Ventilator-Associated Pneumonia After Cardiac Arrest
What is the effect of systematic administration of empirical 2-day antibiotic therapy in preventing early ventilator-associated pneumonia and related complications in patients with out-of-hospital cardiac arrest treated with targeted temperature management?
The ANTHARTIC investigators conducted a multicenter, double-blind, randomized, placebo-controlled trial involving 198 adult patients (>18 years of age) in intensive care units (ICUs) who were being mechanically ventilated after out-of-hospital cardiac arrest related to initial shockable rhythm and treated with targeted temperature management at 32-34°C. Patients with ongoing antibiotic therapy, chronic colonization with multidrug-resistant bacteria, or moribund status were excluded. Either intravenous amoxicillin–clavulanate (at doses of 1 g and 200 mg, respectively) or placebo was administered three times a day for 2 days, starting <6 hours after the cardiac arrest. The primary outcome was early ventilator-associated pneumonia (during the first 7 days of hospitalization). An independent adjudication committee determined diagnoses of ventilator-associated pneumonia. Cumulative incidence curves of the primary outcome were estimated and compared with the use of the Fine–Gray approach.
A total of 198 patients underwent randomization, and 194 were included in the analysis. After adjudication, 60 cases of ventilator-associated pneumonia were confirmed, including 51 of early ventilator-associated pneumonia. The incidence of early ventilator-associated pneumonia was lower with antibiotic prophylaxis than with placebo (19 patients [19%] vs. 32 [34%]; hazard ratio, 0.53; 95% confidence interval, 0.31-0.92; p = 0.03). No significant differences between the antibiotic group and the control group were observed with respect to the incidence of late ventilator-associated pneumonia (4% and 5%, respectively), the number of ventilator-free days (21 days and 19 days), ICU length of stay (5 days and 8 days if patients were discharged and 7 days and 7 days if patients had died), and mortality at day 28 (41% and 37%). At day 7, no increase in resistant bacteria was identified. Serious adverse events did not differ significantly between the two groups.
The authors concluded that a 2-day course of antibiotic therapy with amoxicillin–clavulanate in patients receiving targeted temperature management strategy after out-of-hospital cardiac arrest with initial shockable rhythm resulted in a lower incidence of early ventilator-associated pneumonia than placebo.
This study reports that in patients treated with targeted temperature management after resuscitation of out-of-hospital cardiac arrests with shockable rhythm, a 2-day treatment with amoxicillin–clavulanate resulted in a lower incidence of early ventilator-associated pneumonia than placebo. Of note, treatment did not affect mortality at day 28 or the number of ventilator-free days. Additional treatment strategies need to be investigated to improve survival in this high-risk group.
Keywords: Acute Coronary Syndrome, Arrhythmias, Cardiac, Amoxicillin-Potassium Clavulanate Combination, Anti-Bacterial Agents, Antibiotic Prophylaxis, Bacteria, Hypothermia, Induced, Intensive Care Units, Length of Stay, Out-of-Hospital Cardiac Arrest, Pneumonia, Ventilator-Associated, Secondary Prevention
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