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David W Kimberlin,
Richard J Whitley,
Wen Wan,
Dwight A Powell, Gregory Storch,
Amina Ahmed,
April Palmer,
Pablo J Sánchez,
Richard F Jacobs,
John S Bradley, [......],
Leonard B Weiner,
Judith Guzman-Cottrill,
Carol A McCarthy,
Jill Griffin,
Penelope Jester,
Misty Parker,
Fred D Lakeman,
Huichien Kuo,
Choo Hyung Lee,
Gretchen A Cloud
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ABSTRACT: Poor neurodevelopmental outcomes and recurrences of cutaneous lesions remain unacceptably frequent among survivors of neonatal herpes simplex virus (HSV) disease.
We enrolled neonates with HSV disease in two parallel, identical, double-blind, placebo-controlled studies. Neonates with central nervous system (CNS) involvement were enrolled in one study, and neonates with skin, eye, and mouth involvement only were enrolled in the other. After completing a regimen of 14 to 21 days of parenteral acyclovir, the infants were randomly assigned to immediate acyclovir suppression (300 mg per square meter of body-surface area per dose orally, three times daily for 6 months) or placebo. Cutaneous recurrences were treated with open-label episodic therapy.
A total of 74 neonates were enrolled--45 with CNS involvement and 29 with skin, eye, and mouth disease. The Mental Development Index of the Bayley Scales of Infant Development (in which scores range from 50 to 150, with a mean of 100 and with higher scores indicating better neurodevelopmental outcomes) was assessed in 28 of the 45 infants with CNS involvement (62%) at 12 months of age. After adjustment for covariates, infants with CNS involvement who had been randomly assigned to acyclovir suppression had significantly higher mean Bayley mental-development scores at 12 months than did infants randomly assigned to placebo (88.24 vs. 68.12, P=0.046). Overall, there was a trend toward more neutropenia in the acyclovir group than in the placebo group (P=0.09).
Infants surviving neonatal HSV disease with CNS involvement had improved neurodevelopmental outcomes when they received suppressive therapy with oral acyclovir for 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; CASG 103 and CASG 104 ClinicalTrials.gov numbers, NCT00031460 and NCT00031447, respectively.).
New England Journal of Medicine 10/2011; 365(14):1284-92. · 53.30 Impact Factor
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David W. Kimberlin,
Marwan Shalabi,
Mark J. Abzug,
David Lang,
Richard F. Jacobs, Gregory Storch,
John S. Bradley,
Kelly C. Wade,
Octavio Ramilo,
José R. Romero, [......],
Charles Leach,
Judith Guzman-Cottrill,
Joan Robinson,
Nazha Abughali,
Janet Englund,
Jill Griffin,
Penny Jester,
Gretchen A. Cloud,
Richard J. Whitley,
and the NIAID Collaborative Antiviral Study Group
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ABSTRACT: Background: When oseltamivir is administered in extremely high doses (500–1000 mg/kg) to young juvenile rats, central nervous system toxicity and death occurred in some animals. Mortality was not observed in older juvenile rats, suggesting a possible relationship between neurotoxicity and an immature blood-brain barrier. To assess potential neurologic adverse effects of oseltamivir use in infants, a retrospective chart review was performed in infants less than 12 months of age who received oseltamivir, amantadine, or rimantadine.
Methods: The primary objective was to describe the frequency of neurologic adverse events among children less than 12 months of age who received oseltamivir compared with those receiving adamantanes. Medical record databases, emergency department databases, and/or pharmacy records at 15 medical centers were searched to identify patients.
Results: Of the 180 infants identified as having received antiviral therapy, 115 (64%) received oseltamivir, 37 (20%) received amantadine, and 28 (16%) received rimantadine. The median dose of oseltamivir was 2.0 mg/kg/dose in 3- to 5-month-old and 2.2 mg/kg/dose in 9- to 12-month-old infants. The maximum dose administered was 7.0 mg/kg/dose. There were no statistically significant differences in the occurrence of adverse neurologic events during therapy among subjects treated with oseltamivir versus those treated with the adamantanes (P = 0.13).
Conclusions: This is the largest report to date of oseltamivir use in children less than 12 months of age. Neurologic events were not more common with use of oseltamivir compared with that of the adamantanes. Dosing of oseltamivir was variable, illustrating the need for pharmacokinetic data in this younger population.
