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.)

Zygomycosis, an infection that is associated with significant morbidity and mortality, is becoming common in immunocompromised patients. Posaconazole is a new extended-spectrum azole antifungal that has demonstrated in vitro and in vivo activity against zygomycetes. This report provides the results from the first 24 patients with active zygomycosis who were enrolled in two open-label, nonrandomized, multicentered compassionate trials that evaluated oral posaconazole as salvage therapy for invasive fungal infections. Posaconazole was usually given as an oral suspension of 200 mg four times a day or 400 mg twice a day. Eleven (46%) of the infections were rhinocerebral. Duration of posaconazole therapy ranged from 8 to 1,004 days (mean, 292 days; median, 182 days). Rates of successful treatment (complete cure and partial response) were 79% in 19 subjects with zygomycosis refractory to standard therapy and 80% in 5 subjects with intolerance to standard therapy. Overall, 19 of 24 subjects (79%) survived infection. Survival was also associated with surgical resection of affected tissue and stabilization or improvement of the subjects' underlying illnesses. Failures either had worsening of underlying illnesses or requested all therapy withdrawn; none of the failures received more than 31 days of posaconazole. Posaconazole oral solution was well tolerated and was discontinued in only one subject due to a drug rash. Posaconazole appears promising as an oral therapy for zygomycosis in patients who receive required surgery and control their underlying illness.Zygomycosis (also known as mucormycosis) is an infection caused by saprophytic fungi of the class Zygomycetes, which are primarily opportunists that invade immunocompromised hosts and produce angioinvasive disease (49). Transmission is mainly through inhalation of small airborne spores, by traumatic skin implantation, or by ingestion and translocation of the organism through the gut. Patients at highest risk for zygomycosis are those with (i) immunosuppression related to neutropenia, corticosteroid use, hematologic malignancies, and solid-organ transplants, (ii) diabetes mellitus, especially those with ketoacidosis, (iii) conditions of iron overload with associated desferoxamine use, and (iv) skin disruption by trauma or other serious conditions, such as burns or heatstroke. In recipients of a hematopoietic stem cell transplant (HSCT), infection often occurs during periods of graft-versus-host disease due to escalation of immunosuppressant regimens (1,4,12,21,25,27,36,41,44). Common sites of infection include pulmonary, rhinocerebral, or disseminated disease (36). The outcome of zygomycosis is closely related to the overall health of the patients and the control of their underlying diseases.Roden and associates analyzed 929 cases of zygomycosis reported since 1885 (38). Survival was reported in 65% of patients with no underlying condition, 56% with diabetes, and 34% with malignancy. Survival varied with infection site: localized skin, 90%; rhinocerebral, 38%; lung, 24...

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Increased circulation of enterovirus D68 in 2014 and 2016 temporally and geographically coincided with increases in cases of acute flaccid myelitis, an uncommon condition of paralysis due to lesions in the anterior horn of the spinal cord. The identification of enterovirus D68 in respiratory specimens from cases of acute flaccid myelitis worldwide further supports an association, yet the absence of direct virus isolation from affected tissues, infrequent detection in cerebrospinal fluid, and the absence, until recently, of an animal model has left the causal nature of the relationship unproven. In this Personal View we evaluate epidemiological and biological evidence linking enterovirus D68 and acute flaccid myelitis. We applied the Bradford Hill criteria to investigate the evidence for a causal relationship and highlight the importance of comprehensive surveillance and research to further characterise the role of enterovirus D68 in acute flaccid myelitis and pursue effective therapies and prevention strategies.

