Management of newborns exposed to mothers with confirmed or suspected COVID-19.

There is limited information about newborns with confirmed or suspected COVID-19. Particularly in the hospital after delivery, clinicians have refined practices in order to prevent secondary infection. While guidance from international associations is continuously being updated, all facets of care of neonates born to women with confirmed or suspected COVID-19 are center-specific, given local customs, building infrastructure constraints, and availability of protective equipment. Based on anecdotal reports from institutions in the epicenter of the COVID-19 pandemic close to our hospital, together with our limited experience, in anticipation of increasing numbers of exposed newborns, we have developed a triage algorithm at the Penn State Hospital at Milton S. Hershey Medical Center that may be useful for other centers anticipating a similar surge. We discuss several care practices that have changed in the COVID-19 era including the use of antenatal steroids, delayed cord clamping (DCC), mother-newborn separation, and breastfeeding. Moreover, this paper provides comprehensive guidance on the most suitable respiratory support for newborns during the COVID-19 pandemic. We also present detailed recommendations about the discharge process and beyond, including providing scales and home phototherapy to families, parental teaching via telehealth and in-person education at the doors of the hospital, and telehealth newborn follow-up.

Customizing an Electronic Medical Record to Automate the Workflow and Tracking of an Antimicrobial Stewardship Program.

BACKGROUND: Documenting the actions and effects of an antimicrobial stewardship program (ASP) is essential for quality improvement and support by hospital leadership. Thus, our ASP tallies the number of charts reviewed, types of recommendations, how and to whom they were communicated, whether they were followed, and any effects on antimicrobial days of therapy. Here we describe how we customized the electronic medical record at our institution to facilitate our workflow and data analysis, while highlighting principles that should be adaptable to other ASPs. METHODS: The documentation system involves creation of a novel and intuitive ASP form in each chart reviewed and 2 mutually exclusive tracking systems: 1 for active forms to facilitate the daily ASP workflow and 1 for finalized forms to generate cumulative reports. The ASP form is created by the ASP pharmacist, edited by the ASP physician, reopened by the pharmacist to assess whether the recommendation was followed and to quantify any antimicrobial days avoided or added, then reviewed and finalized by the ASP physician. Active forms are visible on a real-time "MPage," whereas all finalized forms are compiled nightly into 65 informative tables and associated graphs. RESULTS AND CONCLUSIONS: This system and its underlying principles have automated much of the documentation, facilitated follow-up of interventions, improved the completeness and validity of recorded data and analysis, enabled our ASP to expand its activities, and been associated with decreased antimicrobial usage, drug resistance, and C. difficile infections.

Residual NADPH oxidase activity and isolated lung involvement in x-linked chronic granulomatous disease.

Chronic granulomatous disease (CGD) is characterized by inherited immune defects resulting from mutations in the NADPH oxidase complex genes. The X-linked type of CGD is caused by defects in the CYBB gene that encodes gp91-phox, a fundamental component of the NADPH oxidase complex. This mutation originates the most common and severe form of CGD, which typically has absence of NADPH oxidase function and aggressive multisystemic infections. We present the case of a 9-year-old child with a rare CYBB mutation that preserves some NADPH oxidase activity, resulting in an atypical mild form of X-linked CGD with isolated lung involvement. Although the clinical picture and partially preserved oxidase function suggested an autosomal recessive form of CGD, genetic testing demonstrated a mutation in the exon 3 of CYBB gene (c.252 G>A, p.Ala84Ala), an uncommon X-linked CGD variant that affects splicing. Atypical presentation and diagnostic difficulties are discussed. This case highlights that the diagnosis of mild forms of X-linked CGD caused by rare CYBB mutations and partially preserved NADPH function should be considered early in the evaluation of atypical and recurrent lung infections.

Isoniazid pharmacokinetics, pharmacodynamics, and dosing in South African infants.

