ProPICU: Impact of a Procalcitonin Testing and Treatment Algorithm on Antibiotic Use and Outcomes in the Pediatric Intensive Care Unit

• Sponsor: Vanderbilt University Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT03440918
• Collaborator: National Institutes of Health (NIH) (NIH)
• Enrollment: 271
• Location: 1
• Arms: 2
• Actual Duration (Months): 14.9
• Patients Per Site Per Month: 18.2

Study Details

Study Description

Brief Summary

The timely use of antibiotics can reduce morbidity and mortality associated with bacterial infections, particularly in the intensive care unit setting (ICU). Long courses of antibiotics, however, are associated with the emergence of multi-drug resistant organisms and antibiotic-associated adverse events, such as C. difficile infections. Thus, antibiotic de-escalation is an important goal of antimicrobial stewardship programs.

Procalcitonin (PCT) has been investigated as a biomarker for critically ill adult patients with bacterial infection, particularly pneumonia and sepsis. The proposed project will evaluate whether a PCT testing and treatment algorithm, implemented through daily antimicrobial stewardship audit and feedback, can promote early and safe antibiotic de-escalation in the pediatric ICU.

Condition or Disease	Intervention/Treatment	Phase
Sepsis; Procalcitonin; Antimicrobial Stewardship	Other: Procalcitonin-Guided Antimicrobial Stewardship; Other: Baseline Antimicrobial Stewardship	N/A

Detailed Description

The timely use of effective antibiotics can markedly reduce the morbidity and mortality associated with bacterial infections, particularly in the intensive care unit (ICU). However, in this setting, much antibiotic use is empiric, and administered to patients with non-bacterial or non-infectious causes of inflammation that do not respond to antibiotics. This widespread empiric use of antibiotics drives the emergence of multi-drug resistant organisms and antibiotic-associated adverse events, such as C. difficile infections. De-escalation of broad-spectrum empiric antibiotics for ICU patients without proven bacterial infections can reduce unnecessary antibiotic use, slow the development of antibiotic resistance, and reduce complications associated with antibiotic therapy. Thus, antibiotic de-escalation is an important goal of antimicrobial stewardship programs. Specific tests and pathways to predict which patients have bacterial infections and those that would benefit from antibiotic therapy would accelerate de-escalation and greatly facilitate antimicrobial stewardship efforts.

Procalcitonin (PCT) has been investigated as a biomarker for critically ill adult patients with bacterial infection, particularly pneumonia and sepsis. Following bacteria-induced activation of monocytes and adherence of monocytes to endothelial surfaces, procalcitonin is expressed and secreted. PCT levels have been shown to rise rapidly and remain elevated during ongoing bacterial infections, and PCT levels are more specific for bacterial infections than CRP or total white blood cell count. PCT rises approximately 4 hours after bacterial exposure, peaks between 12-24 hours, and has a half-life of 24 hours once the infectious stimulus is removed.

In many adult trials investigating PCT-guided algorithms for antibiotic cessation (refer to section 3.0), a high proportion of providers (up to 50%) chose not to follow algorithm guidance for subjects randomized to the PCT-guided group. Thus, although PCT appears to be a useful guide for safe antibiotic de-escalation in the ICU, the ideal method for implementing the test and integrating it into clinical care in order to maximize its impact in the pediatric population is unclear. Notably, none of the prior trials evaluated PCT-associated outcomes in critically ill children nor integrated PCT testing into antimicrobial stewardship activities.

The investigators propose the evaluation of a PCT testing and treatment algorithm on patient outcomes in the pediatric ICU, a setting in which PCT-guided antibiotic de-escalation has not been previously studied.

