Open AccessFrequency and Mechanism of Spontaneous Resistance to Sulbactam Combined with the Novel β-Lactamase Inhibitor ETX2514 in Clinical Isolates of Acinetobacter baumannii
Author(s) -
Sarah M. McLeod,
Adam B. Shapiro,
Samir H. Moussa,
Michele Johnstone,
Robert E. McLaughlin,
Boudewijn L. M. de Jonge,
Alita A. Miller
Publication year - 2017
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.01576-17
Subject(s) - sulbactam , acinetobacter baumannii , microbiology and biotechnology , penicillin binding proteins , biology , beta lactamase inhibitors , acinetobacter , penicillin , bacteria , antibiotic resistance , antibiotics , genetics , imipenem , pseudomonas aeruginosa
The novel diazabicyclooctenone ETX2514 is a potent, broad-spectrum serine β-lactamase inhibitor that restores sulbactam activity against resistantAcinetobacter 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 inA. baumannii via inhibition of PBP2.
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