Assessment of C-Reactive Protein Diagnostic Test Accuracy for Late-Onset Infection in Newborn Infants

Brown, Jennifer Valeska Elli; Meader, Nick; Wright, Kath; Cleminson, Jemma; McGuire, William

doi:10.1001/jamapediatrics.2019.5669

Cited by 78 publications

(48 citation statements)

References 54 publications

(120 reference statements)

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“…CRP is the most commonly available test in hospitals for neonatal sepsis [ 10 , 11 , 21 , 22 ]. It is both used for diagnosing sepsis and monitoring disease progression.…”

Section: Discussionmentioning

confidence: 99%

“…It is both used for diagnosing sepsis and monitoring disease progression. However, a recent meta-analyses by Brown and colleagues in 2255 infants showed that CRP is insensitive and nonspecific for LONS diagnosis [ 11 ]. Based on the kinetics of CRP, it is not preferred as an early prognostic and diagnostic marker; however, it has been shown that serial measurements of CRP could reliably rule-out infection 24 h after suspicion [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…CRP, the most frequently used laboratory test for the diagnosis of neonatal sepsis, is extensively studied in routine practice and available as point of care test [ 10 ]. However, CRP level at onset is proven not predictive of LONS diagnosis [ 11 ]. PCT is an acute phase reactant and the PCT response is more rapid than the elevation of CRP [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Association of inflammatory biomarkers with subsequent clinical course in suspected late onset sepsis in preterm neonates

et al. 2021

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Background Sepsis is a major health issue in preterm infants. Biomarkers are used to diagnose and monitor patients with sepsis, but C-reactive protein (CRP) is proven not predictive at onset of late onset neonatal sepsis (LONS) diagnosis. The aim of this study was to evaluate the association of interleukin-6(IL-6), procalcitonin (PCT) and CRP with subsequent sepsis severity and mortality in preterm infants suspected of late onset neonatal sepsis. Methods The study was conducted at the Erasmus University Medical Center–Sophia Children’s Hospital Rotterdam. Patient data from January 2018 until October 2019 were reviewed for all preterm neonates born with a gestational age below 32 weeks with signs and symptoms suggestive of systemic infection, in whom blood was taken for blood culture and for inflammatory biomarkers determinations. Plasma IL-6 and PCT were assessed next to CRP at the moment of suspicion. We assessed the association with 7-day mortality and sepsis severity (neonatal sequential organ failure assessment (nSOFA) score, need for inotropic support, invasive ventilation and thrombocytopenia). Results A total of 480 suspected late onset neonatal sepsis episodes in 208 preterm neonates (gestational age < 32 weeks) were retrospectively analyzed, of which 143 episodes were classified as sepsis (29.8%), with 56 (11.7%) cases of culture negative, 63 (13.1%) cases of gram-positive and 24(5.0%) cases of gram-negative sepsis. A total of 24 (5.0%) sepsis episodes resulted in death within 7 days after suspicion of LONS. Both IL-6 (adjusted hazard ratio (aHR): 2.28; 95% CI 1.64–3.16; p < 0.001) and PCT (aHR: 2.91; 95% CI 1.70–5.00; p < 0.001) levels were associated with 7-day mortality; however, CRP levels were not significantly correlated with 7-day mortality (aHR: 1.16; 95% CI (0.68–2.00; p = 0.56). Log IL-6, log PCT and log CRP levels were all significantly correlated with the need for inotropic support. Conclusions Our findings show that serum IL-6 and PCT levels at moment of suspected late onset neonatal sepsis offer valuable information about sepsis severity and mortality risk in infants born below 32 weeks of gestation. The discriminative value was superior to that of CRP. Determining these biomarkers in suspected sepsis may help identify patients with imminent severe sepsis, who may require more intensive monitoring and therapy.

