Procalcitonin for Stewardship in Respiratory Infections A Stewardship Project
Condition: LRTI
Study type: Interventional

Summary: 
      Antibiotics are overused in hospitals nationwide, leading to unnecessary drug costs and
      adverse events. Antibiotic stewardship is now a national and international priority and
      regulatory authorities are mandating antibiotic stewardship programs in all hospitals.
      Respiratory infections account for a large percentage of antibiotic overuse. Procalcitonin
      has been shown to help providers significantly shorten the duration of antibiotic therapy in
      respiratory infections. As such, this institution seeks to evaluate the impact of PCT-guided
      antibiotic management on antibiotic use in subjects with acute Lower Respiratory Tract
      Infection (LRTI) with or without sepsis. Multiple studies have been conducted in Europe and
      demonstrate the safety of the PCT-guided antibiotic management in pneumonia as well as
      sepsis. This study will apply PCT-guided therapy to those populations in an all-US study
      evaluating patient outcomes along with safety and efficacy.
    

Detailed description: 
      The study will enroll 200 patients in the Procalcitonin (PCT)-guided care cohort and 200
      patients in the control cohort, using alternating 2 week time blocks until enrollment targets
      are reached. Patients during control or non-intervention periods will be prospectively
      identified and enrolled for the purposes of medical record review and follow up, but will not
      undergo PCT testing.

      Patient Identification/ Recruitment: Intervention Periods

      Patients will be identified either by the PI, research assistant, or co-investigator using an
      Epic system list of patients admitted to a medical service (intensive care unit (ICU) or
      ward) within the past 48 hours with a diagnosis of respiratory infection and receiving
      antibiotics for <24 hours, or via referrals from the Emergency Department and admitting
      teams. Candidate patients will have evidence of an acute lower respiratory tract infection
      (pneumonia or acute exacerbation of chronic bronchitis) as defined as follows:

      o New onset within past 28 days

      -At least one respiratory symptom: cough, sputum production, dyspnea, tachypnea, pleuritic
      chest pain, wheezing

      Plus: At least one :

        -  auscultation abnormality suggestive of pneumonia (rales, ronchi, egophony)

        -  OR a new consolidation on chest radiology consistent with pneumonia

        -  OR at least one sign of systemic infection: fever >38.1 or white blood cell (WBC) count
           >10,000 or <4,000 o AND provider initiating empiric antibiotics The PI or
           co-investigator will contact the primary provider, if the patient was not referred by
           the team, and ask permission to approach the patient to discuss study participation. The
           PI or consenting delegate will then obtain written consent from the patient within 48
           hours of antibiotic initiation. Baseline PCT will be added on to admission blood
           obtained prior to initiation of antibiotics after consent is obtained, Patients will be
           included if first PCT is performed on blood drawn between 0-24 hours prior to antibiotic
           initiation.

      Serial PCT levels will be obtained and antibiotic decisions guided as follows:

        1. Inpatient Non-ICU units (Figure 1) - Med A, Med B, Bridgeview Unit,

           • Antibiotic initiation and de-escalation for patients admitted with moderate severity
           respiratory infections (CURB-65 = 2-3 pneumonia, chronic obstructive pulmonary disease
           (COPD) exacerbations), based on a Day 0 value and a Day 2 value (repeat q48 hours up
           through D7 if previous values are >0.25 ug/L). Withhold antibiotics for initial values
           <0.1-0.25 (recommend a repeat value 4-6 hours later if antibiotics are held),
           discontinue antibiotics when PCT drops 80% from the peak value or to an absolute value
           of <0.25 ug/L. [Not routine care] i. If a patient is planned to discharge from the
           hospital prior to the 48 hour PCT level, the team may draw the lab early for the
           purposes of discharge antibiotic decisions, provided the values are drawn at least 6
           hours apart.

           ii. Recommend use in conjunction with blood cultures in select patients, universal
           respiratory viral polymerase chain reaction (PCR) panel, urine Streptococcal and
           Legionella antigens, and sputum cultures ("the diagnostic bundle" similar to Gelfer 2015
           and Branche 2015). [Routine care]

        2. Intensive Care Unit (Figure 2) -MICU/Cardiac Intensive Care unit (CICU)/ Progressive
           Care Unit (PCU)

           • Antibiotic de-escalation for patients with severe sepsis and community acquired
           pneumonia (CAP)/ hospital-acquired pneumonia (HAP) / ventilator associated pneumonia
           (VAP)/COPD exacerbations, based on a Day 0 value, with daily follow up levels.
           Discontinuation recommended for a PCT decrease by ≥80% of peak value over the Day 0
           value, or to <0.5 ug/L.[Not routine care] i. Recommend use in conjunction with blood
           cultures, universal respiratory viral PCR panel, urine Streptococcal and Legionella
           antigens, and sputum cultures ("the diagnostic bundle" similar to Gelfer 2015 and
           Branche 2015). [Routine care]

        3. Emergency Department (ED): No antibiotic prescribing decisions will be made in the
           Emergency Department using the PCT-guided algorithm for this study. The ED will only be
           a site of patient identification, referral, and recruitment as well as lab collection.

