A Comprehensive Meta-Analysis on Antimicrobial Resistance Patterns of the Two Major Brucella species in Mediterranean...

Antimicrobial resistance (AMR) of brucellosis major causative bacteria Brucella abortus and Brucella melitensis is complicating human treatment strategies in the Mediterranean basin, where the disease was first reported and is still endemic. The current meta-analysis examines the prevalence and patterns of AMR in 119 Brucella abortus and 1344 Brucella melitensis isolates across Mediterranean countries, highlighting significant geographical disparities in resistance data. The E-test and disc diffusion were mostly used for measuring antimicrobial susceptibility, which was validated by the CLSI guidelines of Haemophilus spp. or bacteria of bioterrorism. Genotypic detection of resistance was conducted in a few studies. Despite the documented burden of brucellosis, studies on AMR remain scarce, particularly in North Africa, the Middle East, and several European Mediterranean nations. Comparative phenotypic-genotypic resistograms were reported in only a few studies, yet they are essential for understanding the mechanisms of AMR in this serious zoonotic pathogen. The analysis revealed a high overall AMR proportion (32%, 95% confidence interval [CI]: 16%-51%) with considerable heterogeneity (I ² = 97%, p < 0.01). Notable differences in resistance were observed between regions, with African Mediterranean countries exhibiting the highest resistance rates (71%, 95% CI: 44%-94%) and European Mediterranean countries the lowest (9%, 95% CI: 0%-42%). Eastern Mediterranean countries exhibited higher resistance rates than their western counterparts (p=0.11). Brucella abortus showed higher resistance (63%, 95% CI: 25%-95%) than Brucella melitensis (24%, 95% CI: 8%-43%). Isolates of bovine origin displayed the highest percentage of resistance (89%, 95% CI: 69%-100%) compared to isolates of other origins. Resistance to rifampicin and trimethoprim-sulfamethoxazole was generally low, but macrolide resistance, especially to azithromycin, was notably higher in African countries (p < 0.01). This study underscores the need for standardized AMR surveillance based on Brucella-specific validation criteria, which are lacking, improved testing methodologies, and region-specific interventions to address AMR in brucellosis, particularly in livestock, where resistance is more prevalent. The findings highlight the importance of targeted antibiotic stewardship and monitoring to mitigate the spread of resistant Brucella strains and protect public health.