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Voriconazole in childrens

Catherine E Foster, Morven S Edwards, Julienne Brackett, Deborah A Schady, C Mary Healy, Carol J Baker
Background.: Trichosporonosis is an emerging and often fatal opportunistic fungal infection in immunocompromised patients, particularly those with hematologic malignancy, but data in children are lacking. Methods.: We report here 3 cases of invasive infection caused by Trichosporon asahii in pediatric patients with acute lymphoblastic leukemia at Texas Children's Hospital in Houston, Texas. We also conducted a literature review and identified 16 additional reports of pediatric patients with invasive T asahii infection and an underlying malignant or nonmalignant hematologic disorder...
May 16, 2017: Journal of the Pediatric Infectious Diseases Society
Shirley Qiong Yan, Brian Seyboth, Rachel Kobos, Anne Eaton, Susan K Seo, Nina Cohen
There are limited pediatric population pharmacokinetic data for voriconazole dosing, particularly in younger children. In a cohort of 34 patients younger than 3 years receiving voriconazole, the majority (n = 23, 68%) had a low initial serum concentration <1 mg/L. Among 23 children <2 years old, 19 (83%) had an initial trough <1 mg/L. There was large intra- and interindividual variability in trough levels. Dosing also varied from 3.3 to 19.6 mg/kg per dose. Only 2 of 34 patients had a documented adverse drug reaction attributable to voriconazole...
April 12, 2017: Journal of the Pediatric Infectious Diseases Society
Romina Valenzuela, Juan P Torres, Carolina Salas, Iván Gajardo, Julia Palma, Paula Catalán, M Elena Santolaya, Jorge Morales
BACKGROUND: Drug interactions (DI) in patients receiving hematopoietic stem cell transplantation (HSCT) are common and clinically significant, highlighting: anticonvulsants, voriconazole (VCZ) and cyclosporine (CsA), which require monitoring. OBJECTIVE: To describe the interactions between CsA-VCZ in children undergoing HSCT. METHODS: Retrospective, descriptive study in immunocompromised children hospitalized since January 2013 to December 2014 at Bone Marrow Transplant Unit, Hospital Dr...
February 2017: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
Issam S Hamadeh, Kenneth P Klinker, Samuel J Borgert, Ashley I Richards, Wenhui Li, Naveen Mangal, John W Hiemenz, Stephan Schmidt, Taimour Y Langaee, Charles A Peloquin, Julie A Johnson, Larisa H Cavallari
OBJECTIVES: Voriconazole, a first-line agent for the treatment of invasive fungal infections (IFIs), is metabolized by CYP2C19. A significant proportion of patients fail to achieve therapeutic trough concentrations with standard weight-based voriconazole dosing, placing them at increased risk for treatment failure, which can be life threatening. We sought to test the association between the CYP2C19 genotype and subtherapeutic voriconazole concentrations in adults with IFIs. PATIENT AND METHODS: Adults receiving weight-based voriconazole dosing for the treatment of IFIs were genotyped for the CYP2C19*2, *3, and *17 polymorphisms, and CYP2C19 metabolizer phenotypes were inferred...
May 2017: Pharmacogenetics and Genomics
Liang Liu, Xing Zhou, Tingting Wu, Hongliang Jiang, Sitao Yang, Yang Zhang
The pharmacokinetic profile of voriconazole is highly variable, rendering inconsistent and/or inadequate dosing, especially in children <2 years old. A retrospective analysis was performed in children receiving voriconazole with at least one plasma trough level (Ctrough) monitored. Statistical analyses were performed to examine the dose-exposure relationship as well as other factors potentially affecting voriconazole Ctrough in children of different ages. A total of 107 paediatric patients were included, of whom 75 were <2 years old...
April 2017: International Journal of Antimicrobial Agents
Stephanie Natale, John Bradley, William Huy Nguyen, Tri Tran, Pamela Ny, Kirsten La, Eva Vivian, Jennifer Le
Limited data exist for appropriate drug dosing in obese children. This comprehensive review summarizes pharmacokinetic (PK) alterations that occur with age and obesity, and these effects on antimicrobial dosing. A thorough comparison of different measures of body weight and specific antimicrobial agents including cefazolin, cefepime, ceftazidime, daptomycin, doripenem, gentamicin, linezolid, meropenem, piperacillin-tazobactam, tobramycin, vancomycin, and voriconazole is presented. PubMed (1966-July 2015) and Cochrane Library searches were performed using these key terms: children, pharmacokinetic, obesity, overweight, body mass index, ideal body weight, lean body weight, body composition, and specific antimicrobial drugs...
