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Background Since November 2019, the SARS-CoV-2 pandemic has created challenges for preventing and managing COVID-19 in children and adolescents. Most research to develop new therapeutic interventions or to repurpose existing ones has been undertaken in adults, and although most cases of infection in pediatric populations are mild, there have been many cases of critical and fatal infection. Understanding the risk factors for severe illness and the evidence for safety, efficacy, and effectiveness of therapies for COVID-19 in children is necessary to optimize therapy. Methods A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacology, and pediatric intensive care medicine from 21 geographically diverse North American institutions was re-convened. Through a series of teleconferences and web-based surveys and a systematic review with meta-analysis of data for risk factors, a guidance statement comprising a series of recommendations for risk stratification, treatment, and prevention of COVID-19 was developed and refined based on expert consensus. Results There are identifiable clinical characteristics that enable risk stratification for patients at risk for severe COVID-19. These risk factors can be used to guide the treatment of hospitalized and non-hospitalized children and adolescents with COVID-19 and to guide preventative therapy where options remain available. [ABSTRACT FROM AUTHOR]

The diagnosis of nontuberculous mycobacterial infections is challenging in pediatric solid organ transplant and hematopoietic cell transplant recipients due to the absence of specific clinical manifestations, limitations of sampling, prolonged times for culture and identification, and difficulty discerning colonization from clinical disease. Treatment is dependent on the nontuberculous mycobacterial species, disease type, and pattern of drug resistance. Treatment of nontuberculous mycobacterial infections involves prolonged durations of therapy using multiple medications, which are limited by toxicities and drug–drug interactions. [ABSTRACT FROM AUTHOR]

Pediatric Infectious Disease (ID) clinicians play a critical role in helping prevent and mitigate infectious risks in children peri- and post-transplantation. Prevention starts during the pre-transplant evaluation and persists throughout the solid organ transplant and hematopoietic cell transplant continuum. The pre-transplant evaluation is an opportunity to screen for latent infections, plan preventative strategies, optimize immunizations, and discuss risk mitigation practices. An ideal pre-transplant evaluation establishes a relationship with the family that further promotes post-transplant infectious risk reduction. This manuscript builds on shared pediatric ID prevention strategies, introduces updated ID testing recommendations for transplant donors/candidates, highlights emerging data, and identifies ongoing knowledge gaps that are potential areas of research. [ABSTRACT FROM AUTHOR]

Despite current prophylaxis regimens, cytomegalovirus (CMV) is common in hematopoietic cell transplantation (HCT) and solid organ transplantation (SOT) and remains a significant cause of morbidity and mortality. Newer antiviral medications are reshaping the landscape for prevention and treatment of CMV DNAemia, infection, and disease. Letermovir is approved for CMV prevention in adult HCT patients and is attractive due to the absence of marrow suppression seen with ganciclovir/valganciclovir. Letermovir should not be routinely used for CMV treatment due to its low threshold for resistance. Maribavir is approved for the treatment of refractory or resistant CMV disease in HCT and SOT recipients ≥12 years of age, though it has no current role in CMV prevention. More research is needed to fully elucidate the roles, efficacy, and safety of these newer agents in prevention and treatment of CMV in pediatric transplant recipients. [ABSTRACT FROM AUTHOR]

The incidence of invasive Group A Streptococcus (iGAS) has varied throughout the COVID-19 pandemic. We reviewed iGAS infections in infants ≤1 year from 2012 to 2022. Twenty-five percent of cases occurred in the last quarter of 2022. Pneumonia (21.8%) was the most common presentation. Twenty-one patients (65.6%) were successfully transitioned to oral antibiotics. [ABSTRACT FROM AUTHOR]

School-based COVID-19 vaccine clinics were more likely to vaccinate children who identified as a racial minority, who lacked a regular source of primary care, and who lacked private insurance compared to those vaccinated in non-school-based community locations. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies for COVID-19 are authorized in high-risk patients aged ≥12 years, but evidence in pediatric patients is limited. In our cohort of 142 patients treated at seven pediatric hospitals between 12/1/20 and 7/31/21, 9% developed adverse events, 6% were admitted for COVID-19 within 30 days, and none received ventilatory support or died. [ABSTRACT FROM AUTHOR]

