Prognostic Impact of Early Appropriate Antimicrobial Therapy in Critically Ill Patients With Nosocomial Pneumonia Due to Gram-Negative Pathogens: A Multicenter Cohort Study

Objectives: To evaluate whether early appropriate antimicrobial therapy (EAAT) is associated with improved outcomes in critically ill patients with hospital-acquired pneumonia (HAP), ventilated HAP (vHAP), or ventilator-associated pneumonia (VAP) involving Gram-negative bacteria (GNB). Design: Retrospective cohort study based on prospectively collected data. Setting: Thirty-two-French ICUs (OutcomeRéa network). Patients: All patients with a first HAP, vHAP, or VAP due to GNB during their ICU stay. Interventions: None. Measurements and Main Results: The relationship between EAAT and day 28 all-cause mortality (primary endpoint) was explored through Cox proportional-hazard models, with subgroup analyses according to pneumonia types, causative GNB, features of EAAT, and the occurrence of septic shock at pneumonia diagnosis. The course of Sequential Organ Failure Assessment (SOFA) score values, the clinical cure rate at day 14, and the time to mechanical ventilation (MV) weaning and ICU discharge after pneumonia diagnosis were investigated as secondary endpoints. Among the 804 included patients, 495 (61.6%) received EAAT (single-drug, 25.4%; combination, 36.2%). Day 28 mortality was 32.6%. EAAT was not independently associated with this outcome (adjusted hazard ratio, 0.87; 95% CI, 0.67–1.12). This result was confirmed in subgroup analyses as in a second model considering all episodes of pneumonia occurring during the ICU stay. EAAT was not associated with a faster decrease in SOFA score values ( p = 0.11), a higher day 14 clinical cure rate (overall, 43.7%), or a shorter MV duration (cause-specific hazard ratio [HR] for extubation, 0.84; 95% CI, 0.69–1.01) or ICU stay (cause-specific HR for discharge alive, 0.85; 95% CI, 0.72–1.00). Conclusions: In this study, EAAT was not associated with a reduced day 28 mortality, a faster resolution of organ failure, a higher day 14 clinical cure rate, or a shorter time to MV weaning or ICU discharge in critically ill patients with HAP, vHAP, or VAP due to GNB. However, a prognostic benefit from EAAT cannot be ruled out due to lack of statistical power.