March 2017: Pharmacotherapy
David S Bayard, Michael Neely
An experimental design approach is presented for individualized therapy in the special case where the prior information is specified by a nonparametric (NP) population model. Here, a NP model refers to a discrete probability model characterized by a finite set of support points and their associated weights. An important question arises as to how to best design experiments for this type of model. Many experimental design methods are based on Fisher information or other approaches originally developed for parametric models...
April 2017: Journal of Pharmacokinetics and Pharmacodynamics
Elena M Marín Martínez, Ana Isabel Aller García, Estrella Martín-Mazuelos
BACKGROUND: Invasive fungal infection (IFI) has increased in recent years due to there being a greater number of risk factors. IFI caused by Candida is the most frequent, and although Candida albicans is the most isolated species, there is currently a decrease of C. albicans and an increase of other species of the genus. AIMS: To analyse the epidemiology, risk factors, and antifungal susceptibility of blood culture isolates of non-C.albicans Candida species in our hospital in the last 12years...
October 2016: Revista Iberoamericana de Micología
Tracy N Zembles, Nathan E Thompson, Peter L Havens, Bruce A Kaufman, Anna R Huppler
STUDY OBJECTIVE: To describe our experience with voriconazole in three patients younger than 2 years using an optimized dosing strategy for voriconazole that incorporates intensive therapeutic drug monitoring (TDM). DESIGN: Case series. SETTING: Large pediatric hospital. PATIENTS: Three patients younger than 2 years who received voriconazole therapy and had serum trough concentrations measured between January 1, 2010, and October 31, 2015...
October 2016: Pharmacotherapy
Kathleen M Job, Jared Olson, Chris Stockmann, Jonathan E Constance, Elena Y Enioutina, Joseph E Rower, Matthew W Linakis, Alfred H Balch, Tian Yu, Xiaoxi Liu, Emily A Thorell, Catherine M T Sherwin
INTRODUCTION: Voriconazole is a broad-spectrum antifungal agent commonly used to treat invasive fungal infections (IFI), including aspergillosis, candidiasis, Scedosporium infection, and Fusarium infection. IFI often occur in immunocompromised patients, leading to increased morbidity and mortality. AREAS COVERED: The objective of this review is to summarize the pharmacodynamic properties of voriconazole and to provide considerations for potential optimal dosing strategies...
August 2016: Expert Review of Anti-infective Therapy
Hirozumi Sano, Ryoji Kobayashi, Daiki Hori, Kenji Kishimoto, Daisuke Suzuki, Kazue Yasuda, Kunihiko Kobayashi
BACKGROUND: Pediatric patients under treatment for acute myeloid leukemia (AML) are at high risk for invasive fungal infection (IFI). We evaluated the efficacy of prophylactic administration of voriconazole (VRCZ) with two different doses. METHODS: Between October 2005 and June 2011, 17 children and adolescents (aged 0-20 years) undergoing chemotherapy for AML were prophylactically administered with 5 mg/kg/d of oral VRCZ. Furthermore, 22 AML patients (aged 0-19 years) were administered 10 mg/kg/d of oral VRCZ between July 2011 and December 2014...
June 2, 2016: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
Sahana M Srinivas, Vykuntaraju K Gowda, S Mahantesh, Rajeshwari Mannapur, Sanjay K Shivappa
Chromoblastomycosis is a chronic granulomatous infection of the skin and subcutaneous tissue caused by specific group of dematiaceous fungi. The infection results from traumatic injury and is seen more commonly on feet and lower legs. It is rarely seen in children and metastatic spread to other systems is exceptionally rare. We report a 12-year-old immunocompetent male child diagnosed with chromoblastomycosis on the lower leg, who in a span of few months developed osteomyelitis and left hemiparesis. Fungal culture showed growth of Exophiala spinifera...
May 2016: Indian Journal of Dermatology
Nawal Al-Maskari, Ibrahim Hussain, Suleiman Jumaa, Essam A Al-Shail
Intracranial aspergillosis is an extremely rare manifestation of invasive aspergillosis in immunocompetent children and is associated with high morbidity and mortality. We report a 12-year-old immunocompetent male child who was referred to the King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia, in May 2010 after a sudden-onset headache and loss of consciousness. Brain imaging revealed a large right space-occupying occipital lesion and the patient underwent a craniotomy and resection. Histopathology of the lesion revealed necrotising granulomatous fungal encephalitis with many hyphae engulfed by multinucleated giant histiocytes...
May 2016: Sultan Qaboos University Medical Journal
Gaoqi Xu, Liqin Zhu, Tingyue Ge, Shasha Liao, Na Li, Fang Qi
The objective of this study was to investigate the cumulative fraction of response of various voriconazole dosing regimens against six Candida and six Aspergillus spp. in immunocompromised children, immunocompromised adolescents, and adults. Using pharmacokinetic parameters and pharmacodynamic data, 5000-subject Monte Carlo simulations (MCSs) were conducted to evaluate the ability of simulated dosing strategies in terms of fAUC/MIC targets of voriconazole. According to the results of the MCSs, current voriconazole dosage regimens were all effective for children, adolescents and adults against Candida albicans, Candida parapsilosis and Candida orthopsilosis...
