ANTHARTIC
Trial question
What is the role of preventive short-term antibiotic therapy in patients treated with targeted temperature management after out-of-hospital cardiac arrest with shockable rhythm?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
20.0% female
80.0% male
N = 194
194 patients (38 female, 156 male).
Inclusion criteria: adult patients in ICUs who were being mechanically ventilated after out-of-hospital cardiac arrest related to initial shockable rhythm and treated with targeted temperature management at 32 to 34°C.
Key exclusion criteria: ongoing antibiotic therapy, chronic colonization with multidrug-resistant bacteria, or moribund status.
Interventions
N=99 antibiotic (intravenous amoxicillin/clavulanate at doses of 1 g and 200 mg TID for 2 days, starting < 6 hours after the cardiac arrest).
N=95 control (intravenous saline TID for 2 days, starting < 6 hours after the cardiac arrest).
Primary outcome
Early ventilator-associated pneumonia
19%
34%
34.0 %
25.5 %
17.0 %
8.5 %
0.0 %
Antibiotic
Control
Significant
decrease ▼
NNT = 6
Significant decrease in early ventilator-associated pneumonia (19% vs. 34%; HR 0.53, 95% CI 0.31 to 0.92).
Secondary outcomes
Borderline significant increase in the rate of days with antibiotic use during the ICU stay (23% vs. 50%).
Significant decrease in the rate of cumulative incidence of ventilator-associated pneumonia on day 5 (17% vs. 31%; HR 0.53, 95% CI 0.3 to 0.95).
No significant difference in death at day 28 (41% vs. 37%; AD 4%, 95% CI -10 to 18).
Safety outcomes
No significant difference in serious adverse events.
Significant differences in heart diseases (0.12% vs. 0.06%), respiratory, thoracic, and mediastinal diseases (0.02% vs. 0.08%).
Conclusion
In adult patients in ICUs who were being mechanically ventilated after out-of-hospital cardiac arrest related to initial shockable rhythm and treated with targeted temperature management at 32 to 34°C, antibiotic was superior to control with respect to early ventilator-associated pneumonia.
Reference
Bruno François, Alain Cariou, Raphaël Clere-Jehl et al. Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest. N Engl J Med. 2019 Nov 7;381(19):1831-1842.
Open reference URL