[Show abstract][Hide abstract] ABSTRACT: Voriconazole is the treatment of choice for invasive aspergillosis and its use is increasing in pediatrics. Minimal pharmacokinetic data exist in young children. We report voriconazole concentrations for 10 children <3 years of age and pharmacokinetic parameters for 1 infant who had therapeutic drug monitoring performed. Trough concentrations were unpredictable based on dose, highlighting the need to follow values during therapy.
Full-text · Article · Feb 2012 · The Pediatric Infectious Disease Journal
[Show abstract][Hide abstract] ABSTRACT: Invasive candidiasis is a leading cause of mortality and morbidity in neonatal intensive care units. Treatment recommendations are limited by a lack of comparative outcomes data.
We identified all infants ≤ 120 days of age with positive blood, urine, or cerebrospinal fluid cultures for Candida species who received amphotericin B deoxycholate, fluconazole, amphotericin B lipid products, or combination therapy admitted to one of 192 neonatal intensive care units in the United States between 1997 and 2003. Primary outcome measures included overall mortality and therapeutic failure (combined outcome of duration of infection >7 days, need for additional antifungal therapy, or death before discharge). We compared outcomes by antifungal therapy using logistic regression, controlling for gestational age, day of life at start of antifungal therapy, delay in therapy, and site of infection.
Overall, 138 of 730 (19%) infants died. On multivariable logistic regression, we observed higher overall mortality for infants receiving amphotericin B lipid products compared with infants receiving amphotericin B deoxycholate (odds ratio 1.96 [95% confidence intervals: 1.16, 3.33]; P = 0.01) or fluconazole (odds ratio 2.39 [1.18, 4.83]; P = 0.02).
Infants treated with amphotericin B lipid products had higher mortality than infants treated with either amphotericin B deoxycholate or fluconazole. This finding may be related to inadequate penetration of amphotericin B lipid products into the kidneys, inappropriate dosing in premature infants, or unknown differences in acuity of illness in infants treated with amphotericin B lipid products.
Preview · Article · Dec 2011 · The Pediatric Infectious Disease Journal
[Show abstract][Hide abstract] ABSTRACT: Bone marrow necrosis is a rare histopathology finding with the majority of cases occurring in the setting of a hematologic malignancy. This article reports a case of diffuse marrow necrosis in a child secondary to acute lymphoblastic leukemia and summarizes the clinical features and outcomes for children with bone marrow necrosis secondary to leukemia from 20 published reports. This review demonstrated that the most common presenting features were bone pain, fever, pancytopenia, and that outcomes were less favorable when compared with those without necrosis. However, contemporary literature suggests that outcomes are similar for children who have bone marrow necrosis secondary to leukemia when compared with overall survival rates for pediatric leukemia.
No preview · Article · Oct 2011 · Journal of Pediatric Hematology/Oncology
[Show abstract][Hide abstract] ABSTRACT: The information gained from pharmacogenomic testing is becoming increasingly recognized as an opportunity to improve our current dosing strategies for children. The identification of gene polymorphisms that influence drug disposition and effect can be used to help predict a child's susceptibility to toxicity and/or response to a particular drug or therapeutic regimen. However, the potential consequences of performing genomic analysis in children raise important ethical considerations. Although the level of risk introduced remains partially hypothetical, awareness of the ethical concerns and protective legislation will be an important part of fully informing patients, families, clinicians, and researchers about the risks and benefits of pharmacogenomic testing in children. Where it can be done without loss of benefit, risk reduction is a moral imperative, and so the ethical complexities related to pharmacogenomics must be addressed in an ongoing way as we continue to learn more about the value of the technology to children.
