Procalcitonin Antibiotic Consensus Trial (ProACT) (ProACT)

• Total antibiotic exposure days [ Time Frame: 30 days ]
  Total antibiotic exposure, defined as the total number of antibiotic-days by Day 30.
• Combined endpoint of adverse outcomes that could be attributable to withholding antibiotics in LRTI [ Time Frame: 30 days ]

There is a need for improved decision-making for antibiotic prescription in acute suspected infection. Infections, particularly in the early stages, can have protean manifestations, often do not manifest with "classic" signs, and clinically overlap with non-infectious conditions. However, the imperative to quickly give antibiotics for bacterial infection has led to antibiotic overuse and resistance.

Strategies that combine novel diagnostics with therapeutics have improved decision-making in oncology, cardiology, and other fields. These strategies aim to identify those patients most likely to be helped or harmed by the therapeutic intervention and allow more individualized care. This approach takes diagnostics to the next level, by demanding a test not only measure well, but also that clinical care be improved by tying the test to a treatment strategy.

Procalcitonin, a novel biomarker of bacterial infection, may help physicians make more appropriate antibiotic decisions. Lower respiratory tract infection (LRTI) is an ideal trial population. LRTI accounts for a large proportion of antibiotic prescription, and exemplifies the imprecise clinical phenotype of infection.However, key questions of generalizability and safety preclude widespread application.

• Other: Procalcitonin level
  A procalcitonin (PCT) will be drawn level within one hour after randomization in the ED, and if hospitalized, 6-24 hours after the initial ED blood draw, and on Days 3, 5, and 7. Days 3, 5, and 7 blood draws for procalcitonin will only occur in hospitalized patients on antibiotics and/or at the treating physician's discretion.
  Other Name: PCT level
• Other: Results of procalcitonin (PCT) level to treating clinician
  In the ED, we will quickly (<1 hour goal) provide clinicians the procalcitonin result.
• Other: Provide procalcitonin guideline to treating clinician

  Procalcitonin antibiotic guideline --

  Procalcitonin level (ug/L) -- Bacterial etiology -- Recommendation

  < 0.1 -- Very unlikely -- Antibiotics strongly discouraged(1)

  0.1 - 0.25 -- Unlikely -- Antibiotics discouraged(1)

  > 0.25 - 0.5 -- Likely -- Antibiotics recommended(2)

  > 0.5 -- Very likely -- Antibiotics strongly recommended(2)

  1. Initial antibiotics can be considered for critical illness, Legionella pneumophilia. Procalcitonin should be evaluated in context with all findings and the total clinical status; clinical judgment always necessary.
  2. For outpatients, antibiotic duration based on level (> 0.25-0.5 ug/L:3 days; > 0.5-1.0 ug/L:5 days; >1.0 ug/L:7 days). Physician follow-up is recommended.
• Other: Telephone Visit
  We will collect the number of antibiotic days during telephone visits occurring on or around Day 15 and Day 30

• Experimental: Procalcitonin (PCT) group
  Procalcitonin (PCT) level; Results of procalcitonin level to treating clinician; Provide procalcitonin guideline to treating clinician; Telephone Visit at Day 15 and Day 30
  Interventions:

  • Other: Procalcitonin level
  • Other: Results of procalcitonin (PCT) level to treating clinician
  • Other: Provide procalcitonin guideline to treating clinician
  • Other: Telephone Visit
• Active Comparator: Usual Care group
  Telephone Visit at Day 15 and Day 30
  Intervention: Other: Telephone Visit

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Inclusion Criteria:

• ≥ 18 years old
• A primary clinical diagnosis in the ED of acute LRTI (< 28 days duration)
• Clinician willing to consider procalcitonin in antibiotic decision-making

Exclusion Criteria:

• Systemic antibiotics before ED presentation (All prophylactic antibiotic regimens, OR received >1 dose within 72 hours prior to ED presentation)
• Current vasopressor use
• Mechanical ventilation (via endotracheal tube)
• Known severe immunosuppression
• Accompanying non-respiratory infections
• Known lung abscess or empyema
• Chronic dialysis
• Metastatic cancer
• Surgery in the past 7 days (excluding minor surgery such as skin biopsy)
• Incarcerated or homeless
• Enrolled in ProACT in the past 30 days

• National Institute of General Medical Sciences (NIGMS)
• BioMérieux