Since the initial discovery of penicillin by Sir Alexander Fleming in 1928, antimicrobial use has been the backbone of infectious diseases management. While it is widely recognized that inappropriate antibiotic use can lead to antimicrobial resistance, up to 50% antimicrobial agents prescribed in the inpatient setting is considered to be inappropriate or unnecessary.1 The Center for Disease Control and Prevention has estimated that antibiotic-resistant organisms are responsible for more than 2 million infections and 23,000 deaths annually in the United States. The economic impact of antibiotic resistance varies, but may be as high as $20 billion in excess direct healthcare costs and $35 billion due to lost productivity to society.2
Procalcitonin (PCT) is a biomarker that can be used to assist clinicians in the diagnosis and management of bacterial infection. PCT is a 116 amino acid precursor of calcitonin, calcitonin is secreted by thyroid C-cells. Under normal circumstances, PCT concentration is found to be less than 0.05ng/mL but in response to bacterial infection accompanied by systemic inflammation, PCT is produced in large quantities. PCT has an early and highly specific increase in response to systemic bacterial infections and sepsis. It is detectable within 2 to 4 hours upon infectious insult and peaks within 6 to 24 hours.
The use of PCT has been studied extensively in lower respiratory tract infections and sepsis, as well as its role to reduce duration of antimicrobial therapy.
Evidence for procalcitonin use in lower respiratory tract infection (LRTI)
In a meta-analysis and systematic review by Li et al, randomized controlled trials with a total of 3,431 patients with suspected respiratory tract infections were evaluated. 3 While the use of PCT-guided therapy did not impact mortality, ICU admission, or length of hospital stay, a high degree of heterogeneity in these outcomes were noted. The use of PCT in LRTI resulted in a 31% decrease in antibiotic prescriptions and a reduction in antibiotic duration of 1.3 days without significantly impacting the overall hospital length of stay.
Evidence for procalcitonin use in sepsis
A number of studies have been conducted to evaluate the benefits of procalcitonin in the management of sepsis, including:
Hohn et al. conducted a retrospective analysis of the impact of PCT-guided algorithm to reduce length of antibiotic therapy in septic patients. 4 One hundred forty-one (141) patients were included in the study, primary outcomes included: antibiotic day on ICU, ICU re-infection rate, 28-day mortality rate, ICU length of stay (LOS), mean antibiotic costs (per patient) and ventilation hours. The study showed a reduction of antibiotic therapy duration by 1 day per year (p=0.02), a 35.1% reduction in ICU re-infection rate (p=0.014), a reduction in ventilation hours by 42 hours per year (p=0.008) and ICU LOS was shortened by 2.7 days per year (p<0.001). There was no statistical significance for 28-day mortality and mean cost for antibiotic therapy outcome.
In another systematic review by Heyland et al., 5 articles were evaluated. PCT-guided strategies were associated with a significant reduction in antibiotic days (mean difference -2.14 days, p<0.00001).5 No effects on hospital mortality, ICU and overall hospital LOS were observed.
While the use of PCT does not improve mortality and/or length of stay, there is overwhelming evidence to attest to the use of a PCT-guided strategy for significantly reducing antibiotic therapy duration.
When to utilize procalcitonin?
- Differentiating bacterial vs. viral respiratory tract infection
- Considering discontinuation or reduction of antibiotic therapy duration
- Diagnosing, risk stratifying and monitoring sepsis and septic shock
- Assist in monitoring response of antibiotic in sepsis and bacterial pneumonias
- Localized infections do not result in circulating PCT increase
- PCT does not respond in viral infections: interferon-gamma blocks the up regulation of PCT
- PCT may be elevated due to the following non-bacterial cause*:
- Newborns (<48-72hrs)
- Stress-induced elevation (trauma, surgery, cardiac shock, burns)
- Treatment with agents that can stimulate cytokine levels (alemtuzumab, granulocyte transfusion)
- Malaria and fungal infections
- Organ perfusion abnormalities
- Autoimmune disease (vasculitis, acute graft vs. host disease)
- Severely compromised renal function (ESRD or hemodialysis)
*Credits to Nebraska Medicine Procalcitonin (PCT) Guidance
It is important to note that decisions on antimicrobial therapy should not be based solely on procalcitonin serum concentration but rather should be placed into clinical context of the patient's overall clinical status:
- Serial measurement for PCT is needed: PCT measurement should be obtained upon admission and repeated every 2 to 3 days (for LRTI) and every 1 to 2 days (for sepsis); clinical re-evaluation as appropriate
- While evaluating PCT levels and patient clinical status, consider the nature of the disease
- Be aware of any conditions that can elevate PCT due to non-bacterial cause (see limitations section above)
If you want to learn more about procalcitonin testing and how to set up testing at your facility, here are some considerations:
- Education: I would highly recommend any clinicians who are interested in PCT to learn more about the current use of PCT and the evidence behind it. You can start off by reviewing some of the resources below.
- Cost consideration: While there is increasing data to support the use of PCT for reducing antibiotic therapy duration, the increased cost associated with additional tests should be considered. While PCT tests may be available as a send-out lab, it is essential that results of PCT tests are available during the decision-making process. Clinicians should speak to their facility administrator for financial considerations and development of a cost model to determine the benefits versus the costs.
- Implementing PCT: Keep in mind that PCT cannot be used solely to drive decision on antimicrobial therapy. An established process involving antimicrobial stewardship physicians and pharmacists should be in place to interpret the PCT serum concentration, along with patient's overall clinical status.
Helpful resources on PCT
- Providence Washington Health & Services Procalcitonin Algorithm for Guidance of Antibiotic Therapy Decisions
- Nebraska Medicine Procalcitonin (PCT) Guidance
- Procalcitonin Algorithms for Antibiotic Therapy Decisions: A Systematic Review of Randomized Controlled Trials and Recommendations for Clinical Algorithms (Schuetz P et al. Arch Intern Med. 2011;171(15):1322-1331. doi:10.1001/archinternmed.2011.318.)6
- John JF, Fishman NO. Programmatic role of the infectious diseases physician in controlling antimicrobial costs in the hospital. Clin Infect Dis. 1997; 24:471-85.
- Center for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013. S. Department of Health and Human Services. Retrieved from http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf
- Li H, et al. Meta-analysis and systematic review of procalcitonin-guided therapy in respiratory tract infections. Antimicrob Agents Chemother. 2011;55:5900-6
- Hohn A, Schroeder S, Gehrt A, et al. Procalcitonin-guided algorithm to reduce length of antibiotic therapy in patients with severe sepsis and septic shock. BMC Infectious Diseases. 2013; 13:158.
- Heyland DK, et al. Procalcitonin for reduced antibiotic exposure in the critical care setting: a systematic review and an economic evaluation. Crit Care Med. 2011; 39:1792-9.
- Schuetz P, Chiappa V, Briel M, et al. Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendation for clinical algorithms. Arch Intern Med. 2011; 171(15):1322-31.
- Jensen JU, et al. Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit. Crit Care Med. 2011; 39:2048-58.
- Smith KJ, Wateska A, Nowalk MP, et al. Cost-effectiveness of procalcitonin-guided antibiotic use in community acquired pneumonia. J Gen Intern Med; 2013: 28(9):1157-64.
- Wacker C, Prkno A, Brunkhorst F, et al. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis. 2013; 13: 426-35.