Acute fulminant cerebral edema in children following SARS-CoV-2 infection has been rarely reported. Such patients frequently demonstrate rapid progression and are usually fatal. In this retrospective study, we describe the detailed clinical, laboratory, and neuroimaging features of six fatal cases in Taiwan. All patients had shock initially, five showed rapid progression to multiorgan failure and disseminated intravascular coagulation, and three developed acute respiratory distress syndromes. The inflammatory biomarkers in the first 3 days, including interleukin 6, ferritin, lactate dehydrogenase, and D-dimer, showed significant elevation in all cases. The hyperinflammatory response may play a role in the pathophysiology. [ABSTRACT FROM AUTHOR]

Background Phaeohyphomycosis is an infection caused by pigmented fungi, which can be life-threatening in immunocompromised hosts and in disseminated disease. In adults with disseminated disease, mortality is as high as 79%. Data in children are derived from case reports and series. We conducted this study to review the characteristics of phaeohyphomycoses in children. Methods We conducted this study following the PRISMA 2020 guideline for reporting systematic reviews. We performed a review of the reported cases of pediatric phaeohyphomycoses in core bibliographic databases published in the English and Spanish language, between June 1977 and October 2021. We included all eligible cases in patients <18 years to determine the clinical characteristics, diagnosis, treatment, and outcomes. Results A total of 130 cases were reviewed. The mean age was 8 years. The most common underlying conditions and risk factors included hematologic malignancies (32.5%), neutropenia (26.9%), steroid therapy (24.6%), trauma or surgery (23.1%), and children that received a transplant (14.6%). The most common presentation was localized infection (61.5%); skin and soft tissue infections were the most prevalent (25.4%). Exserohilum spp (20.8%) and Exophiala spp (17.7%) were the most common organisms isolated. Antifungal therapy remains as the most frequent treatment (87%). Overall mortality rate was 22.3% (localized 13.7% vs disseminated 37.3%). Conclusion The findings of this review suggest that phaeohyphomycoses in children have a better outcome compared to adults. We report a lower mortality rate in children when compared with adults in disseminated infection (37.3% vs 79%) and CNS infection (50% vs 60–70%). However, there is a wide variation in mortality rates according to the infection site, treatment, and underlying conditions. Prospective studies are needed. [ABSTRACT FROM AUTHOR]

While most children with coronavirus 2019 (COVID-19) experience mild illness, some are vulnerable to severe disease and develop long-term complications. Children with disabilities, those from lower-income homes, and those from racial and ethnic minority groups are more likely to be hospitalized and to have poor outcomes following an infection. For many of these same children, a wide range of social, economic, and environmental disadvantages have made it more difficult for them to access COVID-19 vaccines. Ensuring vaccine equity in children and decreasing health disparities promotes the common good and serves society as a whole. In this article, we discuss how the pandemic has exposed long-standing injustices in historically marginalized groups and provide a summary of the research describing the disparities associated with COVID-19 infection, severity, and vaccine uptake. Last, we outline several strategies for addressing some of the issues that can give rise to vaccine inequity in the pediatric population. [ABSTRACT FROM AUTHOR]

Background The severity and reach of the COVID-19 pandemic drove the development of various therapeutic approaches to combat SARS-CoV-2, including several neutralizing monoclonal antibody (mAb) therapies. A January 2021 pediatric consensus statement opposed routine use and recommended individualized risk assessments when considering COVID-19 mAb therapies in children and adolescents due to limited data. This report describes the implementation of a mAb referral process and the clinical outcomes of patients who received a mAb infusion in a pediatric hospital. Methods We developed a tiered allocation system based on underlying medical conditions and incorporated it into a standardized COVID-19 mAb referral and approval process. Demographics and clinical data were collected on all patients who received mAb therapy for treatment or post-exposure prophylaxis. Data recorded included sociodemographics, qualifying underlying medical conditions, clinical manifestations of infection, and overall course of treatment and disease. Results A total of 182 patients ≤21 years old received a COVID-19 mAb infusion between November 27, 2020 and January 26, 2022. Patient age ranged from 10 months to 21 years, with a median age of 15 years. In total, 7 patients (4%) had suspected adverse reactions during the infusion, and 15 (8%) patients required a COVID-19-related visit within 30 days of the mAb infusion. Conclusions A tiered allocation process may provide the framework for the stratification and efficient distribution of mAb therapies. Future research must focus on the efficacy of these therapies in the pediatric population, standardized therapeutic prioritization, and the optimal timeframe for mAb delivery to prevent progression to severe disease. [ABSTRACT FROM AUTHOR]

