Aggressive Antimicrobial Initiation for Suspected Intensive Care Unit-Acquired Infection Is Associated with Decreased Long-Term Survival after Critical Illness

Background: The long-term significance of early and prolonged antibiotic use in critically ill patients is yet to be described. Several studies suggest that antimicrobial exposure may have as yet unrecognized long-term effects on clinically meaningful outcomes. Our group previously conducted a quasi-experimental, before and after observational cohort study of hemodynamically stable surgical patients suspected of having an intensive care unit-acquired infection. This study demonstrated that aggressive initiation of antimicrobial therapy was associated with increased 30-day deaths. In a follow-up survival analysis, we hypothesized that aggressive antimicrobial treatment would not be a significant predictor of long-term death.

Methods: Survival data for the 201 patients included in the initial study were obtained from our clinical data repository. Univariable analysis, Kaplan-Meier, and Cox proportional hazards models were used. Survival was evaluated at one and four years. Age, gender, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and co-morbidities were chosen a priori for potential inclusion in the model. Variables that met the model assumptions after testing were included in the final model.

Results: Follow-up data were available for 190 patients (95 in each group) representing 94.5% of the initial cohort. Twenty-four (25.3%) patients in the aggressive group had initial APACHE II scores of less than 15 compared with 13 (13.7%) patients in the conservative group (p = 0.04). There was a trend toward higher deaths in the aggressive group at four years (41.1% vs. 30.5%; p = 0.13). Kaplan-Meier analysis demonstrated a difference in survival at one year but not at four years. The Cox proportional hazards model showed a higher long-term death for patients in the aggressive antimicrobial group at both one and four years (hazard rate: 2.26 and 1.70, respectively).

Conclusion: Aggressive initiation of antimicrobial therapy is independently associated with decreased long-term survival after critical illness. While further work is needed to confirm these findings, waiting for evidence of infection before initiation of antibiotic agents may be beneficial.