Ceftriaxone to prevent early-onset pneumonia in comatose patients after out-of-hospital cardiac arrest: a pilot randomized controlled trial and resistome assessment (PROTECT).

Authors

David J Gagnon, MaineHealthFollow
Kristin M Burkholder
Alexandra J Weissman
Richard R. Riker, MaineHealthFollow
Sergey Ryzhov, MaineHealthFollow
Teresa May, MaineHealthFollow
John DiPalazzo, MaineHealthFollow
Joanne dekay, MaineHealthFollow
Laccey Knudsen, MaineHealthFollow
Meagan W Moore, MaineHealth
Mary Weatherbee, MaineHealth
Muriel Kelly
Adane S Nigatu
Joseph L Sevigny
Stephen Simpson
W Kelley Thomas
Clifton W Callaway
Bram J. Geller, MaineHealthFollow
Douglas Sawyer, MaineHealthFollow
David Seder, MaineHealthFollow

Document Type

Article

Publication Date

8-28-2025

Institution/Department

Center for Clinical & Translational Science; Center for Molecular Science; Cardiology; Critical Care Services

Journal Title

Chest

Abstract

BACKGROUND: Antibiotic prophylaxis after out-of-hospital cardiac arrest (OHCA) reduces early-onset pneumonia, but has uncertain impact on mortality and non-infectious outcomes, with ongoing concerns about the subsequent development of antibiotic resistance.

RESEARCH QUESTION: Does prophylactic ceftriaxone reduce the incidence of early-onset pneumonia without increasing the acquisition of antibiotic resistance genes after OHCA?

STUDY DESIGN: and Methods: Comatose survivors of OHCA treated with targeted temperature management without a clinical diagnosis of pneumonia at admission were randomized to ceftriaxone 2 gm or matching placebo every 12 hours for three days. The primary outcome was early-onset pneumonia occurring ≤4 days after intubation confirmed by blinded adjudicators. Abundance of antibiotic resistance genes recovered from rectal swabs before-and-after study drug administration were analyzed with metagenomic sequencing.

RESULTS: 411 subjects were screened, 53 (13%) were randomized, and one subject withdrew, leaving 26 in each group in the final analysis. Early-onset pneumonia was diagnosed in 10 (38%) subjects receiving ceftriaxone and 18 (69%) subjects receiving placebo (RR 0.57, 95% CI 0.21-1.001; p=0.05). Open-label antibiotics were administered to 14 (54%) subjects receiving ceftriaxone and 22 (85%) receiving placebo (RR 0.64, 95%CI 0.43-0.94), most of which were broad-spectrum (93% and 100%, respectively). After adjusting for differences in abundance of antibiotic resistance genes prior to study drug administration, subjects randomized to ceftriaxone acquired significantly fewer antibiotic resistance genes to frequently used antibiotics in the ICU compared to those randomized to placebo (IRR 0.30, 95% CI 0.13-0.70). Serious adverse drug effects were not reported in either treatment group.

INTERPRETATION: This trial was inconclusive regarding the impact of ceftriaxone prophylaxis to reduce the incidence of EOP after OHCA but ceftriaxone was associated with less frequent administration of open-label antibiotics, and reduced acquisition of ARGs to frequently used antibiotics in the ICU.

CLINICAL TRIAL REGISTRATION: National Library of Medicine at www.

CLINICALTRIALS: gov (NCT04999592).

ISSN

1931-3543

Recommended Citation

Gagnon, David J; Burkholder, Kristin M; Weissman, Alexandra J; Riker, Richard R.; Ryzhov, Sergey; May, Teresa; DiPalazzo, John; dekay, Joanne; Knudsen, Laccey; Moore, Meagan W; Weatherbee, Mary; Kelly, Muriel; Nigatu, Adane S; Sevigny, Joseph L; Simpson, Stephen; Thomas, W Kelley; Callaway, Clifton W; Geller, Bram J.; Sawyer, Douglas; and Seder, David, "Ceftriaxone to prevent early-onset pneumonia in comatose patients after out-of-hospital cardiac arrest: a pilot randomized controlled trial and resistome assessment (PROTECT)." (2025). MaineHealth Maine Medical Center. 4167.
https://knowledgeconnection.mainehealth.org/mmc/4167