Background Although coronavirus disease 2019 (COVID-19) is mild in nearly all children, a small proportion of pediatric patients develop severe or critical illness. Guidance is therefore needed regarding use of agents with potential activity against severe acute respiratory syndrome coronavirus 2 in pediatrics. Methods A panel of pediatric infectious diseases physicians and pharmacists from 18 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of best available evidence and expert opinion. Results Given the typically mild course of pediatric COVID-19, supportive care alone is suggested for the overwhelming majority of cases. The panel suggests a decision-making framework for antiviral therapy that weighs risks and benefits based on disease severity as indicated by respiratory support needs, with consideration on a case-by-case basis of potential pediatric risk factors for disease progression. If an antiviral is used, the panel suggests remdesivir as the preferred agent. Hydroxychloroquine could be considered for patients who are not candidates for remdesivir or when remdesivir is not available. Antivirals should preferably be used as part of a clinical trial if available. Conclusions Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For those rare cases of severe or critical disease, this guidance offers an approach for decision-making regarding antivirals, informed by available data. As evidence continues to evolve rapidly, the need for updates to the guidance is anticipated.

We found a predominance of non-albicans Candida infection in children and similar outcomes based on antifungal class used. This international collaborative study sets the foundation for large epidemiologic studies focusing on the unique features of neonatal and pediatric candidiasis and comparative studies of therapeutic interventions in these populations.

The nonpoliovirus enteroviruses commonly infect newborns, with consequences ranging from asymptomatic infection and benign illness, to severe, life-threatening disease. Frequently occurring symptoms include fever, irritability, lethargy, anorexia, and rash. Although most illnesses are mild, severe disease develops in a subset of newborns infected in the first 2 weeks of life. Severe disease may consist of sepsis, meningoencephalitis, myocarditis, pneumonia, hepatitis, and/or coagulopathy. Substantial mortality rates have been reported, and long-term sequelae may occur among survivors. Risk factors and clinical features associated with severe disease include absence of neutralizing antibody to the infecting serotype, maternal illness prior to or at delivery, prematurity, illness onset within the first few days of life, multiorgan disease, severe hepatitis, positive serum viral culture, and specific infecting serotype (e.g. group B coxsackieviruses and echovirus 11). Whereas the mainstay of diagnosis has traditionally been viral isolation in tissue culture, the polymerase chain reaction has been demonstrated to be more sensitive than culture, highly specific, and rapid. Immunoglobulin has been used as a therapeutic agent for neonates with enterovirus disease; however, clinical efficacy has not been proven. Specific antiviral therapy for enteroviruses is in development. Pleconaril is an investigational agent that inhibits viral attachment to host cell receptors and uncoating of viral nucleic acid. It has broad and potent anti-enterovirus activity, excellent oral bioavailability, and is well tolerated. Some clinical trials have demonstrated benefit in children and adults with enterovirus meningitis, and in adults with upper respiratory tract infections caused by picornaviruses (rhinoviruses or enteroviruses). Data summarizing compassionate use for severe enterovirus diseases (including neonatal sepsis) also suggest possible benefit. Limited pharmacokinetic data are available in infants and neonates. A multicenter, placebo-controlled, randomized trial of pleconaril in neonates with severe hepatitis, coagulopathy, and/or myocarditis is currently being conducted.

A prospective study of the virology of and serological responses to enterovirus infection in 16 neonates (< or = 2 weeks of life) and their mothers was performed. At study entry, 11 neonates did not have detectable serum neutralizing antibody to their own viral isolates, despite the presence of neutralizing antibody in 9 of 11 mothers of these infants. Viremia and viruria were demonstrated in 8 and 7 neonates, respectively, with maximal detected titers of 6.3 x 10(3) 50% tissue culture infective dose per mL (TCID50) and 6.8 x 10(1) TCID50/mL, respectively. Viremia was associated with onset of illness in the first 5 days of life, low initial serum neutralization titer, and the presence of echovirus serotypes. Randomized administration of intravenous immune globulin (IVIG; 750 mg/kg) to nine neonates overall modestly increased serum neutralization titers but did not reduce the daily incidence of viremia and viruria compared with that of controls. However, receipt of IVIG containing a neutralization titer of > or = 1:800 to the patients' own viral isolates was associated with significantly higher serum neutralization titers and more rapid cessation of viremia and viruria. Future trials of IVIG for neonatal enterovirus disease should assess the efficacy and safety of higher or repeated doses of this agent and/or of IVIG selected for their high titers to frequently circulating and/or particularly virulent enterovirus serotypes.