Early Antibiotics After Aspiration in ICU Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the use of early antibiotics in ICU patients who appear to have aspirated, to help determine whether this improves outcomes by reducing the later incidence of pneumonia and other negative consequences.

Detailed Description
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ICU patients with signs of aspiration on imaging and a clinical history supportive of aspiration, but with no clear signs of infectious pneumonia, will be randomized to receive either 5 days of empiric antibiotics or supportive care only. They will be followed for 30 days with a primary outcome of ICU length-of-stay and various secondary outcomes including mortality, ventilator days, and antibiotic days.

Official Title
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Antibiotic Prophylaxis in Critically Ill Patients After Suspected Aspiration

Conditions
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Aspiration, Aspiration Pneumonia

Intervention / Treatment
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* Drug: Ceftriaxone
* Drug: Amoxicillin clavulanic acid
* Drug: Cefepime
* Drug: Vancomycin
* Drug: Levofloxacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admitted to the ICU within the last 24 hours, or with a witnessed aspiration event in the last 24 hours while in the ICU Radiographic findings on chest x-ray or CT deemed by the treating ICU team to be consistent with aspiration (e.g. dependent infiltrates or intraluminal airway debris) Clinical history consistent with possible aspiration (e.g. cardiac arrest, found unconscious, or with a witnessed aspiration event). Exclusion Criteria: Already received 3 or more doses of any antibiotic since hospital presentation, unless the last dose was greater than 1 week before enrollment Requires antibiotic therapy for the treatment of other infections Patient comfort measures only at time of screening Currently participating in other trials using investigational drugs or interventions Currently pregnant Currently a prisoner The consenting party (patient or their legally authorized representative) is unable to understand or read English at a fifth-grade level. 2 or more of the following are present at the time of screening: White blood cell count: ≥ 11.0 Temperature ≥ 38.0C (100.4F) Purulent secretions S/F (pulse oximetry saturation to FiO2) ratio ≤ 215

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Antibiotics<br>5 days of empiric antibiotics selected from a guideline-appropriate regimen. Alternate agents may be selected by the treating team if allergies or other patient factors mandate, but are still recommended for a 5 day course. Supportive care including oxygen and ventilation can be offered ad libitum. Options include ceftriaxone, Augmentin, cefepime, vancomycin, levofloxacin. | Drug: Ceftriaxone<br>* If there is low risk for P. aeruginosa and/or methicillin-resistant staphylococcus aureus (MRSA), as deemed by the treating team: Ceftriaxone 2 g IV, every 24 hours for 5 days<br>Drug: Amoxicillin clavulanic acid<br>* At any point after 24 hours, clinicians may (but are not required to) transition stable patients on ceftriaxone to the oral agent Amoxicillin + clavulanate (Augmentin) 875 mg PO or per feeding tube, twice daily for the remainder of 5 days<br>* Other names: Augmentin;Drug: Cefepime<br>* If there is significant risk of P. aeruginosa and/or MRSA as deemed by the treating team: Cefepime 2 g IV, every 8 hours for 5 days, plus vancomycin<br>Drug: Vancomycin<br>* If there is significant risk of P. aeruginosa and/or MRSA as deemed by the treating team: Vancomycin IV, dosed by trough or AUC/MIC (area under the curve/minimum inhibitory concentration) monitoring for 5 days, plus cefepime. Order nasal MRSA swab and consider discontinuing vancomycin if MRSA swab is negative.<br>Drug: Levofloxacin<br>* At any point after 24 hours, clinicians may (but are not required to) transition stable patients on cefepime to levofloxacin PO or per feeding tube, 750 mg every 24 hours for the remainder of 5 days<br>|
| No Intervention: Control<br>No initial antibiotic therapy unless clinical picture changes or worsens. Supportive care including oxygen and ventilation can be offered ad libitum. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU-free days |  | From admission to 30 days, death, or hospital discharge, whichever occurs first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilator-free days |  | From admission to 30 days, death, or hospital discharge, whichever occurs first | 
| Hospital-free days |  | From admission to 30 days, death, or hospital discharge, whichever occurs first | 
| Antibiotic-free days |  | Days with no antibiotics from admission to 30 days, death, or hospital discharge, whichever occurs first | 
| Intubated after enrollment | Yes/no | Between admission to 30 days, death, or hospital discharge, whichever occurs first | 
| Tracheostomy after enrollment | Yes/no | Between admission to 30 days, death, or hospital discharge, whichever occurs first | 
| Developed pneumonia after enrollment | Yes/no, by criteria: 2 or more present simultaneously of temperature >38c, WBC >11k, S/F ratio <215, and purulent secretions | Between admission to 30 days, death, or hospital discharge, whichever occurs first | 
| Days before developing pneumonia criteria | By criteria: 2 or more present simultaneously of temperature >38c, WBC >11k, S/F ratio <215, and purulent secretions | Between admission to 30 days, death, or hospital discharge, whichever occurs first | 
| Additional antibiotics prescribed | Yes/no. Excluding prophylactic antibiotics and excluding perioperative prophylactic antibiotics. | Between admission to 30 days, death, or hospital discharge, whichever occurs first | 
| Positive sputum culture with presumed pathogen | Yes/no | Between enrollment and 30 days, death, or hospital discharge, whichever occurs first | 
| Any positive culture with organism resistant to prophylactic antibiotics | Yes/no | Between admission and 30 days, death, or hospital discharge, whichever occurs first | 
| Positive C. Difficile stool toxin assay after enrollment | Yes/no | Between enrollment and 30 days, death, or hospital discharge, whichever occurs first | 
| Temperature >38 centigrade on day 3 | Yes/no | Day 3 after enrollment | 
| White blood cell count >11k on day 3 | Yes/no | Day 3 after enrollment | 
| Arterial oxygen saturation / Fraction of inspired oxygen (S/F) <215 on day 3 | Yes/no | Day 3 after enrollment | 
| Purulent secretions | Yes/no | Day 3 after enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ventilator associated pneumonia