Pre-analytic factors and initial biomarker levels in community-acquired pneumonia patients

Abstract

BackgroundBlood biomarkers are increasingly used to diagnose, guide therapy in, and risk-stratify community-acquired pneumonia (CAP) patients in emergency departments (EDs). How pre-analytic factors affect these markers’ initial levels in this population is unknown.MethodsIn this secondary analysis of consecutive ED patients with CAP from a large multicentre antibiotic stewardship trial, we used adjusted multivariate regression models to determine the magnitude and statistical significance of differences in mean baseline concentrations of five biomarkers (procalcitonin [PCT], C-reactive protein [CRP], white blood cells count [WBC], proadrenomedullin [ProADM], copeptin) associated with six pre-analytic factors (antibiotic or corticosteroid pretreatment, age, gender, chronic renal failure or chronic liver insufficiency).ResultsOf 925 CAP patients (median age 73 years, 58.8% male), 25.5% had antibiotic pretreatment, 2.4%, corticosteroid pretreatment, 22.3%, chronic renal failure, 2.4% chronic liver insufficiency. Differences associated with pre-analytic factors averaged 6.1% ±4.6%; the three largest statistically significant changes (95% confidence interval) were: PCT, +14.2% (+2.1% to +26.4%, p = 0.02) with liver insufficiency; ProADM, +13.2% (+10.2% to +16.1%, p < 0.01) with age above median; CRP, -12.8% (-25.4% to -0.2%, p = 0.05) with steroid pretreatment. In post hoc sensitivity analyses, reclassification statistics showed that these factors did not result in significant changes of biomarker levels across clinically used cut-off ranges.ConclusionsDespite statistically significant associations of some pre-analytic factors and biomarker levels, a clinically relevant influence seems unlikely. Our observations reinforce the concept of using biomarkers in algorithms with widely-separated cut-offs and overruling criteria considering the entire clinical picture.Trial registrationIdentifier ISRCTN95122877.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2253-14-102) contains supplementary material, which is available to authorized users.

Pros and cons of using biomarkers versus clinical decisions in start and stop decisions for antibiotics in the critical care setting

“…However, several relevant causes of false-positive and false-negative results have to be considered for both PCT and CRP [22]. For instance, the CRP response is blunted in fulminant hepatic failure, but overall the clinical relevance of renal dysfunction, chronic liver insufficiency, and corticosteroid treatment on PCT and CRP seems to be negligible [23]. As recently summarized, patients with chronic kidney disease and active infection have higher levels than those without infections [24].…”

“…The increased PCT levels are likely primarily due to increased proinflammatory cytokines as a consequence of renal insufficiency and only slight changes in PCT clearance. However, the clinical relevance of this increase remains questionable [23] as patients with acute or chronic renal failure and patients requiring dialysis were included in randomized controlled trials (RCTs) without adaption of cutoff levels. For instance, 22.2 and 17.6 % of patients in the ProHOSP and the ProRATA RCTs had renal failure, respectively [23,25], but chronic renal failure resulted in only 1.2 % higher PCT values in the ProHOSP study [23].…”

“…However, the clinical relevance of this increase remains questionable [23] as patients with acute or chronic renal failure and patients requiring dialysis were included in randomized controlled trials (RCTs) without adaption of cutoff levels. For instance, 22.2 and 17.6 % of patients in the ProHOSP and the ProRATA RCTs had renal failure, respectively [23,25], but chronic renal failure resulted in only 1.2 % higher PCT values in the ProHOSP study [23]. These results suggested that in at least this large RCT of 925 patients with communityacquired pneumonia (CAP) no adjustment of PCT cutoff values was necessary [23].…”

“…For instance, 22.2 and 17.6 % of patients in the ProHOSP and the ProRATA RCTs had renal failure, respectively [23,25], but chronic renal failure resulted in only 1.2 % higher PCT values in the ProHOSP study [23]. These results suggested that in at least this large RCT of 925 patients with communityacquired pneumonia (CAP) no adjustment of PCT cutoff values was necessary [23]. Other authors proposed different PCT cutoff values for patients with chronic kidney disease but these have not been prospectively tested [24].…”

Comparison of Procalcitonin Guidance-Administered Antibiotics with Standard Guidelines on Antibiotic Therapy in Children with Lower Respiratory Tract Infections: A Retrospective Study in China

“…PCT is an established biomarker of bacterial infections and is widely used in high-income countries, particularly in hospital settings [15,16] . PCT measurements flag the presence and track the status of systemic bacterial infection, thereby helping the clinician determine the necessity and optimal duration of antibiotic therapy in patients with respiratory symptoms.…”