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The Use of Procalcitonin to Improve Antibiotic

Stewardship

Patrick A. Laird, DNP, RN, ACNP-BC

Disclosures

I have no actual or potential conflict of interest in relation to this presentation.

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

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Pathophysiology

● Procalcitonin not induced in most viral infections● Some variation in bacterial infections● Noninfectious causes increase procalcitonin

Kinetics

Figure 4: Kinetic Profiles of Various Biomarkers

Use in Bacterial Infections

● 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

(Sager, Kutz, Mueller, & Schuetz, 2017)

Use in Bacterial Infections

● Blood Stream Infections○ No gold standard exists○ Procalcitonin demonstrated a high discriminatory ability○ May help discriminate contamination from BSI

Figure 5: Bloodstream infection

(Sager, Kutz, Mueller, & Schuetz, 2017)

Use in Bacterial Infections

● 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

(Sager, Kutz, Mueller, & Schuetz, 2017; Schuetz, Birkhahn, Sherwin, Jones, Singer, Kline, . . . Shapiro, 2017)

Use in Bacterial Infections

● Congestive Heart Failure○ May help differentiate heart failure exacerbation from infection○ More information is needed

Figure 6: Heart failure(Sager, Kutz, Mueller, & Schuetz, 2017)

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Use in Bacterial Infections

● Urinary Tract Infections○ Reductions in antibiotic use○ No negative effects

(Sager, Kutz, Mueller, & Schuetz, 2017)

Use in Bacterial Infections

● Febrile Neutropenia○ Accurate marker of infection ○ Predictor of severity○ Not suitable for determining treatment cessation

(Sager, Kutz, Mueller, & Schuetz, 2017)

Use in Bacterial Infections

● Meningitis○ Reduces antimicrobial consumption ○ Helps differentiate viral from bacterial meningitis○ Useful in prognostication

Figure 7: Meningitis(Sager, Kutz, Mueller, & Schuetz, 2017)Figure 8: Summary of evidence for PCT

Figure 9: Procalcitonin-based algorithm for antibiotics

Figure 10: Procalcitonin-based algorithm for antibiotics

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Figure 11: PCT algorithm for antibiotic therapy

Who cares?

Antibiotic Resistance

● 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)

Figure 12: Antibiotic Resistance Threats

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

(CDC, 2016)

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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)

Antibiotic Resistance

● 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

Antibiotic Resistance● 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

Antibiotic Resistance

● Fiscal year 2017--Congress appropriated $163 million● Antibiotic Resistance Solutions Initiative

○ Detect, Respond, and Contain○ Prevent○ Innovate

(CDC, 2018)

(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

(Karanika, Paudel, Grigoras, Kalbasi, & Mylonakis, 2016)

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GOALS

Cost

Con

tain

men

t

Ensure Patient Safety

Reduce Resistance

CDC Core Elements

● 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

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Figure 13: Questions

ReferencesAntibiotic / Antimicrobial Resistance. (2018, January 31). Retrieved August 10, 2018, from https://www.cdc.gov/drugresistance/solutions-initiative/index.html

Antibiotic Resistance 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

Contact Information

Patrick A. Laird, DNP, RN, ACNP-BC

patrick.a.laird@uth.tmc.edu