Antibiotic Susceptibility Screening and Detection of Glycopeptide and β-Lactam Resistance Genes in Yersinia pestis Clinical Isolates from Plague Outbreaks in Natural Foci of Kazakhstan (1926–2003)

Objectives: Antimicrobial resistance (AMR) is a growing global threat that complicates the treatment of infectious diseases, including plague. Yersinia pestis, the causative agent of plague, remains a serious public health concern in natural foci, such as those in Kazakhstan, where approximately 40% of the territory is plague-endemic. Despite the last reported human case in 2003, data on antibiotic resistance among Y. pestis isolates from these foci, especially historical ones, remain limited. Methods: This study analyzed 75 Y. pestis isolates, including 61 from epidemic outbreaks (1926–2003) and 14 from other natural foci. Taxonomic identification was conducted using the Vitek 2 Compact 30 system. Antibiotic susceptibility was assessed by Kirby–Bauer disk diffusion and E-test methods. Extended-spectrum β-lactamase (ESBL) activity was evaluated phenotypically, and resistance genes to glycopeptides and β-lactams were screened by real-time PCR using the BacResista GLA Detection Kit. Results: All isolates showed complete susceptibility (100%) to β-lactams, tetracyclines, aminoglycosides, amphenicols, glycopeptides, lincosamides, and quinolones. The overall susceptibility rate across antibiotic classes was 97.5%. Macrolides exhibited low activity (0.0–58.0%), consistent with known limitations against Gram-negative bacteria. No ESBL production was detected phenotypically, and RT-PCR screening found no resistance genes (vanA/B, mecA, tem, ctx-M-1, shv, oxa, imp, kpc, ndm, etc.). Conclusions: These findings confirm a lack of resistance to key antibiotic classes in historical Y. pestis isolates from Kazakhstan. Despite the absence of recent human cases, ongoing epizootics among wild animals highlight a persistent risk of transmission. The results have important implications for public health preparedness and clinical management during plague outbreaks.