Synergistic and antagonistic interactions between colistin and cell-free supernatants of Lactobacillus species against clinical isolates of Acinetobacter baumannii.

Acinetobacter baumannii is a major contributor to hospital-acquired infections and presents substantial therapeutic challenges due to its extensive antibiotic resistance. Although colistin remains one of the final treatment options, the rising incidence of colistin resistance underscores the urgent need for alternative or complementary therapeutic strategies. Probiotics such as Lactobacillus rhamnosus and Lactobacillus fermentum have gained attention for their antimicrobial activities and ability to interfere with biofilm formation; however, their combined effects with antibiotics against resistant pathogens remain insufficiently characterized. This study investigated the antimicrobial potential of colistin in combination with L. rhamnosus and L. fermentum against clinical isolates of A. baumannii, aiming to support the development of more effective therapeutic approaches. A total of 97 clinical isolates of A. baumannii were subjected to phenotypic identification and molecular confirmation. Biofilm-forming capacity was assessed, and only isolates exhibiting strong biofilm production and multidrug resistance were included in subsequent analyses. Cell-free supernatants (CFS) of L. rhamnosus and L. fermentum were obtained, and their auto-aggregation and co-aggregation capabilities with A. baumannii were evaluated. Minimum inhibitory concentrations (MIC), interaction profiles between CFS and colistin, and minimum biofilm inhibitory concentrations (MBIC) were determined using broth microdilution and checkerboard assays, with fractional inhibitory concentration (FIC) indices used to interpret interaction patterns. Among the 97 isolates, 13 strong biofilm-forming and multidrug-resistant strains were identified. The CFS of both probiotic species significantly inhibited the growth of colistin-resistant isolates at higher concentrations and demonstrated enhanced co-aggregation with A. baumannii. Combination assays revealed strain-specific patterns of synergy, indifference, and antagonism, with L. rhamnosus exhibiting more favorable interactions in both growth inhibition and biofilm suppression. Overall, these findings suggest that metabolites produced by lactic acid bacteria, particularly L. rhamnosus, may augment the efficacy of colistin against certain colistin-resistant A. baumannii isolates, highlighting the potential of combination-based therapeutic approaches for managing infections caused by resistant strains.