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Background The management of febrile infants under the age of 3 months has long been a controversial topic, often requiring them to be subject to a battery of tests, antibiotics, and hospitalization. Multiplex polymerase chain reaction (PCR) panels can provide a rapid diagnosis, but their role in managing these patients is still unknown. Our objective was to determine if multiplex respiratory and meningitis/encephalitis PCR panels decreased antibiotic duration of therapy (DOT) and hospital length of stay (LOS) when used in sepsis evaluations of febrile infants less than 90 days of age. Methods We performed a retrospective chart review of infants younger than 90 days old who were admitted to the pediatric ward for concerns of fever or sepsis from 1/1/2016 to 9/30/2019. Subjects with documented bacterial infections were excluded. Our primary outcomes were differences in DOT and LOS between patients admitted before and after PCR panels became available (Pre-PCR era and PCR era). Results 118 subjects were included in our analysis, with 52 (44.1%) coming from the Pre-PCR group. Descriptive statistics, stratified by era, are available in Table 1. The unadjusted mean LOS and DOT decreased by 8.4 (P = .003) and 32.8 (P < .001) hours, respectively. Multivariate regression demonstrated that LOS was 1.16 times longer in the Pre-PCR era (95% CI: 1.10 - 1.22; P < .001). Similarly, patients in the Pre-PCR era had DOT that was 1.95 times longer (95% CI: 1.55 - 2.46; P < .001) when adjusting for covariates. Adjusted LOS and DOT by Era and Diagnosis PCR panel results by pathogen Conclusion We conclude that multiplex PCR panels can potentially influence the management of young febrile infants admitted for sepsis evaluations by rapidly diagnosing viral infections and thus decreasing DOT and LOS. In turn, that may improve patient outcomes and satisfaction, as well as possibly decrease costs. Multiplex PCR panels should be considered as part of routine sepsis evaluations in young febrile infants. Larger studies are needed, including in depth cost analysis. Table 1: Demographics Table 2: Results between Eras Disclosures All Authors: No reported disclosures