Abstract Sun405: Effect of Prophylactic Antibiotics on Days of Antibiotic Spectrum Coverage in Comatose Post-cardiac Arrest Patients: A <i>Post-hoc</i> Analysis of PROTECT

Abstract

Background: Antibiotic resistance is a public health threat driven in part by indiscriminate antibiotic administration, which can exert changes in the resistome. Days of antibiotic spectrum coverage (DASC) is a novel metric to quantify antibiotic exposure, but it has not been tested as an endpoint in a clinical trial or tested for association with resistome changes. Research Questions: Do prophylactic antibiotics alter subsequent antibiotic exposure, as measured by DASC, and is there a correlation between DASC and presence of new antibiotic resistance genes (ARGs)? Goals/Aims: Determine if DASC differs in subjects randomized to ceftriaxone (CTX) or placebo and if DASC correlates with presence of new ARGs using data from the Ceftriaxone to Prevent Pneumonia and Inflammation after Cardiac Arrest (PROTECT) trial. Methods: PROTECT (NCT04999592) randomized mechanically ventilated, comatose, OHCA subjects to CTX 2 grams IV every 12 hours for 3 days or placebo. ARGs were measured from rectal swab fecal material collected at days 0, 3, and 7 post randomization. DASC post intervention was calculated post hoc for each subject and compared using a two-sided Mann Whitney U test with the Somers’ D estimation for 95% confidence intervals (CI). Correlation between DASC and presence of new ARGs sequenced from the resistome at days 3 and 7 post randomization was compared using the Greiner’s rho (ρ) transformation of Kendall’s T α . Results: PROTECT enrolled 52 subjects, 26 per treatment group. Treatment groups were similar at baseline: CTX age 60 (52, 67) and 85% male versus placebo age 59 (52, 65) and 92% male; numerically lower rate of shockable rhythm and higher rate of witnessed arrest with bystander CPR in the CTX group ( Table 1 ). Median DASC scores were lower in the CTX group (19.5 [0, 43]) compared to placebo (53 [16, 81]); Somers’ D = -0.374, 95% CI [-0.624, -0.055]; p=0.012). Correlation between DASC and new ARGs at 3 days was Greiner’s ρ = 0.095, 95% CI -0.284, 0.448 (p=0.628) and at 7 days was Greiner’s ρ = 0.244, 95% CI -0.294, 0.665 (p=0.357) ( Table 2 ). Conclusions: DASC post intervention was lower in the CTX group, corresponding to less antibiotic exposure following receipt of the intervention. There was no correlation between presence of new ARGs and DASC. Low enrollment and early trial termination are limitations. Further study is needed to understand the relationship between antibiotic prophylaxis, subsequent antibiotic exposure, and resistome changes in the critically ill.