Deep Dive: Procalcitonin

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Background:

  • Procalcitonin is an acute phase reactant that is a propeptide processed into the hormone calcitonin

  • When you aren’t sick your body produces procalcintonin from the thyroid

  • We don’t know what its role in healthy patients are except as a precursor to calcitonin

  • A wide range of tissues produce procalitonin in infection

  • We still don’t know what it’s role in the body’s response to infection is

  • elevated somewhere between 2-12 hours after bacterial infection

  • Peak levels are typically reached at 24-48 hours after bacterial infection

  • broken down from peptide to an amino acid by enzymes

Why does it matter?

  • Reduce antibiotic use

    • A global health priority by numerous organizations

  • Providers still giving antibiotics for bronchitis and similar diseases despite CDC recommendations against it

Procalcitonin Use in LRTI’s (CAP, Bronchitis, COPD AE)

  • ProHOSP the initial trial published in JAMA 2009 that created the procalcitonin guidelines we still use

 Large  Cochrane review  by Dr. Scheutz which was revised in 10/2017. High quality of evidence for mortality and reduction of antibiotic exposure in acute LRTI’s

Large Cochrane review by Dr. Scheutz which was revised in 10/2017. High quality of evidence for mortality and reduction of antibiotic exposure in acute LRTI’s

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  1. Alba GA, Truong QA, Gaggin HK, et al. Diagnostic and Prognostic Utility of Procalcitonin in Patients Presenting to the Emergency Department with Dyspnea. Am J Med 2016; 129:96.

  2. Wang W, Zhang X, Ge N, et al. Procalcitonin testing for diagnosis and short-term prognosis in bacterial infection complicated by congestive heart failure: a multicenter analysis of 4,698 cases. Crit Care 2014; 18:R4.

  3. Maisel A, Neath SX, Landsberg J, et al. Use of procalcitonin for the diagnosis of pneumonia in patients presenting with a chief complaint of dyspnoea: results from the BACH (Biomarkers in Acute Heart Failure) trial. Eur J Heart Fail 2012; 14:278.

 

Bottom line:

Don’t Use PCT to Withhold or Stop Antibiotics in Severe COPD AE going to ICU

https://link.springer.com/article/10.1007%2Fs00134-018-5141-9

PCT and Sepsis: Abx Discontinuation

  • Do not use to determine initiation of antibiotics in sepsis

  • Can be used to guide antibiotic discontinuation in sepsis (SAPS)

    • Number is < 0.5 in Sepsis (0.25 in LRTI)

PCT and Sepsis: Risk Assessment

  • Independent predictor of mortality (MOSES Study CCM 5/2017)

    • Used by Paul Marik to determine who got Marik Protocol in that famous study

  • Reduction of PCT by 80% in 72 hours shows treatment effectiveness in sepsis and the lack of 80% reduction or increase in PCT indicates treatment failure.

New Study: ProACT:

  • Large, multicenter RCT, > 1600 patients at 14 academic centers

  • They looked specifically at patients that presented to the ED with a suspected LRTI and for whom the treating physician was uncertain whether abx therapy was indicated

  • primary endpoints were antibiotic days and percentage of patients with adverse outcomes

  • No reduction in antibiotic days (4.2 vs 4.3) and no difference in adverse events

  • Clinicians adhered to the PCT guideline recommendation 73% of the time in the PCT group

  • CAP had the lowest adherence at 39%

  • study did not force clinicians in the PCT group to stop abx based on the PCT level

  • hospitals with excellent pneumonia quality metrics

What else can elevate PCT?

  • Cancer

    • Medullary thyroid carcinoma or islet cell tumors can have elevations in PCT > 10,000

  • Trauma, burns, multiorgan failure, and recent major surgery

  • patients with ESRD who haven’t had regular dialysis treatments in a few days can have elevated PCT levels without an infection

  • pancreatitis, prolonged cardiogenic shock, MODS, autoimmune disorders, liver dysfunction or recent liver transplant, prolonged arrest and resuscitation, and rhabdo

Guidelines:

FDA Executive Summary:

  • FDA recommendations which were expanded for PCT in February 2017.

  • It is recommended to be used when starting and stopping antibiotics in community acquired LRTIs

  • Recommended to be used in stopping antibtiocs in sepsis.

  • It was initially recommendation was to assess mortality in sepsis

2016 IDSA Antimicrobial Stewardship Guidelines: weak recommendation

2018 Surviving Sepsis Campaign: weak recommendation

2016 IDSA/ATS HAP/VAP Guidelines: weak recommendation for discontinuation, do not use for initiation

2007 IDSA CAP Guidelines: currently refreshing

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Attributions

"Reddit”, “Breezin”, “Filaments”, “Am-Trans” and “Squirrel Commotion” by Podington Bear is licensed under CC BY-NC 3.0 / Songs have been cropped in length from original form

Lee Corso “Not so fast” via youtube