Evaluation of the Synergistic Activity and In Vitro Efficacy of Imipenem/Relebactam in Combination with Amikacin and Tigecycline Against Clinical Burkholderia cepacia Complex Isolates

Objectives

The Burkholderia cepacia complex (BCC) comprises significant opportunistic pathogens frequently associated with healthcare-related infections and high levels of multidrug resistance. Due to extensive intrinsic and acquired resistance mechanisms, these infections pose a major therapeutic challenge . This study aimed to investigate the in vitro activity of imipenem/relebactam (IMI/REL) and to evaluate its synergistic effects when combined with amikacin (AMK) and tigecycline (TGC) against clinical BCC isolates.

Methods

A total of 20 non-epidemiologically related clinical BCC isolates were included. Minimum inhibitory concentrations (MICs) were determined by means of the broth microdilution method according to CLSI (2023) guidelines. Synergistic potential was assessed using time-kill assays following CLSI M26-A standards.

Results

IMI/REL showed 80% susceptibility against the tested BCC isolates. Based on MIC₅₀ and MIC₉₀ values, the activity profiles were as follows: IMI/REL (1/4 and 128/4 mg/L), TGC (2 and 4 mg/L), and AMK (32 and 128 mg/L). Time-kill analyses revealed that the IMI/REL–AMK combination produced the most pronounced synergistic effect, achieving ≥3 log₁₀ reduction in bacterial counts relative to the initial inoculum within 24 hours. Sustained bactericidal activity was observed throughout the experiment. No antagonistic interactions were detected among the tested combinations.

Conclusion

Our findings indicate that IMI/REL possesses significant in vitro activity against clinical BCC isolates. The observed synergy and bactericidal activity underscore the IMI/REL–AMK combination as a promising therapeutic strategy for combating infections caused by this challenging, multidrug-resistant pathogen.