Effect of prophylactic antibiotics on days of antibiotic spectrum coverage in comatose post-cardiac arrest patients: a secondary analysis of PROTECT
Abstract
Abstract Background Antibiotic resistance is a threat to public health driven in part by widespread antibiotic administration. Days of antibiotic spectrum coverage (DASC) is a novel metric to quantify both duration and breadth of antibiotic exposure that has not previously been used as an endpoint in a clinical trial. We calculated DASC using data from the Ceftriaxone to Prevent Pneumonia and Inflammation after Cardiac Arrest (PROTECT) trial to determine the association of ceftriaxone prophylaxis with DASC and with the acquisition of antibiotic resistance genes (ARGs). Methods PROTECT randomized out-of-hospital cardiac arrest subjects to ceftriaxone or placebo for 3 days. ARGs were measured from rectal swabs collected at Days 0, 3 and 7 post randomization. DASC was calculated for each subject and compared using a two-sided Mann–Whitney U-test. Correlations between DASC and new ARGs, antibiotic-free days (AFD) and days of therapy (DOT) were tested using Kendall’s tau-alpha. Results PROTECT enrolled 52 subjects, 26 per treatment group, and treatment groups were similar at baseline. Median DASC scores were lower in the ceftriaxone group (19.5; IQR: 0, 43) compared with placebo (53; IQR: 16, 81). We found no correlation between DASC and new ARGs at either timepoint, or between DASC and AFD. DASC was correlated with DOT. Conclusions DASC post intervention was lower in the ceftriaxone group, representing less antibiotic exposure following the intervention. There was no correlation…
How strong is the evidence?
Evidence Hub reads this as a secondary / pooled analysis, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 52 participants or records.
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