Two new articles describe the use and implementation of monoclonal antibodies to treat COVID-19 in children. While these studies provide valuable guidance for pediatric clinicians, more studies of monoclonal antibodies and other COVID-19 therapies in children are needed. [ABSTRACT FROM AUTHOR]

Using hospital surveillance data, we estimated Human metapneumovirus (hMPV) hospitalization incidence by age and HIV-exposure status. hMPV-associated hospitalization incidence was highest in <1-year children. Incidence rate ratios of HIV-exposed over unexposed children were 1.5 (95%CI 0.9–2.4) for <6-month children, 1.4 (95%CI 0.7–2.4) for 6- to 11-month children and 0.9 (95%CI 0.4–1.9) for 12- to 59-month children. [ABSTRACT FROM AUTHOR]

Among 182 children with influenza infection in 2016–2017, 18% had neurologic manifestations of influenza (NMI), including seizures and encephalopathy; 85% of these children were infected with the H3N2 strain. Children with NMI had 3.5-times-higher odds of having a neurologic comorbidity than those without NMI and a 10-fold increased odds of hospitalization. [ABSTRACT FROM AUTHOR]

Background Virologic failure (VF) is highly prevalent in sub-Saharan African children on antiretroviral therapy (ART) and is often associated with human immunodeficiency virus drug resistance (DR). Most children still lack access to routine viral load (VL) monitoring for early identification of treatment failure, with implications for the efficacy of second-line ART. Methods Children aged 1 to 14 years on ART for ≥12 months at 6 public facilities in Maputo, Mozambique were consecutively enrolled after informed consent. Chart review and caregiver interviews were conducted. VL testing was performed, and specimens with ≥1000 copies/mL were genotyped. Results Of the 715 children included, the mean age was 103 months, 85.8% had no immunosuppression, 73.1% were taking stavudine/lamivudine/nevirapine, and 20.1% had a history prevention of mother-to-child transmission exposure. The mean time on ART was 60.0 months. VF was present in 259 patients (36.3%); 248 (95.8%) specimens were genotyped, and DR mutations were found in 238 (96.0%). Severe immunosuppression and nutritional decline were associated with DR. M184V and Y181C were the most common mutations. In the 238 patients with DR, standard second-line ART would have 0, 1, 2, and 3 effective antiretrovirals in 1 (0.4%), 74 (31.1%), 150 (63.0%), and 13 (5.5%) patients, respectively. Conclusion This cohort had high rates of VF and DR with frequent compromise of second-line ART. There is urgent need to scale-up VL monitoring and heat-stable protease inhibitor formulations or integrase inhibitorsfor a more a durable first-line regimen that can feasibly be implemented in developing settings. [ABSTRACT FROM AUTHOR]

Background Bacterial infections caused by group A Streptococcus (GAS) are common in childhood. Few study reports have provided data on pediatric-specific trends in the epidemiology and bacterial strain characteristics of GAS infections. Methods We prospectively collected GAS isolates from the clinical microbiology laboratory at Texas Children's Hospital between July 1, 2013, and June 30, 2017. Patient characteristics and GAS disease categories were determined through chart review. GAS isolates were obtained from patients in either the inpatient or outpatient setting, and cases were defined as pharyngeal disease, skin and soft-tissue infection (SSTI), or invasive disease on the basis of predefined criteria. All isolates were emm typed to determine trends over time. Results We identified 930 cases over the 4-year period, including 432 (46.4%) pharyngeal, 235 (25.3%) SSTI, and 263 (28.3%) invasive disease types. The most frequently encountered emm types were emm1 (21.4%), emm12 (15.7%), emm89 (14.6%), emm4 (9.2%), and emm3 (8.2%). We observed significant changes over the 4-year period in the relative frequency of infections caused by emm1 (−17.7%; P =.046), emm4 (8.7%; P =.023), or emm6 (−7.9%; P =.024). Using bioinformatic analyses and targeted gene sequencing, we also discovered that all GAS emm28 and emm87 types harbored mutations that rendered them incapable of producing capsule. The relative frequency of GAS disease cases caused by capsule-negative GAS emm types (emm4 , emm22 , emm28 , emm87 , and emm89) increased over the 4-year period (32.2%–44.4%), although the difference was statistically significant for only nonpharyngeal disease types (27.1%–43.9%; P =.038). Conclusions Our data suggest an evolving epidemiology of GAS in the Houston pediatric population characterized by an increase in the frequency of capsule-negative emm types. [ABSTRACT FROM AUTHOR]

