English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background Pseudomonas aeruginosa (PSA) is an opportunistic pathogen known to cause complications in critically ill patients worldwide. In those at risk of infection with multidrug-resistant strains (MDR-PSA), dual antibiotic therapy is often considered. However, this practice may contribute to rising resistance rates and poor outcomes if empirical selection is suboptimal. WCK 5222 (cefepime/zidebactam), a novel β-lactam/β-lactam enhancer, may offer a solution. Methods Minimum inhibitory concentrations (MICs) were determined for WCK 5222, amikacin (AMK), fosfomycin (FOF), cefepime (FEP), ceftolozane/tazobactam (C/T), and meropenem (MEM) against 18 clinical PSA isolates using gradient diffusion strip (GDS) methods. Activities of FEP, C/T, and MEM in combination with AMK and FOF were assessed using GDS for isolates nonsusceptible to the β-lactam (MICs >8 mg/L, >4/4 mg/L, and >2 mg/L, respectively). Synergy was defined as a fractional inhibitory concentration index ≤ 0.5. Instances of restored β-lactam susceptibility when tested in combination were compared with the proportion of WCK 5222 MICs ≤ 8 mg/L. Results WCK 5222 MICs ranged from 2 to 32 mg/L (MIC50, 8 mg/L). Rates of susceptibility were: AMK (67%), FOF (44%, MIC ≤ 64 mg/L), FEP (6%), C/T (33%), MEM (0%). Combinations with C/T most frequently demonstrated synergy (C/T-FOF, 42%; C/T-AMK, 33%) and restored C/T susceptibility was observed in 42% of assessments with FOF and in 50% with AMK. For FEP combinations, synergy was observed in 29% and 18% of assessments with FOF and AMK, respectively, with restored susceptibility in 6% for both combinations. Synergy occurred in 11% and 6% of assessments of MEM with FOF and AMK, respectively, with zero instances of restored susceptibility. In total, β-lactam susceptibility was restored in 14% (13/94) of combinations compared with 78% (14/18) of WCK 5222 MICs ≤ 8 mg/L. Conclusion In a selection of MDR-PSA isolates that included carbapenem- and C/T-resistant strains, WCK 5222 MICs ≤ 8 mg/L (cefepime susceptible) were observed more frequently than restoration of susceptibility in select β-lactams in combination with FOF or AMK. WCK 5222 monotherapy may offer enhanced coverage of MDR-PSA over empirically selected combination therapies. Disclosures All authors: No reported disclosures.

open forum infectious diseases

725. WCK 5222 (Cefepime/Zidebactam): An In Vitro Assessment of Activity Compared with Current Dual-Antibiotic Options Against Multidrug-Resistant Pseudomonas aeruginosa