Abstract
Bacterial Infections remains a leading cause of death in the Paediatric Intensive Care Unit (PICU). In this era of rising antimicrobial resistance, new tools are needed to guide antimicrobial use. The aim of this study was to investigate the accuracy of procalcitonin (PCT), neutrophil gelatinase-associated lipocalin (NGAL), resistin, activated partial thromboplastin time (aPTT) waveform and C-reactive protein (CRP) for the diagnosis of serious bacterial infection (SBI) in children on admission to PICU and their use as prognostic indicators. A regional PICU in the United Kingdom. Consecutive PICU admissions between October 2010 and June 2012. Blood samples were collected daily for biomarker measurement. The primary outcome measure was performance of study biomarkers for diagnosis of SBI on admission to PICU based on clinical, radiological and microbiological criteria. Secondary outcomes included durations of PICU stay and invasive ventilation and 28-day mortality. Patients were followed up to day 28 post-admission. A total of 657 patients were included in the study. 92 patients (14%) fulfilled criteria for SBI. 28-day mortality was 2.6% (17/657), but 8.7% (8/92) for patients with SBI. The combination of PCT, resistin, plasma NGAL and CRP resulted in the greatest net reclassification improvement compared to CRP alone (0.69, p<0.005) with 10.5% reduction in correct classification of patients with SBI (p 0.52) but a 78% improvement in correct classification of patients without events (p <0.005). A statistical model of prolonged duration of PICU stay found log-transformed maximum values of biomarkers performed better than first recorded biomarkers. The final model included maximum values of CRP, plasma NGAL, lymphocyte and platelet count (AUC 79%, 95% CI 73.7% to 84.2%). Longitudinal profiles of biomarkers showed PCT levels to decrease most rapidly following admission SBI. Combinations of biomarkers, including PCT, may improve accurate and timely identification of SBI on admission to PICU.
Highlights
Invasive bacterial infections account for over a quarter of all deaths in Paediatric Intensive Care Unit (PICU) [1] whilst up to 31% of paediatric sepsis survivors are affected by disability at discharge [2]
The primary aim of this study was to determine the discriminative ability of PCT, activated Partial Thromboplastin Time (aPTT) waveform, Neutrophil gelatinase- associated lipocalin (NGAL) and resistin individually, in combination and compared to C-reactive protein (CRP) to diagnose serious bacterial infection (SBI) in children on admission to PICU
A total of 2468 children were admitted to the PICU from October 2010 to June 2012; 1339 were not eligible for inclusion and consent could not be obtained in 472 cases, 657 patients were enrolled (Fig 1)
Summary
Invasive bacterial infections account for over a quarter of all deaths in PICU [1] whilst up to 31% of paediatric sepsis survivors are affected by disability at discharge [2]. Recognition of sepsis and prompt anti-microbial therapy reduce mortality and duration of organ dysfunction [3,4,5], but indiscriminate antimicrobial use contributes to resistance [6, 7]. A reliable marker, or combination of markers, that change early in bacterial infection, correlate with real-time clinical progression and have a rapid laboratory turn-around time is an urgent unmet clinical need. Procalcitonin (PCT) has been shown in comparatively small studies to be a better diagnostic marker of bacterial infection in PICU than C-reactive protein (CRP) [8, 9] and to be a prognostic marker in meningococcal disease [10]. Resistin an adipokine which contributes to inflammation-induced insulin resistance, has been shown to correlate with sepsis severity in adults [18, 19]. The performance of the aPTT waveform, NGAL and resistin in paediatric infection is unknown
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