The Pediatric Infectious Disease Journal 02/2010; 29(3):195-198. · 3.58 Impact Factor
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David W Kimberlin,
Marwan Shalabi,
Mark J Abzug,
David Lang,
Richard F Jacobs, Gregory Storch,
John S Bradley,
Kelly C Wade,
Octavio Ramilo,
José R Romero,
Mark Shelton,
Charles Leach,
Judith Guzman-Cottrill,
Joan Robinson,
Nazha Abughali,
Janet Englund,
Jill Griffin,
Penny Jester,
Gretchen A Cloud,
Richard J Whitley
[show abstract]
[hide abstract]
ABSTRACT: When oseltamivir is administered in extremely high doses (500-1000 mg/kg) to young juvenile rats, central nervous system toxicity and death occurred in some animals. Mortality was not observed in older juvenile rats, suggesting a possible relationship between neurotoxicity and an immature blood-brain barrier. To assess potential neurologic adverse effects of oseltamivir use in infants, a retrospective chart review was performed in infants less than 12 months of age who received oseltamivir, amantadine, or rimantadine.
The primary objective was to describe the frequency of neurologic adverse events among children less than 12 months of age who received oseltamivir compared with those receiving adamantanes. Medical record databases, emergency department databases, and/or pharmacy records at 15 medical centers were searched to identify patients.
Of the 180 infants identified as having received antiviral therapy, 115 (64%) received oseltamivir, 37 (20%) received amantadine, and 28 (16%) received rimantadine. The median dose of oseltamivir was 2.0 mg/kg/dose in 3- to 5-month-old and 2.2 mg/kg/dose in 9- to 12-month-old infants. The maximum dose administered was 7.0 mg/kg/dose. There were no statistically significant differences in the occurrence of adverse neurologic events during therapy among subjects treated with oseltamivir versus those treated with the adamantanes (P = 0.13).
This is the largest report to date of oseltamivir use in children less than 12 months of age. Neurologic events were not more common with use of oseltamivir compared with that of the adamantanes. Dosing of oseltamivir was variable, illustrating the need for pharmacokinetic data in this younger population.
The Pediatric Infectious Disease Journal 11/2009; 29(3):195-8. · 3.58 Impact Factor
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ABSTRACT: Studies have reported the presence of KI polyomavirus (KIPyV) and WU polyomavirus (WUPyV) in respiratory secretions of young patients. So far, evidence has not supported a link between infections with either virus and respiratory tract disease; however, there has not been a large comparison of KIPyV-infected patients to age-matched patient groups.
A retrospective study comparing clinical aspects of KIPyV-positive patients with respiratory syncytial virus (RSV)-positive, WUPyV-positive, and respiratory-virus negative patients. Using real-time polymerase chain reaction, 2599 respiratory samples from patients ranging from 1 day to 88 years of age were tested for KIPyV. Electronic medical records were reviewed for 65 cases, for a comparison group consisting of 195 patients negative for common respiratory viruses, and for 56 WUPyV-positive patients drawn from the same population. Twelve patients testing positive for KIPyV as the sole pathogen were matched to 36 RSV-positive patients and clinical features of both groups were compared.
Seventy-two (2.8%) respiratory samples were positive for KIPyV. Another virus was detected in 71% of the KIPyV-positive samples. Analysis showed no statistically significant differences in clinical manifestations between KIPyV-positive patients and patients negative for common respiratory viruses, however, clinical characteristics of KIPyV-positive patients were less severe than those of patients positive for RSV. KIPyVpositive patients >or=3 years of age were usually immunocompromised in contrast to the younger children with KIPyV.
This study did not demonstrate a link between KIPyV infection and symptomatic respiratory disease. Patients positive for KIPyV exhibited less severe clinical symptoms than patients positive for RSV.
The Pediatric Infectious Disease Journal 11/2009; 29(4):329-33. · 3.58 Impact Factor
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ABSTRACT: Respiratory syncytial virus (RSV) bronchiolitis is a common cause of hospitalizations in children and has been increasingly identified as a risk factor in the development of asthma. Little is known about what determines the severity of RSV bronchiolitis, which may be helpful in the initial assessment of these children.
We evaluated a variety of environmental and host factors that may contribute to the severity of RSV bronchiolitis in the RSV Bronchiolitis in Early Life prospective cohort study. Severity of bronchiolitis was based on the quantization of lowest O(2) saturation and the length of stay. These factors included the child's and family's demographics, presence of household allergens (dust mite, cat, dog, and cockroach), peripheral blood eosinophil count, immunoglobulin E level, infant feeding, prior illnesses, exposure to intrauterine and postnatal cigarette smoke, and family history of atopy.
