Neonatal sepsis definitions from randomised clinical trials

Hayes, Rían; Hartnett, Jack; Semova, Gergana; Murray, Ciaran; Murphy, Katherine; Carroll, Leah; Plapp, Helena Maria; Hession, Louise; O’Toole, Jonathan; McCollum, Danielle; Roche, Edna; Jenkins, Elinor; Mockler, David; Hurley, Tim; McGovern, Matthew; Allen, John A.; Meehan, Judith; Plötz, Frans B.; Strunk, Tobias; Boode, Willem P. de; Polin, Richard A.; Wynn, James L.; Degtyareva, Marina; Küster, Helmut; Janota, Jan; Giannoni, Éric; Schlapbach, Luregn J.; Keij, Fleur M; Reiss, Irwin; Bliss, Joseph M.; Koenig, Joyce M.; Turner, Mark A.; Gale, Chris; Molloy, Eleanor J.

doi:10.1038/s41390-021-01749-3

Cited by 58 publications

(36 citation statements)

References 117 publications

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“…To date, no consensus definition has been developed for neonatal sepsis [ 15 , 16 , 28 , 103 ]. As the neonatal population is uniquely different from adults and older children, current adult and pediatric clinical criteria cannot be simply adapted [ 15 , 32 , 103 ].…”

Section: Discussionmentioning

confidence: 99%

“…As the neonatal population is uniquely different from adults and older children, current adult and pediatric clinical criteria cannot be simply adapted [ 15 , 32 , 103 ]. A recently published systematic review [ 16 ] highlighted the variance in the currently used definitions of neonatal sepsis in randomized controlled trials. Surprisingly, the most commonly used definition was microbiological culture by itself or in combination with clinical signs and symptoms, despite the proven low sensitivity of this method and the high incidence of culture-negative sepsis among the neonatal population [ 14 , 16 , 102 ].…”

Section: Discussionmentioning

confidence: 99%

“…A recently published systematic review [ 16 ] highlighted the variance in the currently used definitions of neonatal sepsis in randomized controlled trials. Surprisingly, the most commonly used definition was microbiological culture by itself or in combination with clinical signs and symptoms, despite the proven low sensitivity of this method and the high incidence of culture-negative sepsis among the neonatal population [ 14 , 16 , 102 ]. Similarly, some studies included in this review required a positive culture test to diagnose neonatal sepsis.…”

Section: Discussionmentioning

confidence: 99%

“…The definition of pediatric septic shock, a severe and often fatal progression of sepsis, was refined by the 2020 Surviving Sepsis Campaign guidelines to “severe infection leading to cardiovascular dysfunction (including hypotension, need for treatment with vasoactive medication, or impaired perfusion)” [ 13 ]. There is currently no formal definition of sepsis distinct to the neonatal population [ 14 , 15 ]; however, a recent systematic review of randomized controlled trials found neonatal sepsis to be most commonly defined by blood culture alone, followed closely by blood culture combined with clinical signs [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Computerized Clinical Decision Support Systems for the Early Detection of Sepsis Among Pediatric, Neonatal, and Maternal Inpatients: Scoping Review

