Procalcitonin kinetics in Gram-negative bloodstream infections and its value for infection management

Introduction. Gram-negative bloodstream infections (BSIs), particularly those caused by Enterobacterales, are associated with significant morbidity and mortality. Procalcitonin (PCT) has been proposed as a biomarker to guide antimicrobial management, although its role in BSIs remains unclear.Hypothesis/Gap Statement. While PCT has been widely studied in respiratory infections and critical illness, the clinical utility of early PCT kinetics in guiding antimicrobial adequacy and source control in BSIs is not well defined.Aim. To evaluate whether early changes in PCT are associated with antimicrobial appropriateness, source control and clinical outcomes in Enterobacterales BSIs and to compare these findings with C-reactive protein (CRP).Methodology. We conducted a cohort study of 170 hospitalized adults with monomicrobial Enterobacterales BSIs. Serum PCT and CRP were measured at blood culture positivity (day 0) and serially on days 2 and 5. Biomarker kinetics were analysed using non-parametric methods, including proportional change from baseline to day 5. Associations with clinical variables and outcomes were assessed, and multivariable logistic regression was used to evaluate relationships between baseline biomarker concentrations and illness severity.Results. Median baseline PCT was 5.81 ng ml^-1 (IQR 1.28-38.19) and CRP 124.1 mg l^-1 (IQR 60.5-203.0). Both biomarkers increased from day 0 to day 2 and declined by day 5 (P<0.001). Absolute PCT concentrations were lower in patients receiving inappropriate empiric therapy (P=0.016), but neither proportional nor absolute changes in PCT or CRP were associated with antimicrobial appropriateness, source control, infecting organism or infection source. Baseline PCT was independently associated with intensive care unit admission (adjusted odds ratio, 1.24; 95% confidence interval, 1.03-1.49) and a quick Sequential Organ Failure Assessment score of two or greater (adjusted odds ratio, 1.21; 95% confidence interval, 1.00-1.45), whereas CRP was not. Neither PCT nor CRP kinetics were associated with 30-day mortality (P=0.677 and P=0.475, respectively).Conclusion. Early PCT kinetics do not provide clinically useful information to guide antimicrobial management in Enterobacterales BSIs. While baseline PCT reflects illness severity, serial measurements appear to reflect host inflammatory response rather than treatment effect, limiting their utility in early clinical decision-making.