C-Reactive Protein, Procalcitonin, and White Blood Count to Rule Out Neonatal Early-onset Sepsis Within 36 Hours: A Secondary Analysis of the Neonatal Procalcitonin Intervention Study

Stocker, Martin; Herk, Wendy van; Helou, Salhab el; Dutta, Sourabh; Schuerman, Frank A B A; Groot, Rita K van den Tooren-de; Wieringa, Jantien W; Janota, Jan; Meer-Kappelle, Laura H van der; Moonen, Rob; Sie, Sintha D.; Vries, Esther de; Donker, Albertine E.; Zimmerman, Urs; Schlapbach, Luregn J.; Mol, Arjen; Hoffman-Haringsma, Angelique; Roy, Madan; Tomaske, Maren; Kornelisse, René F.; Gijsel, Juliette van; Visser, Eline G.; Plötz, Frans B.; Heath, Paul T; Achten, Niek B.; Lehnick, Dirk; Rossum, Annemarie M. C. van

doi:10.1093/cid/ciaa876

Cited by 75 publications

(60 citation statements)

References 27 publications

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“…Therefore, both the start and the length of antibiotic treatment to prevent EOS should not be guided only by CRP measurements [ 3 ]. Furthermore, Stocker et al demonstrated that the negative predictive value of CRP does not increase from 36 h onward [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, C-reactive protein (CRP) and procalcitonin (PCT) are the most widely used markers to guide antibiotic therapy, although their early increase after birth is not always related to the onset of infections [ 3 , 4 ]. Recent studies have shown that in cases of suspected EOS, when the neonate has no uncertain symptoms and the blood culture is negative at 36–48 h, the discontinuation of empiric antibiotics, guided by the negativity or reduction of the biomarkers of infection (CRP, PCT, and/or PSEP) is a safe practice and saves improperly used antibiotics and costs, with a low rate of suspected re-infections (less than 1%) but no culture-proven bacterial re-infections [ 5 ], and above all, without study-related mortality [ 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Time to Positivity of Blood Cultures Could Inform Decisions on Antibiotics Administration in Neonatal Early-Onset Sepsis

et al. 2021

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(1) Background: Empirical antibiotics for suspected neonatal early-onset sepsis are often prolonged administered, even in the absence of clinical signs of infection, while awaiting the blood cultures results. The C-reactive protein is widely used to guide antibiotic therapy, although its increase in the first hours of life is not always evidence of infection. The aim of this study was to evaluate the time to positivity (TTP) of blood cultures (BC) that develop pathogens in our population of neonates and determine whether TTP could safely inform the decisions on empirical antibiotic discontinuation in neonatal early-onset sepsis and reduce the use of unnecessary antibiotics. (2) Methods: We retrospectively collected data of all newborns ≥ 34 weeks admitted to the Neonatal Intermediate-Care Unit at Policlinico “A. Gemelli” University Hospital (Rome, Italy) from 2014 to 2018, with suspected early-onset sepsis (EOS). The TTP was the time in hours from the first BC inoculation to the bacterial growth. We defined as positive BC only those with a pathogenic organism. (3) Results: In total, 103 out of 20,528 infants born in the five-year study period were admitted to our Neonatal Intermediate-Care Unit because of a suspected EOS and enrolled into the study. The mean TTP of pathogenic organisms was 17.7 ± 12.5 h versus 80.5 ± 55.8 h of contaminants (p = 0.003). We found ten positive BCs. The TTP of BC was lower than 12, 36, and 48 h in 80%, 90%, and 100% of cases, respectively. CRP levels on admission were similar in infants with a positive and negative BC (p = 0.067). The discontinuation of therapy in asymptomatic infants 48 h after initiation would have resulted in a saving of 217 days of antibiotics (31.1% of total days administered). (4) Conclusion: From our data, the TTP of blood cultures that develop pathogens is less than 48 h in 100% of cases. Therefore, in late preterm and full-term infants with suspected EOS, stopping empiric antibiotics 48 h after initiation may be a safe practice to reduce unnecessary antibiotic use, when blood cultures are negative and infants asymptomatic.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Time to Positivity of Blood Cultures Could Inform Decisions on Antibiotics Administration in Neonatal Early-Onset Sepsis

et al. 2021

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“…Studies have demonstrated that CRP is a determining predictor and risk factor for sepsis in adults and newborns. [7][8][9] Albumin (ALB) is another protein produced by the liver, which makes up 40% to 60% of the total proteins in the blood. 10 Serum albumin concentration is frequently used as an indicator of malnutrition.…”