[Show abstract][Hide abstract] ABSTRACT: Candida infections are common and often fatal in infants and neonates. Anidulafungin has excellent activity against Candida species, but the pharmacokinetics (PK) and safety of the drug in infants and neonates are unknown. The object of our study was to determine the PK and safety of anidulafungin in infants and neonates at risk for invasive candidiasis. Intravenous anidulafungin (1.5 mg/kg/day maintenance dose) was administered to 15 infants and neonates over 3 to 5 days. Plasma samples were collected after the first dose and again after the third to fifth doses. The pharmacokinetic parameters of the drug were determined by noncompartmental analysis. Safety was assessed using National Cancer Institute common toxicity criteria. The study showed that drug exposure levels were similar between neonates and infants; the median areas under the concentration-time curve (range) was 75 (30-109) µg·h/ml and 98 (55-278) µg·h/ml (P = 0.12) for neonates and infants, respectively. No drug-related serious adverse events were observed. The study results indicate that neonates and infants receiving 1.5 mg/kg/day have anidulafungin exposure levels similar to those in children receiving similar weight-based dosing and in adult patients receiving 100 mg/day.
[Show abstract][Hide abstract] ABSTRACT: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a reactive, proliferative disorder of the immune system resulting in lymphohistiocytic proliferation, hemophagocytosis, and cytokine dysregulation. The most common infectious trigger in sHLH is Epstein-Barr virus (EBV-HLH). Current treatment protocols for EBV-HLH have a cure rate of approximately 75%; however, there are significant toxicities associated with these therapies. We present two patients with EBV-HLH who experienced spontaneous resolution of their disease prior to the initiation of therapy, suggesting there may be a subgroup of patients with EBV-HLH who do well with conservative management and can avoid potentially toxic therapies.
No preview · Article · Oct 2010 · Pediatric Blood & Cancer
[Show abstract][Hide abstract] ABSTRACT: We describe a 4-year-old female patient with a persistent paraspinal mass following chemotherapy for Wilms tumor. A discordant response to chemotherapy prompted biopsy of the persistent mass, which revealed a ganglioneuroma. This report highlights the synchronous occurrence of different tumors in the same patient, and suggests that repeat biopsies should be considered when contiguous tumor masses do not respond as expected.
No preview · Article · Sep 2010 · Pediatric Blood & Cancer
[Show abstract][Hide abstract] ABSTRACT: Children with short bowel syndrome requiring long-term total parenteral nutrition are at high risk for catheter-associated infections. The optimal management of catheter infections in this patient population is unknown. We conducted a retrospective observational study in children with short bowel syndrome to compare outcomes of catheter-associated infections treated with catheter removal plus antibiotic therapy versus antibiotic therapy alone.
Preview · Article · Feb 2010 · Journal of pediatric gastroenterology and nutrition
[Show abstract][Hide abstract] ABSTRACT: Invasive candidiasis is a leading cause of infection-related morbidity and mortality in premature infants (Stoll et al. Kremer
et al. Lee et al. Mittal et al. Friedman et al. Benjamin et al. Risk factors for candidiasis include extreme prematurity,
post natal age, and center (Kaufman, ). Several studies have reported a 20% mortality rate, despite antifungal treatment (Stoll
et al. Benjamin et al., ). Antifungal therapy failure is correlated with birthweight: for those with a birthweight 751–1000 g
the failure rate is 14%, and for those with a birthweight of 400–750 g, it is 31% (Benjamin et al.). While much progress has
been made in this area, definitive management guidelines for prophylaxis and treatment are limited (Benjamin et al., ). Routine
prophylaxis is not recommended for neonates and use of either fluconazole or amphotericin B deoxycholate is considered 1st
line therapy for treatment of invasive disease. However, new therapeutic options that may be safer and more efficacious are
on the horizon
No preview · Article · Jan 2010 · Advances in Experimental Medicine and Biology
[Show abstract][Hide abstract] ABSTRACT: Survival for premature neonates has improved dramatically over the past 20 years; however, there has been minimal improvement in prematurity-associated morbidities. Morbidity rates and assessment of outcomes vary across neonatology intensive care units (NICUs). Here, we address the reasons underlying these differences, note the impact that this center variation has on trial design and interpretation, and highlight the success of the efforts in pediatric oncology to develop standards of care through the conduct of multicenter clinical trials.
[Show abstract][Hide abstract] ABSTRACT: Preterm birth is increasing worldwide, and late preterm births, which comprise more than 70% of all preterm births, account for much of the increase. Early and late onset sepsis results in significant mortality in extremely preterm infants, but little is known about sepsis outcomes in late preterm infants.
