Participant- and Disease-Related Factors as Independent Predictors of Treatment Outcomes in the RESTORE-IMI 2 Clinical Trial: A Multivariable Regression Analysis

BACKGROUND: In the RESTORE-IMI 2 trial, imipenem/cilastatin/relebactam (IMI/REL) was noninferior to piperacillin/tazobactam in treating hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia. This post hoc analysis was conducted to determine independent predictors of efficacy outcomes in the RESTORE-IMI 2 trial, to assist in treatment decision making. METHODS: A stepwise multivariable regression analysis was conducted to identify variables that were independently associated with day 28 all-cause mortality (ACM), favorable clinical response at early follow-up (EFU), and favorable microbiologic response at end of treatment (EOT). The analysis accounted for the number of baseline infecting pathogens and in vitro susceptibility to randomized treatment. RESULTS: Vasopressor use, renal impairment, bacteremia at baseline, and Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II scores ≥15 were associated with a greater risk of day 28 ACM. A favorable clinical response at EFU was associated with normal renal function, an APACHE II score <15, no vasopressor use, and no bacteremia at baseline. At EOT, a favorable microbiologic response was associated with IMI/REL treatment, normal renal function, no vasopressor use, nonventilated pneumonia at baseline, intensive care unit admission at randomization, monomicrobial infections at baseline, and absence of Acinetobacter calcoaceticus-baumannii complex at baseline. These factors remained significant after accounting for polymicrobial infection and in vitro susceptibility to assigned treatment. CONCLUSIONS: This analysis, which accounted for baseline pathogen susceptibility, validated well-recognized patient- and disease-related factors as independent predictors of clinical outcomes. These results lend further support to the noninferiority of IMI/REL to piperacillin/tazobactam and suggests that pathogen eradication may be more likely with IMI/REL. CLINICAL TRIALS REGISTRATION: NCT02493764.