Dataset Information

Protocol for the diagnostic performance of C reactive protein, procalcitonin and interleukin-6 for serious bacterial infections among children ≤36 months old presenting with fever without source: a systematic review and meta-analysis.

ABSTRACT:

Introduction

The management of fever without source in children ≤36 months old remains a diagnostic challenge as the underlying aetiologies can vary from self-limiting viral infections to serious bacterial infections (SBIs). Biomarkers such as C reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) have varying thresholds in the prediction of SBIs due to differences in SBI definitions, SBI prevalence, patient characteristics and timing of presentation. This protocol describes a systematic review and meta-analysis that aims to determine the thresholds at which CRP, PCT and IL-6 can perform optimally in distinguishing the presence of SBIs in children ≤36 months old, as well as to determine their performances in early detection of bacterial infections within 48 hours of fever onset.

Methods and analysis

We will systematically search electronic databases including MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane CENTRAL, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and Science Citation Index from 1 July 2023 to 31 July 2023. We will include studies that report the diagnostic accuracy of CRP, PCT and IL-6 in detecting SBIs in children aged ≤36 months presenting with fever without apparent source. Randomised controlled trials (RCTs) and non-randomised studies including non-RCTs and controlled before-and-after studies will be included. A meta-analysis will be performed and diagnostic performances of these biomarkers will be reported.

Ethics and dissemination

The results of this study will provide guidance on clinical decision-making in young children presenting with fever without source. Ethics approval will not be required for this study. The authors aim to publish the findings in a peer-reviewed journal as well as present at international conferences.

Prospero registration number

CRD42023439093.

SUBMITTER: Sutiman N

PROVIDER: S-EPMC10952928 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

Protocol for the diagnostic performance of C reactive protein, procalcitonin and interleukin-6 for serious bacterial infections among children ≤36 months old presenting with fever without source: a systematic review and meta-analysis.

Sutiman Natalia N Yao Sarah Hui Wen SHW Goh Sharon Si Min SSM Sultana Rehena R Chong Shu-Ling SL

BMJ paediatrics open 20240318 1

<h4>Introduction</h4>The management of fever without source in children ≤36 months old remains a diagnostic challenge as the underlying aetiologies can vary from self-limiting viral infections to serious bacterial infections (SBIs). Biomarkers such as C reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) have varying thresholds in the prediction of SBIs due to differences in SBI definitions, SBI prevalence, patient characteristics and timing of presentation. This protocol descri ...[more]

PMID: 38499348

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Project description:BackgroundAnti-infective therapy against pathogens is the key to treatment of sepsis. Metagenomic next-generation sequencing (mNGS) has higher sensitivity than blood culture. The aim of this study was to use mNGS to identify DNAaemia of pathogens and to assess the diagnostic accuracy of presepsin (PSEP), procalcitonin (PCT), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP) in differentiating between bacterial and nonbacterial infections in patients with sepsis.MethodsThis retrospective study included patients with sepsis from November 2020 to September 2022 in the Shenzhen Second People's Hospital. Blood samples were sent for blood culture and mNGS when the patients were diagnosed with sepsis. Plasma PSEP, PCT, and IL-6 levels were measured using whole blood specimens that were collected and analyzed after a diagnosis of sepsis. Area under the receiver operating characteristic curve (AUC) was used to evaluate the accuracy of PSEP, PCT, IL-6, and hsCRP for prediction of bacterial DNAaemia detected by mNGS in patients with sepsis.ResultsThis study included 230 patients with sepsis. The bacterial DNAaemia rate was 53.0% [Gram-positive DNAaemia (GPD), Gram-negative DNAaemia (GND), and fungi DNAaemia rate was 18.2%, 37.8%, and 10.9%, respectively]. Among GND, Klebsiella was the most common, followed by Escherichia coli; meanwhile, the GPD were mainly Enterococcus, and Aspergillus was identified in 5 patients with sepsis. The PSEP median values were significantly higher in GND than in non-GND [GND: 1,291 pg/mL, interquartile range (IQR) 456-3,502 pg/mL; non-GND: 707 pg/mL, IQR 332-2,417 pg/mL; P=0.035]. There was no significant difference in PSEP values between GPD and non-GPD groups, or between fungi DNAaemia and non-fungi DNAaemia groups. Receiver operating characteristics analysis indicated that the best cutoff values for PSEP, PCT, IL-6, and hsCRP were 869 pg/mL, 1.14 ng/mL, 85.5 pg/mL, and hsCRP 96.2 mg/L, respectively. Logistic regression indicated that PSEP, PCT, IL-6, and hsCRP had significant predictive value for GND in patients with sepsis. The levels of PCT and IL-6 were different between patients with GPD and those with non-GPD. Only PCT levels differed significantly between fungal DNAaemia and nonfungal DNAaemia.ConclusionsBacterial-DNAaemia was detected in half of the patients with sepsis. PSEP, PCT, IL-6, and hsCRP demonstrated significant predictive value for GND, PCT and IL-6 levels demonstrated significant predictive value for GPD. Meanwhile, only PCT demonstrated significant predictive value for fungal DNAaemia.