This is an observational cohort study of infants <121 days of age (119,130 infants less than or equal to 3 days of life and 106,142 infants between 4 and 120 days of life) with estimated gestational age at birth between 34 and 36 weeks, admitted to 248 neonatal intensive care units in the United States between 1996 and 2007.
During the study period, the cumulative incidence of early and late onset sepsis was 4.42 and 6.30 episodes per 1000 admissions, respectively. Gram-positive organisms caused the majority of early and late onset sepsis episodes. Infants with early onset sepsis caused by Gram-negative rods and infants with late onset sepsis were more likely to die than their peers with sterile blood cultures (odds ratio [OR]: 4.39, 95% CI: 1.71-11.23, P = 0.002; and OR: 3.37, 95% CI: 2.35-4.84, P < 0.001, respectively).
Late preterm infants demonstrate specific infection rates, pathogen distribution, and mortality associated with early and late onset sepsis. The results of this study are generalizable to late preterm infants admitted to the special care nursery or neonatal intensive care unit.
Full-text · Article · Dec 2009 · The Pediatric Infectious Disease Journal
[Show abstract][Hide abstract] ABSTRACT: Our aim was to determine the incidence of anatomical abnormalities after a urinary tract infection (UTI) in infants <2 months of age hospitalized in the neonatal intensive care unit (NICU).
This was a retrospective, single-center cohort study of infants <2 months of age in the NICU with a UTI and documented renal imaging.
We identified 141 infants with UTIs. The mean gestational age and birth weight were 28 weeks and 1254 g, respectively. The most commonly identified pathogen was coagulase-negative Staphylococcus (28%, 44 of 156). A major abnormality was found on at least one imaging study for 4% (5 of 118) of infants. Major abnormalities were noted on 4% (5 of 114) of renal ultrasounds and 2% (2 of 82) of voiding cystourethrography examinations.
Among infants in the NICU <2 months of age at the time of a UTI, the prevalence of major anatomical abnormalities is <5%.
Full-text · Article · Oct 2009 · Journal of perinatology: official journal of the California Perinatal Association
[Show abstract][Hide abstract] ABSTRACT: In immunocompromised hosts, invasive fungal infections are common and fatal. In the past decade, the antifungal armamentarium against invasive mycoses has expanded greatly. The purpose of the present report is to review the most recent literature addressing the use of antifungal agents in children.
Most studies evaluating the safety and efficacy of antifungal agents are limited to adults. However, important progress has been made in describing the pharmacokinetics and safety of newer antifungal agents in children, including the echinocandins.
Dosage guidelines for newer antifungal agents are currently based on adult and limited pediatric data. Because important developmental pharmacology changes occur throughout childhood impacting the pharmacokinetics of these agents, antifungal studies specifically designed for children are necessary.
Preview · Article · Oct 2009 · Current Opinion in Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: We compared length of stay, inpatient costs, and mortality associated with Candida albicans and non-albicans bloodstream infections in adults and children. Compared with adults, children with Candida bloodstream infections had longer lengths of stay (36.7 vs. 20.7 days; P < 0.001) and higher inpatient costs ($133,871 vs. $56,725; P < 0.001) but lower mortality (28.3% vs. 43.5%; P < 0.001).
[Show abstract][Hide abstract] ABSTRACT: Background: Candida bloodstream infections (BSI) are associated with substantial morbidity, mortality and costs. We evaluated clinical and economic outcomes associated with candidemia, focusing on differences between C. albicans and non-albicans species, and between children and adults. Methods: The study included all patients hospitalized at Duke University Medical Center from February 1996 to July 2007 with a blood culture positive for Candida. Cost data were available for patients hospitalized since December 2002. Total costs and length of stay (LOS) represent all costs and inpatient days incurred from the date of the first positive blood culture. We used generalized linear models to compare costs, negative binomial models to compare LOS, and chi-square tests to compare inpatient mortality. Results: 1134 patients were identified with Candida BSI (45% albicans, 22% <18 years). Cost data were available for 446 (39%). Children had higher costs compared to adults ($137,024 vs. $56,083, p<0.0001), longer LOS (42.5 vs. 20.7 days, p<0.0001), and lower mortality (31% vs. 44%, p=0.0004). Among children, there were no significant differences between those with C. albicans and non-albicans in terms of costs ($120,991 vs. $151,824, p=0.26), LOS (46 vs. 40 days, p=0.29), or mortality (27% vs. 34%, p=0.22). Among adults, those with C. albicans versus non-albicans had lower costs ($46,851 vs. $62,357, p=0.009), shorter LOS (19 vs. 22 days, p=0.008), but comparable mortality (43% vs. 44%, p=0.69). Conclusions: Candida BSI are associated with high inpatient costs, extended LOS, and high mortality. Adults infected with non-albicans incurred higher costs and longer stays than adults with C. albicans. Future studies that estimate costs and LOS attributable to Candida BSI are needed to study the value of strategies to reduce the incidence of candidemia.