The proposed project will evaluate whether a procalcitonin (PCT) testing and treatment algorithm, implemented through daily antimicrobial stewardship audit and feedback, can promote early and safe antibiotic de-escalation in the pediatric ICU. The investigators will conduct a pragmatic, prospective randomized controlled trial comparing antimicrobial use and outcomes among children admitted to the ICU who receive either: 1) Routine laboratory testing and treatment with antimicrobial stewardship review (control), or 2) PCT testing and treatment with antimicrobial stewardship review (intervention). In both arms, baseline daily review of antimicrobial management by the stewardship team will occur. In the intervention arm, the stewardship provider also will recommend PCT testing and antibiotic modifications using a PCT-based treatment algorithm. PCT levels will be measured a total of four times in the intervention arm - on enrollment, then daily through day 3 post-randomization and on day 5 post-randomization. This research is not to determine if PCT is a good test; this has already been established and evaluated as part of the FDA approval process. This pragmatic outcomes trial is evaluating if use of the PCT, implemented together with antimicrobial stewardship program oversight, improves the quality of care the investigators can provide for children at Vanderbilt Children's Hospital. The investigators hypothesize that patients in the intervention arm will have shorter duration of antibiotic therapy and similar outcomes, as compared to patients in the control arm.

Specific Aims

1. Compare antimicrobial utilization among children in the ICU who receive standard-of-care testing plus stewardship vs. PCT-based treatment plus stewardship. The investigators will compare days of antibiotic therapy in the first 14 days following randomization between the study arms. The investigators will test the hypothesis that duration of antibiotic therapy will be 2 days shorter in the group with PCT-guided management vs. the group with standard of care testing and treatment.

2. Compare clinical outcomes and safety among children in the ICU who receive standard-of-care testing plus stewardship vs. PCT-based treatment plus stewardship. The investigators will compare mortality, length of stay, recurrence of infection, and antibiotic-associated adverse events (rash, myelosuppression, renal impairment, hepatotoxicity, C. difficile infection) between the study arms. The investigators will test the hypothesis that outcomes and safety will be comparable between the study arms.

Study Design

• Study Type: Interventional
• Actual Enrollment: 271 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prospective, Randomized Controlled Trial to Evaluate the Impact of a Procalcitonin Testing and Treatment Algorithm on Antibiotic Use and Outcomes in the Pediatric Intensive Care Unit
• Actual Study Start Date: Feb 12, 2018
• Actual Primary Completion Date: May 11, 2019
• Actual Study Completion Date: May 11, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Baseline Antimicrobial Stewardship Baseline audit of antimicrobial orders with feedback to providers by the antimicrobial stewardship team.	Other: Procalcitonin-Guided Antimicrobial Stewardship; In addition to baseline audit of antimicrobial orders, the stewardship team will additionally recommend procalcitonin (PCT) testing and treatment per algorithm. PCT will be used in conjunction with clinical status and exam, and results of radiographic and laboratory studies, to make medical decisions about antibiotic therapy.; Other: Baseline Antimicrobial Stewardship; Baseline audit of antimicrobial orders with feedback to providers by the antimicrobial stewardship team.
Experimental: Procalcitonin-Guided Antimicrobial Stewardship In addition to baseline audit of antimicrobial orders, the stewardship team will additionally recommend procalcitonin (PCT) testing and treatment per algorithm. PCT will be used in conjunction with clinical status and exam, and results of radiographic and laboratory studies, to make medical decisions about antibiotic therapy.	Other: Procalcitonin-Guided Antimicrobial Stewardship; In addition to baseline audit of antimicrobial orders, the stewardship team will additionally recommend procalcitonin (PCT) testing and treatment per algorithm. PCT will be used in conjunction with clinical status and exam, and results of radiographic and laboratory studies, to make medical decisions about antibiotic therapy.

Outcome Measures

Primary Outcome Measures

1. Days of Antibiotic Therapy in the First 14 Days Following Randomization [14 days]

   Days of antibiotic therapy a participant receives following randomization will be measured

Secondary Outcome Measures

1. Duration of Broad-spectrum Antibiotic Therapy [up to14 days]

   Defined as vancomycin, daptomycin, amikacin, ceftazidime, cefepime, piperacillin/tazobactam, aztreonam, carbapenems

2. Number of Patients With an Antibiotic Change [up to 14 days]

   Number of patients with an appropriate antibiotic escalation or de-escalation based on patient's clinical status and available supporting laboratory evidence, or lack thereof, of specific type of infection

3. 30-day Mortality [up to 30 days]

