Sunil K. Sood

Emergence of Candida parapsilosis as the Predominant Species Causing Candidemia in Children

An increase in the rate of isolation of Candida parapsilosis, relative to other Candida species, in our childrens hospital led us to analyze the clinical and epidemiological variables associated with candidemia. We sought to determine if these variables are different for patients infected with C. parapsilosis. All episodes of candidemia occurring over a 7-year period were analyzed retrospectively. Of 81 episodes in 80 patients, 35 (43%) were in neonates, and 46 (57%) were in nonneonates. C. parapsilosis was isolated in 40 episodes (49%). C. parapsilosis was significantly more likely than non-C. parapsilosis species to be associated with prematurity (P = .001), presence of a central venous catheter (P = .002), and use of total parenteral nutrition (P = .03). C. parapsilosis has emerged as the predominant species in our childrens hospital. The mortality rate associated with candidemia in children is lower than previously reported and may be associated with the high rate of isolation of C. parapsilosis.

Pharmacokinetic and Pharmacodynamic Assessment of Oral Valganciclovir in the Treatment of Symptomatic Congenital Cytomegalovirus Disease

BACKGROUND Intravenous ganciclovir administered for 6 weeks improves hearing outcomes in infants with symptomatic congenital cytomegalovirus (CMV) disease involving the central nervous system. METHODS Twenty-four subjects received antiviral therapy for 6 weeks. Serial pharmacokinetic assessments were performed after administration of valganciclovir oral solution and of intravenous ganciclovir. RESULTS On the basis of a previous pharmacokinetic study of the use of intravenous ganciclovir in this population, a target AUC12 (area under the concentration-time curve over a 12-h period) of 27 mg x h/L was defined. The median dose of oral valganciclovir administered in the present trial was 16 mg/kg, which produced a geometric mean AUC12 of 27.4 mg x h/L. The bioavailability of valganciclovir was 41.1%. Of the 18 subjects who had detectable CMV in whole blood at baseline or during therapy, 11 had <4 log viral DNA copies/mL at baseline, and 7 had > or =4 log viral DNA copies/mL at baseline; subjects who started the study with the higher viral burden experienced greater decreases in viral load but did not clear virus during the 42-day course of therapy. Neutropenia of grade 3 or 4 developed in 38% of subjects. CONCLUSIONS In neonates with symptomatic congenital CMV disease, valganciclovir oral solution provides plasma concentrations of ganciclovir comparable to those achieved with administration of intravenous ganciclovir. The results of the present study cannot be extrapolated to extemporaneously compounded liquid formulations of valganciclovir.

Pseudotumor cerebri in Lyme disease : A case report and literature review

Pseudotumor cerebri is an unusual presentation of Lyme disease. The case of an 8-year-old girl with pseudotumor cerebri secondary to acute neuroborreliosis is reported. She presented with acute onset of headache, papilledema, sixth nerve palsy, increased intracranial pressure, and cerebrospinal fluid pleocytosis. Serum and cerebrospinal fluid Lyme antibodies were positive. Twelve reported cases that mostly presented with systemic findings and signs of Lyme disease before development of pseudotumor cerebri were reviewed. We conclude that acute neuroborreliosis can present with pseudotumor cerebri as an initial manifestation. It is important to include Lyme disease in the differential diagnosis of pseudotumor cerebri in an area endemic for Lyme disease.

A Randomized, Double-Blind, Placebo-Controlled Trial of Pleconaril for the Treatment of Neonates With Enterovirus Sepsis

BACKGROUND Neonatal enterovirus sepsis has high mortality. Antiviral therapy is not available. METHODS Neonates with suspected enterovirus sepsis (hepatitis, coagulopathy, and/or myocarditis) with onset at ≤15 days of life were randomized 2:1 to receive oral pleconaril or placebo for 7 days. Serial virologic (oropharynx, rectum, urine, serum), clinical, pharmacokinetic, and safety evaluations were performed. RESULTS Sixty-one subjects were enrolled (43 treatment, 18 placebo), of whom 43 were confirmed enterovirus infected (31 treatment, 12 placebo). There was no difference in day 5 oropharyngeal culture positivity (primary endpoint; 0% in both groups). However, enterovirus-infected subjects in the treatment group became culture negative from all anatomic sites combined faster than placebo group subjects (median 4.0 versus 7.0 days, P = .08), and fewer subjects in the treatment group remained polymerase chain reaction (PCR)-positive from the oropharynx when last sampled (23% versus 58%, P = .02; median, 14.0 days). By intent to treat, 10/43 (23%) subjects in the treatment group and 8/18 (44%) in the placebo group died (P = .02 for 2-month survival difference); among enterovirus-confirmed subjects, 7/31 (23%) in the treatment group died versus 5/12 (42%) in the placebo group (P = .26). All pleconaril recipients attained concentrations greater than the IC90 after the first study day, but 38% were less than the IC90 during the first day of treatment. One subject in the treatment group and three in the placebo group had treatment-related adverse events. CONCLUSIONS Shorter times to culture and PCR negativity and greater survival among pleconaril recipients support potential efficacy and warrant further evaluation.