[Show abstract][Hide abstract] ABSTRACT: The CYP3A5(*)1 allele has been associated with differences in the metabolism of some CYP3A substrates. CYP3A5 polymorphism may also influence susceptibility for certain drug interactions. We have previously noted a correlation between basal CYP3A activity and the inductive effects of dexamethasone using the erythromycin breath test (ERBT). To determine whether CYP3A5 polymorphism influences induction of CYP3A activity, we examined the effect of an antiemetic regimen of dexamethasone, and the prototypical inducer rifampin, on the ERBT in African American volunteers prospectively stratified by CYP3A5(*)1 allele carrier status. Mean basal ERBTs were significantly higher in CYP3A5(*)1 carriers (2.71 +/- 0.53%) versus noncarriers (2.12 +/- 0.37%, P = 0.006). Rifampin increased ERBTs in CYP3A5(*)1 carriers (4.68 versus 2.60%, P = 0.0008) and noncarriers (3.55 versus 2.11%, P = 0.0017), whereas dexamethasone increased ERBTs only in CYP3A5(*)1 noncarriers (3.03 versus 2.14%, P = 0.031). CYP3A5 polymorphism appears to influence susceptibility to induction-type drug interactions for some inducers, and CYP3A5(*)1 noncarriers may be more susceptible to the inductive effects of dexamethasone as a result of lower basal CYP3A activity.
Full-text · Article · Sep 2008 · Drug metabolism and disposition: the biological fate of chemicals
[Show abstract][Hide abstract] ABSTRACT: Opsoclonus-myoclonus (OM) is a paraneoplastic syndrome of probable autoimmune origin. Despite current therapies aimed at decreasing autoantibody formation, OM is difficult to control and may impact long-term neurologic outcome. We present a case of a 19-month-old patient who initially presented with OM, neuroblastoma and a constitutional cytogenetic abnormality t(5;12)(q11.2;q15). The patient's OM was recalcitrant to conventional therapies, but showed significant improvement following treatment with rituximab.
No preview · Article · Feb 2008 · Pediatric Blood & Cancer
[Show abstract][Hide abstract] ABSTRACT: The Centers for Disease Control and Prevention (CDC) monitors the occurrence of respiratory syncytial virus (RSV) in the United States and has historically reported on activity at the regional level. Prior to the 2007-2008 RSVseason, the CDC did not report seasonal RSV data for cities within North Carolina or for the state. The purpose of the present study is to characterize RSV seasonal activity within North Carolina and to determine the appropriate months in which at-risk children should receive prophylaxis.
We prospectively collected RSV test data monthly over three seasons (fall through spring), from September 2003 through July 2006, from a diverse group of hospitals and a community pediatric practice located within five regions throughout North Carolina.
Approximately 14,000 laboratory tests, including 23.7% that were RSV positive, were evaluated over the three seasons, and RSV was detected within the state during all but three months of the study. Seasonal variation in the onset (October-November) of RSV activity and duration (six to seven months) of the RSV season according to the specified definition of seasonality was noted yearly within individual regions and among regions. On average over the study period, the greatest percentage of positive tests (33.8%) statewide occurred during January.
Our data suggest the RSV season in North Carolina is longer than the national average, and RSV epidemics persist during months that fall outside of those in which RSV prophylaxis is given to high-risk children. Guidelines on the administration of RSV prophylaxis should ideally be based on results of local RSV test data.
Preview · Article · Jan 2008 · North Carolina medical journal