We prospectively enrolled 206 hospitalized infants, all under 12 months old (4.0 +/- 3.3 months old), with their first episode of severe RSV bronchiolitis (mean O(2) saturation: 91.6 +/- 7.3%; length of stay: 2.5 +/- 2.5 days; presence of radiographic opacities: 75%). Patients were excluded for a variety of reasons including previous wheezing, regular use of bronchodilator or antiinflammatory medications, any preexisting lung disease including asthma, chronic lung disease of prematurity/bronchopulmonary dysplasia, or cystic fibrosis; gastroesophageal reflux disease on medical therapy; or congenital anomalies of the chest or lung.
Age was found to be a significant factor in the severity of infection. The younger an infant was, the more severe the infection tended to be as measured by the lowest oxygen (O(2)) saturation. We also found that infants exposed to postnatal cigarette smoke from the mother had a lower O(2) saturation than those not exposed. However, there was no significant difference in RSV bronchiolitis severity between infants exposed only to intrauterine smoke and those infants never exposed to cigarette smoke. Infants with a family history of atopy, especially a maternal history of asthma or hay fever, had a higher O(2) saturation. Although a history of maternal atopy seemed to be protective, there was no association between allergens and bronchiolitis severity, although 25% of households had elevated allergen levels. Black infants demonstrated less severe RSV bronchiolitis than their white counterparts. Multivariate analysis revealed age, race, maternal atopy, and smoking to be associated with severity of RSV bronchiolitis.
The severity of RSV bronchiolitis early in life seems modified by postnatal maternal cigarette smoke exposure and atopy and age of the infant, not by levels of allergens in the home environment.
PEDIATRICS 02/2005; 115(1):e7-14. · 4.47 Impact Factor
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ABSTRACT: We evaluated the artus RealArt Parvovirus B19 LC PCR reagent (artus biotech USA, San Francisco, Calif.) for real-time PCR detection of parvovirus B19 DNA by retesting 71 specimens previously submitted to our laboratory. The artus assay, which produces a quantitative result and provides an internal PCR control, appeared to be slightly more sensitive than our conventional qualitative PCR assay.
Journal of Clinical Microbiology 08/2004; 42(7):3326-8. · 4.15 Impact Factor
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The Pediatric Infectious Disease Journal 12/2003; 22(11):1027-8. · 3.58 Impact Factor
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John M Trang,
Lauren Kidd,
William Gruber, Gregory Storch,
Gail Demmler,
Richard Jacobs,
Wayne Dankner,
Stuart Starr,
Robert Pass,
Sergio Stagno,
Charles Alford,
Seng-Jaw Soong,
Richard J Whitley,
Jean-Pierre Sommadossi,
Niaid Collaborative Antiviral Study Group
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ABSTRACT: The pharmacokinetic characteristics of ganciclovir were determined in neonates (age range, 2 to 49 days) after an 1-hour intravenous infusion of a single dose of either 4 mg/kg (n = 14) or 6 mg/kg (n = 13). Twenty-seven newborns with symptomatic cytomegalovirus inclusion disease were enrolled in this open phase I-II pharmacokinetics, safety, and tolerance trial of ganciclovir at one of two doses. Ganciclovir disposition was best described by a one-compartment open model with zero-order input and first-order elimination. The mean elimination half-life (t((1/2))) for both dose groups was 2.4 hours. The mean apparent volume of distribution (Vd) was 669 +/- 70 ml/kg for the 4 mg/kg group and 749 +/- 59 ml/kg for the 6 mg/kg group. The mean total body clearance (CL) for the 4 mg/kg and 6 mg/kg groups was 189 +/- 28 ml/hr/kg and 213 +/- 21 ml/hr/kg, respectively. No significant differences were observed in Vd or CL between the two groups. The Vd, expressed in milliliters, increased with increasing patient weight (r = 0.689; p = 0.0001). The CL, expressed in milliliters per hour per kilogram, increased with increasing age (r = 0.413; p = 0.032). No significant differences were observed between the two dose groups for the area under the curve normalized for dose (AUC/Dose) or the maximum plasma concentration normalized for dose (C(max)/Dose), indicating that ganciclovir exhibited linear pharmacokinetics in these neonates.Clinical Pharmacology and Therapeutics (1993) 53, 15-21; doi:10.1038/clpt.1993.4.
Clinical Pharmacology & Therapeutics 02/1993; 53(1):15-21. · 6.04 Impact Factor
