Framework for Considering Abnormal Heart Rate Characteristics and Other Signs of Sepsis in Very Low Birth Weight Infants.

OBJECTIVE: A heart rate characteristics index (HeRO score), incorporating low variability and superimposed decelerations, was developed as a sepsis risk indicator for preterm infants in the neonatal intensive care unit (NICU). A rise in the risk score should prompt consideration of other clinical changes that may be signs of sepsis to decide whether a workup and antibiotics are needed. We aimed to develop a framework to systematically consider signs potentially indicating sepsis in very low birth weight (VLBW) infants. STUDY DESIGN: We developed easy-recall acronyms for 10 signs of sepsis in VLBW infants. Over 12 months in a level IV NICU, neonatology fellows completed a brief survey after each shift to document changes prompting sepsis workups. We analyzed associations between survey data, hourly heart rate characteristic data, and the diagnosis of the workup, grouped as culture-positive sepsis (CXSEP, positive blood or urine culture), clinical sepsis (CLINSEP, negative cultures treated with antibiotics ≥5 days), or sepsis ruled out (SRO, negative cultures and <3 days antibiotics). RESULTS: We analyzed 93 sepsis workups in 48 VLBW infants (35 CXSEP, 20 CLINSEP, and 38 SRO). The most frequently cited changes prompting the workups were heart rate patterns and respiratory deterioration, which were common in all three categories. Low blood pressure and poor perfusion were uncommonly cited but were more likely to be associated with CXSEP than the other signs. A rise in the HeRO score ≥1 from 0 to 12 hours before compared with 12to 72 hours prior the blood culture occurred in 31% of workups diagnosed as CXSEP, 16% CLINSEP, and 31% SRO. CONCLUSION: The HeRO score can alert clinicians to VLBW infants at high or increasing risk of a sepsis-like illness, but heart rate characteristic patterns are highly variable in individual babies. The easy-recall NeoSEP-10 framework can assist clinicians in considering other clinical changes when making decisions about sepsis workups and the duration of antibiotics. KEY POINTS: · Abnormal heart rate characteristics can indicate sepsis or other pathologies in preterm infants.. · We developed a simple bedside tool to consider clinical signs potentially associated with sepsis.. · Considering vital sign trends together with clinical changes is a key to right-timing antibiotics..

Inflammatory biomarkers and physiomarkers of late-onset sepsis and necrotizing enterocolitis in premature infants.

Background: Early diagnosis of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in very low birth weight (VLBW, <1,500 g) infants is challenging due to non-specific clinical signs. Inflammatory biomarkers increase in response to infection, but non-infectious conditions also cause inflammation. Cardiorespiratory data contain physiological biomarkers, or physiomarkers, of sepsis that may be useful in combination with inflammatory hematologic biomarkers for sepsis diagnosis. Objectives: To determine whether inflammatory biomarkers measured at the time of LOS or NEC diagnosis differ from times without infection and whether biomarkers correlate with cardiorespiratory sepsis physiomarkers in VLBW infants. Methods: Remnant plasma sample collection from VLBW infants occurred with blood draws for routine laboratory testing and suspected sepsis. We analyzed 11 inflammatory biomarkers and a pulse oximetry sepsis warning score (POWS). We compared biomarker levels obtained at the time of gram-negative (GN) bacteremia or NEC, gram-positive (GP) bacteremia, negative blood cultures, and no suspected infection. Results: We analyzed 188 samples in 54 VLBW infants. Several biomarkers were increased at the time of GN LOS or NEC diagnosis compared with all other samples. POWS was higher in patients with LOS and correlated with five biomarkers. IL-6 had 78% specificity at 100% sensitivity to detect GN LOS or NEC and added information to POWS. Conclusions: Inflammatory plasma biomarkers discriminate sepsis due to GN bacteremia or NEC and correlate with cardiorespiratory physiomarkers.

Implementation of a 24-hour empiric antibiotic duration for negative early-onset sepsis evaluations to reduce early antibiotic exposure in premature infants.

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.

Inflammatory Biomarkers and Physiomarkers of Late-Onset Sepsis and Necrotizing Enterocolitis in Premature Infants.

Background: Early diagnosis of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in VLBW (<1500g) infants is challenging due to non-specific clinical signs. Inflammatory biomarkers increase in response to infection, but non-infectious conditions also cause inflammation in premature infants. Physiomarkers of sepsis exist in cardiorespiratory data and may be useful in combination with biomarkers for early diagnosis. Objectives: To determine whether inflammatory biomarkers at LOS or NEC diagnosis differ from times without infection, and whether biomarkers correlate with a cardiorespiratory physiomarker score. Methods: We collected remnant plasma samples and clinical data from VLBW infants. Sample collection occurred with blood draws for routine laboratory testing and blood draws for suspected sepsis. We analyzed 11 inflammatory biomarkers and a continuous cardiorespiratory monitoring (POWS) score. We compared biomarkers at gram-negative (GN) bacteremia or NEC, gram-positive (GP) bacteremia, negative blood cultures, and routine samples. Results: We analyzed 188 samples in 54 VLBW infants. Biomarker levels varied widely, even at routine laboratory testing. Several biomarkers were increased at the time of GN LOS or NEC diagnosis compared with all other samples. POWS was higher in patients with LOS and correlated with five biomarkers. IL-6 had 78% specificity at 100% sensitivity to detect GN LOS or NEC and added information to POWS (AUC POWS = 0.610, POWS + IL-6 = 0.680). Conclusions: Inflammatory biomarkers discriminate sepsis due to GN bacteremia or NEC and correlate with cardiorespiratory physiomarkers. Baseline biomarkers did not differ from times of GP bacteremia diagnosis or negative blood cultures.

Difficulty in the Clinical Diagnosis of Tularemia: Highlighting the Importance of a Physical Exam.

We report an 18-month-old male who presented with fever and nonspecific symptoms. He was evaluated for multiple differential diagnoses including Kawasaki disease and JIA and received treatment for them. After he was readmitted, tularemia was considered based on the physical exam finding of an ulcer on the scalp and enlarged lymph nodes. Tularemia titers were positive, and the patient was given the appropriate antibiotic and was discharged home. Follow-up of the patient showed complete resolution of symptoms. This is a case that demonstrates the importance of physical exam in identifying rare diseases presenting with common signs and symptoms.