1. Transcending the challenge of evolving resistance mechanisms in Pseudomonas aeruginosa through β-lactam-enhancer-mechanism-based cefepime/zidebactam.
- Author
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Hujer AM, Marshall SH, Mack AR, Hujer KM, Bakthavatchalam YD, Umarkar K, Palwe SR, Takalkar S, Joshi PR, Shrivastava R, Periasamy H, Bhagwat SS, Patel MV, Veeraraghavan B, and Bonomo RA
- Subjects
- Drug Resistance, Multiple, Bacterial genetics, beta-Lactamase Inhibitors pharmacology, Cefepime pharmacology, Pseudomonas Infections microbiology, Pseudomonas Infections drug therapy, beta-Lactams pharmacology, Humans, beta-Lactamases genetics, beta-Lactamases metabolism, Drug Combinations, Piperidines, Pseudomonas aeruginosa drug effects, Pseudomonas aeruginosa genetics, Anti-Bacterial Agents pharmacology, Azabicyclo Compounds pharmacology, Cyclooctanes pharmacology, Microbial Sensitivity Tests, Cephalosporins pharmacology
- Abstract
Compared to other genera of Gram-negative pathogens, Pseudomonas is adept in acquiring complex non-enzymatic and enzymatic resistance mechanisms thus remaining a challenge to even novel antibiotics including recently developed β-lactam and β-lactamase inhibitor combinations. This study shows that the novel β-lactam enhancer approach enables cefepime/zidebactam to overcome both non-enzymatic and enzymatic resistance mechanisms associated with a challenging panel of P. aeruginosa . This study highlights that the β-lactam enhancer mechanism is a promising alternative to the conventional β-lactam/β-lactamase inhibitor approach in combating ever-evolving MDR P. aeruginosa ., Competing Interests: Some of the coauthors are employees of Wockhardt. R.A.B. receives grant funding from Wockhardt.
- Published
- 2023
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