Molecular Characterization of Extensively Drug Resistant Salmonella Enterica Serovar Typhi Clinical Isolates from Lahore, Pakistan

Kokab Jabeen; Sidrah Saleem; Shah Jahan; Summiya Nizamudin; Faiqa Arshad; Zill-E Huma; Syed Mohsin Raza; Maria Mehmood; Muhammad Roman; Faiz Ul Haq

doi:10.2147/IDR.S406253

Molecular Characterization of Extensively Drug Resistant Salmonella Enterica Serovar Typhi Clinical Isolates from Lahore, Pakistan

Infect Drug Resist. 2023 May 12:16:2987-3001. doi: 10.2147/IDR.S406253. eCollection 2023.

Authors

Affiliations

¹ Department of Microbiology, University of Health Sciences, Lahore, Pakistan.
² Department of Microbiology, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore, Pakistan.
³ Department of Allied Health Sciences, University of Health Sciences, Lahore, Pakistan.

Abstract

Background: The emergence of extensively drug-resistant (XDR) typhoid in Pakistan has endangered the treatment options available to manage this infection. Third generation cephalosporin were the empiric choice to treat typhoid fever in Pakistan, but acquisition of ESBLs have knocked them out of the arsenal. The current empiric choice is azithromycin which is vulnerable to resistance too. This study aimed to assess the burden of XDR typhoid and the frequency of resistance determinants in blood culture samples collected from different hospitals in Lahore, Pakistan.

Methods: A total of 835 blood cultures were collected from different tertiary care hospitals in Lahore during January 2019 to December 2021. Among 835 blood cultures, 389 Salmonella Typhi were identified, and 150 were XDR S. Typhi (resistant to all recommended antibiotics). Antibiotics resistance genes of the first-line drugs (bla_TEM-1, catA1, sul1, and dhfR7) and second line drugs (gyrB, gyrA, qnrS, ParC and ParE) were investigated among XDR S. Typhi. There were different CTX-M genes isolated using the specific primers, bla_CTX-M-U, bla_CTX-M-1, bla_CTX-M-15, bla_CTX-M-2, bla_CTX-M-8 and bla_CTX-M-9.

Results: Antibiotic resistant genes of the first-line drugs were isolated with different frequency, bla_TEM-1 (72.6%), catA1 (86.6%), sul1 (70%), and dhfR7 (56%). Antibiotics resistance genes of second-line drugs were isolated as: gyrB (60%), gyrA (49.3%), qnrS (32.6%), parC (44%) and parE (28%). Among CTX-M genes, bla_CTX-M-U (63.3%) was the most frequent followed by bla_CTX-M-15 (39.3%) and bla_CTX-M-1 (26%).

Conclusion: Our study concluded that XDR isolates circulating in Pakistan have acquired first-line and second-line antibiotic resistant genes quite successfully along with CTX-M genes (ESBLs) rendering them resistant to the third generation cephalosporins as well. Emergence of azithromycin resistance in XDR S. Typhi which is currently used as an empiric treatment option is worrisome and needs to be monitored carefully in endemic countries like Pakistan.

Keywords: Salmonella; XDR typhoid; antimicrobial resistance; plasmids.