   All-cause mortality

4. Re-initiation of Antibiotics for a Bacterial Infection [up to 30 days]

   Re-initiation of any antibiotic for a proven or suspected bacterial infection

5. Length of Intensive Care Unit Stay [up to 14 days]

   Hospital days spent in the intensive care unit

6. Length of Overall Hospital Stay [Until hospital discharge, an average of 7 days]

   Hospital days admitted to the hospital

7. Ventilator Days [up to 14 days]

   Days spent using invasive ventilation methods (not including supplementary oxygen via nasal cannula or Vapotherm support)

8. Number of Participants With Antibiotic-associated Complications [up to 14 days]

   Antibiotic-associated complications including rash, neutropenia, thrombocytopenia, acute kidney injury [defined as increase in serum creatinine > 0.3 mg per dL or > 1.5-fold from baseline, or urine output < 0.5 mL per kg per hour for more than six hours], hepatotoxicity [defined as > 2-fold increase in alanine aminotransferase, ALT, or conjugated bilirubin], or C. difficile infection will be recorded

9. Infection With a Multi-drug Resistant Organism [up to 30 days]

   Identification/growth of a multi-drug resistant organism from a sterile culture site. Multi-drug resistant organisms will be defined as methicillin-resistant S. aureus, vancomycin-resistant Enterococcus, 3rd generation cephalosporin non-susceptible Enterobacteriaceae, multi-drug resistant Pseudomonas aeruginosa [resistant to aminoglycosides, cephalosporins, floroquinolones and carbepenems], carbepenem-resistant Acinetobacter, and Candida spp obtained from otherwise sterile sites [i.e. blood or urine cultures]

10. Antibiotic Cost [up to 14 days]

    Cost of antibiotic course will be obtained from hospital billing data

11. Number of Participants Whose Provider Adhered to the Procalcitonin-guided Algorithm [up to 5 days]

    Rate of clinical provider compliance with adherence to suggested antibiotic escalation or de-escalation made by the antimicrobial stewardship team based on procalcitonin levels will be tracked

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Hours to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18 years of age or younger

• Prescribed or administered antibiotics in the hospital less than or equal to 24 hours prior to enrollment

• Have parents or legal guardians who provide informed consent

• Provide assent (if > 7 years of age)

Exclusion Criteria:

• Are not prescribed antibiotics in the hospital

• Receive intravenous antibiotics within 7 days prior to identification for study enrollment

• Primary or secondary immune deficiency

• History of malignancy, bone marrow transplant or solid organ transplant

• A diagnosis of cystic fibrosis

• Neonates < 34 weeks gestation

• Patients receiving treatment for endocarditis, osteomyelitis, meningitis, mediastinitis or other invasive infection, for which long duration of antibiotics is needed

• Do not provide informed consent/assent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Vanderbilt University Medical Center
• National Institutes of Health (NIH)

Investigators

• Principal Investigator: Ritu Banerjee, MD, PhD, Vanderbilt University Medical Center

Study Documents (Full-Text)

• Study Protocol - Mar 27, 2019
• Statistical Analysis Plan - Jun 4, 2019

More Information

Publications

None provided.

• Responsible Party: Sophie Katz, Postdoctoral Fellow, Vanderbilt University Medical Center
• ClinicalTrials.gov Identifier: NCT03440918
• Other Study ID Numbers: 170778
• First Posted: Feb 22, 2018
• Last Update Posted: Apr 22, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Sophie Katz, Postdoctoral Fellow, Vanderbilt University Medical Center: Infection
• Additional relevant MeSH terms: Anti-Infective Agents; Anti-Bacterial Agents

Study Results

Participant Flow

Recruitment Details	528 patients in the pediatric ICU were on antibiotics < 1 calandar day and were assessed for eligibility during the study period, February 15, 2018 to April 11, 2019. 257 were excluded and did not undergo randomization.
Pre-assignment Detail	No patients enrolled in the study were excluded before assignment to groups.

