Procalcitonin-guided antibiotic therapy in intensive care unit patients: a systematic review and meta-analysis
EJRC Article Review
Procalcitonin (PCT) is an acute-phase protein that has been extensively studied as a specific marker of bacterial infection. Its main proposed value is reduced use of antibiotics. PCT measurement has been recommended in the most recent edition of the Surviving Sepsis Campaign guidelines “to support shortening the duration of antibiotic therapy”, although with weak recommendation. Studies addressing PCT effectiveness in ICU antibiotic prescription and discontinuation have yielded contradictory results. Huang and colleagues did an up-to-date and robust meta-analysis to overcome previous meta-analysis limitations, stratifying by outcomes and strategies.
After considering 553 papers, they narrowed down the number of papers eligible for analysis to 13, with a total of 5136 patients. They then divided the papers into three groups: those in which pro-calcitonin had been used as a guide for discontinuation of antibiotic therapy, those in which it had been used as a guide for initiation and those in which it had been used for both purposes.
The first group (procalcitonin as a guide for discontinuation), was the largest with 8 studies included, and the only one with statistically and clinically significant results:
- A definite antibiotic-sparing effect of PCT of 1.67 days (n = 3404; median − 1.66 days; 95% CI − 2.36 to − 0.96; I2=71%; p< 0.01).
- Reduced short-term ICU mortality with a RR 0.86 (n = 3414; 95% CI 0.76–0.98; I2=0%; p<0.05).
The strength of this meta-analysis is that it adds the most recent works not covered in previous meta-analyses with improved methodology (stratification) to overcome pervious meta-analysis bias and limitations. Its main weakness is that the vast majority of the weight of its conclusions derives from two studies only: Bloos 2016 and De Jong 2016; that mortality effect was an unexpected result and thus not designed to assess it; and finally that the other strategies evaluated had poor methodology (low compliance to study protocol in control and PCT groups) so the results are not interpretable.
Take home message
PCT remains a safe and useful marker in the treatment of infections in intensive care, and there is good evidence that it should be used as guidance for the discontinuation of antibiotic therapy. However, precise cut-off point for antibiotic discontinuation, mortality reduction and other strategies warrant further studies.
Article review for the EJRC on behalf of the Antimicrobial Use-WG provided by Dr. Enrico Sorrentino and Dr. Barbara Borgatta.
- Huang HB, Peng JM, Weng L, Wang CY, Jiang W, Du B. “Procalcitonin-guided antibiotic therapy in intensive care unit patients: a systematic review and meta-analysis”. Ann Intensive Care. 2017 Nov 22;7(1):114.
- Bloos F, Trips E, Nierhaus A, Briegel J, Heyland DK, Jaschinski U, Moerer O, Weyland A, Marx G, Gründling M, Kluge S, Kaufmann I, Ott K, Quintel M, Jelschen F, Meybohm P, Rademacher S, Meier-Hellmann A, Utzolino S, Kaisers UX, Putensen C, Elke G, Ragaller M, Gerlach H, Ludewig K, Kiehntopf M, Bogatsch H, Engel C, Brunkhorst FM, Loeffler M, Reinhart K., “Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic Shock: A Randomised Clinical Trial”. JAMA Intern Med. 2016;176(9):1266–1276.
- De Jong E, van Oers JA, Beishuizen A, Vos P, Vermeijden WJ, Haas LE, Loef BG, Dormans T, van Melsen GC, Kluiters YC, Kemperman H, van den Elsen MJ, Schouten JA, Streefkerk JO, Krabbe HG, Kieft H, Kluge GH, van Dam VC, van Pelt J, Bormans L, Otten MB, Reidinga AC, Endeman H, Twisk JW, van de Garde EMW, de Smet AMGA, Kesecioglu J, Girbes AR, Nijsten MW, de Lange DW. “Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial”. Lancet Infect Dis. 2016 Jul;16(7):819-827.