TY - JOUR
T1 - Participant- and Disease-Related Factors as Independent Predictors of Treatment Outcomes in the RESTORE-IMI 2 Clinical Trial
T2 - A Multivariable Regression Analysis
AU - Martin-Loeches, Ignacio
AU - Shorr, Andrew F.
AU - Kollef, Marin H.
AU - Du, Jiejun
AU - Losada, Maria C.
AU - Paschke, Amanda
AU - DeRyke, C. Andrew
AU - Wong, Michael
AU - Jensen, Erin H.
AU - Chen, Luke F.
N1 - Funding Information:
Acknowledgments. Medical writing and editorial assistance was provided by Meredith Rogers, MS, CMPP, of The Lockwood Group, Stamford, Connecticut. This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, New Jersey. The authors also thank Dominik Wolf, of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, for his critical review of the manuscript.
Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
PY - 2023/6/1
Y1 - 2023/6/1
N2 - 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.
AB - 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.
KW - HABP
KW - VABP
KW - antibiotic
KW - imipenem
KW - relebactam
UR - http://www.scopus.com/inward/record.url?scp=85164218531&partnerID=8YFLogxK
U2 - 10.1093/ofid/ofad225
DO - 10.1093/ofid/ofad225
M3 - Article
C2 - 37383243
AN - SCOPUS:85164218531
SN - 2328-8957
VL - 10
JO - Open Forum Infectious Diseases
JF - Open Forum Infectious Diseases
IS - 6
M1 - ofad225
ER -