Judith Guzman-Cottrill

Oral Acyclovir Suppression and Neurodevelopment after Neonatal Herpes

BACKGROUND Poor neurodevelopmental outcomes and recurrences of cutaneous lesions remain unacceptably frequent among survivors of neonatal herpes simplex virus (HSV) disease. METHODS 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. RESULTS 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). CONCLUSIONS 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.).

Safety and Efficacy of CMX001 as Salvage Therapy for Severe Adenovirus Infections in Immunocompromised Patients

No therapeutic agent has yet been established as the definitive therapy for adenovirus infections. We describe the clinical experience of 13 immunocompromised patients who received CMX001 (hexadecyloxypropyl cidofovir), an orally bioavailable lipid conjugate of cidofovir, for adenovirus disease. We retrospectively analyzed 13 patients with adenovirus disease and viremia treated with CMX001; data were available for ≥ 4 weeks after initiation of CMX001 therapy. Virologic response (VR) was defined as a 99% drop from baseline or undetectable adenovirus DNA in serum. The median age of the group was 6 years (range, 0.92-66 years). One patient had severe combined immunodeficiency, 1 patient was a small bowel transplant recipient, and 11 were allogeneic stem cell transplant recipients. Adenovirus disease was diagnosed at a median of 75 days (range, 15-720 days) after transplantation. All patients received i.v. cidofovir for a median of 21 days (range, 5-90 days) before CMX001 therapy. The median absolute lymphocyte count at CMX001 initiation was 300 cells/μL (range, 7-1500 cells/μL). Eight patients (61.5%) had a ≥ 1 log10 drop in viral load after the first week of therapy. By week 8, 9 patients (69.2%) demonstrated a VR, with a median time to achieve VR of 7 days (range, 3-35 days). The change in absolute lymphocyte count was inversely correlated with the change in log10 viral load only at week 6 (r = -0.74; P = .03). Patients with VR had longer survival than those without VR (median 196 days versus 54.5 days; P = .04). No serious adverse events were attributed to CMX001 during therapy. CMX001 may be a promising therapeutic option for the treatment of severe adenovirus disease in immunocompromised patients.

Safety of Oseltamivir Compared With the Adamantanes in Children Less Than 12 Months of Age

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.

Effect of Catheter Dwell Time on Risk of Central Line–Associated Bloodstream Infection in Infants

BACKGROUND AND OBJECTIVE: Central venous catheters in the NICU are associated with significant morbidity and mortality because of the risk of central line–associated bloodstream infections (CLABSIs). The purpose of this study was to determine the effect of catheter dwell time on risk of CLABSI. METHODS: Retrospective cohort study of 13 327 infants with 15 567 catheters (93% peripherally inserted central catheters [PICCs], 7% tunneled catheters) and 256 088 catheter days cared for in 141 NICUs. CLABSI was defined using National Health Surveillance Network criteria. We defined dwell time as the number of days from line insertion until either line removal or day of CLABSI. We generated survival curves for each week of dwell time and estimated hazard ratios for CLABSI at each week by using a Cox proportional hazards frailty model. We controlled for postmenstrual age and year, included facility as a random effect, and generated separate models by line type. RESULTS: Median postmenstrual age was 29 weeks (interquartile range 26–33). The overall incidence of CLABSI was 0.93 per 1000 catheter days. Increased dwell time was not associated with increased risk of CLABSI for PICCs. For tunneled catheters, infection incidence was significantly higher in weeks 7 and 9 compared with week 1. CONCLUSIONS: Clinicians should not routinely replace uninfected PICCs for fear of infection but should consider removing tunneled catheters before week 7 if no longer needed. Additional studies are needed to determine what daily maintenance practices may be associated with decreased risk of infection, especially for tunneled catheters.

Short-term weather variability in Chicago and hospitalizations for Kawasaki disease.

Background: Kawasaki disease exhibits a distinct seasonality, and short-term changes in weather may affect its occurrence. Methods: To investigate the effects of weather variability on the occurrence of this syndrome, we conducted a time-between-events analysis of consecutive admissions for Kawasaki disease to a large pediatric hospital in Chicago. We used gamma regression to model the times between admissions. This is a novel application of gamma regression to model the time between admissions as a function of subject-specific covariates. Results: We recorded 723 admissions in the 18-year (1986–2003) study period, of which 700 had complete data for analysis. Admissions for Kawasaki disease in Chicago were seasonal: The mean time between admissions was 34% shorter (relative time = 0.66, 95% confidence interval 0.54–0.81) from January–March than from July–September. In 1998, we recorded a larger number of admissions for Kawasaki disease (n = 65) than in other years (mean n = 37). January–March months of 1998 were warmer by a mean of 3°C (1.5°C–4.4°C) and the mean time between admissions was 48% shorter (relative time = 0.52, 0.36–0.75) than in equivalent periods of other study years. Conclusions: Our findings show that atypical changes in weather affect the occurrence of Kawasaki disease and are compatible with a link to an infectious trigger. The analysis of interevent times using gamma regression is an alternative to Poisson regression in modeling a time series of sparse daily counts.