Arm/Group Title	Usual Care Antimicrobial Stewardship	Procalcitonin-Guided Antimicrobial Stewardship
Arm/Group Description	Participants received usual care audit of antimicrobial orders with feedback to providers by the antimicrobial stewardship team.	In addition to usual care audit and feedback of antimicrobial orders, the stewardship team additionally recommended procalcitonin (PCT) testing and treatment per algorithm. PCT was used in conjunction with clinical status and exam, and results of radiographic and laboratory studies, to make medical decisions about antibiotic therapy.
Period Title: Overall Study
STARTED	133	138
COMPLETED	133	122
NOT COMPLETED	0	16

Baseline Characteristics

Arm/Group Title	Usual Care	Procalcitonin-Guided Antimicrobial Stewardship	Total
Arm/Group Description	Usual Care audit of antimicrobial orders with feedback to providers by the antimicrobial stewardship team.	In addition to usual care audit and feedback of antimicrobial orders, the stewardship team additionally recommended procalcitonin (PCT) testing and treatment per algorithm. PCT was be used in conjunction with clinical status and exam, and results of radiographic and laboratory studies, to make medical decisions about antibiotic therapy.	Total of all reporting groups
Overall Participants	133	137	270
Age (Count of Participants)
<=18 years	126 94.7%	132 96.4%	258 95.6%
Between 18 and 65 years	7 5.3%	5 3.6%	12 4.4%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	2.3	1.6	1.89
Sex: Female, Male (Count of Participants)
Female	73 54.9%	57 41.6%	130 48.1%
Male	60 45.1%	80 58.4%	140 51.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 7.5%	20 14.6%	30 11.1%
Not Hispanic or Latino	114 85.7%	112 81.8%	226 83.7%
Unknown or Not Reported	9 6.8%	5 3.6%	14 5.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.7%	1 0.4%
Asian	2 1.5%	0 0%	2 0.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	18 13.5%	18 13.1%	36 13.3%
White	103 77.4%	106 77.4%	209 77.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	10 7.5%	12 8.8%	22 8.1%
Region of Enrollment (participants) [Number]
United States	133 100%	137 100%	270 100%
Location at Enrollment (Count of Participants)
Medical / Surgical ICU	111 83.5%	112 81.8%	223 82.6%
Cardiac ICU	22 16.5%	25 18.2%	47 17.4%
Vasopressor Support (Count of Participants)
Count of Participants [Participants]	33 24.8%	27 19.7%	60 22.2%
Mechanical Ventilation (Count of Participants)
Count of Participants [Participants]	61 45.9%	45 32.8%	106 39.3%
Fever at enrollment (Count of Participants)
Count of Participants [Participants]	79 59.4%	61 44.5%	140 51.9%
Recent surgery (Count of Participants)
Count of Participants [Participants]	37 27.8%	24 17.5%	61 22.6%
Antibiotic Indication (Count of Participants)
Sepsis	51 38.3%	64 46.7%	115 42.6%
Pneumonia	59 44.4%	48 35%	107 39.6%
Other	23 17.3%	25 18.2%	48 17.8%
Final Diagnosis (Count of Participants)
Pneumonia	44 33.1%	41 29.9%	85 31.5%
Aspiration pneumonia	10 7.5%	10 7.3%	20 7.4%
Tracheitis	6 4.5%	12 8.8%	18 6.7%
Viral illness	16 12%	12 8.8%	28 10.4%
Non-infectious etiology	23 17.3%	35 25.5%	58 21.5%
Other	34 25.6%	27 19.7%	61 22.6%

Outcome Measures

1. Primary Outcome

Title	Days of Antibiotic Therapy in the First 14 Days Following Randomization
Description	Days of antibiotic therapy a participant receives following randomization will be measured
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

Intention to treat

Arm/Group Title	Baseline Antimicrobial Stewardship	Procalcitonin-Guided Antimicrobial Stewardship
Arm/Group Description	Baseline audit of antimicrobial orders with feedback to providers by the antimicrobial stewardship team.	In addition to baseline audit of antimicrobial orders, the stewardship team will additionally recommend procalcitonin (PCT) testing and treatment per algorithm. PCT will be used in conjunction with clinical status and exam, and results of radiographic and laboratory studies, to make medical decisions about antibiotic therapy.
Measure Participants	133	137
Median (Inter-Quartile Range) [days]	7.6	6.6

2. Secondary Outcome

Title	Duration of Broad-spectrum Antibiotic Therapy
Description	Defined as vancomycin, daptomycin, amikacin, ceftazidime, cefepime, piperacillin/tazobactam, aztreonam, carbapenems
Time Frame	up to14 days

