Journal of the Pediatric Infectious Diseases Society

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...

BACKGROUND: The BioFire FilmArray Pneumonia Panel (BFPP), a multiplex PCR panel for diagnosis of lower respiratory tract infections, has been proposed as a tool for antimicrobial stewardship. Few studies evaluate real-world implementation of the BFPP and no studies focus exclusively on children. Our institution implemented BFPP testing without restrictions. METHODS: We conducted a retrospective cohort study in children hospitalized at St. Louis Children's Hospital to 1) characterize use of the BFPP in pediatric patients and 2) assess how results impacted antibiotic use...

Pandemic-related disruptions led to lower BCG vaccine coverage in Brazil. This study highlights a link between reduced vaccinations and increased tuberculosis pulmonary and extrapulmonary cases in infants. Addressing vaccine hesitancy and ensuring healthcare stability are vital for mitigating impacts.

BACKGROUND: Nearly half of all pediatric musculoskeletal infections (MSKIs) are culture- negative. Plasma microbial cell-free DNA (mcfDNA) sequencing is non-invasive and not prone to the barriers of culture. We evaluated the performance of plasma mcfDNA sequencing in identifying a pathogen, and examined the duration of pathogen detection in children with MSKIs. METHODS: We conducted a prospective study of children, aged 6 months to 18 years, hospitalized from July 2019 to May 2022 with MSKIs, in whom we obtained serial plasma mcfDNA sequencing samples and compared the results with cultures...

BACKGROUND: Acute otitis media (AOM) is the most common reason children are prescribed antibiotics. Bacteria that produce beta-lactamase are an increasingly frequent cause of AOM and may be resistant to amoxicillin, the currently recommended treatment for AOM. We aimed to evaluate clinical outcomes of children treated with amoxicillin for AOM and assessed whether outcomes vary by infecting pathogen or beta-lactamase production. METHODS: 205 children 6-35 months old diagnosed with AOM and prescribed amoxicillin were included...

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Advanced Practice Providers (APPs) are a rapidly growing segment of the pediatric infectious diseases workforce. APPs offer many advantages to divisions that are struggling to counter a smaller fellowship applicant pool and faculty workforce transitions as a result of the pandemic. Many divisions still have yet to incorporate APPs into their inpatient or outpatient teams. This review will discuss the diverse pool of APPs, summarize how APPs are currently being used in the field, discuss the financial considerations of hiring APPs and highlight future needs for embracing APPs as critical members of the pediatric ID workforce...

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive and maladaptive inflammation. Classic clinical and laboratory features associated with the diagnosis of HLH, including fever, cytopenias, hyperferritinemia and splenomegaly, are not specific to HLH and can be caused by infections. Fulfillment of these clinical and laboratory criteria alone are not sufficient to diagnose HLH or initiate HLH-directed therapies. In this manuscript, we review the pathogenesis of HLH and HLH-like syndromes associated with infection...

The microbial communities that inhabit our bodies have been increasingly linked to host physiology and pathophysiology. This microbiome, through its role in colonization resistance, influences the risk of infections after transplantation, including those caused by multidrug-resistant organisms. In addition, through both direct interactions with the host immune system and via the production of metabolites that impact local and systemic immunity, the microbiome plays an important role in the establishment of immune tolerance after transplantation, and conversely, in the development of graft-versus-host disease and graft rejection...

Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in pediatric transplantation. However, currently utilized CMV prevention paradigms have limitations, leading to research aimed at novel strategies for mitigation of CMV infection. Cell-mediated immunity (CMI) is crucial in controlling CMV infection and the use of CMV-specific CMI assays to guide prevention and treatment of CMV infection in both solid organ transplant and hematopoietic cell transplant recipients shows great promise. In this article, we review the immune response to CMV infection to highlight the rationale for CMI assays, describe available commercial assays and strategies for their use, and summarize relevant literature regarding the use of CMI assays in transplant recipients...

Invasive fungal disease (IFD) remains a significant cause of morbidity and mortality in children undergoing transplantation. There is a growing armamentarium of novel antifungal agents recently approved for use or in late stages of clinical development. The overarching goal of this review is to discuss the mechanisms of action, spectrum of activity, stage of development, and pediatric-specific data for the following agents: encochleated amphotericin B deoxycholate, fosmanogepix, ibrexafungerp, isavuconazole, olorofim, opelconazole, oteseconazole, and rezafungin...

Viral infections are a major source of morbidity and mortality in the context of immune deficiency and immunosuppression following allogeneic hematopoietic cell (allo-HCT) and solid organ transplantation (SOT). The pharmacological treatment of viral infections is challenging and often complicated by limited efficacy, the development of resistance, and intolerable side effects. A promising strategy to rapidly restore antiviral immunity is the adoptive transfer of virus-specific T cells (VST). This therapy involves the isolation and ex vivo expansion or direct selection of antigen-specific T cells from healthy seropositive donors, followed by infusion into the patient...

Epstein-Barr Virus (EBV) diseases, including EBV-associated post-transplant lymphoproliferative disorder (PTLD) remain important causes of morbidity and mortality in children undergoing solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT). Despite progress in the prevention of EBV disease including PTLD (EBV/PTLD) in HCT, key questions in the prevention, and management of these infectious complications remain unanswered. The goal of this manuscript is to highlight key points and recommendations derived from the consensus guidelines published by the International Pediatric Transplant Association and the European Conference on Infections in Leukemia for children undergoing SOT and HCT, respectively...

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...

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...

Respiratory viral infections (RVIs) are among the leading cause of morbidity and mortality in pediatric hematopoietic stem cell transplant (HCT) and solid organ transplant (SOT) recipients. Transplant recipients remain at high risk for super imposed bacterial and fungal pneumonia, chronic graft dysfunction, and graft failure as a result of RVIs. Recent multicenter retrospective studies and prospective studies utilizing contemporary molecular diagnostic techniques have better delineated the epidemiology and outcomes of RVIs in pediatric transplant recipients and have advanced the development of preventative vaccines and treatment interventions in this population...

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...

BACKGROUND: Palivizumab is recommended for prevention of severe respiratory syncytial virus (RSV) disease in immunocompromised children, despite a lack of strong supporting evidence. The recent approval of substitute RSV-neutralizing monoclonal antibodies against RSV, offers an opportunity to synthesize the most current evidence supporting the palivizumab standard of care. OBJECTIVE: To evaluate the efficacy of palivizumab in preventing acute respiratory tract infection- or RSV-related hospitalization, or mortality in immunocompromised children...

BACKGROUND: Antimicrobial stewardship programs (ASPs) promote optimal antimicrobial use to prevent resistance, improve outcomes, and reduce costs. We explored how pediatric ASPs enact prospective audit and feedback (PAF) and preauthorization and characterized programs' perceptions of how these choices affected attainment of stewardship goals. METHODS: We conducted focus groups with US pediatric ASP practitioners, organized by predominant strategy: PAF, preauthorization, or a hybrid...

BACKGROUND: Respiratory viral infections are common among pediatric transplant patients, with human rhinovirus (HRV) being the most frequent. In pediatric patients undergoing hemopoietic cell transplant (HCT), infection with HRV has been associated with progression to lower respiratory tract infection (LRTI) and adverse outcomes. We describe the clinical presentation and outcomes of HRV infection in children undergoing HCT. METHODS: Single-center retrospective study...