      Patient Identification/ Recruitment: Control Periods Patients will be identified either by
      the PI, research assistant, or co-investigator using the same EPIC screening process and
      inclusion strategy described above. The PI, research assistant, or co-investigator will
      approach the patient and obtain verbal consent to enroll the patient in the comparison
      cohort. The study team member will notify the primary provider of the patient's consent, but
      no PCT will be ordered. The patient will receive antibiotics at the provider's discretion.

      Physicians overrides will be considered algorithm-compliant if during the initial prescribing
      decision any of the following conditions exist:

        -  Respiratory or hemodynamic instability

        -  Life-threatening comorbidity

        -  Initial ICU admission

        -  PCT < 0.1 μg/l: CAP with pneumonia severity index (PSI) V or (Confusion, uremia,
           respiratory, blood pressure (CURB) 65 >3, COPD with Global Initiative for Chronic
           Obstructive Lung Disease (GOLD) Class IV

        -  PCT < 0.25 μg/l: CAP with PSI ≥IV or CURB 65>2, COPD with GOLD Class > III

      Physicians may deviate from the algorithm at any point, but deviations for other reasons will
      be considered "provider discretion." In case of overruling or deviation, a repeated PCT
      measurement and early discontinuation of antibiotic therapy after 3, 5,or 7 days will be
      suggested.

      Implementation Strategy

      Success of procalcitonin use requires confidence and leadership by the physician leaders in a
      given area, support from ancillary staff (nursing) to obtain timely blood draws and cultures,
      and prompting for algorithm use by clinical pharmacists or the stewardship team. Since
      procalcitonin has already been in use at JHBMC for several years, many clinicians are
      familiar with the test, but are not confident in its utility based on a lack of clinical
      guidance/ protocol development. The project would require physician champions in each of the
      service areas in order to educate providers on its use, help distribute the diagnostic
      algorithms, and encourage implementation. The Antibiotic Stewardship Team is committed to
      providing needed education and support for all clinical areas, and following up on
      procalcitonin levels as able.

      Antibiotic Stewardship Team:

        -  To generate pocket cards with PCT algorithms, inclusion, and exclusion criteria (to
           include Figure 1 + Detailed exclusion criteria on the floor; Figure 2 + detailed
           exclusion criteria for the ICU).

        -  To prepare educational materials for providers

        -  To educate providers on the PCT protocol and evidence for use

        -  To collect antibiotic use data

      Pathology Lab:

      • To provide a list of all procalcitonin values to designated person in each unit every day
      (via secure means).

      Physician Lead (2 housestaff, 2 hospitalists, 1 CICU, 1 MICU, 1 PCU):

        -  To assist with the distribution of algorithms and prompt providers in their service area
           to use the algorithm.

        -  To appoint a person to review the PCT results from their unit every day (ideally a
           Clinical Pharmacy Specialist, or a charge registered nurse (RN), chief resident, etc)
           and prompt providers to de-escalate antibiotics accordingly.

      Timeline for Study:

      March 1, 2017- December 30, 2017: Study period

        -  Algorithm distribution

        -  Provider education by the Stewardship Team, in coordination with physician lead

        -  Physician champion-led implementation of daily PCT reviews (at least 5 per day) specific
           to unit needs and workflow.

             1. Hospitalist service (Bridgeview Unit, Med A, Med B)

             2. House-staff service (Med A, Med B)

             3. ICU services (MICU/ CICU/ PCU)
    

Intervention name(s): PCT Arm
Intervention type(s): Device
Intervention description(s): PCT-guided antibiotic therapy per study protocol
Other intervention name(s): B·R·A·H·M·S PCT sensitive KRYPTOR®
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Will identify eligible patients and controls prospectively in 2 week alternating blocks. Study candidates enrolled during the intervention blocks will receive PCT-guided therapy. Study candidates enrolled during the control periods will receive standard care.
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: MICU; CICU; PCT - Procalcitonin; B·R·A·H·M·S PCT sensitive Kryptor®; Antibiotic initiation; Antibiotic de-escalation