Year: 2025
Type: article
Study design: Observational Study
Abstract: Typhoid fever, caused by Salmonella enterica subsp. enterica serovar Typhi (S. typhi), remains a major public health concern, particularly in low-resource settings with poor sanitation. The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains have significantly complicated treatment, especially in vulnerable pediatric populations. This study aimed to characterize the genetic profiles of drug resistance in MDR and XDR S. typhi isolates from pediatric patients. Methods: A cross-sectional study was conducted on 800 blood samples from pediatric typhoid patients. S. typhi isolates were identified using the BacT/ALERT 3D system, followed by culture on MacConkey and blood agar. Antimicrobial susceptibility was assessed using the disk diffusion method according to CLSI 2022 guidelines. Whole-genome sequencing (WGS) was performed on 29 isolates using Illumina MiSeq technology, and resistance genes and mutations were analyzed. Results: Antimicrobial susceptibility testing revealed that 68 (48.57%) of S. typhi isolates were XDR and 61 (43.57%) were MDR, exhibiting widespread resistance to ciprofloxacin, ampicillin, chloramphenicol, ceftriaxone, and co-trimoxazole. WGS identified key resistance genes across all 29 isolates, including bla_CTX-M-15, bla_TEM-1B, qnrS1, aac(6′)-Iaa, catA1, dfraA7, sul1, qacEΔ1, and the gyrA-S83F mutation. Notably, gyrA-S83F and qnrS1 were detected in all isolates and strongly correlated with ciprofloxacin resistance. Virulence genes were consistently present in all isolates, indicating a high pathogenic potential. The IncY plasmid, found in four (14%) isolates, was linked to resistance against third-generation cephalosporins, including ceftriaxone. Conclusion: This study underscores the alarming prevalence of MDR and XDR S. typhi isolates among pediatric patients, driven by resistance genes such as bla_CTX-M-15, bla_TEM-1B, and gyrA-S83F. These findings highlight the urgent need for targeted therapeutic strategies and robust surveillance systems to combat the growing threat of drug-resistant typhoid fever.
Source: Pathogens
Authors: Muhammad Riaz, Shabir Ahmad, Fazal Sattar, Ganwu Li, Zia Ud Din, Sajjad Ahmad, Azra, Aiman Waheed, Ihtisham Ul Haq, Jody E. Phelan, Gulab Fatima Rani, Otavio Cabral-Marques, Susana Campino, Taj Ali Khan, Taane G. Clark
Institutions: Sarhad University of Science and Information Technology, Khyber Medical University, National Institute for Biotechnology and Genetic Engineering, Pakistan Institute of Engineering and Applied Sciences, Iowa State University, Kohat University of Science and Technology, University of Peshawar, Universidade Federal de Minas Gerais, London School of Hygiene & Tropical Medicine, Universidade de São Paulo, D’Or Institute for Research and Education
Language: English
Subfield: Food Science
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,654
OpenAlex ID: W4414515854