Lower risk of early ventilator-associated pneumonia with antibiotics in patients with out-of-hospital cardiac arrest

Reference

Francois B, Cariou A, Clere-Jehl R, et al, for the CRICS-TRIGGERSEP Network and the ANTHARTIC Study Group. Prevention of early ventilator-associated pneumonia after cardiac arrest. N Engl J Med 2019;381(19):1831-1842.

Synopsis

Patients with out-of-hospital cardiac arrest with shockable rhythms who are mechanically ventilated and treated with targeted temperature management at 32 to 34 degrees Celsius are at higher risk of VAP. These investigators randomized patients within 6 hours of the return of spontaneous circulation to receive either 2 days of empiric antibiotic therapy (n = 99) or placebo (n = 99). The antibiotic group received amoxicillin-clavulanate 1000 mg/200 mg intravenously 3 times daily for 2 days, while the control group received saline injections. Both groups also received rapid initiation of targeted temperature management. The 2 groups had similar characteristics at baseline: median age was 61 years, 80% were men, and the median APACHE II score was 24 (scale of 0 to 71, with higher scores indicating a higher risk of death). In the control group, 2 patients who withdrew consent and 2 patients who did not receive any doses of study medications were excluded from the analysis. A central adjudication committee unaware of study-group assignments confirmed reported VAP according to predefined criteria. For the primary outcome of early VAP, defined as occurring during the first 7 days of hospitalization, the antibiotic group fared better than the control group (19% vs 34%; hazard ratio 0.53; 95% CI 0.31 - 0.92; P = .03). There were no differences detected in incidence of late VAP, number of ventilator-free days, intensive care unit length of stay, or 28-day mortality. Gram-negative bacilli were the predominant bacteria found in patients with confirmed VAP, with more enterobacteria in the antibiotic group than in the control group. Rectal swabbing before and after the intervention did not show a higher number of multidrug-resistant bacteria. No serious adverse events were attributed to the study drugs.