The rise of Extended spectrum β-lactamase (ESBL) producing ceftriaxone resistant Salmonella Typhi from western Rajasthan, India.

Introduction: Typhoid fever, caused by Salmonella Typhi and Paratyphi, remains a sig-nificant public health concern, particularly in developing countries. The emergence of antimicrobial resistance, including resistance to first-line drugs, fluoroquinolones, and the development of re-sistance to ceftriaxone, poses a significant threat to effective treatment. Methods: This study investigated extended-spectrum β-lactamase (ESBL)-producing Salmonella Typhi isolates from blood samples of patients with suspected typhoid fever at a tertiary care hospital in Western Rajasthan, India, between April 2022 and May 2024. Antimicrobial susceptibility testing followed by PCR for ESBL-producing genes (blaTEM, blaSHV, blaCTX-M) and blaCTX-M sub-types (blaCTX-M1, blaCTX-M2, blaCTX-M8, blaCTX-M9, blaCTX-M10, blaCTX-M14, and blaCTX-M15) was performed. Results: Among 79 Salmonella Typhi isolates, 18 (22.8%) exhibited resistance to ceftriaxone. PCR analysis revealed blaCTX-M as the predominant ESBL gene, detected in 77.8% of resistant isolates. Notably, blaCTX-M1, blaCTX-M15, and blaCTX-M10 types were identified among the blaCTX-M-positive isolates. Discussion: In our study, 48% of Salmonella Typhi strains were resistant to fluoroquinolones, while chloramphenicol and co-trimoxazole showed re-emerging susceptibility (87%), likely due to their restricted use. Emerging ceftriaxone resistance, mediated by ESBL genes, predominantly blaCTX-M (especially blaCTX-M-15 and blaCTX-M-1) and blaSHV, poses challenges in clinical management. Notably, our study detected blaCTX-M10, which has not been previously reported in S. Typhi. Re-sistance gene spread is attributed to plasmids prevalent in E. coli and Klebsiella, which facilitate horizontal transfer. Study limitations include a small sample size, the absence of whole-genome se-quencing, and a lack of clinical outcome data. Conclusion: This study highlights the emergence of ceftriaxone-resistant Salmonella Typhi in West-ern Rajasthan, India. The high prevalence of blaCTX-M-producing isolates underscores the im-portance of ongoing surveillance and the implementation of infection control measures to prevent the further spread of antimicrobial resistance. Additionally, this study also highlights the re-emergence of sensitivity to chloramphenicol and co-trimoxazole.