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“…CRP is the most commonly available test in hospitals for neonatal sepsis [ 10 , 11 , 21 , 22 ]. It is both used for diagnosing sepsis and monitoring disease progression.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of inflammatory biomarkers with subsequent clinical course in suspected late onset sepsis in preterm neonates

et al. 2021

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“…It may be more useful in excluding infections in suspected cases and enable earlier discontinuation of antibiotics. This may be cost-effective, decreasing the development of resistance and hospital stay duration [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Procalcitonin, C-Reactive Protein, and Interleukin-6 as Early Markers for Diagnosis of Neonatal Sepsis

Morad

Rabie

Almalky

et al. 2020

International Journal of Microbiology

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Background. Neonatal sepsis diagnosis is a challenge because of its nonspecific presentation together with low sensitivity of the time-consuming bacterial cultures. So, many sepsis markers, like C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6), are emerging to improve its diagnosis. Aim. This study was done to investigate the role of CRP, PCT, and IL-6 in promoting the early diagnosis of neonatal sepsis in an attempt to decrease morbidity and mortality. Methods. This cross-sectional study was conducted on 50 neonates suspected with sepsis enrolled from the neonatal intensive care unit (NICU) of Zagazig University Hospitals, Egypt. Blood cultures for these neonates were done before starting antibiotics. Also, bacterial DNA was revealed from the blood by broad-range 16S rDNA polymerase chain reaction (PCR). Measurements of CRP using the immunoturbidimetry method, PCT using fluorescence immunoassay quantitative method, and IL-6 using commercially available ELISA kit were done to all enrolled neonates. Results. Forty-one neonates with proved sepsis were found to be positive in blood culture and/or PCR for bacterial 16S rDNA. The most common isolated organisms were Klebsiella (61.3%), followed by E. coli (9.7%) and CONS (9.7%). We detected much significant higher levels of PCT, CRP, and IL-6 in the proved sepsis group than the suspected neonatal sepsis cases (p≤0.001, 0.001, and 0.004, respectively). Serum PCT levels showed the highest sensitivity, specificity, PPV, NPV, and accuracy of 97.6%, 89%, 97%, 88.9%, and 96% than other studied sepsis markers. Conclusion. PCT has satisfactory characteristics as a good marker than IL-6 and CRP for the diagnosis of neonatal sepsis.

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“…CRP can interact with DNA and histones, and it may scavenge nuclear material released from damaged circulating cells. The concentration of CRP in plasma increases greatly during acute phase response to tissue injuries, infections, cancers, and renal and cardiovascular diseases [ 2 ]. It is induced by interleukin-1 and interleukin-6.…”

Section: Introductionmentioning

confidence: 99%

Handheld pH meter–assisted immunoassay for C-reactive protein using glucose oxidase–conjugated dendrimer loaded with platinum nanozymes

Lyu

et al. 2021

Microchim Acta

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A simple and feasible pH meter–based immunoassay is reported for detection of C-reactive protein (CRP) using glucose oxidase (GOD)–conjugated dendrimer loaded with platinum nanozyme. Initially, platinum nanozymes were loaded into the dendrimers through an in situ synthetic method. Then, GOD and monoclonal anti-CRP antibody with a high molar ratio were covalently conjugated onto carboxylated dendrimers via typical carbodiimide coupling. The immunoreaction was carried out with a competitive mode in a CRP-coated microplate. Along with formation of immunocomplex, the added glucose was oxidized into gluconic acid and hydrogen peroxide by GOD, and the latter was further decomposed by platinum nanozyme, thus accelerating chemical reaction in the positive direction. The produced gluconic acid changed the pH of detection solution, which was determined using a handheld pH meter. Under optimum conditions, the pH meter–based immunoassay gave a good signal toward target CRP from 0.01 to 100 ng mL−1. The limit of detection was 5.9 pg mL−1. An intermediate precision ≤ 11.2% was acquired with batch-to-batch identification. No nonspecific adsorption was observed during a series of procedures to detect target CRP, and the cross-reaction against other biomarkers was very low. Importantly, our system gave well-matched results for analysis of human serum samples relative to a referenced ELISA kit.Graphical abstract

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Assessment of C-Reactive Protein Diagnostic Test Accuracy for Late-Onset Infection in Newborn Infants

Cited by 78 publications

References 54 publications

Association of inflammatory biomarkers with subsequent clinical course in suspected late onset sepsis in preterm neonates

Association of inflammatory biomarkers with subsequent clinical course in suspected late onset sepsis in preterm neonates

Evaluation of Procalcitonin, C-Reactive Protein, and Interleukin-6 as Early Markers for Diagnosis of Neonatal Sepsis

Handheld pH meter–assisted immunoassay for C-reactive protein using glucose oxidase–conjugated dendrimer loaded with platinum nanozymes

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