Use of Procalcitonin-Guided Decision-Making to Shorten Antibiotic Therapy in Suspected Neonatal Early-Onset Sepsis: Prospective Randomized Intervention Trial

Stocker, Martin; Fontana, Matteo; Helou, Salhab el; Wegscheider, Karl; Berger, Thomas M.

doi:10.1159/000241296

Cited by 139 publications

(112 citation statements)

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“…1 However, cultures require several days to allow for bacterial growth in culture medium. In central referral hospitals, procalcitonin and CRP examinations can help in diagnosing neonatal sepsis, 6,7 but these examinations cannot be performed in primary health care facilities. As such, several approaches, including a scoring system, may be implemented to simplify the diagnosis of neonatal sepsis.…”

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confidence: 99%

A hematologic scoring system and C-reactive protein compared to blood cultures for diagnosing bacterial neonatal sepsis

Liestiadi

Azlin

Nafianti

2017

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Background Neonatal sepsis is the leading cause of death after pneumonia. Definitive bacterial sepsis diagnoses are made by blood culture results, which require a lengthy time. C-reactive protein (CRP) levels and a hematologic scoring system by Rodwell et al. are rapid tests that may be useful for diagnosing neonatal sepsis. Objective To determine the diagnostic value of CRP measurement and a hematologic scoring system compared to blood culture as the gold standard for diagnosing neonatal sepsis. Methods A cross-sectional study was conducted from April to August 2015 in the Neonatology Ward of Haji Adam Malik Hospital, Medan. A total of 43 neonates who were clinically suspected to have sepsis underwent CRP, hematologic scoring, and blood cultures. The IT ratio and procalcitonin indices were also examined. Diagnostic values were analyzed by a 2x2 table.Results Fourteen percent from all sample had positive bacterial culture. The CRP measurements had a sensitivity of 92.8%, specificity of 62%, positive predictive value (PPV) of 54.1%, negative predictive value (NPV) of 94.7%, positive likelihood ratio (PLR) of 2.44, and negative likelihood ratio (NLR) of 0.11. The hematologic scoring system had a sensitivity of 100%, specificity of 82.7%, PPV of 73.6%, NPV of 100%, PLR of 5.78, and NLR of 0. Procalcitonin and IT ratio show a good value of sensitivity and NPV, respectively. Conclusion The hematologic scoring system has better specificity than CRP measurement as compared to blood culture. However, both tests have good sensitivity for diagnosing neonatal sepsis.

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A hematologic scoring system and C-reactive protein compared to blood cultures for diagnosing bacterial neonatal sepsis

Liestiadi

Azlin

Nafianti

2017

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“…Procalcitonin can be also a useful tool to shorten the duration of antibiotic therapy. According to rare paediatric studies, inclusion of PCT measurements within decision algorithms of antibiotic management for specific infections may be appropriate in neonates and young children under 36 months [25,26].…”

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The role of CRP, PCT, IL-6 and presepsin in early diagnosis of bacterial infectious complications in paediatric haemato-oncological patients