Outcome Measure Data

Analysis Population Description

intention to treat

Arm/Group Title	Baseline Antimicrobial Stewardship	Procalcitonin-Guided Antimicrobial Stewardship
Arm/Group Description	Baseline audit of antimicrobial orders with feedback to providers by the antimicrobial stewardship team.	In addition to baseline audit of antimicrobial orders, the stewardship team will additionally recommend procalcitonin (PCT) testing and treatment per algorithm. PCT will be used in conjunction with clinical status and exam, and results of radiographic and laboratory studies, to make medical decisions about antibiotic therapy.
Measure Participants	133	137
Median (Inter-Quartile Range) [days]	0	0.086

3. Secondary Outcome

Title	Number of Patients With an Antibiotic Change
Description	Number of patients with an appropriate antibiotic escalation or de-escalation based on patient's clinical status and available supporting laboratory evidence, or lack thereof, of specific type of infection
Time Frame	up to 14 days

Outcome Measure Data

Analysis Population Description

intention to treat (all participants assigned to baseline antimicrobial stewardship or procalcitonin-guided antimicrobial stewardship)

Arm/Group Title	Baseline Antimicrobial Stewardship	Procalcitonin-Guided Antimicrobial Stewardship
Arm/Group Description	Baseline audit of antimicrobial orders with feedback to providers by the antimicrobial stewardship team.	In addition to baseline audit of antimicrobial orders, the stewardship team will additionally recommend procalcitonin (PCT) testing and treatment per algorithm. PCT will be used in conjunction with clinical status and exam, and results of radiographic and laboratory studies, to make medical decisions about antibiotic therapy.
Measure Participants	133	137
Count of Participants [Participants]	111 83.5%	108 78.8%

4. Secondary Outcome

Title	30-day Mortality
Description	All-cause mortality
Time Frame	up to 30 days

Outcome Measure Data

Analysis Population Description

intention to treat (all participants assigned to baseline antimicrobial stewardship or procalcitonin-guided antimicrobial stewardship)

Arm/Group Title	Baseline Antimicrobial Stewardship	Procalcitonin-Guided Antimicrobial Stewardship
Arm/Group Description	Baseline audit of antimicrobial orders with feedback to providers by the antimicrobial stewardship team.	In addition to baseline audit of antimicrobial orders, the stewardship team will additionally recommend procalcitonin (PCT) testing and treatment per algorithm. PCT will be used in conjunction with clinical status and exam, and results of radiographic and laboratory studies, to make medical decisions about antibiotic therapy.
Measure Participants	133	137
Count of Participants [Participants]	4 3%	3 2.2%

5. Secondary Outcome

Title	Re-initiation of Antibiotics for a Bacterial Infection
Description	Re-initiation of any antibiotic for a proven or suspected bacterial infection
Time Frame	up to 30 days

Outcome Measure Data

Analysis Population Description

intention to treat (all participants assigned to baseline antimicrobial stewardship or procalcitonin-guided antimicrobial stewardship)

Arm/Group Title	Baseline Antimicrobial Stewardship	Procalcitonin-Guided Antimicrobial Stewardship
Arm/Group Description	Baseline audit of antimicrobial orders with feedback to providers by the antimicrobial stewardship team.	In addition to baseline audit of antimicrobial orders, the stewardship team will additionally recommend procalcitonin (PCT) testing and treatment per algorithm. PCT will be used in conjunction with clinical status and exam, and results of radiographic and laboratory studies, to make medical decisions about antibiotic therapy.
Measure Participants	133	137
Count of Participants [Participants]	NA NaN	NA NaN

6. Secondary Outcome

Title	Length of Intensive Care Unit Stay
Description	Hospital days spent in the intensive care unit
Time Frame	up to 14 days

Outcome Measure Data

Analysis Population Description

intention to treat (all participants assigned to baseline antimicrobial stewardship or procalcitonin-guided antimicrobial stewardship)

