Inactivation of the Pseudomonas-Derived Cephalosporinase-3 (PDC-3) by Relebactam.

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Barnes MD, Bethel CR, Alsop J, Becka SA, Rutter JD, Papp-Wallace KM, Bonomo RA

Inactivation of the Pseudomonas-Derived Cephalosporinase-3 (PDC-3) by Relebactam.

Antimicrob Agents Chemother. 2018 Apr 26;62(5). pii: AAC.02406-17. doi: 10.1128/AAC.02406-17. Print 2018 May.

PubMed ID
29530851 [ View in PubMed
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Abstract

Pseudomonas aeruginosa is a prevalent and life-threatening Gram-negative pathogen. Pseudomonas-derived cephlosporinase (PDC) is the major inducible cephalosporinase in P. aeruginosa In this investigation, we show that relebactam, a diazabicyclooctane beta-lactamase inhibitor, potently inactivates PDC-3, with a k2/K of 41,400 M(-1) s(-1) and a koff of 0.00095 s(-1) Relebactam restored susceptibility to imipenem in 62% of multidrug-resistant P. aeruginosa clinical isolates, while only 21% of isolates were susceptible to imipenem-cilastatin alone. Relebactam promises to increase the efficacy of imipenem-cilastatin against P. aeruginosa.

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