mortality in fungal infections is lower than recent mortality reports of 41–58% in this population (44–47) and may suggest improvement from new antifungal agents and diagnostic tests (44). These results also show that hematologic cancer patients and PID patients have different infection patterns posttransplant, with hematologic patients at higher risk for fungal infections and PID patients at higher risk for Gram-negative and viral infections.…”

Section: Discussionsupporting

confidence: 89%

New Insights Into Multicenter PICU Mortality Among Pediatric Hematopoietic Stem Cell Transplant Patients*

Zinter

Dvorak

Spicer

et al. 2015

Critical Care Medicine

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Objectives Over 2,500 children undergo hematopoietic stem cell transplantation in the United States each year, and up to 35% require PICU support for life-threatening complications. PICU mortality has dropped from 85% to 44%, but interpretation is confounded by significant cohort heterogeneity. Reports conflict regarding outcomes for patients with different underlying hematopoietic stem cell transplantation indications, and the burden of infectious complications for these patients has not been evaluated. We aim to describe infections, critical care interventions, and mortality for pediatric hematopoietic stem cell transplantation patients requiring PICU admission. Design A retrospective multicenter cohort analysis. Setting One hundred twelve centers in the Virtual PICU Systems database, January 1, 2009, to June 30, 2012. Patients A total of 1,782 admissions for patients who are 21 years old or younger with prior hematopoietic stem cell transplantation. Interventions None. Measurements and Main Results Pediatric Index of Mortality-2, Pediatric Risk of Mortality-3, transplant indication, infections, interventions, and mortality were recorded from admission through PICU death or discharge. Pediatric hematopoietic stem cell transplantation patients comprised 0.7% of all PICU admissions (1,782/246,346), which resulted in 16.2% mortality compared with 2.4% mortality for non-hematopoietic stem cell transplantation admissions (odds ratio, 7.8; 95% CI, 6.8–8.8; p < 0.001). Mortality for admissions with underlying hematologic malignancy (22.7%) was similar to that of admissions with primary immunodeficiency (19.4%; p = 0.41) but significantly greater than admissions with underlying nonmalignant non-primary immunodeficiency hematologic disease (15.4%; p = 0.020), metabolic disorder (8.1%; p < 0.001), or solid malignancy (5.7%; p < 0.001). Infection was documented in 45.7% of admissions with 22.2% mortality; viral and fungal mortality were 28.5% and 33.7%, respectively. Invasive positive pressure ventilation and renal replacement therapy were used in only 34.6% and 11.9% of admissions, with mortality of 42.5% and 51.9%, respectively. Conclusions PICU mortality for pediatric hematopoietic stem cell transplantation patients may be as low as 16.2% but higher for those receiving intubation (42.5%) or replacement therapy (51.9%). Hematologic malignancy and primary immunodeficiency had greater risk for mortality than other transplant indications. Greater understanding of other risk factors affecting mortality and the need for critical care support is needed.

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Section: Discussionsupporting

confidence: 89%

New Insights Into Multicenter PICU Mortality Among Pediatric Hematopoietic Stem Cell Transplant Patients*

Zinter

Dvorak

Spicer

et al. 2015

Critical Care Medicine

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“…Patients with prolonged (>10 days) neutropenia (<500 cells/μL) are commonly at the highest risk of mold infections [41], which may affect the lungs, sinuses, and soft tissues [41, 42]. In immunocompetent hosts, Aspergillus can cause clinical diseases of chronic aspergillosis and allergic bronchopulmonary aspergillosis, but invasive disease is uncommon [43].…”

Section: Fungal Diseases In Immunocompromised Hostsmentioning

confidence: 99%

Use of Fungal Diagnostics and Therapy in Pediatric Cancer Patients in Resource-Limited Settings

Mukkada

Kirby

Apiwattanakul

et al. 2016

Curr Clin Micro Rpt

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Fungal diseases are an important cause of mortality in immunocompromised hosts, and their incidence in pediatric cancer patients in low- to middle-income countries is underestimated. In this review, we present relevant, up-to-date information about the most common opportunistic and endemic fungal diseases among children with cancer, their geographic distribution, and recommended diagnostics and treatment. Efforts to improve the care of children with cancer and fungal disease must address the urgent need for sustainable and cost-effective solutions that improve training, fungal disease testing capability, and the use of available resources. We hope that the collective information presented here will be used to advise healthcare providers, regional and country health leaders, and policymakers of the current challenges in diagnosing and treating fungal infections in children with cancer in low- to middle-income countries.

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“…[5] There are few reports of invasive fusariosis in children. In an international cohort study that enrolled 22 pediatric centers and 131 children with invasive fungal disease only 4 had Fusarium infection [6]. There are 4 reports of fusariosis in children with onco-hematologic disease, 2 of them using caspofungin [7][8][9][10] and two reviews included some pediatric cases among the predominant adults cases [1,5].…”

Section: Introductionmentioning

confidence: 99%

An outbreak of invasive fusariosis in a children’s cancer hospital

Litvinov

Silva

Heijden

et al. 2015

Clinical Microbiology and Infection

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Fusarium is considered an emerging pathogen, and there are few reports of fusariosis in children. The objective of this study was to describe an outbreak of invasive fusariosis in a children's cancer hospital. A neutropenic 17-year-old male patient hospitalized for 10 days for a relapse of acute myeloid leukaemia, under chemotherapy, presented fever without any other symptoms; a thoracic computerized tomography showed bilateral pulmonary nodules. During voriconazole treatment, 1-cm reddened and painful subcutaneous nodules appeared on arms and legs and the culture of a skin biopsy revealed F. solani. Another case occurred 11 days later and started an outbreak investigation. Water samples for cultures were collected from taps, showers and water reservoirs. Air from all patient rooms was sampled. Faucets and the drains of sinks and showers were swabbed and cultured. Environmental and clinical isolates were typed. There were 10 confirmed cases of infection caused by Fusarium spp. F. oxysporum and F. solani were isolated from water, swabs and air in patient rooms. Many control measures were instituted, but the outbreak was only controlled 1 year after the first case, when water filters filtering 0.2 μm were installed at the exit of all faucets and showers in all patient rooms (points-of-use). Typing demonstrated that clinical isolates of F. oxysporum were similar to those of the environment. In conclusion, to our knowledge this is the first reported outbreak of invasive fusariosis in children with oncohaematologic disease. It was controlled using 0.2-μm filters in all tap faucets and showers.

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A Prospective, International Cohort Study of Invasive Mold Infections in Children

Cited by 97 publications

References 29 publications

New Insights Into Multicenter PICU Mortality Among Pediatric Hematopoietic Stem Cell Transplant Patients*

New Insights Into Multicenter PICU Mortality Among Pediatric Hematopoietic Stem Cell Transplant Patients*

Use of Fungal Diagnostics and Therapy in Pediatric Cancer Patients in Resource-Limited Settings

An outbreak of invasive fusariosis in a children’s cancer hospital

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