In Vitro Activity of Zosurabalpin Against Clinical Isolates of Carbapenem Resistant Acinetobacter baumannii

Abstract

The global rise of carbapenem-resistant Acinetobacter baumannii (CRAB) represents a major clinical challenge due to the limited availability of effective therapeutic options. Zosurabalpin (ZAB) is a novel macrocyclic peptide antibiotic that targets the lipopolysaccharide transport system (Lpt). The novel mechanism of action of ZAB has allowed it to emerge as a promising candidate for the treatment of carbapenem-resistant Acinetobacter baumannii. In this study, the in vitro activity of zosurabalpin was evaluated using broth microdilution (BMD) . A diverse collection of clinical isolates of Acinetobacter species was included in this study. Colistin was used as a comparator. ZAB demonstrated efficacy against all tested isolates. The minimum inhibitory concentration (MIC) values were distributed within a range below 1 μg/mL. Several isolates were resistant to colistin with MIC ranges far above established breakpoints. ZAB maintained efficacy even against colistin resistant isolates. MICs of these isolates were well within the excpected range. Several antimicrobial resistance genes , most notably OXA-type carbapenemases and metallo-β-lactamases (MBL) , were identified in the isolates that were tested. No clear association was established between the presence of these resistance determinants and activity of zosurabalpin. This is consistent with its novel mechanism of action that allows it to evade established mechanisms of antimicrobial resistance. Overall, these findings further support that zosurabalpin exhibits potent in vitro activity against multidrug-resistant (MDR) Acinetobacter isolates, including those resistant to colistin. These findings also support its potential as a novel therapeutic option for the treatment of infections caused by carbapenem resistant Acinetobacter baumannii.