Ackermann¹,

Baker²,

Festa³

et al. 2022

JMIR Med Inform

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Background Sepsis is a severe condition associated with extensive morbidity and mortality worldwide. Pediatric, neonatal, and maternal patients represent a considerable proportion of the sepsis burden. Identifying sepsis cases as early as possible is a key pillar of sepsis management and has prompted the development of sepsis identification rules and algorithms that are embedded in computerized clinical decision support (CCDS) systems. Objective This scoping review aimed to systematically describe studies reporting on the use and evaluation of CCDS systems for the early detection of pediatric, neonatal, and maternal inpatients at risk of sepsis. Methods MEDLINE, Embase, CINAHL, Cochrane, Latin American and Caribbean Health Sciences Literature (LILACS), Scopus, Web of Science, OpenGrey, ClinicalTrials.gov, and ProQuest Dissertations and Theses Global (PQDT) were searched by using a search strategy that incorporated terms for sepsis, clinical decision support, and early detection. Title, abstract, and full-text screening was performed by 2 independent reviewers, who consulted a third reviewer as needed. One reviewer performed data charting with a sample of data. This was checked by a second reviewer and via discussions with the review team, as necessary. Results A total of 33 studies were included in this review—13 (39%) pediatric studies, 18 (55%) neonatal studies, and 2 (6%) maternal studies. All studies were published after 2011, and 27 (82%) were published from 2017 onward. The most common outcome investigated in pediatric studies was the accuracy of sepsis identification (9/13, 69%). Pediatric CCDS systems used different combinations of 18 diverse clinical criteria to detect sepsis across the 13 identified studies. In neonatal studies, 78% (14/18) of the studies investigated the Kaiser Permanente early-onset sepsis risk calculator. All studies investigated sepsis treatment and management outcomes, with 83% (15/18) reporting on antibiotics-related outcomes. Usability and cost-related outcomes were each reported in only 2 (6%) of the 31 pediatric or neonatal studies. Both studies on maternal populations were short abstracts. Conclusions This review found limited research investigating CCDS systems to support the early detection of sepsis among pediatric, neonatal, and maternal patients, despite the high burden of sepsis in these vulnerable populations. We have highlighted the need for a consensus definition for pediatric and neonatal sepsis and the study of usability and cost-related outcomes as critical areas for future research. International Registered Report Identifier (IRRID) RR2-10.2196/24899

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Computerized Clinical Decision Support Systems for the Early Detection of Sepsis Among Pediatric, Neonatal, and Maternal Inpatients: Scoping Review

Ackermann¹,

Baker²,

Festa³

et al. 2022

JMIR Med Inform

View full text Add to dashboard Cite

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“…Definitions of neonatal sepsis in premature infants vary widely among published studies 45,46 due to challenges in developing a consensus definition for sepsis in this unique population 47 . We chose to model events of culture-proven sepsis, knowing that this definition, while unequivocal, also excludes many clinically important events associated with a negative blood culture.…”

Section: Limitationsmentioning

confidence: 99%

Cardiorespiratory signature of neonatal sepsis: Development and validation of prediction models in 3 NICUs

Kausch

Brandberg

Qiu

et al. 2022

Preprint

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Background: Heart rate characteristics aid early detection of late-onset sepsis (LOS), but respiratory data contain additional signatures of illness due to infection. Predictive models using machine learning and cardiorespiratory data may improve early sepsis detection. Objective: Test the hypothesis that heart rate (HR) and oxygenation (SpO2) data contain signatures that improve continuous sepsis risk prediction over HR or demographics alone. Methods: We analyzed cardiorespiratory data from very low birth weight (VLBW, <1500g) infants admitted to three NICUs from 2012-2021 with annotated blood cultures. We developed and externally validated four machine learning models to predict imminent LOS using features calculated every 10m: mean, standard deviation, skewness, kurtosis of HR and SpO2, and their cross-correlation. We compared feature importance, discrimination, calibration, and dynamic risk prediction across modeling methods and cohorts. We built logistic regression models of demographics and HR or SpO2 features alone for comparison with HR-SpO2 models. Results: Data were available for 2,494 VLBW infants who had 302 LOS events. Performance, feature importance, and calibration were similar among modeling methods. SD of HR, skewness of HR, and kurtosis of SpO2 ranked as important features most consistently across models. All models had favorable external validation performance. The HR-SpO2 model performed better than models using either HR or SpO2 alone. Demographics improved the discrimination of all physiologic data models but dampened their dynamic performance. Conclusion: Cardiorespiratory signatures detect LOS in VLBW infants at 3 NICUs. Demographics risk-stratify, but predictive modeling with both HR and SpO2 features provides the best dynamic risk prediction.

