Low Diagnostic Utility of Frequent Serial Tracheal Aspirate Cultures in the PICU.

OBJECTIVES: To determine the diagnostic outcomes of serial tracheal aspirate cultures (TACs) in the PICU. DESIGN: A retrospective chart review of TAC utilization was performed. Items recorded for each TAC included the time and date of culture acquisition, result, changes in microbial resistance patterns, antimicrobial therapy, and patient clinical course. SETTING: A single urban tertiary care children's hospital in the United States. SUBJECTS: Patients admitted to the PICU from January 1, to October 31, 2021, for whom a TAC was performed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred fifty unique subjects had 582 TACs performed during the study period, of which 145 (24.9%) were serially repeated within 72 hours. Of these serial TACs, 82 (56.6%) had no growth, 41 (28.3%) grew the same organism as the prior culture, with most (36/41) displaying no major change in antimicrobial susceptibilities, 11 (7.6%) grew a new organism previously grown during the admission, and 11 (7.6%) grew a new organism not previously grown during the admission. Overall, only 26 of these serial TACs (17.9%) provided new diagnostic information, whereas only five (3.4%) led to a change in management. CONCLUSIONS: Frequent serial TAC sampling in the PICU is common and infrequently yields new data that impact clinical decision-making. Considering worsening antimicrobial resistance and the role of diagnostic stewardship in mitigating it, these findings further support a 72-hour reassessment period before performing a repeat TAC in critically ill children.

Risk Variants in the Exomes of Children With Critical Illness.

Importance: Diagnostic genetic testing can lead to changes in management in the pediatric intensive care unit. Genetic risk in children with critical illness but nondiagnostic exome sequencing (ES) has not been explored. Objective: To assess the association between loss-of-function (LOF) variants and pediatric critical illness. Design, Setting, and Participants: This genetic association study examined ES first screened for causative variants among 267 children at the Morgan Stanley Children's Hospital of NewYork-Presbyterian, of whom 22 were otherwise healthy with viral respiratory failure; 18 deceased children with bronchiolitis from the Office of the Chief Medical Examiner of New York City, of whom 14 were previously healthy; and 9990 controls from the Institute for Genomic Medicine at Columbia University Irving Medical Center. The ES data were generated between January 1, 2015, and December 31, 2020, and analyzed between January 1, 2017, and September 2, 2022. Exposure: Critical illness. Main Outcomes and Measures: Odds ratios and P values for genes and gene-sets enriched for rare LOF variants and the loss-of-function observed/expected upper bound fraction (LOEUF) score at which cases have a significant enrichment. Results: This study included 285 children with critical illness (median [range] age, 4.1 [0-18.9] years; 148 [52%] male) and 9990 controls. A total of 228 children (80%) did not receive a genetic diagnosis. After quality control (QC), 231 children harbored excess rare LOF variants in genes with a LOEUF score of 0.680 or less (intolerant genes) (P = 1.0 × 10-5). After QC, 176 children without a diagnosis harbored excess ultrarare LOF variants in intolerant genes but only in those without a known disease association (odds ratio, 1.8; 95% CI, 1.3-2.5). After QC, 25 children with viral respiratory failure harbored excess ultrarare LOF variants in intolerant genes but only in those without a known disease association (odds ratio, 2.8; 95% CI, 1.1-6.6). A total of 114 undiagnosed children were enriched for de novo LOF variants in genes without a known disease association (observed, 14; expected, 6.8; enrichment, 2.05). Conclusions and Relevance: In this genetic association study, excess LOF variants were observed among critically ill children despite nondiagnostic ES. Variants lay in genes without a known disease association, suggesting future investigation may connect phenotypes to causative genes.