Imagine for a moment you are counseling a patient with a suspicious mass and symptoms that are concerning but nonspecific. Although there are several possible diagnoses, one hangs unspoken between you and the patient-a diagnosis that carries significant morbidity and mortality. You propose an immediate biopsy. After all, a tissue diagnosis is the criterion standard, and this matter is urgent. The patient agrees, and as the patient begins to stand, you raise a hand and mention another test you would like to order. The patient is curious. "What are the benefits of this test?" You explain that the test involves sending a portion of the biopsied tissue to a separate part of the laboratory, where the pathology department will look for other markers of disease. Of course, the patient nods; that makes sense. "If this extra test result is negative, I will be okay, right?" "No," you answer, "a negative test result does not mean the biopsy result will be negative." The patient frowns. "Well, is it a bad sign if the test result is positive?" "Not necessarily," you explain. "Many things can make the other test results abnormal, so we'll still have to wait on the biopsy results. The biopsy is the key." The patient sits down again, looking confused. "If the biopsy is so important, why are we wasting tissue on this other test?" "Well," you glance helplessly toward the window then look back to your frowning patient. "It's just what we've always done in these cases."This exchange is hypothetical, but in the case of Creactive protein (CRP) for neonatal sepsis, it is all too real. The nonspecific signs of late-onset infection in infants, particularly those born preterm, combined with the high risk of morbidity and mortality have underscored the need for accurate diagnosis of neonatal sepsis. 1 Culture of blood and other sterile sites is the criterion standard for neonatal sepsis. However, myriad ancillary laboratory tests have been suggested as potential biomarkers for neonatal sepsis; these include CRP, complete blood counts with differential, procalcitonin, a variety of interleukins, and presepsin. 2 The value of those tests in the clinical management of suspected sepsis is questionable. In this issue of JAMA Pediatrics, Brown et al 3 report their systematic review and meta-analysis of the sensitivity, specificity, and test accuracy of CRP for late-onset neonatal sepsis. They analyzed 22 studies including 2255 infants, the majority being 32 weeks or less gestational age or 1500 g or less birth weight. The median specificity of CRP was 0.74 and median sensitivity was 0.62. Assuming a cohort of 1000 preterm infants with a 20% prevalence rate of late-onset sepsis, this means that 76 cases of infection would be missed, and 208 infants would be incorrectly diagnosed as having sepsis-more than the number of infants with sepsis (200).

Objective: Antibiotic exposure increases the risk of morbidity and mortality in premature infants. Many centers use at least 48 hours of antibiotics in the evaluation of early-onset sepsis (EOS, <72 hours after birth), yet most important pathogens grow within 24 hours. We investigated the safety and efficacy of reducing empiric antibiotic duration to 24 hours. Design: Quality improvement study. Setting: A tertiary-care neonatal intensive care unit. Patients: Inborn infants <35 weeks gestational age at birth (ie, preterm) admitted January 2019 through December 2020. Intervention: In December 2019, we changed the recommended duration of empiric antibiotics for negative EOS evaluations from 48 hours to 24 hours. Results: Patient characteristics before and after the intervention were similar. After the intervention, 71 preterm infants (57%) with negative EOS evaluations received ≤24 hours of antibiotics, an increase from 15 (10%) before the intervention. These 71 infants comprised 77% of infants with negative EOS blood cultures after excluding those treated as clinical sepsis (≥5 days of antibiotics). For all negative EOS blood cultures, the mean treatment duration decreased by 0.5 days from 3.9 days to 3.4 days. This finding equated to 2.4 fewer antibiotic days per 100 patient days for negative EOS blood cultures but similar antibiotic days per 30 patient days (7.2 days vs 7.5 days). This measure did not change over time. Subsequent sepsis evaluations <7 days after a negative EOS blood culture did not increase. Excluding contaminants, the median time to positivity was 13.2 hours (range, 8–23) in 8 positive blood cultures. Conclusion: Implementation of a 24-hour antibiotic course for negative EOS evaluations safely reduced antibiotic exposure in 77% of infants <35 weeks gestational age at birth in whom EOS was ruled out. All clinically significant pathogens grew within 24 hours.

Background Incidence of blood stream infections (BSI) among NICU admissions remains high, with associated mortality and morbidity. Due to COVID-19, there are increased infection prevention (IP) measures in NICUs including universal masking for all healthcare workers and families, social distancing, visitation restrictions, and increased attention to hand hygiene. These measures may also affect late-onset infection rates and offer understanding of novel interventions for prevention. Methods We examined infection rates during the 24 months prior to implementation of COVID-19 IP measures (PRE-period) compared to the months after implementation from April 2020 (POST-period). Late-onset infections were defined as culture-confirmed infection of the blood, urine, or identification of respiratory viral pathogens. An interrupted time series analysis of infection per 1000 patient days was performed based on a change-point Poisson regression with a lagged dependent variable and the number of patient days used as offsets. Each month was treated as independent with additional analysis using an observation-driven model to account for serial dependence. Results Multicenter analysis to date included all infants cared for at three centers (Level 3 and 4) from 2018-2020. Monthly BSI rates decreased in the POST-period at the three centers (Figure 1). At all centers actual BSI rate was lower than the expected rate in the POST-period (Figure 2). The combined BSI rate per 1000 patient days was 41% lower compared to the rate prior to implementation (95% CI, 0.42 to 0.84, P=0.004) (Table 1). In subgroup analysis by birthweight, infants&lt; 1000g had a 39% reduction in BSI (P=0.023), for1000-1500g patients there was a 44% reduction (P=0.292) and in those &gt; 1500g there was a 53% reduction (0.083). Figure 1. PRE and POST MASKING and other COVID Infection Prevention Measures and Monthly BSI Rates. Figure 2. PRE and POST MASKING and other COVID infection prevention measures and BSI Trends. At all centers actual BSI rate was lower than the expected rate for that center in the POST period. UVA and Duke showed a baseline decrease and Pennsylvania Hospital showed a downward trend in infection rates. There was an approximate decrease in expected bloodstream infection events at Pennsylvania Hospital by 7 events, at UVA by 22 events and at Duke by 23 events. Overall, all three centers saw a decrease in their expected infections after COVID-19 infection prevention measures were implemented. Table 1. Percent reduction in Bloodstream Infection at each center. Conclusion In this preliminary analysis, we found a reduction of BSI after the implementation of COVID-19 infection prevention measures. Additionally, there were fewer viral infections, though there were a limited number of episodes. Further analyses of multicenter data and a larger number of patients will elucidate the significance of these findings and the role some of these IP measures such as universal masking may have in infection prevention in the NICU. Disclosures All Authors: No reported disclosures