Ceftriaxone to Prevent Early-Onset Pneumonia in Comatose Patients Following Out-of-Hospital Cardiac Arrest: A Pilot Randomized Controlled Trial and Resistome Assessment (PROTECT)

Gagnon, DJ; Burkholder, KM; Weissman, AJ; Riker, RR; Ryzhov, S; May, TL; DiPalazzo, J; deKay, JT; Knudsen, L; Moore, MW; Pozzessere, NA; Weatherbee, M; Kelly, M; Nigatu, AS; Sevigny, JL; Simpson, S; Thomas, WK; Callaway, CW; Geller, BJ; Sawyer, DB; Seder, DB

doi:10.1016/j.chest.2025.08.007

Cardiac arrest & resuscitation

Ceftriaxone to Prevent Early-Onset Pneumonia in Comatose Patients Following Out-of-Hospital Cardiac Arrest: A Pilot Randomized Controlled Trial and Resistome Assessment (PROTECT)

ChestPublished 28 Aug 2025Randomised controlled trial

Primary result · Early-onset pneumoniaResultRelative risk 0.57 95% CI 0.21–1.001

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Authors' conclusion

This trial was inconclusive regarding the impact of ceftriaxone prophylaxis on reducing the incidence of early-onset pneumonia following OHCA. However, ceftriaxone was associated with less frequent administration of open-label antibiotics and reduced acquisition of antibiotic resistance genes to frequently used antibiotics in the ICU.

Study context

Population: Comatose out-of-hospital cardiac arrest (OHCA) survivors treated with TTM without clinical diagnosis of pneumonia at admissionrandomized
Participants: 53 survivors

Comparison: Ceftriaxone 2 g vs placebo every 12 hours for 3 days
Ceftriaxonen = 26
Placebon = 26reference
Primary endpoint: Early-onset pneumonia ≤ 4 days after intubation, confirmed by masked adjudicators
Follow-up: ≤ 4 days following intubation

Methodological detailsplacebo-controlled, masked outcome adjudication

Placebo-controlled
Masked outcome adjudication

Primary result

Early-onset pneumonia

Relative risk

0.57

95% CI 0.21–1.001

P = 0.05

Events by treatment group

Ceftriaxone38%10 of 26

Placebo69%18 of 26

Ceftriaxone vs Placebo

RR 0.57 (95% CI 0.21–1.001); P = 0.05

As reported in the abstract

Further findings

Outcome	Ceftriaxone	Placebo	← Lower risk with ceftriaxone ←→ Higher risk with ceftriaxone →	Estimate
Open-label antibiotic administration	54%	85%	0.10.31310	RR 0.64 (95% CI 0.43–0.94)
Broad-spectrum agents	93%	100%
Acquisition of antibiotic resistance genes to frequently used ICU antibiotics (rectal swab metagenomics)Adjusted for baseline abundance of resistance genes			0.10.31310	IRR 0.30 (95% CI 0.13–0.70)
			0.10.31310Ratio (log scale)

Safety

Serious adverse drug effects

Not reported in either treatment group

Original publication

Ceftriaxone to Prevent Early-Onset Pneumonia in Comatose Patients Following Out-of-Hospital Cardiac Arrest: A Pilot Randomized Controlled Trial and Resistome Assessment (PROTECT). Chest. Published 28 August 2025. doi:10.1016/j.chest.2025.08.007

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