Oseltamivir Pharmacokinetics, Dosing, and Resistance Among Children Aged <2 Years With Influenza

BACKGROUND Children <2 years of age are at high risk of influenza-related mortality and morbidity. However, the appropriate dose of oseltamivir for children <2 years of age is unknown. METHODS The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group evaluated oseltamivir in infants aged <2 years in an age-de-escalation, adaptive design with a targeted systemic exposure. RESULTS From 2006 to 2010, 87 subjects enrolled. An oseltamivir dose of 3.0 mg/kg produced drug exposures within the target range in subjects 0-8 months of age, although there was a greater degree of variability in infants <3 months of age. In subjects 9-11 months of age, a dose of 3.5 mg/kg produced drug exposures within the target range. Six of 10 subjects aged 12-23 months receiving the Food and Drug Administration-approved unit dose for this age group (ie, 30 mg) had oseltamivir carboxylate exposures below the target range. Virus from 3 subjects developed oseltamivir resistance during antiviral treatment. CONCLUSIONS The appropriate twice-daily oral oseltamivir dose for infants ≤8 months of age is 3.0 mg/kg, while the dose for infants 9-11 months old is 3.5 mg/kg.

What we have learned about Lyme borreliosis from studies in children.

SummaryAlthough pediatric Lyme borreliosis (LB) need not be a separate nosological entity, there are clinically important differences in presentation, antibiotic regimens and outcomes in children, which provide lessons that can be extrapolated to the disease as it affects adults. A large proportion of the worldwide data is obtained from children. The aim of this presentation is not to present an exhaustive review of the pediatric literature, but to review a selection of pediatric studies that have made a significant contribution to our body of knowledge in Lyme borreliosis.

Prolonged Candidemia in Infants Following Surgery for Congenital Heart Disease

OBJECTIVES To describe a group of infants with complex congenital heart disease (CCHD) who had candidemia postoperatively and to perform a case-control study of risk factors. DESIGN Descriptive and case-control study. SETTING Tertiary-care medical centers. PATIENTS Infants with CCHD who underwent cardiac surgery and developed candidemia. Controls were matched for congenital heart disease lesions, age, and postoperative hospital stay. RESULTS Of 95 infants younger than 6 months with CCHD who underwent cardiac surgery between January 1999 and April 2001, 6 (6.3%) developed candidemia with 5 different species. The candidemia was prolonged (range, 12 to 32 days; median, 17 days). The interval between cardiac surgery and onset of candidemia was 12 to 57 days (median, 24 days). All had a central venous catheter inserted 8 to 50 days prior to the onset of candidemia. The mortality rate was 83%, compared with 13% for the group without candidemia. A univariate analysis of the potential risk factors revealed that duration of total parenteral nutrition (TPN), duration of antibiotics, intraoperative cardiopulmonary bypass time, and documentation of an intravascular thrombus were associated with candidemia. In multivariate analysis, long duration of TPN and documentation of a thrombus were associated with candidemia. CONCLUSIONS Candidemia following cardiac surgery for infants with CCHD was persistent and associated with high mortality. The variety of species indicates that this was not a common-source outbreak. Risk factors associated with candidemia were duration of TPN and documentation of an intravascular thrombus.

Effective Retrieval of Lyme Disease Information on the Web

The spirochetal infection Lyme disease, although now usually easily diagnosed and treated, has acquired an aura of ambiguity for many laypersons and medical professionals. The existence of controversy makes it difficult for infectious diseases physicians and scientists to readily obtain accurate information on Lyme disease by casually browsing the World Wide Web. Informative and current Web sites on the diagnosis, epidemiology, treatment, and prevention of Lyme disease can be found on-line, as can clear images of its clinical variants and of ticks. There are a handful of on-line resources on the biology of Borrelia and ticks, which can be tapped by the research community. These Web sites are described in the present article.

Comparison of the Clinical Features of Children Hospitalized With Pandemic 2009 A:H1N1 and Seasonal Influenza

Introduction: We compared the demographics, clinical presentation, course and outcome of children hospitalized with pandemic A:H1N1 and seasonal influenza. Methods: Sixty seven patients hospitalized from April 1st through August 31st 2009 with pandemic A:H1N1 influenza were enrolled. Two seasonal influenza cohorts were identified: 38 inpatients from January 1st 2004 through March 31st 2009, diagnosed by viral culture or direct fluorescent antibody testing; and 42 inpatients from January 1st 2007 through December 31st 2008 diagnosed via a rapid test. The two seasonal cohorts were not significantly different and were combined. Results: Patients with pandemic influenza were older (median age 6.5 years versus 1.3 years, P <.0001); were more often black (46% versus 23%, P <.0002); more frequently had an underlying condition (72% versus 49% P <.0049); and more often had wheezing (57% versus 16%, P <.0001). Conclusion: There was no significant difference between the groups in measures of severity during hospitalization.

Lyme Disease in Children

The diagnosis and management of Lyme disease in children is similar to that in adults with a few clinically relevant exceptions. The use of doxycycline as an initial empiric choice is to be avoided for children 8 years old and younger. Children may present with insidious onset of elevated intracranial pressure during acute disseminated Lyme disease; prompt diagnosis and treatment of this condition is important to prevent loss of vision. Children who acquire Lyme disease have an excellent prognosis even when they present with the late disseminated manifestation of Lyme arthritis. Guidance on the judicious use of serologic tests is provided. Pediatricians and family practitioners should be familiar with the prevention and management of tick bites, which are common in children.