AIMS: There are limited data on isoniazid (INH) pharmacokinetics in infants and young children and, therefore, uncertainty on appropriate dosing. METHODS: Pharmacokinetic data were obtained from perinatally HIV-exposed South African infants aged 3-24 months receiving INH 10-20 mg·kg·d orally for Mycobacterium tuberculosis prophylaxis. INH pharmacokinetic parameters were characterized using a population pharmacokinetic approach. Dosing simulations were performed to evaluate weight-based INH doses in children based on N-acetyltransferase 2 enzyme (NAT2) genotype, age, maximum concentrations (Cmax) ≥3 mg/L, and area under the curve (AUC0-24) ≥10.52 mg·h/L. RESULTS: In 151 infants (53% female, 48% HIV positive) receiving a mean INH dose of 14.5 mg·kg·d, mean (±SD) Cmax at 3, 6, and 23 months of age were 10.0 (3.5), 8.6 (2.6), and 9.3 (3.8) mg/L, respectively, mean (±SD) AUC0-24 were 53.6 (26.8), 42 (19.9), and 44 (30.7) mg·h/L, respectively, and mean (±SD) half-lives were 2.1 (0.7), 1.9 (0.6), and 1.8 (0.9) hours, respectively. A trimodal apparent oral clearance of INH as a function of the NAT2 genotype was apparent as early as 3 months. INH was well tolerated. At an average INH dose of 14.5 mg·kg·d, 99% of infants aged 3-24 months have an INH Cmax ≥3 mg/L, and 98% have an INH AUC0-24 ≥10.52 mg·h/L. CONCLUSIONS: INH at an average dose of 14.5 mg/kg once daily was well tolerated in infants and achieved INH Cmax values ≥3 mg/L and AUC0-24 values ≥10.52 mg·h/L.

Psychological factors, beliefs about medication, and adherence of youth with human immunodeficiency virus in a multisite directly observed therapy pilot study.

This study examined psychological functioning and beliefs about medicine in adolescents with human immunodeficiency virus (HIV) on highly active antiretroviral therapy in a community-based directly observed therapy (DOT) pilot feasibility study. Participants were youth with behaviorally acquired HIV (n = 20; 65% female; median age, 21 years) with adherence problems, who received once-daily DOT. Youth were assessed at baseline, week 12 (post-DOT), and week 24 (follow-up). At baseline, 55% of youth reported having clinical depressive symptoms compared to 27% at week 12 with sustained improvements at week 24. At baseline, substance use was reported within the borderline clinical range (T(score) = 68), with clinical but statistically nonsignificant improvement (T(score) = 61) at week 12. Hopelessness scores reflected optimism for the future. Coping strategies showed significantly decreased cognitive avoidance (p = .02), emotional discharge (p = .004), and acceptance/resignation ("nothing I can do," p = .004), whereas positive reappraisal and seeking support emerged. With the exception of depressive symptoms, week 12 improvements were not sustained at week 24. DOT adherence was predicted by higher baseline depression (p = .05), beliefs about medicine (p = .006) and perceived threat of illness scores (p = .03). Youth with behaviorally acquired HIV and adherence problems who participated in a community-based DOT intervention reported clinically improved depressive symptoms, and temporarily reduced substance use and negative coping strategies. Depressive symptoms, beliefs about medicine, and viewing HIV as a potential threat predicted better DOT adherence.

Development of a directly observed therapy adherence intervention for adolescents with human immunodeficiency virus-1: application of focus group methodology to inform design, feasibility, and acceptability.

