Procalcitonin Algorithm in Critically Ill Adults with Undifferentiated Infection or Suspected Sepsis. A Randomized Controlled Trial

Yahya Shehabi, Martin Sterba, Peter Maxwell Garrett, Kanaka Sundaram Rachakonda, Dianne Stephens, Peter Harrigan, Alison Walker, Michael J. Bailey, Bronwyn Johnson, David Millis, Geoff Ding, Sandra Peake, Helen Wong, Jane Thomas, Kate Smith, Loretta Forbes, Miranda Hardie, Sharon Micallef, John F. Fraser

Rationale: The role of Procalcitonin (PCT), a widely used sepsis biomarker, in critically ill patients with sepsis is undetermined. Objectives: To investigate the effect of a low PCT cut-off on antibiotic prescription and to describe the relationships between PCT plasma concentration and sepsis severity and mortality. Methods: Multicenter (11 Australian ICUs) prospective, single blind, randomized controlled trial involving 400 patients with suspected bacterial infection/sepsis and expected to receive antibiotics and stay in ICU longer than 24 hours. The primary outcome was the cumulative number of antibiotics treatment days at day 28. Measurements and main results: PCT was measured daily while in ICU. A PCT algorithm including 0.1ng/ml cut-off, determined antibiotic cessation. Published Guidelines and Antimicrobial Stewardship were utilized in all patients. Primary analysis included 196 (PCT) versus 198 standard care (STDC) patients. 93 patients in each group had septic shock. The overall median (inter-quartile range) number of antibiotic treatment days were 9[6-21] vs 11[6-22], P=0.58, in patients with positive pulmonary culture 11[7-27] vs 15[8-27], P=0.33 and in patients with septic shock 9[6-22] vs 11[6-24], P=0.64 with an overall 90-day all-cause mortality of 35(18%) vs. 31(16%), P=0.54 in the PCT vs STDC respectively. Using logistic regression, adjusted for age, ventilation status and positive culture, the decline rate in log(PCT) over first 72 hours independently predicted hospital and 90-day mortality [Odds ratio (95% confidence intervals) 2.76(1.10-6.96), P=0.03, 3.20(1.30-7.89), P=0.01], respectively. Conclusion: In critically ill adults with undifferentiated infections, a PCT algorithm including 0.1ng/ml cut-off did not achieve 25% the reduction in duration of antibiotic treatment. Clinical trial registration information available at http://www.anzctr.org.au, ID ACTRN12610000809033.