Procalcitonin testing to guide antibiotic therapy for the treatment of sepsis in intensive care settings and for suspected bacterial infection in emergency department settings: A systematic review and cost-effectiveness analysis

Background: Determination of the presence or absence of bacterial infection is important to guide appropriate therapy and reduce antibiotic exposure. Procalcitonin (PCT) is an inflammatory marker that has been suggested as a marker for bacterial infection. Objectives: To assess the clinical effectiveness and cost-effectiveness of adding PCT testing to the information used to guide antibiotic therapy in adults and children (1) with confirmed or highly suspected sepsis in intensive care and (2) presenting to the emergency department (ED) with suspected bacterial infection. Methods: Twelve databases were searched to June 2014. Randomised controlled trials were assessed for quality using the Cochrane Risk of Bias tool. Summary relative risks (RRs) and weighted mean differences (WMDs) were estimated using random-effects models. Heterogeneity was assessed visually using forest plots and statistically using the I2 and Q statistics and investigated through subgroup analysis. The cost-effectiveness of PCT testing in addition to current clinical practice was compared with current clinical practice using a decision tree with a 6 months’ time horizon. Results: Eighteen studies (36 reports) were included in the systematic review. PCT algorithms were associated with reduced antibiotic duration [WMD -3.19 days, 95% confidence interval (CI) -5.44 to -0.95 days, I2 = 95.2%; four studies], hospital stay (WMD -3.85 days, 95% CI -6.78 to -0.92 days, I2 = 75.2%; four studies) and a trend towards reduced intensive care unit (ICU) stay (WMD -2.03 days, 95% CI -4.19 to 0.13 days, I2 = 81.0%; four studies). There were no differences for adverse clinical outcomes. PCT algorithms were associated with a reduction in the proportion of adults (RR 0.77, 95% CI 0.68 to 0.87; seven studies) and children (RR 0.86, 95% CI 0.80 to 0.93) receiving antibiotics, reduced antibiotic duration (two studies). There were no differences for adverse clinical outcomes. All but one of the studies in the ED were conducted in people presenting with respiratory symptoms. Cost-effectiveness: the base-case analyses indicated that PCT testing was cost-saving for (1) adults with confirmed or highly suspected sepsis in an ICU setting; (2) adults with suspected bacterial infection presenting to the ED; and (3) children with suspected bacterial infection presenting to the ED. Cost-savings ranged from £368 to £3268. Moreover, PCT-guided treatment resulted in a small quality-adjusted life-year (QALY) gain (ranging between < 0.001 and 0.005). Cost-effectiveness acceptability curves showed that PCT-guided treatment has a probability of ≥ 84% of being cost-effective for all settings and populations considered (at willingness-to-pay thresholds of £20,000 and £30,000 per QALY).

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