PURPOSE: To obtain input from adolescents with human immunodeficiency virus-1 (HIV-1) infection to inform the design of a community-based modified directly observed therapy (MDOT) antiretroviral adherence intervention. METHODS: Pediatric AIDS Clinical Trials Group (PACTG) protocol 1036A conducted three focus groups with 17 adolescents aged 17-22 years (10 female, 65% African-American) from three geographically distinct US PACTG sites. Focus group sessions were scripted, audio-taped, and transcribed verbatim. A coding dictionary was developed and validated; Ethnograph version 5.08 was used to summarize coded data across and within the three sites. Prevalent themes were identified via frequencies and are reported as percentages. RESULTS: Adolescents provided the following specific input: the MDOT provider should be familiar with the participant and empathic; the MDOT location should be mutually agreed on, flexible, and private; and participant and provider communication should be bidirectional, preferably by phone. Ideally the MDOT program should be continued until adolescents independently demonstrate adherence and should include a weaning phase as a test of skill acquisition. The most commonly endorsed barrier to the proposed program was that MDOT would be an invasion of privacy. Initially, after introduction to the purpose of the focus group, all but one adolescent expressed the belief that MDOT could benefit persons other than themselves; however, at the conclusion of the focus group discussion, a significant shift in openness to the intervention occurred, in that 11 participants indicated they would consider participation in an MDOT program if such a program were offered. CONCLUSIONS: Focus group feedback clarified the feasibility, logistics, and patient concerns about the design and implementation of a proposed MDOT intervention for adolescents with HIV-1 infection who struggle with medication adherence.

Persistent non-gastrointestinal metabolic acidosis in pediatric HIV-1 infection.

OBJECTIVES: To determine the incidence and to identify the clinical parameters associated with non-gastrointestinal renal tubular and high anion gap acidosis in a cohort of HIV-1-infected children. METHODS: Records of 202 HIV-1-infected children were reviewed to identify patients with metabolic acidosis. Serum and urine chemistries of those children with persistent non-gastrointestinal acidosis were then studied prospectively. Serum and urinary anion gaps (SAG and UAG) were calculated. Those with acidosis (group 1) were compared with children without acidosis (group 2). Associations were determined with Pediatric HIV classification, height, weight, antiretroviral therapy, and Pneumocystis carinii pneumonia prophylaxis. RESULTS: Persistent acidosis was noted in 34 out of 202 children (17%): 16 out of 34 (47%, group 1A) had elevated SAG acidosis, and 18 out of 34 (53%) had normal SAG acidosis with a positive UAG (distal renal tubular) acidosis (group 1B). Those with acidifying defects more often received P. carinii pneumonia prophylaxis (P = 0.02 and 0.01 for groups 1 and 1A, respectively) independently of HIV-1 classification. This group was shorter in height than group 2 (P = 0.007). Differences in weight were not significant (P = 0.1). However, acidotic subjects were more immunocompromised than those in group 2 (multivariate P < 0.001 for HIV classification C3). CONCLUSIONS: Elevated SAG acidosis and renal tubular acidosis are not uncommon among HIV-infected children with advanced disease. These disorders may be associated with height growth failure and prophylaxis with sulfur/sulfone containing antibiotics. HIV infection and/or its associated therapies may cause renal tubular damage. The causes of elevated SAG acidosis require further investigation.

Pharmacokinetics and tolerance of zidovudine in preterm infants.

OBJECTIVE: To determine zidovudine pharmacokinetics and tolerance in premature human human immunodeficiency virus-exposed infants. STUDY DESIGN: Pediatric AIDS Clinical Trials Group Study 331 was a multicentered prospective, open-label study of the use of zidovudine in premature infants. Thirty-eight infants <35 weeks' gestational age (GA) were studied while receiving zidovudine 1.5 mg/kg every 12 hours until 2 weeks of age, then 2.0 mg/kg every 8 hours until 6 weeks of age. Population pharmacokinetics were evaluated at 1, 2, and 4 weeks' postnatal age; zidovudine doses were adjusted to maintain troughs <3 microM. RESULTS: Zidovudine clearance was lower than reported in term infants at similar postnatal ages. Nine premature infants required dose reduction because of high levels (7/19 <30 weeks' and 2/19 >/=30 weeks' GA). Postnatal age, GA, serum creatinine, and furosemide use independently predicted zidovudine clearance. Zidovudine was generally well tolerated in this high-risk population. CONCLUSIONS: Zidovudine clearance is greatly reduced in premature infants. We recommend the following zidovudine dosing schedule in this population: 1.5 mg/kg (intravenous) or 2.0 mg/kg (oral) every 12 hours increased to every 8 hours at 2 weeks of age (>/=30 weeks' GA) or at 4 weeks (<30 weeks' GA).