Affiliation:
1. Antabio SAS, Labège, France
2. IHMA Europe, Monthey/VS, Switzerland
3. Evotec, Macclesfield, United Kingdom
Abstract
ABSTRACT
ANT3310 is a novel broad-spectrum diazabicyclooctane serine β-lactamase inhibitor being developed in combination with meropenem (MEM) for the treatment of serious infections in hospitalized patients where carbapenem-resistant Gram-negative pathogens are expected. In this study, we evaluated the
in vitro
antibacterial activity of MEM in the presence of ANT3310 at 8 µg/mL against global clinical isolates that included
Acinetobacter baumannii
(
n
= 905), carbapenem-resistant Enterobacterales (CRE), carrying either oxacillinase (OXA) (
n
= 252) or
Klebsiella pneumoniae
carbapenemase (KPC) (
n
= 180) carbapenemases, and
Pseudomonas aeruginosa
(
n
= 502). MEM was poorly active against
A. baumannii,
as were MEM-vaborbactam, ceftazidime-avibactam, aztreonam-avibactam, cefepime-taniborbactam, cefepime-zidebactam, and imipenem-relebactam (MIC
90
values of ≥32 µg/mL). On the other hand, MEM-ANT3310 displayed an MIC
90
value of 4 µg/mL, similar to that observed with sulbactam-durlobactam, a drug developed to specifically treat
A. baumannii
infections. ANT3310 (8 µg/mL) additionally restored the activity of MEM against OXA- and KPC-producing CREs decreasing MEM MIC
90
values from >32 µg/mL to 0.25 and 0.5 µg/mL, respectively. The combination of 8 µg/mL of both MEM and ANT3310 prevented growth of 97.5% of
A. baumannii
and 100% of OXA- and KPC-positive CREs, with ~90% of
P. aeruginosa
isolates also displaying MEM MICs ≤8 µg/mL. Furthermore, MEM-ANT3310 was efficacious in both thigh and lung murine infection models with OXA-23
A. baumannii
. This study demonstrates the potent
in vitro
activity of the MEM-ANT3310 combination against both carbapenem-resistant
A. baumannii
and Enterobacterales clinical isolates, a key differentiator to other β-lactam/β-lactamase combinations.
Funder
Contrat Innovation, Region Occitanie
Publisher
American Society for Microbiology
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