Project description:Most children with fever without source (FWS) require diagnostic laboratory tests to exclude a serious bacterial infection (SBI), often followed by admission and empirical antibiotics. As febrile children with a viral infection are less likely to have a SBI, identifying patients with systemic viral infection could contribute to exclude SBI. We evaluated whether the presence of virus in the blood could be used as a biomarker to rule out SBI. Children < 3 years old with FWS were prospectively enrolled and had real-time (reverse-transcription) PCR performed on the blood for adenovirus, enterovirus, parechovirus, and HHV6. 20/135 patients had SBI, and in 47/135, at least one virus was detected in the blood. Viremia had a higher sensitivity and negative predictive value (90% and 96%) to rule out SBI compared to CRP (65% and 93%) and PCT (55% and 90%). The odds ratio (OR) for the presence of SBI among non-viremic patients was 5.8 (p = 0.0225), compared to 5.5 for CRP ≥ 40 mg/l (p = 0.0009) and 3.7 for PCT ≥ 0.5 ng/mL (0.0093). This remained significant after adjusting for CRP and PCT (OR 5.6 and 5.9, respectively; p = 0.03 for both). Area under the ROC curve for CRP and PCT were 0.754 and 0.779, respectively, but increased to 0.803 and 0.832, respectively, when combined with viremia.ConclusionThe presence of viremia had a better performance than commonly used biomarkers to rule-out SBI and could potentially be used in conjunction with CRP and/or PCT in the evaluation of children with FWS. Larger studies should evaluate the role of point-of-care testing of viruses by (revere-transcription) PCR in the plasma in management algorithms of children with FWS.What is known• Most children with FWS have a viral infection, but up to 15% have a SBI; most require laboratory tests, and many admission and empirical antibiotics. • Children with a viral infection are less likely to have a SBI.What is new• Children with a systemic viral infection are less likely to have an SBI. • Viremia is a better predictor of absence of SBI than commonly used biomarkers and could potentially be used in conjunction with CRP and/or PCT in the evaluation of children with FWS.

Project description:ObjectiveGram-negative bloodstream infections (GNBSIs), especially those caused by antibiotic-resistant species, have become a public health challenge. Procalcitonin (PCT) showed promising potential in early diagnosis of GNBSI; however, little was known about its performance under different clinical settings. We here systematically assessed the diagnostic accuracy of PCT in recognizing GNBSI and made direct comparisons with C-reactive protein (CRP) and interleukin 6 (IL-6).MethodsPubMed, Embase, ISI Web of Knowledge, and Scopus were searched from inception to March 15th, 2019. Area under the summary receiver operating characteristic curve (AUC), pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated. Hierarchical summary receiver operating characteristic (HSROC) model was used for the investigation of heterogeneity and for comparisons between markers.Results25 studies incorporating 50933 suspected BSI episodes were included. Pooled sensitivity and specificity for PCT were 0.71 and 0.76, respectively. The overall AUC was 0.80. The lowest AUCs were found in patients with febrile neutropenia (0.69) and hematological malignancy (0.69). The highest AUC was found in groups using electrochemiluminescence immunoassay (0.87). In direct comparisons, PCT showed better overall performance than CRP with the AUC being 0.85 (95% CI 0.81-0.87) for PCT and 0.78 (95% CI 0.74-0.81) for CRP, but the relative DORs varied with thresholds between PCT and CRP (p < 0.001). No significant difference was found either in threshold (p < 0.001). No significant difference was found either in threshold (p < 0.001). No significant difference was found either in threshold (.ConclusionsPCT was helpful in recognizing GNBSI, but the test results should be interpreted carefully with knowledge of patients' medical condition and should not serve as the only criterion for GNBSI. Further prospective studies are warranted for comparisons between different clinical settings.

Dataset Information

Protocol for the diagnostic performance of C reactive protein, procalcitonin and interleukin-6 for serious bacterial infections among children ≤36 months old presenting with fever without source: a systematic review and meta-analysis.

Introduction

Methods and analysis

Ethics and dissemination

Prospero registration number

Publications

Protocol for the diagnostic performance of C reactive protein, procalcitonin and interleukin-6 for serious bacterial infections among children ≤36 months old presenting with fever without source: a systematic review and meta-analysis.

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