The safety of targeted antibiotic therapy for ventilator-associated pneumonia: A multicenter observational study

Purpose: The aim of this study was to determine the safety of targeted antibiotic therapy (TT) in ventilator-associated pneumonia (VAP). Materials and Methods: This was a secondary analysis from a multicenter trial of 740 patients with suspected VAP randomized to bronchoscopy or endotracheal aspirate cultures; all received empirical broad-spectrum antibiotics. Patients were grouped by whether they received TT, defined as tailoring or discontinuing antibiotics in response to enrolment culture results. Results: For patients with a positive culture (n = 412), baseline demographics, clinical progression of infection and multiple organ dysfunction scores (MODS), and mortality were similar for those on TT (n = 320) or those who did not receive TT (NoTT) (n = 92). The TT group had more days alive and off broad-spectrum antibiotics (14.5 vs 13.2, P = .04). In patients with a negative culture (n = 327), those on TT (n = 230) had similar baseline demographics, less frequent final adjudicated diagnosis of VAP (63.0% vs 76.3%, P = .02), and less severe clinical progression of infection and MODS compared with NoTT (n = 97). The TT group had more days alive and off broad-spectrum antibiotics (15.9 vs 13.1, P b .001), lower δ MODS (2.0 vs 3.0, P = .01), fewer mechanical ventilation days (9.8 vs 14.7, P = .03), and similar mortality compared to NoTT. Conclusions: Targeted therapy is associated with less antibiotic use and no evidence of harm in the management of patients with VAP.