Comparative Analysis of Phenotypic and Genotypic Antibiotic Susceptibility of Pasteurella multocida Isolated from Various Host Species in France and Hungary

<b>Background/Objectives</b>: <i>Pasteurella multocida</i> is responsible for a wide variety of animal diseases worldwide, causing major economic losses. These infections are usually treated with antibiotics; however, the emergence of multidrug-resistant (MDR) strains is increasingly hindering. Understanding antibiotic resistance in <i>P. multocida</i> is important for effective treatment strategies and public health, as it impacts both animal and human welfare. <b>Methods</b>: In this study, the antibiotic susceptibility of 80 <i>P. multocida</i> isolates was evaluated by phenotypic (disk diffusion and broth microdilution) and genotypic analysis via whole-genome sequencing, with particular attention to the occurrence of MDR strains. The strains were tested against antibiotics from nine antimicrobial classes (penicillins, cephalosporins, aminoglycosides, tetracyclines, macrolides, fluoroquinolones, lincosamides, phenicols, and sulfonamides). Antimicrobial resistance gene (ARG) sequences and single-nucleotide polymorphisms (SNPs) were evaluated in paired reads using the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) and the Comprehensive Antibiotic Resistance Database (CARD) via Resistance Gene Identifier (RGI), respectively. <b>Results</b>: Phenotypic results indicated that cephalosporins and phenicols were the most effective drugs against <i>P. multocida</i>; however, the majority of strains were also susceptible to fluoroquinolones and tetracyclines. In contrast, high resistance rates were observed to sulfamethoxazole and clindamycin. The most prevalent resistance genes were <i>str</i>A, <i>sul</i>2, and <i>tet</i>H, while none of the strains harbored the <i>bla</i>-_TEM or <i>erm</i> (42) genes. <b>Conclusions</b>: Of the two phenotypic methods, MIC values showed a stronger positive correlation with genotypic results, making it a more suitable method for determining antibiotic susceptibility. The phenotypic results for phenicols, tetracyclines, and fluoroquinolones showed a strong correlation with the detected resistance genes. In contrast, resistance to sulfamethoxazole, β-lactams, and macrolides remained genetically unexplained, suggesting the existence of additional resistance mechanisms to be explored.