June 2016: International Journal of Antimicrobial Agents
Nelesh P Govender, Jaymati Patel, Rindidzani E Magobo, Serisha Naicker, Jeannette Wadula, Andrew Whitelaw, Yacoob Coovadia, Ranmini Kularatne, Chetna Govind, Shawn R Lockhart, Inge L Zietsman
OBJECTIVES: To compare Candida species distribution and antifungal susceptibility at South African public- and private-sector hospitals. METHODS: From February 2009 through to August 2010, laboratory-based surveillance for candidaemia was undertaken at 11 public-sector hospitals and >85 private-sector hospitals across South Africa. A case was defined as a patient of any age admitted to a sentinel hospital with isolation of Candida species from blood culture. Viable isolates were identified and tested for antifungal susceptibility at a reference laboratory...
July 2016: Journal of Antimicrobial Chemotherapy
Alison Boast, Nigel Curtis, Noel Cranswick, Amanda Gwee
OBJECTIVES: Therapeutic drug monitoring (TDM) of voriconazole is recommended to achieve trough concentrations of 1-5 mg/L. In children, this is challenging due to age-related variability in voriconazole pharmacokinetics. This study describes our experience with voriconazole, focusing on dosing regimens, dose adjustment and TDM. METHODS: We reviewed the medical records of immunocompromised children who received voriconazole from July 2009 to January 2015 and had TDM...
July 2016: Journal of Antimicrobial Chemotherapy
Te-Fu Weng, Kang-Hsi Wu, Han-Ping Wu, Ching-Tien Peng, Yu-Hua Chao
BACKGROUND: Invasive aspergillosis (IA) has recently increased and has a high mortality rate in immunocompromised patients. IA before hematopoietic stem cell transplantation (HSCT) is not uncommon, but how to cope with it is very tough. The serum aspergillus galactomannan antigen (GM) is a helpful marker for diagnosis of IA, and a serial follow-up of GM levels is important to evaluate the response of treatment. However, data on the changes of GM during HSCT are very limited. CASE PRESENTATION: Patient 1 was a 2-year-old female with severe aplastic anemia...
March 9, 2016: Italian Journal of Pediatrics
Yong Li, Guangmin Nong, Min Jiang, Jing Liu, Xiuan Liang
OBJECTIVE: To investigate the diagnosis and treatment of invasive pulmonary aspergillosis (IPA) in children. METHOD: The clinical data of 16 cases of proven or probable IPA who had been in our Hospital from January 2006 to June 2014 were retrospectively analyzed. RESULT: Among the 16 patients, 11 were males and 5 were females. One child had proven IPA and 15 children had probable IPA. Host risk included long duration use of multiple broad-spectrum antibiotics in 16 cases, neutropenia in 9 cases, invasive mechanical ventilation in 3 cases, primary immunodeficiency disease in 2 cases, long-term use of glucocorticoids in 2 cases, measles in 2 cases, and congenital pulmonary hypoplasia in 1 case...
March 2016: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
Luc J Huurneman, Michael Neely, Anette Veringa, Fernando Docobo Pérez, Virginia Ramos-Martin, Wim J Tissing, Jan-Willem C Alffenaar, William Hope
Voriconazole is the agent of choice for the treatment of invasive aspergillosis in children at least 2 years of age. The galactomannan index is a routinely used diagnostic marker for invasive aspergillosis and can be useful for following the clinical response to antifungal treatment. The aim of this study was to develop a pharmacokinetic-pharmacodynamic (PK-PD) mathematical model that links the pharmacokinetics of voriconazole with the galactomannan readout in children. Twelve children receiving voriconazole for treatment of proven, probable, and possible invasive fungal infections were studied...
April 2016: Antimicrobial Agents and Chemotherapy
Jessica M Lee, Ana Lia Graciano, Lukasz Dabrowski, Brenik Kuzmic, Mary Anne Tablizo
INTRODUCTION: In contrast to adults, coccidioidomycosis is a rare disease in infants and the mechanisms of disease acquisition are not well described in infants. The purpose of this study was to describe the clinical presentation, treatment, and outcome of pulmonary coccidioidomycosis in infants in an endemic area. METHODS: We performed a retrospective observational study of all patients less than 12 months of age admitted to a tertiary free standing children's hospital from 2003-2012 diagnosed with coccidioidomycosis...
August 2016: Pediatric Pulmonology
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