We performed a retrospective study to determine the time frame for symptom resolution in 78 pediatric patients hospitalized with laboratory-confirmed early-disseminated or late-stage Lyme disease. The vast majority of the patients improved promptly after receiving appropriate antibiotics. Patients with a longer duration of arthritis before the institution of therapy experienced a longer time to recovery. [ABSTRACT FROM AUTHOR]

Background Hospital practice patterns vary for switching from intravenous to oral antibiotics for community-acquired pneumonia in pediatric patients, but it is unknown how these practice patterns affect hospital lengths of stay and costs. Methods We conducted a retrospective study of 78673 pediatric patients (aged 3 months to 17 years) hospitalized for community-acquired pneumonia. Analyses were performed with data from the Pediatric Health Information System between 2007 and 2016, including discharge data from 48 freestanding children's hospitals. Patients who received antibiotics used to treat aspiration pneumonia and patients with a complex chronic condition were excluded to focus the study on uncomplicated cases. We modeled hospital practice patterns using hospital-level averages for the last day of service on which patients received antibiotics intravenously or first day of service on which patients received antibiotics orally. Results We found that a 1-day decrease in the hospital-level average last day of service on which a patient received antibiotics intravenously reduced the average length of stay by 0.58 day (95% confidence interval [CI], −0.69 to −0.47 day) and average cost by $1332 (95% CI, −$2363 to −$300). Results were similar when hospital practice patterns were modeled using the average first day of service on which a patient received antibiotics orally. These reductions in lengths of stay and costs were not associated with a difference in 30-day readmission rates. Conclusions Given the reductions in lengths of stay and costs without sacrificing patient outcomes (readmissions), antimicrobial stewardship programs could target provider education on the duration of intravenous antibiotic therapy as a way to reduce resource utilization. [ABSTRACT FROM AUTHOR]

Background Invasive group A Streptococcus (GAS) disease has an incidence in high-income countries of 3 to 5 per 100000 per annum and a case-fatality ratio of 10% to 15%. Although these rates are comparable to those of invasive meningococcal disease in Australia before vaccine introduction, invasive GAS disease currently requires reporting in only 2 jurisdictions. Methods Data were collected prospectively through active surveillance at the Royal Children's Hospital, Melbourne (October 2014 to September 2016). Isolation of GAS from a sterile site was required for inclusion. Comprehensive demographic and clinical data were collected, and emm typing was performed on all isolates. Disease was considered severe if the patient required inotropic support or mechanical ventilation. Results We recruited 28 patients. The median age of the patients was 3.5 years (range, 4 days to 11 years). Ten (36%) patients had severe disease. Fifteen (54%) children had presented to a medical practitioner for review in the 48 hours before their eventual admission, including 7 of the 10 patients with severe GAS infection. Complications 6 months after discharge persisted in 21% of the patients. emm1 was the most common emm type (29%). Conclusion We found considerable short- and longer-term morbidity associated with pediatric invasive GAS disease in our study. Disease manifestations were frequently severe, and more than one-third of the patients required cardiorespiratory support. More than one-half of the patients attended a medical practitioner for assessment but were discharged in the 48-hour period before admission, which suggests that there might have been a window for earlier diagnosis. Our methodology was easy to implement as a surveillance system. [ABSTRACT FROM AUTHOR]

