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PROCALCITONIN UTILIZATION GUIDELINE PROCALCITONIN ALGORITHM FOR ANTIBIOTIC DEESCALATION See next page for additional details. DECISIONS REGARDING ANTIBIOTIC THERAPY SHOULD NOT BE BASED SOLELY ON PROCALCITONIN LEVELS Other clinical factors need to be considered, including likelihood of bacterial infection, site of infection, and severity of infection Procalcitonin Indicated » Lower respiratory tract infections (e.g. pneumonia, acute COPD exacerbation) » Severe sepsis or septic shock Suspected Infection Obtain cultures & start antibiotics Procalcitonin NOT Indicated » Localized infection (e.g. abscess, osteomyelitis, cellulitis) » Recent (<48 hours) trauma (including post-CPR) » Recent (<48 hours) major surgery (e.g. abdominal, thoracic, organ transplantation) » Immunosuppressed state » Invasive fungal infection » End-stage renal disease, including chronic hemodialysis Obtain procalcitonin (PCT) level If low suspicion of infection, do not order PCT level. PCT can be elevated due to several non-infectious causes (see next page). PCT < 0.25 ng/mL PCT > 0.25 ng/mL Assess disease severity Any disease severity Reassess daily up to 3 days after starting antibiotics Day 1 Low Moderate/Severe Consider stopping antibiotics Continue antibiotics Continue antibiotics Clinical Improvement YES NO PCT levels may or may not assist with clinical decisions to guide therapy Consider non-infectious processes, resistant pathogens, and complications of primary condition Check PCT level PCT < 0.25 ng/mL Consider stopping antibiotics PCT > 0.25 ng/mL Continue antibiotics Tailor antibiotics based on culture results If cultures negative, consider deescalating empiric therapy Revised: 11/17/2015 PROCALCITONIN UTILIZATION GUIDELINE ADDITIONAL INFORMATION ON PROCALCITONIN What is procalcitonin (PCT)? PCT = precursor of calcitonin, mainly produced by thyroid cells under normal conditions Synthesis of calcitonin inhibited by cytokines and endotoxin leads to increase in PCT levels in presence of bacterial infections Usually undetectable in absence of bacterial infections (see below for non-infectious causes of PCT elevation) What is the role of PCT in the management of patients with suspected infection? Has been used to predict systemic bacterial infections and to help determine antibiotic duration in patients in the intensive care unit. Comparison to other biomarkers of infectious disease (e.g. WBC count, C-reactive protein): » Levels of PCT tend to rise earlier in the infectious process and decrease rapidly with clinical improvement » Not significantly affected by steroids or non-steroidal anti-inflammatory drugs (NSAIDs) » Attenuated by release of cytokines involved in viral infections (e.g. interferon-gamma) Has been primarily used to decrease antibiotic use in two clinical settings: » Patients presenting to the emergency department, hospital or outpatient clinic with suspected lower respiratory infection or COPD exacerbation (excluding hypoxemic, septic, or clinically unstable patients) » Guide duration of therapy in patients admitted to the intensive care unit What is the role of PCT in lower respiratory infections? PCT-guided antibiotic therapy is safe and effective in patients presenting to the hospital with suspected lower respiratory infections, including community-acquired pneumonia and COPD exacerbations If PCT is <0.25 ng/mL, antibiotics can be safely held in these patients if clinically stable and not immunosuppressed If antibiotics are started, they can be safely discontinued if the PCT falls to <0.25 ng/mL What is the role of PCT in the intensive care unit? Can be useful in guiding duration of antibiotic therapy in septic patients Should not be used to determine initiation of antibiotics in unstable patients If initially elevated, trending PCT until culture results are available and levels fall below to < 0.25 ng/mL can help determine duration of antibiotic therapy. What are the limitations of PCT? Not useful to diagnose or monitor localized infections (e.g. cellulitis, osteomyelitis, abscesses). Can be elevated due to several non-infectious causes, including: » Recent major surgery or trauma (within 24-48 hours), including post-cardiac arrest » Dysfunction of gut barrier » Tissue ischemia » Renal failure, especially end-stage renal disease and hemodialysis » Treatment with cytokine-stimulating agents (e.g. OKT3, anti-lymphocyte globulins, alemtuzumab, etc.) Data are lacking to support PCT-guided antibiotic protocols in many infection states, including: » Bacteremia and endocarditis, particularly due to S. aureus » Mycobacterial infections » Infections in severely immunocompromised patients, including febrile neutropenia » Central nervous system infection (e.g. meningitis, encephalitis, ventriculitis) References 1. Jensen J, Lundgren J. Procalcitonin monitoring in trauma intensive care patients: how helpful is it? Crit Care Med 2009; 37: 2093-4. 2. Briel M, Scheutz P, Mueller B, et al. Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care. Arch Intern Med 2008; 168: 2000-7. 3. Burkhardt O, Ewig S, Haagen U, et al. Procalcitonin guidance and reduction of antibiotic use in acute respiratory tract infection. Eur Respir J 2010; 36: 601-7. 4. Christ-Crain M, Stolz D, Bingisser R, et al. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med 2006; 174: 84-93. 5. Schuetz P, Christ-Crain M, Thomann R, et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA 2009; 302: 1059-66. 6. Boudama L, Luyt CE, Tubach F, et al. Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010; 375: 463-74. Revised: 11/17/2015