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Management of neonates at risk of early onset sepsis: a probability-based approach and recent literature appraisal

Stocker,

Rosa-Mangeret,

Agyeman

et al. 2024

Eur J Pediatr

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In Switzerland and other high-income countries, one out of 3000 to 5000 term and late preterm neonates develops early onset sepsis (EOS) associated with a mortality of around 3%, while incidence and mortality of EOS in very preterm infants are substantially higher. Exposure to antibiotics for suspected EOS is disproportionally high compared to the incidence of EOS with consequences for future health and antimicrobial resistance (AMR). A safe reduction of unnecessary antibiotic treatment has to be a major goal of new management strategies and guidelines. Antibiotics should be administered immediately in situations with clinical signs of septic shock. Group B streptococcus (GBS) and Escherichia coli (E. coli) are the leading pathogens of EOS. Amoxicillin combined with an aminoglycoside remains the first choice for empirical treatment. Serial physical examinations are recommended for all neonates with risk factors for EOS. Neonates without any clinical signs suggestive of EOS should not be treated with antibiotics. In Switzerland, we do not recommend the use of the EOS calculator, a risk stratification tool, due to its unclear impact in a population with an observed antibiotic exposure below 3%. Not all neonates with respiratory distress should be empirically treated with antibiotics. Isolated tachypnea or respiratory distress starting immediately after delivery by elective caesarean section or a clearly assessed alternative explanation than EOS for clinical signs may point towards a low probability of sepsis. On the other hand, unexplained prematurity with risk factors has an inherent higher risk of EOS. Before the start of antibiotic therapy, blood cultures should be drawn with a minimum volume of 1 ml in a single aerobic blood culture bottle. This standard procedure allows antibiotics to be stopped after 24 to 36 h if no pathogen is detected in blood cultures. Current data do not support the use of PCR-based pathogen detection in blood as a standard method. Lumbar puncture is recommended in blood culture–proven EOS, critical illness, or in the presence of neurological symptoms such as seizures or altered consciousness. The accuracy of a single biomarker measurement to distinguish inflammation from infection is low in neonates. Therefore, biomarker guidance is not a standard part of decision-making regarding the start or stop of antibiotic therapy but may be used as part of an algorithm and after appropriate education of health care teams. Every newborn started on antibiotics should be assessed for organ dysfunction with prompt initiation of respiratory and hemodynamic support if needed. An elevated lactate may be a sign of poor perfusion and requires a comprehensive assessment of the clinical condition. Interventions to restore perfusion include fluid boli with crystalloids and catecholamines. Neonates in critical condition should be cared for in a specialized unit. In situations with a low probability of EOS, antibiotics should be stopped as early as possible within the first 24 h after the start of therapy. In cases with microbiologically proven EOS, reassessment and streamlining of antibiotic therapy in neonates is an important step to minimize AMR. Conclusion: This guideline, developed through a critical review of the literature, facilitates a probability-based approach to the management of neonates at risk of early onset sepsis. What is Known:• Neonatal exposure to antibiotics is disproportionally high compared with the incidence of early onset sepsis with implications for future health and antimicrobial resistance. What is New:• A probability-based approach may facilitate a more balanced management of neonatal sepsis and antibiotic stewardship.

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Neonatal sepsis definitions from randomised clinical trials

Cited by 58 publications

References 117 publications

Computerized Clinical Decision Support Systems for the Early Detection of Sepsis Among Pediatric, Neonatal, and Maternal Inpatients: Scoping Review

Computerized Clinical Decision Support Systems for the Early Detection of Sepsis Among Pediatric, Neonatal, and Maternal Inpatients: Scoping Review

Cardiorespiratory signature of neonatal sepsis: Development and validation of prediction models in 3 NICUs

Management of neonates at risk of early onset sepsis: a probability-based approach and recent literature appraisal

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