The Use of Procalcitonin to Improve Antibiotic Stewardship Disclosures I have no actual or potential conflict of interest in relation to this presentation. Patrick A. Laird, DNP, RN, ACNP-BC Objectives Describe the pathophysiology of procalcitonin. Cite advantages in using procalcitonin levels in patients with bacterial infection and sepsis. Discuss how the use of serial procalcitonin measurements may improve antibiotic stewardship. Background First described in 1975 Precursor for calcitonin in chicken 1981--demonstrated synthesis of calcitonin in humans Currently more than 178 serum biomarkers for infection Procalcitonin most extensively studied (Vijayan et al., 2017) Figure 1: Chicken Pathophysiology Protein consisting of 116 amino acids Peptide precursor of calcitonin Normally undetectable in healthy patients Fig. 2 Procalcitonin: structure and synthesis Pathophysiology Produced primarily by thyroid C-cells Also found in small amounts in neuroendocrine tissue High levels of cytokines and bacterial endotoxins cause increase in procalcitonin levels Figure 3: Fate of Procalcitonin 1
Pathophysiology Kinetics Procalcitonin not induced in most viral infections Some variation in bacterial infections Noninfectious causes increase procalcitonin Figure 4: Kinetic Profiles of Various Biomarkers Respiratory Tract 2012 Cochrane meta-analysis 14 randomized controlled trials Similar protocols Results Strong reduction in initial antibiotic use for low-severity infections Earlier cessation of antibiotics with relative reduction in duration Blood Stream Infections No gold standard exists Procalcitonin demonstrated a high discriminatory ability May help discriminate contamination from BSI Figure 5: Bloodstream infection Sepsis, Severe Sepsis, and Septic Shock Reduced antibiotic treatment courses No increase in 28-day mortality No increase in ICU or hospital length of stay Helps predict severity of illness Congestive Heart Failure May help differentiate heart failure exacerbation from infection More information is needed (Sager, Kutz, Mueller, & Schuetz, 2017; Schuetz, Birkhahn, Sherwin, Jones, Singer, Kline,... Shapiro, 2017) Figure 6: Heart failure 2
Urinary Tract Infections Reductions in antibiotic use No negative effects Febrile Neutropenia Accurate marker of infection Predictor of severity Not suitable for determining treatment cessation Meningitis Reduces antimicrobial consumption Helps differentiate viral from bacterial meningitis Useful in prognostication Figure 7: Meningitis Figure 8: Summary of evidence for PCT Figure 9: Procalcitonin-based algorithm for antibiotics Figure 10: Procalcitonin-based algorithm for antibiotics 3
Who cares? Figure 11: PCT algorithm for antibiotic therapy One of the most urgent threats to the public s health 2 million people infected with antibiotic resistant bacteria 23,000 people die from these infections (CDC, 2013) Economic Impact At least 30% of antibiotic courses prescribed in the outpatient setting unnecessary Antibiotics for children down, but almost 30% still unnecessary Antibiotics cause 1 out of every 5 ED visits for adverse drug events $55 billion in direct and indirect costs annually Figure 12: Antibiotic Resistance Threats (CDC, 2016) 4
Economic Impact Approximately ⅓ of hospitalized patients and ⅔ of critically ill patients are on antimicrobial therapy Up to ½ of antibiotic prescriptions are inappropriate or not necessary (Karanika, Paudel, Grigoras, Kalbasi, & Mylonakis, 2016) Slow the emergence of resistant bacteria and prevent the spread of resistant infections Strengthen national One-Health surveillance efforts to combat resistance Advance development and use of rapid and innovative diagnostic tests for identification and characterization of resistant bacteria Accelerate basic and applied research and development for new antibiotics, other therapeutics, and vaccines Improve international collaboration and capacities for antibiotic-resistance prevention, surveillance, control, and antibiotic research and development Fiscal year 2017--Congress appropriated $163 million Solutions Initiative Detect, Respond, and Contain Prevent Innovate (CDC, 2018) What is Antibiotic Stewardship? Integrated strategy of improving antimicrobial use, including drug resistance and nosocomial infections Selecting the appropriate agent, dose, therapy duration and route of administration (CDC, 2018) (Karanika, Paudel, Grigoras, Kalbasi, & Mylonakis, 2016) 5
CDC Core Elements Reduce Resistance Ensure Patient Safety GOALS Cost Containment Antibiotic Stewardship in Acute Care: A Practical Playbook Hospital Antibiotic Stewardship Programs Outpatient Antibiotic Stewardship MITIGATE Antimicrobial Stewardship Toolkit Antibiotic Stewardship Core Elements at Small and Critical Access Hospitals Core Elements of Hospital Antibiotic Stewardship Leadership Commitment Accountability Drug Expertise Action Tracking Reporting Education Benefits of Antibiotic Stewardship Programs Improves clinical outcomes Decreases costs Helps reduce antibiotic resistance Conclusion Use of serial procalcitonin measurements can help improve Antibiotic Stewardship programs Reduces antibiotic usage Reduces antibiotic duration 6
References Antibiotic / Antimicrobial Resistance. (2018, January 31). Retrieved August 10, 2018, from https://www.cdc.gov/drugresistance/solutions-initiative/index.html Investments. (n.d.). Retrieved August 10, 2018, from https://www.cdc.gov/arinvestments Barlam, T. F., Cosgrove, S. E., Abbo, L. M., MacDougall, C., Schuetz, A. N., Septimus, E. J.,... Trivedi, K. K. (2016). Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clinical Infectious Diseases, 62(10), e51-77. doi:10.1093/cid/ciw118 Karanika, S., Paudel, S., Grigoras, C., Kalbasi, A., & Mylonakis, E. (2016). Systematic Review and Meta-analysis of Clinical and Economic Outcomes from the Implementation of Hospital-Based Antimicrobial Stewardship Programs. Antimicrobial Agents and Chemotherapy, 60(8), 4840-4852. doi:10.1128/aac.00825-16 Sager, R., Kutz, A., Mueller, B., & Schuetz, P. (2017). Procalcitonin-guided diagnosis and antibiotic stewardship revisited. BMC Medicine, 15(1), 15. doi:10.1186/s12916-017-0795-7 Schuetz, P., Birkhahn, R., Sherwin, R., Jones, A. E., Singer, A., Kline, J. A.,... Shapiro, N. I. (2017). Serial Procalcitonin Predicts Mortality in Severe Sepsis Patients: Results From the Multicenter Procalcitonin MOnitoring SEpsis (MOSES) Study. Critical Care Medicine, 45(5), 781-789. doi:10.1097/ccm.0000000000002321 U.S.Cong. (2015). National action plan for combating antibiotic-resistant bacteria[cong.]. Washington, D.C.: U.S. White House. Vijayan, A. L., Vanimaya, Ravindran, S., Saikant, R., Lakshmi, S., Kartik, R., & G, M. (2017). Procalcitonin: a promising diagnostic marker for sepsis and antibiotic therapy. Journal of Intensive Care, 5, 51. doi:10.1186/s40560-017-0246-8 Figure 13: Questions Contact Information Patrick A. Laird, DNP, RN, ACNP-BC patrick.a.laird@uth.tmc.edu 7