2517. Activity of Sulbactam-durlobactam, Antibacterial Combinations, and Comparators Against a Challenge Set of 66 Acinetobacter baumannii-calcoaceticus Species Complex Isolates
Authors: Huband Michael D , Mendes Rodrigo E , Morgan Gina M , Huynh Holly , Castanheira Mariana 
Published: November 2023

Abstract

Background
Sulbactam-durlobactam (SUL-DUR) is in clinical development for the treatment of Acinetobacter baumannii calcoaceticus species complex (ACB) isolates, including multidrug-resistant (MDR) and carbapenem-resistant strains. SUL-DUR is a combination of sulbactam, a β-lactam antibacterial with activity against ACB and durlobactam, a β-lactamase inhibitor with activity against Class A, C and D β-lactamases. In this study, we evaluated the in vitro activity of SUL-DUR, as well as double and triple combinations of SUL, DUR and cefiderocol or imipenem against a set of 66 ACB isolates.
Activity of sulbactam-durlobactam (fixed 4 mg/L), antibacterial combinations, and comparators against a set of 66 A. baumannii-calcoaceticus species complex isolates

Methods
Bacterial isolates consisted of 41 ACB isolates from the Centers for Disease Control and Prevention Antimicrobial Resistance Bank and 25 molecularly characterized cefiderocol-resistant ACB clinical isolates from the SENTRY Antimicrobial Surveillance Program. ACB identifications were confirmed by MALDI-TOF. Susceptibility testing of SUL-DUR and comparators was conducted according to CLSI M07 (2018) and M100 (2023) guidelines. Susceptibility testing of cefiderocol and cefiderocol combinations was conducted in Chelex-treated Mueller-Hinton broth. Cefiderocol and imipenem results were interpreted using CLSI breakpoint criteria

Results
SUL-DUR (MIC50/90, 2/4 mg/L; 98.5% inhibited at ≤4 mg/L), cefiderocol-sulbactam-durlobactam (MIC50/90, 0.5/1 mg/L; 98.5% inhibited at ≤4 mg/L), and imipenem-sulbactam-durlobactam (MIC90, 1/2 mg/L; 98.5% inhibited at ≤2 mg/L) were the most active combinations tested against the set of 66 A. baumannii isolates (Table). Against these isolates, cefiderocol and imipenem susceptibilities were 37.9% (CLSI) and 9.1% (CLSI), respectively.

Conclusion
Overall, SUL-DUR (MIC50/90, 2/4 mg/L; 98.5% inhibited at ≤4 mg/L) was active against the ACB isolates tested regardless of cefiderocol susceptibility, including MDR and carbapenem-resistant isolates. The addition of imipenem or cefiderocol to SUL-DUR did not greatly improve SUL-DUR activity (decreased overall MIC90 values by up to 4-fold) when compared to SUL-DUR tested alone. The potent activity of SUL-DUR against this set of ACB isolates, including cefiderocol-resistant strains, supports the continued development of this combination.

Disclosures
Michael D. Huband, BS, BARDA: This study has been funded in part by BARDA under Contract No. 75A50120C00001.|Entasis: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Entasis: Grant/Research Support|GSK: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Gina M. Morgan, MS, Entasis: Grant/Research Support Holly Huynh, BS, Entasis: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support