ORIGINAL ARTICLE
Invasive Fungal Infections in Children With Hematologic and Malignant Diseases Sevinc N. Ozsevik, MD,* Gulnar Sensoy, MD,w Arzu Karli, MD,w Canan Albayrak, MD,z Ayhan Dagdemir, MD,z Nursen Belet, MD,w Murat Elli, MD,z Tunc Fisgin, MD,z Emel Ozyurek, MD,z Feride Duru, MD,z and Davut Albayrak, MDz
Background: To evaluate the clinical feature and outcome of invasive fungal infections (IFI) in children with hematologic and malign diseases. Patients and Methods: The medical records of children with hematologic and malignant diseases, who were hospitalized at our hospital between January 2010 and December 2011, were reviewed. Proven, probable, and possible IFIs were diagnosed according to the revised definitions of the European Organization for Research and Treatment of Cancer/Mycosis Study Group. The demographic, clinical, and laboratory characteristics of the patients who met the study criteria were evaluated. Results: IFI was diagnosed in 67 (7.2%) febrile episodes of 56 patients, of which 10 (1.2%) were proven, 20 (2%) probable, and 37 (4%) possible IFI. Blood culture of 10 cases with proven IFI yielded yeast and the most common isolated agent was Candida parapsilosis. Seventy percent of cases with fungemia had central venous catheter (CVC). Twenty cases with probable IFI had invasive mold infection. The cases with mold infection had higher median C-reactive protein values, lower neutrophil counts, and longer duration of neutropenia compared with the cases with yeast infection. A total of 14 patients (20.9%) died. Presence of CVC, bone marrow transplantation, total parenteral nutrition, prolonged fever, and proven/probable IFI were detected more often in patients who died, compared with patients who survived. Conclusions: IFIs are important causes of death in children with hematologic and malignant diseases. Mold infections are seen more frequently in cases with prolonged and profound neutropenia, and invasive yeast infections, especially with non-albicans Candida species, in cases with CVC. Early and effective treatment considering these findings will help to decrease the mortality. Key Words: invasive fungal infection, pediatric patients, cancer
(J Pediatr Hematol Oncol 2015;37:e69–e72)
I
nvasive fungal infection (IFI) is the common reason of mortality in children with hematologic or malignant diseases. In this patient group, the incidence of IFI has increased due to aggressive chemotherapeutic and immunosuppressive therapy regimens, severe mucositis, deep and prolonged neutropenia, and usage of wide-spectrum
Received for publication February 13, 2014; accepted June 23, 2014. From the Departments of *Pediatrics; wPediatric Infectious Diseases; and zPediatric Hematology and Oncology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey. The authors declare no conflict of interest. Reprints: Arzu Karli, MD, Department of Pediatric Infectious Diseases, Faculty of Medicine, Ondokuz Mayis University, Zip Code: 55139, Samsun, Turkey (e-mail: [email protected]). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved.
J Pediatr Hematol Oncol
antibiotics or steroids.1–4 IFIs are most frequently developed in relation to the Candida and Aspergillus strains. The spectrum of invasive candidiasis (IC) may vary from catheter-related candidemia to single-organ involvement or disseminated infections, and the mortality of IC may be as high as 31% in children. The most frequent clinical presentation of invasive aspergillosis (IA) is invasive pulmonary aspergillosis. However, hematogeneous dissemination to other organs such as sinuses, brain, or skin may be observed as well. The mortality in IA may vary depending on the underlying disease and may be as high as 88% in disseminated aspergillosis and central nervous system (CNS) involvement.4,5 Early detection and treatment of IFIs are critical for patient survival. However, early specification of the etiological fungal pathogen is really difficult and there are only a limited number of studies on the characteristics of the disease in children. In this study, we aimed to investigate the clinical appearance and prognosis of IFIs in children with hematologic and malignant diseases.