Arm/Group Title	Baseline Antimicrobial Stewardship	Procalcitonin-Guided Antimicrobial Stewardship
Arm/Group Description	Baseline audit of antimicrobial orders with feedback to providers by the antimicrobial stewardship team.	In addition to baseline audit of antimicrobial orders, the stewardship team will additionally recommend procalcitonin (PCT) testing and treatment per algorithm. PCT will be used in conjunction with clinical status and exam, and results of radiographic and laboratory studies, to make medical decisions about antibiotic therapy.
Measure Participants	133	137
Median (Inter-Quartile Range) [days]	2	2

7. Secondary Outcome

Title	Length of Overall Hospital Stay
Description	Hospital days admitted to the hospital
Time Frame	Until hospital discharge, an average of 7 days

Outcome Measure Data

Analysis Population Description

intention to treat (all participants assigned to baseline antimicrobial stewardship or procalcitonin-guided antimicrobial stewardship)

Arm/Group Title	Baseline Antimicrobial Stewardship	Procalcitonin-Guided Antimicrobial Stewardship
Arm/Group Description	Baseline audit of antimicrobial orders with feedback to providers by the antimicrobial stewardship team.	In addition to baseline audit of antimicrobial orders, the stewardship team will additionally recommend procalcitonin (PCT) testing and treatment per algorithm. PCT will be used in conjunction with clinical status and exam, and results of radiographic and laboratory studies, to make medical decisions about antibiotic therapy.
Measure Participants	133	137
Median (Inter-Quartile Range) [days]	7	6

8. Secondary Outcome

Title	Ventilator Days
Description	Days spent using invasive ventilation methods (not including supplementary oxygen via nasal cannula or Vapotherm support)
Time Frame	up to 14 days

Outcome Measure Data

Analysis Population Description

intention to treat (all participants assigned to baseline antimicrobial stewardship or procalcitonin-guided antimicrobial stewardship)

Arm/Group Title	Baseline Antimicrobial Stewardship	Procalcitonin-Guided Antimicrobial Stewardship
Arm/Group Description	Baseline audit of antimicrobial orders with feedback to providers by the antimicrobial stewardship team.	In addition to baseline audit of antimicrobial orders, the stewardship team will additionally recommend procalcitonin (PCT) testing and treatment per algorithm. PCT will be used in conjunction with clinical status and exam, and results of radiographic and laboratory studies, to make medical decisions about antibiotic therapy.
Measure Participants	133	137
Median (Inter-Quartile Range) [days]	3.9	4.4

9. Secondary Outcome

Title	Number of Participants With Antibiotic-associated Complications
Description	Antibiotic-associated complications including rash, neutropenia, thrombocytopenia, acute kidney injury [defined as increase in serum creatinine > 0.3 mg per dL or > 1.5-fold from baseline, or urine output < 0.5 mL per kg per hour for more than six hours], hepatotoxicity [defined as > 2-fold increase in alanine aminotransferase, ALT, or conjugated bilirubin], or C. difficile infection will be recorded
Time Frame	up to 14 days

Outcome Measure Data

Analysis Population Description

intention to treat (all participants assigned to Baseline Antimicrobial Stewardship or Procalcitonin-Guided Antimicrobial Stewardship)

Arm/Group Title	Baseline Antimicrobial Stewardship	Procalcitonin-Guided Antimicrobial Stewardship
Arm/Group Description	Baseline audit of antimicrobial orders with feedback to providers by the antimicrobial stewardship team.	In addition to baseline audit of antimicrobial orders, the stewardship team will additionally recommend procalcitonin (PCT) testing and treatment per algorithm. PCT will be used in conjunction with clinical status and exam, and results of radiographic and laboratory studies, to make medical decisions about antibiotic therapy.
Measure Participants	133	137
Count of Participants [Participants]	2 1.5%	3 2.2%

10. Secondary Outcome

Title	Infection With a Multi-drug Resistant Organism
Description	Identification/growth of a multi-drug resistant organism from a sterile culture site. Multi-drug resistant organisms will be defined as methicillin-resistant S. aureus, vancomycin-resistant Enterococcus, 3rd generation cephalosporin non-susceptible Enterobacteriaceae, multi-drug resistant Pseudomonas aeruginosa [resistant to aminoglycosides, cephalosporins, floroquinolones and carbepenems], carbepenem-resistant Acinetobacter, and Candida spp obtained from otherwise sterile sites [i.e. blood or urine cultures]
Time Frame	up to 30 days

