In vitro activity of imipenem–relebactam against carbapenem-resistant Pseudomonas aeruginosa: correlation with carbapenem MICs and association with β-lactamase classes

Introduction Carbapenem-resistant P. aeruginosa (CRPA) poses a major therapeutic challenge due to the limited number of available treatment options. Imipenem-relebactam (IMP-REL), a carbapenem combined with a Class A/C β -lactamase inhibitor, has demonstrated activity against selected multidrug-resistant isolates. This retrospective, observational, analytical, laboratory-based study represents one of the early reports from Saudi Arabia and the Middle East and North Africa (MENA) region evaluating the in vitro activity of IMP-REL using archived clinical isolates with prospectively performed testing, and examining its association with carbapenem minimum inhibitory concentrations (MICs) and β -lactamase classes. Methods Ninety-nine CRPA isolates were subjected to antimicrobial susceptibility testing, and 66 isolates were selected randomly for whole-genome sequencing. The E -test is used to determine MICs for imipenem, meropenem, and IMP-REL. Correlation analysis, regression modeling, MIC 50 /MIC 90 computation, and comparisons of β -lactamase class subgroups were performed. Scatter plots and MIC distribution curves were generated to visualize these associations. Results IMP-REL MIC values were available for the 99 non-duplicate CRPA isolates. Most isolates originated from respiratory specimens (51%), followed by body fluids (18%) and urine (10%). IMP-REL MICs ranged from 0.38 to 32 mg/L, with a median MIC of 1.5 mg/L and MIC₅₀/₉₀ values of 1.5 and 12 mg/L, respectively. Based on CLSI criteria, 78.8% of isolates were susceptible, 10.1% intermediate, and 11.1% resistant. MIC distributions demonstrated clustering at low concentrations with a distinct resistant tail. Weak but statistically significant positive rank-based correlations were observed between IMP-REL MICs and imipenem ( ρ = 0.21, p = 0.041) and meropenem MICs ( ρ = 0.27, p = 0.0077). Among the 66 isolates with characterized resistance mechanisms, Class C and Class D β -lactamases and efflux pumps were universally present, while Class A (13.6%) and Class B (7.6%) β-lactamases were infrequent. Conclusion IMP-REL shows substantial in vitro activity against CRPA, despite only weak correlations with carbapenem MICs and no meaningful association with predominant Class C and Class D β -lactamases. These findings support IMP-REL as an important therapeutic option for CRPA infections in settings with high antimicrobial resistance.