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

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 Typhi were identified, and 150 were XDR . Typhi (resistant to all recommended antibiotics). Antibiotics resistance genes of the first-line drugs (, A1, 1, and dhfR7) and second line drugs ( and ) were investigated among XDR . Typhi. There were different CTX-M genes isolated using the specific primers, , and .

Results: Antibiotic resistant genes of the first-line drugs were isolated with different frequency, (72.6%), (86.6%), 1 (70%), and (56%). Antibiotics resistance genes of second-line drugs were isolated as: (60%), (49.3%), (32.6%), (44%) and (28%). Among CTX-M genes, (63.3%) was the most frequent followed by (39.3%) and (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 . Typhi which is currently used as an empiric treatment option is worrisome and needs to be monitored carefully in endemic countries like Pakistan.