Assessment of the Synergistic Activity of Imipenem/Relebactam in Combination with Meropenem and Tigecycline Against 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 across multiple antimicrobial classes, these infections pose a major therapeutic challenge, particularly in immunocompromised patients. This study investigated the in vitro activity of imipenem/relebactam (IMI/REL) and evaluated its synergistic and bactericidal effects in combination with meropenem (MEM) and tigecycline (TIG) against clinical BCC isolates.

Methods:

A total of 20 non-epidemiologically related clinical BCC isolates were included. Minimum inhibitory concentrations (MICs) were determined by broth microdilution in accordance with CLSI (2023) guidelines, with Pseudomonas aeruginosa ATCC 27853 as the quality control strain. Synergistic potential and bactericidal activity of IMI/REL-based combinations were assessed using time-kill assays. Bacterial counts (CFU/mL) were measured over 24 hours, and log reductions were calculated relative to the initial inoculum.

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), MEM (4 and 8 mg/L), and TIG (2 and 4 mg/L). Time-kill analyses revealed that the IMI/REL–MEM combination produced the most pronounced synergistic effect, achieving a ≥3-log10 reduction in bacterial counts compared with the initial inoculum within 24 hours. No antagonistic interactions were detected among the tested combinations.

Conclusion:

Our findings indicate that IMI/REL has significant in vitro activity against clinical BCC isolates. The marked synergy and potent bactericidal effect observed with the IMI/REL–MEM combination highlight its potential as a promising therapeutic alternative for treating severe infections in immunocompromised patients caused by this challenging multidrug-resistant pathogen.