PATIENTS AND METHODS The medical records of the inpatients followed up in the Hematology-Oncology Department of Ondokuz Mayis University Hospital due to hematologic or malignant diseases, and receiving chemotherapy, immunosuppressive therapy, and/or bone marrow transplantation (BMT) between January 2010 and December 2011 were analyzed with regard to IFI. The IFI diagnosis was made upon the revised criteria of “European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/ MSG).”6 Proven IFI was defined as fungal growth in normally sterile areas. The probable IFI was defined as presence of host factors, clinical features, and mycological evidence, and possible IFI only in the presence of proper host factors and sufficient clinical evidence compatible with IFI. The demographic, clinical, and laboratory characteristics of the patients who met the study criteria were evaluated: data including the age and sex of the patients, underlying disease, cancer treatment protocol, history of BMT, presence of central venous catheter (CVC), presence of mucositis, long-term (> 7 d) antibiotic usage, corticosteroid usage (> 0.3 mg/kg, > 3 wk), application of total parenteral nutrition (TPN) within the 14 days before the fungal infection, whole blood analysis, radiologic and microbiological tests were recorded into the forms. Fever was defined as an axillary temperature of Z381C in a single measurement or persistence of Z37.71C for >1 hour, neutropenia was defined as an absolute neutrophil count (ANC)
Invasive Fungal Infections in Children With Hematologic and Malignant Diseases Sevinc N. Ozsevik, MD,* Gulnar Sensoy, MD,w Arzu Karli, MD,w Canan Albayrak, MD,z Ayhan Dagdemir, MD,z Nursen Belet, MD,w Murat Elli, MD,z Tunc Fisgin, MD,z Emel Ozyurek, MD,z Feride Duru, MD,z and Davut Albayrak, MDz
Background: To evaluate the clinical feature and outcome of invasive fungal infections (IFI) in children with hematologic and malign diseases. Patients and Methods: The medical records of children with hematologic and malignant diseases, who were hospitalized at our hospital between January 2010 and December 2011, were reviewed. Proven, probable, and possible IFIs were diagnosed according to the revised definitions of the European Organization for Research and Treatment of Cancer/Mycosis Study Group. The demographic, clinical, and laboratory characteristics of the patients who met the study criteria were evaluated. Results: IFI was diagnosed in 67 (7.2%) febrile episodes of 56 patients, of which 10 (1.2%) were proven, 20 (2%) probable, and 37 (4%) possible IFI. Blood culture of 10 cases with proven IFI yielded yeast and the most common isolated agent was Candida parapsilosis. Seventy percent of cases with fungemia had central venous catheter (CVC). Twenty cases with probable IFI had invasive mold infection. The cases with mold infection had higher median C-reactive protein values, lower neutrophil counts, and longer duration of neutropenia compared with the cases with yeast infection. A total of 14 patients (20.9%) died. Presence of CVC, bone marrow transplantation, total parenteral nutrition, prolonged fever, and proven/probable IFI were detected more often in patients who died, compared with patients who survived. Conclusions: IFIs are important causes of death in children with hematologic and malignant diseases. Mold infections are seen more frequently in cases with prolonged and profound neutropenia, and invasive yeast infections, especially with non-albicans Candida species, in cases with CVC. Early and effective treatment considering these findings will help to decrease the mortality. Key Words: invasive fungal infection, pediatric patients, cancer
(J Pediatr Hematol Oncol 2015;37:e69–e72)
I
nvasive fungal infection (IFI) is the common reason of mortality in children with hematologic or malignant diseases. In this patient group, the incidence of IFI has increased due to aggressive chemotherapeutic and immunosuppressive therapy regimens, severe mucositis, deep and prolonged neutropenia, and usage of wide-spectrum
Received for publication February 13, 2014; accepted June 23, 2014. From the Departments of *Pediatrics; wPediatric Infectious Diseases; and zPediatric Hematology and Oncology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey. The authors declare no conflict of interest. Reprints: Arzu Karli, MD, Department of Pediatric Infectious Diseases, Faculty of Medicine, Ondokuz Mayis University, Zip Code: 55139, Samsun, Turkey (e-mail: [email protected]). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved.
J Pediatr Hematol Oncol
antibiotics or steroids.1–4 IFIs are most frequently developed in relation to the Candida and Aspergillus strains. The spectrum of invasive candidiasis (IC) may vary from catheter-related candidemia to single-organ involvement or disseminated infections, and the mortality of IC may be as high as 31% in children. The most frequent clinical presentation of invasive aspergillosis (IA) is invasive pulmonary aspergillosis. However, hematogeneous dissemination to other organs such as sinuses, brain, or skin may be observed as well. The mortality in IA may vary depending on the underlying disease and may be as high as 88% in disseminated aspergillosis and central nervous system (CNS) involvement.4,5 Early detection and treatment of IFIs are critical for patient survival. However, early specification of the etiological fungal pathogen is really difficult and there are only a limited number of studies on the characteristics of the disease in children. In this study, we aimed to investigate the clinical appearance and prognosis of IFIs in children with hematologic and malignant diseases.
PATIENTS AND METHODS The medical records of the inpatients followed up in the Hematology-Oncology Department of Ondokuz Mayis University Hospital due to hematologic or malignant diseases, and receiving chemotherapy, immunosuppressive therapy, and/or bone marrow transplantation (BMT) between January 2010 and December 2011 were analyzed with regard to IFI. The IFI diagnosis was made upon the revised criteria of “European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/ MSG).”6 Proven IFI was defined as fungal growth in normally sterile areas. The probable IFI was defined as presence of host factors, clinical features, and mycological evidence, and possible IFI only in the presence of proper host factors and sufficient clinical evidence compatible with IFI. The demographic, clinical, and laboratory characteristics of the patients who met the study criteria were evaluated: data including the age and sex of the patients, underlying disease, cancer treatment protocol, history of BMT, presence of central venous catheter (CVC), presence of mucositis, long-term (> 7 d) antibiotic usage, corticosteroid usage (> 0.3 mg/kg, > 3 wk), application of total parenteral nutrition (TPN) within the 14 days before the fungal infection, whole blood analysis, radiologic and microbiological tests were recorded into the forms. Fever was defined as an axillary temperature of Z381C in a single measurement or persistence of Z37.71C for >1 hour, neutropenia was defined as an absolute neutrophil count (ANC)