Outcome Measure Data

Analysis Population Description

intention to treat (all participants assigned to Baseline Antimicrobial Stewardship or Procalcitonin-Guided Antimicrobial Stewardship)

Arm/Group Title	Baseline Antimicrobial Stewardship	Procalcitonin-Guided Antimicrobial Stewardship
Arm/Group Description	Baseline audit of antimicrobial orders with feedback to providers by the antimicrobial stewardship team.	In addition to baseline audit of antimicrobial orders, the stewardship team will additionally recommend procalcitonin (PCT) testing and treatment per algorithm. PCT will be used in conjunction with clinical status and exam, and results of radiographic and laboratory studies, to make medical decisions about antibiotic therapy.
Measure Participants	133	137
Count of Participants [Participants]	1 0.8%	2 1.5%

11. Secondary Outcome

Title	Antibiotic Cost
Description	Cost of antibiotic course will be obtained from hospital billing data
Time Frame	up to 14 days

Outcome Measure Data

Analysis Population Description

intention to treat (all participants assigned to Baseline Antimicrobial Stewardship or Procalcitonin-Guided Antimicrobial Stewardship)

Arm/Group Title	Baseline Antimicrobial Stewardship	Procalcitonin-Guided Antimicrobial Stewardship
Arm/Group Description	Baseline audit of antimicrobial orders with feedback to providers by the antimicrobial stewardship team.	In addition to baseline audit of antimicrobial orders, the stewardship team will additionally recommend procalcitonin (PCT) testing and treatment per algorithm. PCT will be used in conjunction with clinical status and exam, and results of radiographic and laboratory studies, to make medical decisions about antibiotic therapy.
Measure Participants	133	137
Number [dollars]	NA	NA

12. Secondary Outcome

Title	Number of Participants Whose Provider Adhered to the Procalcitonin-guided Algorithm
Description	Rate of clinical provider compliance with adherence to suggested antibiotic escalation or de-escalation made by the antimicrobial stewardship team based on procalcitonin levels will be tracked
Time Frame	up to 5 days

Outcome Measure Data

Analysis Population Description

intention to treat (all participants assigned to Baseline Antimicrobial Stewardship or Procalcitonin-Guided Antimicrobial Stewardship)

Arm/Group Title	Baseline Antimicrobial Stewardship	Procalcitonin-Guided Antimicrobial Stewardship
Arm/Group Description	Baseline audit of antimicrobial orders with feedback to providers by the antimicrobial stewardship team.	In addition to baseline audit of antimicrobial orders, the stewardship team will additionally recommend procalcitonin (PCT) testing and treatment per algorithm. PCT will be used in conjunction with clinical status and exam, and results of radiographic and laboratory studies, to make medical decisions about antibiotic therapy.
Measure Participants	133	137
Count of Participants [Participants]	123 92.5%	121 88.3%

Adverse Events

Time Frame	30 days
Adverse Event Reporting Description	Adverse events were collected as part of the safety outcomes. Providers were able to overrule antibiotic stewardship recommendations.
Arm/Group Title	Baseline Antimicrobial Stewardship		Procalcitonin-Guided Antimicrobial Stewardship
Arm/Group Description	Baseline audit of antimicrobial orders with feedback to providers by the antimicrobial stewardship team.		In addition to baseline audit of antimicrobial orders, the stewardship team will additionally recommend procalcitonin (PCT) testing and treatment per algorithm. PCT will be used in conjunction with clinical status and exam, and results of radiographic and laboratory studies, to make medical decisions about antibiotic therapy.
All Cause Mortality
	Baseline Antimicrobial Stewardship		Procalcitonin-Guided Antimicrobial Stewardship
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/133 (3%)		3/137 (2.2%)
Serious Adverse Events
	Baseline Antimicrobial Stewardship		Procalcitonin-Guided Antimicrobial Stewardship
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/133 (0%)		0/137 (0%)
Other (Not Including Serious) Adverse Events
	Baseline Antimicrobial Stewardship		Procalcitonin-Guided Antimicrobial Stewardship
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/133 (0%)		0/137 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.