Quantifying the importance of active antimicrobial therapy among patients with Gram-negative bloodstream infections: Cefepime as a representative agent

The quantitative importance of active antimicrobial treatment relative to other modifiable and non-modifiable risk factors for mortality has not been well defined in the literature. Here we quantify the impact of active antimicrobial treatment on mortality relative to other disease modifiers in patients with Gram-negative bloodstream infection (GNBSI). Patients with at least one positive blood culture who were treated with ≥24 h of cefepime for GNBSI were included in the study. To examine in-hospital survival, a full primary model and a base model with the least significant covariate from the primary model were established. Relative importance of covariates was calculated using percentages of difference in log-likelihood values when each covariate was iteratively added to the base model. A total of 154 unique patients with GNBSI were included. The primary model included active cefepime therapy (P = 0.004), normalised days to positive culture (P = 0.091), intensive care unit (ICU) at time of treatment (P = 0.001), modified Acute Physiology and Chronic Health Evaluation (APACHE) II score on day zero (P = 0.025), history of leukaemia (P = 0.008) and prior immunosuppressive therapy (P = 0.088). Active antimicrobial therapy displayed a relative importance of 32.2%, which was second to ICU residence at the time of culture. Amongst all covariates in the model, active antimicrobial therapy was the only modifiable variable and contributed significantly to in-hospital survival in acutely ill patients with GNBSI.