1583. In Vitro Activity of Imipenem/Relebactam against Klebsiella pneumoniae and Pseudomonas aeruginosa from Patients in ICUs in the Asia/Pacific region – SMART 2015-2018
Authors: Lob Sibylle , Hackel Meredith , Chen Wei-Ting , Khoo Yivonne , Balwani Kanchan , Young Katherine , Motyl Mary , Sahm Daniel F 
Published: January 2021

Abstract

Background
Relebactam (REL) is an inhibitor of class A and C β-lactamases approved in the USA in combination with imipenem (IMI) and cilastatin for the treatment of complicated intraabdominal and urinary tract infections. Elevated antimicrobial resistance rates have been reported in ICUs. Using isolates collected in Asia/Pacific for the SMART surveillance program, we evaluated the activity of IMI/REL and comparators against K. pneumoniae (KP) and P. aeruginosa (PA) from ICU patients.

Methods
In 2015-2018, 51 clinical laboratories in Australia, Hong Kong, Malaysia, New Zealand, Philippines, Singapore, South Korea, Taiwan, Thailand, and Vietnam each collected up to 250 consecutive aerobic gram-negative pathogens per year. Susceptibility was determined using CLSI broth microdilution and CLSI and FDA (IMI/REL) breakpoints. IMI-nonsusceptible KP and PA were screened for β-lactamase genes.

Results
Analyzing only the 6322 isolates from ICU patients, the 3 most common species collected were KP (21.4%), E. coli (20.5%), and PA (19.7%). Tables 1 and 2 show % susceptible and % MBL- and/or OXA-48-like-positive for the most common Enterobacterales species (KP; 70.6% from lower respiratory tract, 17.6% from intraabdominal, 7.1% from urinary tract, and 4.1% from bloodstream infections) and the most common non-Enterobacterales species (PA; 83.6%, 9.9%, 4.3%, and 1.9%, respectively). % IMI/REL-susceptible ranged from 66-79% in Thailand and Vietnam (where 13-36% of isolates carried MBL and/or OXA-48-like carbapenemases, which REL does not inhibit) to ≥95% in 6 countries (0-3% MBL- and/or OXA-48-like-positive). Among 103 IMI/REL-nonsusceptible KP isolates, 66.0% carried MBL, 20.4% OXA-48-like carbapenemases, 2.9% KPC, 2.9% acquired AmpC and/or ESBL, and in 7.8% no acquired β-lactamases were detected. Among 145 IMI/REL- nonsusceptible PA, 54.5% carried MBL, 1.4% GES carbapenemases, 4.1% only ESBL, and 40.0% no acquired β-lactamases.
Table 1. Antimicrobial susceptibility of K. pneumoniae collected from ICU patients

Table 2. Antimicrobial susceptibility of P. aeruginosa collected from ICU patients

Conclusion
IMI/REL was active against 92% of KP and 88% of PA from ICU patients in Asia/Pacific overall, with higher activity in countries with lower prevalence of MBL or OXA-48-like carbapenemases. IMI/REL provides a potential treatment option for ICU patients in Asia/Pacific with infections caused by KP and PA.

Disclosures
Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Wei-Ting Chen, MD, Merck, Sharp & Dohme, Taiwan (Employee) Yivonne Khoo, PhD, Merck, Sharp & Dohme, Malaysia (Employee) Kanchan Balwani, MBBS, MS, Merck, Sharp & Dohme, Hong Kong (Employee) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)