Frequency and Mechanism of Spontaneous Resistance to Sulbactam Combined with the Novel ß-Lactamase Inhibitor ETX2514 in Clinical Isolates of Acinetobacter baumannii.
Antimicrob Agents Chemother
; 62(2)2018 02.
Article
em En
| MEDLINE
| ID: mdl-29133555
ABSTRACT
The novel diazabicyclooctenone ETX2514 is a potent, broad-spectrum serine ß-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 ß-lactamase inhibition, ETX2514 may enhance sulbactam activity in A. baumannii via inhibition of PBP2.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sulbactam
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Regulação Bacteriana da Expressão Gênica
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Farmacorresistência Bacteriana Múltipla
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Acinetobacter baumannii
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Compostos Azabicíclicos
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Inibidores de beta-Lactamases
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Antibacterianos
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article