In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 62, No. 2 ( 2018-02)
Abstract:
The novel diazabicyclooctenone ETX2514 is a potent, broad-spectrum serine β-lactamase inhibitor that restores sulbactam activity against resistant Acinetobacter baumannii . The frequency of spontaneous resistance to sulbactam-ETX2514 in clinical isolates was found to be 7.6 × 10 −10 to 〈 9.0 × 10 −10 at 4× MIC and mapped to residues near the active site of penicillin binding protein 3 (PBP3). Purified mutant PBP3 proteins demonstrated reduced affinity for sulbactam. In a sulbactam-sensitive isolate, resistance also mapped to stringent response genes associated with resistance to PBP2 inhibitors, suggesting that in addition to β-lactamase inhibition, ETX2514 may enhance sulbactam activity in A. baumannii via inhibition of PBP2.
Type of Medium:
Online Resource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/AAC.01576-17
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2018
detail.hit.zdb_id:
1496156-8
SSG:
12
SSG:
15,3
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