Early Antibiotics After Aspiration in ICU Patients

Aspiration Clinical Trial

Official title:

Antibiotic Prophylaxis in Critically Ill Patients After Suspected Aspiration

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05079620
• Other study ID #: 22-004-02
• Status: Recruiting
• Phase: Phase 4
• Start date: November 30, 2021
• Est. completion date: December 30, 2024

Study information

• Verified date: November 2023
• Source: UConn Health
• Contact: Brandon Oto, PA-C
• Phone: 860-679-3107
• Email: oto[@]uchc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 30, 2024
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aspiration
• Aspiration Pneumonia
• Pneumonia
• Pneumonia, Aspiration

Intervention

Drug:
• Ceftriaxone
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
• Amoxicillin clavulanic acid
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
• Cefepime
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
• Vancomycin
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.
• Levofloxacin
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

Locations

Country	Name	City	State
United States	UConn Health, John Dempsey Hospital	Farmington	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
UConn Health

Country where clinical trial is conducted

United States, 

References & Publications (12)

Acquarolo A, Urli T, Perone G, Giannotti C, Candiani A, Latronico N. Antibiotic prophylaxis of early onset pneumonia in critically ill comatose patients. A randomized study. Intensive Care Med. 2005 Apr;31(4):510-6. doi: 10.1007/s00134-005-2585-5. Epub 2005 Mar 8. — View Citation

DiBardino DM, Wunderink RG. Aspiration pneumonia: a review of modern trends. J Crit Care. 2015 Feb;30(1):40-8. doi: 10.1016/j.jcrc.2014.07.011. Epub 2014 Jul 22. — View Citation

Dragan V, Wei Y, Elligsen M, Kiss A, Walker SAN, Leis JA. Prophylactic Antimicrobial Therapy for Acute Aspiration Pneumonitis. Clin Infect Dis. 2018 Aug 1;67(4):513-518. doi: 10.1093/cid/ciy120. — View Citation

El-Solh AA, Pietrantoni C, Bhat A, Aquilina AT, Okada M, Grover V, Gifford N. Microbiology of severe aspiration pneumonia in institutionalized elderly. Am J Respir Crit Care Med. 2003 Jun 15;167(12):1650-4. doi: 10.1164/rccm.200212-1543OC. Epub 2003 Apr 10. — View Citation

Francois B, Cariou A, Clere-Jehl R, Dequin PF, Renon-Carron F, Daix T, Guitton C, Deye N, Legriel S, Plantefeve G, Quenot JP, Desachy A, Kamel T, Bedon-Carte S, Diehl JL, Chudeau N, Karam E, Durand-Zaleski I, Giraudeau B, Vignon P, Le Gouge A; CRICS-TRIGGERSEP Network and the ANTHARTIC Study Group. Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest. N Engl J Med. 2019 Nov 7;381(19):1831-1842. doi: 10.1056/NEJMoa1812379. — View Citation

Lascarrou JB, Lissonde F, Le Thuaut A, Bachoumas K, Colin G, Henry Lagarrigue M, Vinatier I, Fiancette M, Lacherade JC, Yehia A, Joret A, Lebert C, Bourdon S, Martin Lefevre L, Reignier J. Antibiotic Therapy in Comatose Mechanically Ventilated Patients Following Aspiration: Differentiating Pneumonia From Pneumonitis. Crit Care Med. 2017 Aug;45(8):1268-1275. doi: 10.1097/CCM.0000000000002525. — View Citation

Marik PE, Careau P. The role of anaerobes in patients with ventilator-associated pneumonia and aspiration pneumonia: a prospective study. Chest. 1999 Jan;115(1):178-83. doi: 10.1378/chest.115.1.178. — View Citation

Marik PE. Aspiration syndromes: aspiration pneumonia and pneumonitis. Hosp Pract (1995). 2010 Feb;38(1):35-42. doi: 10.3810/hp.2010.02.276. — View Citation

Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, Cooley LA, Dean NC, Fine MJ, Flanders SA, Griffin MR, Metersky ML, Musher DM, Restrepo MI, Whitney CG. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67. doi: 10.1164/rccm.201908-1581ST. — View Citation

Rebuck JA, Rasmussen JR, Olsen KM. Clinical aspiration-related practice patterns in the intensive care unit: a physician survey. Crit Care Med. 2001 Dec;29(12):2239-44. doi: 10.1097/00003246-200112000-00001. — View Citation

Sirvent JM, Torres A, El-Ebiary M, Castro P, de Batlle J, Bonet A. Protective effect of intravenously administered cefuroxime against nosocomial pneumonia in patients with structural coma. Am J Respir Crit Care Med. 1997 May;155(5):1729-34. doi: 10.1164/ajrccm.155.5.9154884. — View Citation

Valles J, Peredo R, Burgueno MJ, Rodrigues de Freitas AP, Millan S, Espasa M, Martin-Loeches I, Ferrer R, Suarez D, Artigas A. Efficacy of single-dose antibiotic against early-onset pneumonia in comatose patients who are ventilated. Chest. 2013 May;143(5):1219-1225. doi: 10.1378/chest.12-1361. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ICU-free days		From admission to 30 days, death, or hospital discharge, whichever occurs first
Secondary	Ventilator-free days		From admission to 30 days, death, or hospital discharge, whichever occurs first
Secondary	Hospital-free days		From admission to 30 days, death, or hospital discharge, whichever occurs first
Secondary	Antibiotic-free days		Days with no antibiotics from admission to 30 days, death, or hospital discharge, whichever occurs first
Secondary	Intubated after enrollment	Yes/no	Between admission to 30 days, death, or hospital discharge, whichever occurs first
Secondary	Tracheostomy after enrollment	Yes/no	Between admission to 30 days, death, or hospital discharge, whichever occurs first
Secondary	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
Secondary	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
Secondary	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
Secondary	Positive sputum culture with presumed pathogen	Yes/no	Between enrollment and 30 days, death, or hospital discharge, whichever occurs first
Secondary	Any positive culture with organism resistant to prophylactic antibiotics	Yes/no	Between admission and 30 days, death, or hospital discharge, whichever occurs first
Secondary	Positive C. Difficile stool toxin assay after enrollment	Yes/no	Between enrollment and 30 days, death, or hospital discharge, whichever occurs first
Secondary	Temperature >38 centigrade on day 3	Yes/no	Day 3 after enrollment
Secondary	White blood cell count >11k on day 3	Yes/no	Day 3 after enrollment
Secondary	Arterial oxygen saturation / Fraction of inspired oxygen (S/F) <215 on day 3	Yes/no	Day 3 after enrollment
Secondary	Purulent secretions	Yes/no	Day 3 after enrollment