Participant- and Disease-Related Factors as Independent Predictors of Treatment Outcomes in the RESTORE-IMI 2 Clinical Trial: A Multivariable Regression Analysis.
HABP
VABP
antibiotic
imipenem
relebactam
Journal
Open forum infectious diseases
ISSN: 2328-8957
Titre abrégé: Open Forum Infect Dis
Pays: United States
ID NLM: 101637045
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
24
01
2023
accepted:
03
05
2023
medline:
29
6
2023
pubmed:
29
6
2023
entrez:
29
6
2023
Statut:
epublish
Résumé
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. 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. 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 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. NCT02493764.
Sections du résumé
Background
UNASSIGNED
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
UNASSIGNED
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
UNASSIGNED
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
Conclusions
UNASSIGNED
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
UNASSIGNED
NCT02493764.
Identifiants
pubmed: 37383243
doi: 10.1093/ofid/ofad225
pii: ofad225
pmc: PMC10297016
doi:
Banques de données
ClinicalTrials.gov
['NCT02493764']
Types de publication
Journal Article
Langues
eng
Pagination
ofad225Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
Déclaration de conflit d'intérêts
Potential conflicts of interest. L. F. C., J. D., M. C. L., A. P., C. A. D., M. W., and E. H. J. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, New Jersey, who may own stock and/or hold stock options in the Merck & Co, Inc, Rahway, New Jersey. All other authors report no potential conflicts.
Références
Int J Infect Dis. 2019 Dec;89:55-61
pubmed: 31479762
Sci Rep. 2019 Jun 11;9(1):8478
pubmed: 31186488
Antimicrob Agents Chemother. 2018 Feb 23;62(3):
pubmed: 29311084
Infect Drug Resist. 2021 Aug 31;14:3509-3518
pubmed: 34511942
Chest. 2012 Jul;142(1):30-39
pubmed: 22194591
Crit Care. 2013 May 03;17(3):R84
pubmed: 23642005
Crit Care. 2021 Aug 11;25(1):290
pubmed: 34380538
Crit Care. 2011;15(1):R62
pubmed: 21324159
Antimicrob Agents Chemother. 2015 Aug;59(8):5029-31
pubmed: 26014931
Crit Care Med. 2007 Sep;35(9):2064-70
pubmed: 17581489
J Antimicrob Chemother. 1983 Dec;12 Suppl D:1-35
pubmed: 6365872
Open Forum Infect Dis. 2018 Sep 21;5(10):ofy241
pubmed: 30364442
Crit Care Med. 2013 Sep;41(9):2151-61
pubmed: 23760154
J Antimicrob Chemother. 2022 Oct 28;77(11):2992-2999
pubmed: 35906810
Br J Clin Pharmacol. 2016 Jun;81(6):1113-23
pubmed: 26852277
Ann Clin Microbiol Antimicrob. 2018 Mar 23;17(1):13
pubmed: 29571291
Clin Infect Dis. 2016 Sep 1;63(5):e61-e111
pubmed: 27418577
Open Forum Infect Dis. 2021 Dec 09;8(12):ofab554
pubmed: 34901302
N Engl J Med. 2014 Mar 27;370(13):1198-208
pubmed: 24670166
Int J Infect Dis. 2015 Jan;30:144-7
pubmed: 25461659
Antimicrob Agents Chemother. 2017 May 24;61(6):
pubmed: 28320716
Diagn Microbiol Infect Dis. 2021 Feb;99(2):115172
pubmed: 33130502
Clin Infect Dis. 2021 Jun 15;72(12):2112-2120
pubmed: 32246147
Crit Care. 2015 May 06;19:219
pubmed: 25944081
Bioorg Med Chem Lett. 2014 Feb 1;24(3):780-5
pubmed: 24433862
Clin Infect Dis. 2022 Aug 25;75(2):187-212
pubmed: 35439291
CPT Pharmacometrics Syst Pharmacol. 2019 Oct;8(10):748-758
pubmed: 31508899
BMC Microbiol. 2019 Jul 4;19(1):150
pubmed: 31272373
J Antimicrob Chemother. 2018 Jul 1;73(7):1872-1879
pubmed: 29659861
Braz J Infect Dis. 2017 May - Jun;21(3):343-348
pubmed: 28399424
Antimicrob Resist Infect Control. 2020 Jan 3;9(1):2
pubmed: 31911830
J Antimicrob Chemother. 2013 Oct;68(10):2286-90
pubmed: 23696619
Rev Esp Quimioter. 2021 Dec;34(6):639-650
pubmed: 34806858
Infect Control Hosp Epidemiol. 2016 Nov;37(11):1288-1301
pubmed: 27573805
J Med Microbiol. 2017 Jan;66(1):61-69
pubmed: 28051952
Clin Infect Dis. 2020 Apr 15;70(9):1799-1808
pubmed: 31400759
J Bras Pneumol. 2021 Jun 23;47(3):e20200569
pubmed: 34190861
J Infect Dis. 2019 Apr 19;219(10):1536-1544
pubmed: 30649434
Pharmacotherapy. 2021 Aug;41(8):658-667
pubmed: 34097763
Open Forum Infect Dis. 2017 Jun 01;4(2):ofx063
pubmed: 28584849
Rev Soc Bras Med Trop. 2017 Mar-Apr;50(2):167-172
pubmed: 28562751
Clin Infect Dis. 2021 Dec 6;73(11):e4539-e4548
pubmed: 32785589
J Hosp Med. 2016 Jan;11(1):21-6
pubmed: 26353076
J Clin Med. 2019 Aug 14;8(8):
pubmed: 31416285
Eur J Clin Microbiol Infect Dis. 2017 Nov;36(11):1999-2006
pubmed: 27287765
Am J Med. 2006 Oct;119(10):897.e13-9
pubmed: 17000224
Eur Respir J. 2017 Sep 10;50(3):
pubmed: 28890434