Plesko¹,

Suvada²,

Makohusová³

et al. 2016

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Bacterial infection is the most common complication in paediatric oncological patients during cancer treatment. A suitable tool for early prediction of unfavourable course of infection is still needed. We performed a prospective longitudinal observational study to evaluate of the role of serum biomarkers (C-reactive protein, procalcitonin, interleukin-6, presepsin) in the early diagnosis of bacteraemia (gram-negative versus gram-positive) in patients with haematological malignancies. We observed 69 febrile episodes in 33 patients (17 male, 16 female; 1.5-18.9 years, mean 7.31 years, median 5 years). Within this sample, there were 22 cases of positive blood cultures, 16 cases of sepsis, 38 cases of fever with no signs or symptoms of sepsis, and two deaths from infectious complications. All markers tested had good negative predictive value (73% -93%). CRP was characterized by good specificity for registration bacteraemia (96%, 95% CI: 85% -99%), but other results were inconclusive. We identified comparably balanced sensitivity (64% -81%) and specificity (61% -88%) for interleukin-6 and procalcitonin, and we proved their quality to predict positive blood culture and clinical signs of sepsis as well. Patients with gram-negative bacteraemia had significantly elevated levels of PCT and IL-6 in comparison with a group of patients with gram-positive bacteraemia (p = 0.04 for PCT and p = 0.005 for IL-6). Presepsin was characterized by poor specificity (27%, 95% CI: 15% -43%) and positive predictive value (24%, 95% CI: 12 -39%) for predicting bacteraemia, and by better sensitivity (84%, 95% CI: 55% -98%) and specificity (58%, 95% CI: 42% -73%) for predicting clinical signs of sepsis. Key words: C-reactive protein, procalcitonin, interleukin-6, presepsin, fever, sepsisBacterial infection is the most common treatment-related complication in patients with haematological malignancies [1]. Documented mortality associated with paediatric febrile neutropenia is 2% [2]. The potential for early diagnosis of bacteraemia through serum biomarkers has been the subject to extensive research [3]. In 2012 Phillips et al published large meta-analysis of 25 studies exploring 14 different biomarkers in 3,585 episodes of febrile neutropenia. CRP, PCT and IL-6 were subject to quantitative meta-analysis. The bivariate estimates of diagnostic precision of these biomarkers and outcomes were done. Data were available for meta-analysis for CRP for microbiologically or clinically documented infection (results: cut off > 50mg/dl, sensitivity 65%, specificity 73%), for PCT assessing microbiologically or clinically documented infection (results: cut off > 0.2 mg/ml, sensitivity 96%, specificity 85%), for IL-6 reporting microbiologically or clinically documented infection (results: cut off > 235 pg/ml, sensitivity 68%, specificity 94%), and gram-negative bacteraemia (results: cut off > 1000 pg/ml, sensitivity 78%, specificity 96%). Huge inconsistencies and heterogeneity in the studies included in this review were the most important limiting factors [...

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“…[5][6][7] A variety of diagnostic biomarkers have been used to identify neonates early in the course of the sepsis [8][9][10] or to monitor response to therapy. 11 However, no single biomarker has yield conclusive results, and therefore, the simultaneous use of several biomarkers has been recommended. 12 Recently, molecular assays based on microbial genome hybridization or amplification aiming at early detection of bacteria in biofluids have yielded disappointing results compared with traditional blood cultures.…”

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Genome-Wide Expression Profiles in Very Low Birth Weight Infants With Neonatal Sepsis

et al. 2014

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BACKGROUND: Bacterial sepsis is associated with high morbidity and mortality in preterm infants. However, diagnosis of sepsis and identification of the causative agent remains challenging. Our aim was to determine genome-wide expression profiles of very low birth weight (VLBW) infants with and without bacterial sepsis and assess differences. METHODS: This was a prospective observational double-cohort study conducted in VLBW (<1500 g) infants with culture-positive bacterial sepsis and non-septic matched controls. Blood samples were collected as soon as clinical signs of sepsis were identified and before antibiotics were initiated. Total RNA was processed for genome-wide expression analysis using Affymetrix gene arrays. RESULTS: During a 19-month period, 17 septic VLBW infants and 19 matched controls were enrolled. First, a three-dimensional unsupervised principal component analysis based on the entire genome (28 000 transcripts) identified 3 clusters of patients based on gene expression patterns: Gram-positive sepsis, Gram-negative sepsis, and noninfected control infants. Furthermore, these groups were confirmed by using analysis of variance, which identified a transcriptional signature of 554 of genes. These genes had a significantly different expression among the groups. Of the 554 identified genes, 66 belonged to the tumor necrosis factor and 56 to cytokine signaling. The most significantly overexpressed pathways in septic neonates related with innate immune and inflammatory responses and were validated by real-time reverse transcription polymerase chain reaction. CONCLUSIONS: Our preliminary results suggest that genome-wide expression profiles discriminate septic from nonseptic VLBW infants early in the neonatal period. Further studies are needed to confirm these findings.

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Use of Procalcitonin-Guided Decision-Making to Shorten Antibiotic Therapy in Suspected Neonatal Early-Onset Sepsis: Prospective Randomized Intervention Trial

Cited by 139 publications

References 47 publications

A hematologic scoring system and C-reactive protein compared to blood cultures for diagnosing bacterial neonatal sepsis

A hematologic scoring system and C-reactive protein compared to blood cultures for diagnosing bacterial neonatal sepsis

The role of CRP, PCT, IL-6 and presepsin in early diagnosis of bacterial infectious complications in paediatric haemato-oncological patients

Genome-Wide Expression Profiles in Very Low Birth Weight Infants With Neonatal Sepsis

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