Variation in Antibiotic Susceptibility of Uropathogens by Age Among Ambulatory Pediatric Patients

We compared uropathogen antibiotic susceptibility across age groups of ambulatory pediatric patients. For Escherichia coli (n=5,099) and other Gram-negative rods (n=626), significant differences (p<0.05) existed across age groups for ampicillin, cefazolin, and trimethoprim/sulfamethoxazole susceptibility. In E. coli, differences in trimethoprim/sulfamethoxazole susceptibility varied from 79% in children under 2 to 88% in ages 16-18 (p<0.001), while ampicillin susceptibility varied from 30% in children under 2 to 53% in ages 2-5 (p=0.015). Uropathogen susceptibility to common urinary anti-infectives may be lower in the youngest children. Further investigation into these differences is needed to facilitate appropriate and prudent treatment of urinary tract infections.

Infection Prevention and Control in Residential Facilities for Pediatric Patients and Their Families

The Society for Healthcare Epidemiology of America (SHEA) guideline “Infection Prevention and Control in Residential Facilities for Pediatric Patients and Their Families” is the first infection prevention and control (IPC) guideline to address preventing transmission of infectious agents in “home away from home” residential settings, of which the Ronald McDonald Houses (RMHs) serve as a prototype. These types of facilities provide support services, including overnight lodging, for ill and injured children and their families. Food preparation occurs in common areas, and cleaning of rooms or apartments is performed by the occupants during their stay and before departure. Pediatric patients are frequent guests of the family-centered facilities while receiving or recovering from specialized medical therapy. Examples of high-risk populations served in these facilities include families of patients with cancer, recipients of stem cell or solid organ transplants, surgical and/or very-low-birthweight infants who receive care in neonatal intensive care units (NICUs), those with cystic fibrosis, and women with high-risk pregnancies awaiting delivery in a nearby medical center. Such facilities are located worldwide and vary in their physical structure and the predominant population served.

Metachronous manifestations of sweet's syndrome in a neutropenic patient with Fanconi anemia

Sweets syndrome (SS) is an acute, febrile neutrophilic dermatosis that frequently presents with leukocytosis and erythematous plaques. Lesions show neutrophilic infiltration of the dermis and rarely other organs. We report the case of an adolescent male with chronic pancytopenia secondary to Fanconi anemia (FA) who presented with acute respiratory distress. Despite an exhaustive and ultimately unrevealing work‐up, the diagnosis of pulmonary SS was not made until he developed characteristic cutaneous lesions 4 months later. Comprehensive review of pathological specimens revealed metachronous SS manifestations with infiltrates in lung parenchyma, dermis, and subcutis in this neutropenic patient. Pediatr Blood Cancer 2008;51:128–130.

Infection Prevention and Control Guidance for Ronald McDonald Houses: A Needs Assessment

We surveyed Ronald McDonald Houses (RMHs) to assess infection prevention and control (IPC) practices. A diverse patient population is served by RMH. Most sites have locally written IPC guidelines, and consultation resources vary, increasing the potential for inconsistent IPC practices. RMH would benefit from a standardized IPC guideline.

Outbreak Response and Incident Management: SHEA Guidance and Resources for Healthcare Epidemiologists in United States Acute-Care Hospitals

David B. Banach, MD, MPH, MS; B. Lynn Johnston, MD, MS, FRCPC; Duha Al-Zubeidi, MD; Allison H. Bartlett, MD, MS; Susan Casey Bleasdale, MD; Valerie M. Deloney, MBA; Kyle B. Enfield, MD, MS; Judith A. Guzman-Cottrill, DO; Christopher Lowe, MD, MSc; Luis Ostrosky-Zeichner, MD; Kyle J. Popovich, MD, MS; Payal K. Patel, MD; Karen Ravin, MD, MS; Theresa Rowe, DO, MS; Erica S. Shenoy, MD, PhD; Roger Stienecker, MD; Pritish K. Tosh, MD; Kavita K. Trivedi, MD; and the Outbreak Response Training Program (ORTP) Advisory Panel