SUMMARY Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), and cell surface antigens, including soluble intercellular adhesion molecule (sICAM) and CD64, are also being increasingly examined for use as nonspecific screening measures for neonatal sepsis. Viruses, in particular enteroviruses, parechoviruses, and herpes simplex virus (HSV), should be considered in the differential diagnosis. Empirical treatment should be based on local patterns of antimicrobial resistance but typically consists of the use of ampicillin and gentamicin, or ampicillin and cefotaxime if meningitis is suspected, until the etiologic agent has been identified. Current research is focused primarily on development of vaccines against GBS.

BACKGROUND The treatment of symptomatic congenital cytomegalovirus (CMV) disease with intravenous ganciclovir for 6 weeks has been shown to improve audiologic outcomes at 6 months, but the benefits wane over time. METHODS We conducted a randomized, placebo-controlled trial of valganciclovir therapy in neonates with symptomatic congenital CMV disease, comparing 6 months of therapy with 6 weeks of therapy. The primary end point was the change in hearing in the better ear (“best-ear” hearing) from baseline to 6 months. Secondary end points included the change in hearing from baseline to follow-up at 12 and 24 months and neurodevelopmental outcomes, with each end point adjusted for central nervous system involvement at baseline. RESULTS A total of 96 neonates underwent randomization, of whom 86 had follow-up data at 6 months that could be evaluated. Best-ear hearing at 6 months was similar in the 6-month group and the 6-week group (2 and 3 participants, respectively, had improvement; 36 and 37 had no change; and 5 and 3 had worsening; P = 0.41). Total-ear hearing (hearing in one or both ears that could be evaluated) was more likely to be improved or to remain normal at 12 months in the 6-month group than in the 6-week group (73% vs. 57%, P = 0.01). The benefit in total-ear hearing was maintained at 24 months (77% vs. 64%, P = 0.04). At 24 months, the 6-month group, as compared with the 6-week group, had better neurodevelopmental scores on the Bayley Scales of Infant and Toddler Development, third edition, on the language-composite component (P = 0.004) and on the receptive-communication scale (P = 0.003). Grade 3 or 4 neutropenia occurred in 19% of the participants during the first 6 weeks. During the next 4.5 months of the study, grade 3 or 4 neutropenia occurred in 21% of the participants in the 6-month group and in 27% of those in the 6-week group (P = 0.64). CONCLUSIONS Treating symptomatic congenital CMV disease with valganciclovir for 6 months, as compared with 6 weeks, did not improve hearing in the short term but appeared to improve hearing and developmental outcomes modestly in the longer term. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00466817.)

A circular economy involves maintaining manufactured products in circulation, distributing resource and environmental costs over time and with repeated use. In a linear supply chain, manufactured products are used once and discarded. In high-income nations, health care systems increasingly rely on linear supply chains composed of singleuse disposable medical devices. This has resulted in increased health care expenditures and health care-generated waste and pollution, with associated public health damage. It has also caused the supply chain to be vulnerable to disruption and demand fluctuations. Transformation of the medical device industry to a more circular economy would advance the goal of providing increasingly complex care in a low-emissions future. Barriers to circularity include perceptions regarding infection prevention, behaviors of device consumers and manufacturers, and regulatory structures that encourage the proliferation of disposable medical devices. Complementary policy-and market-driven solutions are needed to encourage systemic transformation.

BACKGROUND-The treatment of symptomatic congenital cytomegalovirus (CMV) disease with intravenous ganciclovir for 6 weeks has been shown to improve audiologic outcomes at 6 months, but the benefits wane over time.

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BackgroundElectronic learning allows individualized education and may improve student performance. This study assessed the impact of e-modules about infection control and congenital infections on medical knowledge.MethodsA descriptive study was conducted involving third-year medical students on pediatric clerkship. e-Module content in three different formats was developed: a text monograph, a PowerPoint presentation, and a narrated PowerPoint lecture. Students’ use of the e-modules was tracked, as was participation in the infectious disease rotation and the order of pediatric rotation. Pre- and posttests specific to the e-module content and National Board of Medical Examiners (NBME) pediatric exam scores were recorded.ResultsAmong 67 participants, 63% of them visited at least one e-module. Neither accessing any e-modules, timing of pediatric clerkship, nor assignment to ID rotation resulted in improved posttest nor NBME scores. Seventy percent of students rated the e-modules as satisfactory and reported usage improved their confidence with the congenital infections topic.Discussione-Modules did not improve student performance on NBME or posttest; however, they were perceived as satisfactory and to have improved confidence among those who used them. This study underscores the importance of formally evaluating electronic and other innovative curricula when implemented within existing medical education frameworks.

Antigenemia is commonly detected in children with acute rotavirus diarrhea, but the prevalence of viremia has not been clearly defined. We examined antigenemia in plasma and RNAemia in peripheral blood mononuclear cells (PBMC) of children with acute diarrhea by EIA, RT-PCR, and Southern hybridization, using primers and a probe specific to rotavirus NSP4 gene. We detected the presence of rotavirus antigen in 33.3% and almost full-length NSP4 gene in 70.8% of the acute-phase plasma and PBMC, respectively. In contrast, antigenemia and RNAemia were detected in 0% and 4.2% of the convalescent-phase plasma and PBMC, respectively, which were similar to antigenemia (0%) and RNAemia (7.7%) in healthy controls. We demonstrated an increase in the proportions of activated myeloid dendritic cells (mDC) and activated plasmacytoid DC (pDC) in acute-phase PBMC of patients when compared to those in convalescent phase of patients and in PBMC of healthy controls. The activation of mDC peaked on days 2-4 after illness onset, and the activation of acute-phase pDC appeared to correlate with levels of antigenemia. High prevalence of NSP4 gene in acute-phase PBMC indicates possible rotavirus replication in white blood cells, and extraintestinal spread and the activation of DC may have implications for the prevention of rotavirus disease in children.

Background Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease, 10-20% of patients have recrudescent fever as a sign of persistent inflammation and require additional treatment. We aimed to compare infliximab with a second infusion of IVIG for treatment of resistant Kawasaki disease.Methods In this multicentre comparative effectiveness trial, patients (aged 4 weeks to 17 years) with IVIG resistant Kawasaki disease and fever at least 36 h after completion of their first IVIG infusion were recruited from 30 hospitals across the USA. Patients were randomly assigned (1:1) to second IVIG (2 g/kg over 8-12 h) or intravenous infliximab (10 mg/kg over 2 h without premedication), by using a randomly permuted block randomisation design with block size of two or four. Patients with fever 24 h to 7 days following completion of first study treatment crossed over to receive the other study treatment. The primary outcome measure was resolution of fever at 24 h after initiation of study treatment with no recurrence of fever attributed to Kawasaki disease within 7 days post-discharge. Secondary outcome measures included duration of fever from enrolment, duration of hospitalisation after randomisation, and changes in markers of inflammation and coronary artery Z score. Efficacy was analysed in participants who received treatment and had available outcome values. Safety was analysed in all randomised patients who did not withdraw consent. This clinical trial is registered with ClinicalTrials.gov, NCT03065244.