Transcending the challenge of evolving resistance mechanisms in through β-lactam-enhancer-mechanism-based cefepime/zidebactam.

Compared to other genera of Gram-negative pathogens, 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 . 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 .

In-Vitro Selection of Ceftazidime/Avibactam Resistance in OXA-48-Like-Expressing : In-Vitro and In-Vivo Fitness, Genetic Basis and Activities of β-Lactam Plus Novel β-Lactamase Inhibitor or β-Lactam Enhancer Combinations.

Ceftazidime/avibactam uniquely demonstrates activity against both KPC and OXA-48-like carbapenemase-expressing Enterobacterales. Clinical resistance to ceftazidime/avibactam in KPC-producers was foreseen in in-vitro resistance studies. Herein, we assessed the resistance selection propensity of ceftazidime/avibactam in expressing OXA-48-like β-lactamases ( = 10), employing serial transfer approach.

In vitro evolution of cefepime/zidebactam (WCK 5222) resistance in Pseudomonas aeruginosa: dynamics, mechanisms, fitness trade-off and impact on in vivo efficacy.

Objectives: To study the dynamics, mechanisms and fitness cost of resistance selection to cefepime, zidebactam and cefepime/zidebactam in Pseudomonas aeruginosa.

Methods: WT P. aeruginosa PAO1 and its ΔmutS derivative (PAOMS) were exposed to stepwise increasing concentrations of cefepime, zidebactam and cefepime/zidebactam.

In vitro activity of cefepime/zidebactam (WCK 5222) against recent Gram-negative isolates collected from high resistance settings of Greek hospitals.

Cefepime/zidebactam is in clinical development for the treatment of carbapenem-resistant Gram-negative infections. MICs of cefepime/zidebactam (1:1) and comparators against Enterobacterales (n = 563), Pseudomonas (n = 172) and Acinetobacter baumannii (n =181) collected from 15 Greek hospitals (2014-2018) were determined by reference broth microdilution method. The isolates exhibited high carbapenem resistance rates [(Enterobacterales (75%), Pseudomonas (75%) and A.

Retrospective Analysis on Antimicrobial Resistance Trends and Prevalence of β-lactamases in and ESKAPE Pathogens Isolated from Arabian Patients during 2000-2020.

The production of diverse and extended spectrum β-lactamases among and ESKAPE pathogens is a growing threat to clinicians and public health. We aim to provide a comprehensive analysis of evolving trends of antimicrobial resistance and β-lactamases among and ESKAPE pathogens (, and species) in the Arabian region. A systematic review was conducted in Medline PubMed on papers published between January 2000 and February 2020 on countries in the Arab region showing different antibiotic resistance among and ESKAPE pathogens.