Antibiotic Indications and Appropriateness in the Pediatric Intensive Care Unit: A 10-Center Point Prevalence Study.

BACKGROUND: Antibiotics are prescribed to most pediatric intensive care unit (PICU) patients, but data describing indications and appropriateness of antibiotic orders in this population are lacking. METHODS: We performed a multicenter point prevalence study that included children admitted to 10 geographically diverse PICUs over 4 study days in 2019. Antibiotic orders were reviewed for indication, and appropriateness was assessed using a standardized rubric. RESULTS: Of 1462 patients admitted to participating PICUs, 843 (58%) had at least 1 antibiotic order. A total of 1277 antibiotic orders were reviewed. Common indications were empiric therapy for suspected bacterial infections without sepsis or septic shock (260 orders, 21%), nonoperative prophylaxis (164 orders, 13%), empiric therapy for sepsis or septic shock (155 orders, 12%), community-acquired pneumonia (CAP; 118 orders, 9%), and post-operative prophylaxis (94 orders, 8%). Appropriateness was assessed for 985 orders for which an evidence-based rubric for appropriateness could be created. Of these, 331 (34%) were classified as inappropriate. Indications with the most orders classified as inappropriate were empiric therapy for suspected bacterial infection without sepsis or septic shock (78 orders, 24%), sepsis or septic shock (55 orders, 17%), CAP (51 orders, 15%), ventilator-associated infections (47 orders, 14%), and post-operative prophylaxis (44 orders, 14%). The proportion of antibiotics classified as inappropriate varied across institutions (range, 19%-43%). CONCLUSIONS: Most PICU patients receive antibiotics. Based on our study, we estimate that one-third of antibiotic orders are inappropriate. Improved antibiotic stewardship and research focused on strategies to optimize antibiotic use in critically ill children are needed.

Adenoviral Respiratory Infection-Associated Mortality in Children: A Retrospective Case Series.

Viral respiratory infections are a leading cause of illness and hospitalization in young children worldwide. Case fatality rates in pediatric patients with adenoviral lower respiratory tract infection requiring intensive care unit (ICU) admission have been reported between 7 and 22%. We investigated the demographics and clinical characteristics in pediatric mortalities associated with adenoviral respiratory infection at 12 academic children's hospitals in the United States. There were 107 mortality cases included in our study, 73% of which had a chronic medical condition. The most common chronic medical condition was immunocompromised state in 37 cases (35%). The incidences of pediatric acute respiratory distress syndrome (78%) and multiple organ dysfunction syndrome (94%) were profound. Immunocompetent cases were more likely to receive mechanical ventilation within the first hour of ICU admission (60 vs. 14%, p < 0.001) and extracorporeal membrane oxygenation (27 vs. 5%, p = 0.009), and less likely to receive continuous renal replacement therapy (20 vs. 49%, p = 0.002) or have renal dysfunction (54 vs. 78%, p = 0.014) as compared with immunocompromised cases. Immunocompromised cases were more likely to have bacteremia (57 vs. 16%, p < 0.001) and adenoviremia (51 vs. 17%, p < 0.001) and be treated with antiviral medications (81 vs. 26%, p < 0.001). We observed a high burden of nonrespiratory organ system dysfunction in a cohort of pediatric case fatalities with adenoviral respiratory infection. The majority of cases had a chronic medical condition associated with an increased risk of complications from viral respiratory illness, most notably immunocompromised state. Important treatment differences were noted between immunocompromised and immunocompetent cases.

Case Report: Rapid Recognition and Immune Modulation of Secondary HLH Due to Disseminated HSV Infection.

We describe the case of a newborn who presented with multiple organ dysfunction syndrome (MODS) and hyperferritinemia, who eventually met criteria for hemophagocytic lymphohistiocytosis (HLH) due to disseminated herpes simplex virus 1 (HSV-1). While the cytokine storm abated after administration of multiple immune modulatory therapies including dexamethasone, etoposide, intravenous immune globulin, anakinra, as well as the interferon gamma antagonist emapalumab, multiple organ dysfunction syndrome progressed. Care was withdrawn after 5 days. Subsequent genetic testing did not reveal any mutations associated with familial HLH. This case highlights that even with appropriate antiviral treatment and immune suppression, disseminated HSV is often fatal. Further study is warranted to determine whether early immune modulatory therapy including interferon gamma blockade can interrupt the HLH inflammatory cascade and prevent progression of MODS.