Background Trichosporonosis is an emerging and often fatal opportunistic fungal infection in immunocompromised patients, particularly those with hematologic malignancy, but data in children are lacking. Methods We report here 3 cases of invasive infection caused by Trichosporon asahii in pediatric patients with acute lymphoblastic leukemia at Texas Children’s Hospital in Houston, Texas. We also conducted a literature review and identified 16 additional reports of pediatric patients with invasive T asahii infection and an underlying malignant or nonmalignant hematologic disorder. Results Of the 19 cases of invasive T asahii infection, the most commonly reported underlying hematologic disorder was acute lymphoblastic leukenia (47%), followed by acute myelogenous leukemia (21%). Most of the patients (94%) had neutropenia, defined as an absolute neutrophil count of <500 cells/mm3. Antifungal prophylaxis information was available in 6 of the 19 cases, and micafungin use was reported in 5 cases. Treatment regimens frequently included voriconazole monotherapy (47%) or the combination of an azole antifungal with amphotericin B (35%). The mortality rate was 58%. Conclusions Recognizing that echinocandins, which are increasingly used for prophylaxis in patients with a hematologic malignancy, are not active against Trichosporon species is of critical importance. The recommended first-line therapy for trichosporonosis is voriconazole, but successful outcome depends largely on the underlying immune status of the host. [ABSTRACT FROM AUTHOR]

We retrospectively studied the effect of introducing procalcitonin into clinical practice on antibiotic use within a large academic pediatric intensive care unit. In the absence of a standardized algorithm, availability of the procalcitonin assay did not reduce the frequency of antibiotic initiations or the continuation of antibiotics for greater than 72 hours. [ABSTRACT FROM AUTHOR]

Impaired renal function has been associated with an increased risk of thrombocytopenia in adults receiving linezolid. Findings from this retrospective cohort demonstrate an association between thrombocytopenia and lower creatinine clearance in children receiving linezolid. [ABSTRACT FROM AUTHOR]

We report here the isolation of Mucor velutinosus from multiple blood cultures performed on samples from Broviac catheters and culture of a Broviac insertion-site wound sample from a 6-year-old boy with a history of intestinal failure secondary to chronic intestinal pseudo-obstruction, parenteral nutrition, and jejunostomy tube dependence. Examination of a slide from the culture revealed the presence of wide nonseptate hyphae with sporangiophores, columella, and chlamydospores. The fungal isolate was sent to the National Institutes of Health for further evaluation and was identified as Mucor velutinosus by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry and genomic sequencing. The patient was treated successfully with intravenous amphotericin B and prompt removal of his central line. To the best of our knowledge, this is the first case of M velutinosus bloodstream infection in a child without cancer. [ABSTRACT FROM AUTHOR]

Background Clostridium difficile infection (CDI) incidence in hospitalized children has increased over the past decade and disease has been reported in the community. Therefore, population surveillance that includes nonhospitalized cases is important to accurately estimate the burden of CDI in children. We describe the epidemiology of CDI in the pediatric population of Monroe County, New York. Methods Active, laboratory, and population-based surveillance for CDI has been ongoing in Monroe County through the Emerging Infections Program of the Centers for Disease Control and Prevention since 2010. Infants less than 12 months of age are excluded. Results In 2010, the incidence of CDI in the pediatric population was 33.8 per 100 000 population, which increased to 45.8 in 2011and remained stable in 2012. Seventy-one percent of the CDI cases were community-associated, 60% had an underlying medical condition, and 71% received antibiotics before their illness. The North American pulsed-field gel electrophoresis type 1 (NAP1) epidemic strain was identified in 27% of cultured stool specimens. Conclusions Clostridium difficile infection has emerged as a disease affecting children in both the community and hospital settings, with a higher proportion of community illness in our population. The majority of children with CDI had chronic underlying conditions and prior antibiotic exposure. To prevent CDI in this population, the judicious use of antibiotics, especially in the outpatient setting, may be the best strategy. Further population-based studies are warranted to determine preventable risk factors for CDI in the pediatric population. [ABSTRACT FROM PUBLISHER]

Few children with drug-resistant (DR) tuberculosis (TB) are identified, diagnosed, and given an appropriate treatment. The few studies that have described this vulnerable population have used inconsistent definitions. The World Health Organization (WHO) definitions used for adults with DR-TB and for children with drug-susceptible TB are not always appropriate for children with DR-TB. The Sentinel Project on Pediatric Drug-Resistant Tuberculosis was formed in 2011 as a network of experts and stakeholders in childhood DR-TB. An early priority was to establish standardized definitions for key parameters in order to facilitate study comparisons and the development of an evidence base to guide future clinical management. This consensus statement proposes standardized definitions to be used in research. In particular, it suggests consistent terminology, as well as definitions for measures of exposure, drug resistance testing, previous episodes and treatment, certainty of diagnosis, site and severity of disease, adverse events, and treatment outcome. [ABSTRACT FROM PUBLISHER]