1230. Clinical and Microbiologic Outcomes by Causative Pathogen in Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia (HABP/VABP) Treated with Imipenem/Cilastatin (IMI)/Relebactam (REL) Versus Piperacillin/Tazobactam (PIP/TAZ)
Authors: Losada Maria C , Maniar Alok , Du Jiejun , Brown Michelle L , Young Katherine , Hilbert David W , Tipping Robert , DeRyke C Andrew , Butterton Joan R , Paschke Amanda , Chen Luke F 
Published: January 2021

Background

IMI/REL is a combination of IMI and the novel class A and class C β-lactamase inhibitor REL. Here we present per-pathogen outcomes from a recent phase 3 clinical trial (RESTORE-IMI 2), in which IMI/REL was shown to be non-inferior to piperacillin/tazobactam (PIP/TAZ) for empiric therapy of HABP/VABP, in both primary and key secondary endpoints.

Methods

Randomized, controlled, double-blind, multinational, phase 3, non-inferiority trial in adults with HABP/VABP. Lower respiratory tract specimens were obtained ≤48 hours prior to screening. Participants (pts) were randomized 1:1 to IMI/REL 500 mg/250 mg or PIP/TAZ 4 g/500 mg, given intravenously every 6 h for 7-14 d. Pts also received empiric linezolid until baseline cultures confirmed absence of MRSA. This analysis evaluated outcomes by causative LRT pathogen in modified intent to treat (MITT) pts (randomized pts with ≥1 dose of study drug, excluding pts with only gram-positive cocci present on baseline Gram stain) who had ≥1 baseline LRT pathogen susceptible (according to CLSI criteria) to both study drugs. Outcomes assessed were microbiologic response at end of therapy (EOT), clinical response at early follow-up (EFU; 7-14 d after EOT), and Day 28 all-cause mortality (ACM).

Results

Of 531 MITT pts, 51.4% (130 IMI/REL, 143 PIP/TAZ) had ≥1 baseline LRT pathogen susceptible to both study drugs. The most common causative pathogens in this analysis population were Klebsiella spp (30.4% of patients), Pseudomonas aeruginosa (22.3%), Escherichia coli (22.0%), and Haemophilus influenzae (9.2%), consistent with other recent trials in HABP/VABP and with surveillance data. Outcomes by pathogen were generally comparable between IMI/REL and PIP/TAZ (Table). In a separate subgroup analysis of the microbiologic MITT population, in pts with ≥1 ESBL-positive LRT pathogen (45 IMI/REL, 35 PIP/TAZ), microbiologic response at EOT was 82.2% (IMI/REL) vs 68.6%% (PIP/TAZ), clinical response at EFU was 64.4% vs 60.0%, and Day 28 ACM was 20.0% and 22.9%, respectively. In the IMI/REL arm, 8 pts had ≥1 confirmed KPC-positive baseline LRT pathogen; KPC status was not assessed in the PIP/TAZ arm.

Conclusion

IMI/REL is an efficacious treatment option for HABP/VABP, regardless of causative pathogen.

Table. Primary and secondary efficacy outcomes in patients who were in the MITT population and had at least 1 baseline LRT pathogen susceptible to both study drugs

Disclosures

Maria C. Losada, BA, Merck & Co., Inc. (Employee, Shareholder) Jiejun Du, PhD, Merck & Co., Inc. (Employee, Shareholder) Michelle L. Brown, BS, Merck & Co., Inc. (Employee, Shareholder) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Robert Tipping, MS, Merck & Co., Inc. (Employee, Shareholder) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Joan R. Butterton, MD, Merck & Co., Inc. (Employee, Shareholder) Amanda Paschke, MD MSCE, Merck & Co., Inc. (Employee, Shareholder) Luke F. Chen, MBBS MPH MBA FRACP FSHEA FIDSA, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder)