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Adjunctive therapies have been proposed for use in at least 5 inflammation pathobiology phenotypes in pediatric sepsis-induced multiple organ failure (MOF). Here, we provide host-pathogen interaction prototypes to facilitate understanding of the rationale for personalized therapy in these phenotypes. Meningococcemic sepsis and Shiga-like toxin-associated atypical Hemolytic Uremic Syndrome sepsis result in thrombocytopenia and MOF due to endothelial dysfunction and formation of small vessel thromboses that can respond to plasma exchange and C5a monoclonal antibody therapy. H1N1 Influenza A sepsis is associated with immune paralysis that can result in opportunistic secondary infection with invasive methicillin resistant Staphylococcus aureus (MRSA) and MOF that can respond to Granulocyte Macrophage Colony Stimulating Factor therapy. Hyperleukocytosis-associated MOF is associated with critical Bordetella Pertussis pulmonary hypertension and cardiovascular collapse which can respond to leukoreduction therapy. Epstein Barr Virus lymphoproliferative disease-associated sequential MOF has high levels of soluble-Fas Ligand that cause liver failure, and can respond to anti-CD20 monoclonal antibody therapy. Viral hemorrhagic fevers such as Ebola or Dengue can lead to macrophage activation syndrome characterized by hyperferritinemia, hepatobiliary dysfunction and disseminated intravascular coagulation (DIC)-related MOF that can theoretically respond to anti-inflammatory therapies. We discuss the literature on adjunctive anti-inflammatory and immune modulation therapies that, in addition to traditional organ support and infection source control, might be part of a personalized precision medicine approach to reverse of each of these inflammatory pathobiology phenotypes.

Objective To develop a method to perform multiple tests on single nasopharyngeal (NP) swab. Study design We collected a NP swab on children aged 2–12 years with acute sinusitis and processed it for bacterial culture, viruses, cytokine expression, and 16S ribosomal RNA gene sequencing analysis. During the course of the study, we expand the scope of evaluation to include RNA sequencing, which we accomplished by cutting the tip of the swab. Results Of the 174 children enrolled, 126 (72.4%) had a positive bacterial culture and 121(69.5%) tested positive for a virus. Cytokine measurement, as judged by the adequate levels of a housekeeping enzyme (GAPDH), appeared successful. From the samples used for 16S ribosomal sequencing we recovered, on average, 16,000 sequences per sample, accounting for a total of 2,646 operational taxonomic units across all samples sequenced. Samples used for RNA sequencing had a mean RNA Integrity number of 6.0. Cutting the tip of the swab did not affect the recovery yield for viruses or bacteria, nor did it affect species richness in microbiome analysis. Conclusion We describe a minimally invasive sample collection protocol that allows for multiple diagnostic and research investigations in young children.

Background Lower respiratory tract infection (LRTI) is the leading cause of pediatric hospitalizations in the United States, with significant morbidity and mortality. Native American children are at increased risk for severe illness during LRTI. Yet, the reasons for this increased risk are poorly understood. Socio-economic status and/or a genetic predisposition have been postulated as possible causes. In addition, the spectrum of LRTI presentations has not been adequately described in this patient population. The objective of this study was to define the clinical presentations of LRTI and highlight the differences between Native American and non-native American previously healthy patients under the age of 24 months. Methods We performed a retrospective chart review during the 2017–2018 respiratory season. We reviewed 357 medical records, and included 192 patients in the analysis that were full term, previously healthy, and met our inclusion criteria. We recorded demographic information, clinical and laboratory data, and outcomes. Results Of 192 patients, 39 were Native American and 153 were non-native American. We found no differences in gestational age, gender or age (median age was 5 and 7 months, respectively) between groups. We found no difference in rates of vaccination, upper respiratory symptoms, cough, wheezing, crackles, increased work of breathing or peripheral white blood cell count at presentation. In addition, we found no differences in antibacterial use or length of antimicrobial therapy during hospitalization. Native American children had a statistically significant higher length of hospitalization (P = 0.01) as well as days of oxygen supplementation (mean 4.9 vs. 3 days; P = 0.006) compared with non-native Americans. Furthermore, Native American children had a significantly higher percentage of PICU admissions (28% vs. 10.4%; P = 0.008) as well as intubation rate (26% vs. 8%; P = 0.04) compared with non-native Americans. Conclusion Native American children had increased length of hospitalization associated with severe illness including longer oxygen supplementation, higher PICU admission rate and need for mechanical ventilatory support. Disclosures All authors: No reported disclosures.