Section: Introductionmentioning

confidence: 99%

Predictive Value of C-Reactive Protein-to-Albumin Ratio for Neonatal Sepsis

Li¹,

Li²,

Wei³

et al. 2021

JIR

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Previous studies have reported that C-reactive protein-to-albumin ratio (CAR) was a risk factor for sepsis in adults. However, little is known regarding the role of CAR in neonates with sepsis. The aim of this study was to explore the relationship between CAR and neonatal sepsis. Patients and Methods: In this research, from January 2016 to February 2020, a total of 1076 neonates were enrolled at Henan Children's Hospital in China. Complete clinical and laboratory data were collected. To identify the potential independent risk factor for neonatal sepsis, multivariate logistic regression analysis was performed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction accuracy of CAR in identifying neonatal sepsis. Results: CAR levels were higher in neonates with sepsis and showed a gradual increase among the control group, mild sepsis group and severe sepsis group. The prevalence of neonates with overall sepsis, mild sepsis and severe sepsis increased significantly from CAR tertile 1 to tertile 3. Multiple logistic regression analysis showed that CAR was an independent risk factor for the presence of sepsis (OR = 10.144, 95% CI 4.151-24.790, P < 0.001) and severe sepsis (OR = 1.876, 95% CI 1.562-2.253, P < 0.001). ROC curve analysis showed that CAR had a well discriminatory power in predicting sepsis (area under curve (AUC) = 0.74, 95% CI, 0.71-0.77, P < 0.001) and severe sepsis (AUC = 0.70, 95% CI, 0.67-0.74, P < 0.001). Conclusion: CAR was an independent predictor for the presence and severity of neonatal sepsis.

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“…Automatic stop orders enforce proactive decisions on continuation, which may induce more personalized decision-making, and can be highly effective in reducing unnecessary continuation of antibiotic treatment ( 137 , 138 ). Such personalized decisions may be further improved if guided by combining risk stratification and age-dependent reference values for biomarkers such as procalcitonin (PCT) and or CRP ( 139 – 141 ). Serial low CRP values, normal PCT values, or the combination of CRP and PCT can support discontinuation of antibiotics ( 142 ).…”

Section: Treatment Durationmentioning

confidence: 99%

Stratified Management for Bacterial Infections in Late Preterm and Term Neonates: Current Strategies and Future Opportunities Toward Precision Medicine

Keij¹,

Achten²,

Tramper-Stranders³

et al. 2021

Front. Pediatr.

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Bacterial infections remain a major cause of morbidity and mortality in the neonatal period. Therefore, many neonates, including late preterm and term neonates, are exposed to antibiotics in the first weeks of life. Data on the importance of inter-individual differences and disease signatures are accumulating. Differences that may potentially influence treatment requirement and success rate. However, currently, many neonates are treated following a “one size fits all” approach, based on general protocols and standard antibiotic treatment regimens. Precision medicine has emerged in the last years and is perceived as a new, holistic, way of stratifying patients based on large-scale data including patient characteristics and disease specific features. Specific to sepsis, differences in disease susceptibility, disease severity, immune response and pharmacokinetics and -dynamics can be used for the development of treatment algorithms helping clinicians decide when and how to treat a specific patient or a specific subpopulation. In this review, we highlight the current and future developments that could allow transition to a more precise manner of antibiotic treatment in late preterm and term neonates, and propose a research agenda toward precision medicine for neonatal bacterial infections.

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C-Reactive Protein, Procalcitonin, and White Blood Count to Rule Out Neonatal Early-onset Sepsis Within 36 Hours: A Secondary Analysis of the Neonatal Procalcitonin Intervention Study

Cited by 75 publications

References 27 publications

Time to Positivity of Blood Cultures Could Inform Decisions on Antibiotics Administration in Neonatal Early-Onset Sepsis

Time to Positivity of Blood Cultures Could Inform Decisions on Antibiotics Administration in Neonatal Early-Onset Sepsis

Predictive Value of C-Reactive Protein-to-Albumin Ratio for Neonatal Sepsis

Stratified Management for Bacterial Infections in Late Preterm and Term Neonates: Current Strategies and Future Opportunities Toward Precision Medicine

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