In Reply We very much welcome the thoughtful comments of van Oers and colleagues on the SISPCT trial.¹ We agree that the choice of algorithm to guide antimicrobial therapy and the management of sepsis patients by the course of procalcitonin (PCT) may have an impact on the outcome of such studies. The PCT algorithm in our study differed somewhat from previously published algorithms for other trials including their SAPS trial² but also encouraged de-escalation of antimicrobial therapy accordingly.

The SAPS trial² tested the hypothesis that PCT-guided antimicrobial therapy may result in reduced time on antimicrobial therapy. We hypothesized that PCT-guided anti-infectious therapy in patients with severe sepsis might reduce mortality. Duration of antimicrobial therapy was only one of the secondary outcomes. The algorithm in our study was different from the algorithm used in the Procalcitonin And Survival Study (PASS) by Jensen et al.³ These investigators hypothesized similarly to us that the potential of PCT to hasten and improve the diagnosis of sepsis by differentiating infectious from noninfectious causes of inflammation would improve patient survival by reducing the time to appropriate therapy. However, they tested a drug-escalation algorithm and intensified diagnostics based on daily procalcitonin measurements. Any PCT concentration of at least 1.0 ng/mL not decreasing by at least 10% from the previous day prompted antimicrobial escalation and additional diagnostic measures. Clearly, this algorithm and approach did not improve survival but resulted in significantly more antimicrobial consumption, more intensive care unit (ICU) days with at least 3 antimicrobials, and more ICU days on mechanical ventilation compared with the standard care group. Interestingly, the SAPS trial² in contrast to other trials that tested a similar algorithm in patients in the ICU with infections and sepsis resulted not only in a reduction of time on antimicrobials but also in better survival.