Molecular Characterization of Extensively Drug Resistant Salmonella Enterica Serovar Typhi Clinical Isolates from 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 , cat A1, sul 1, 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%), sul 1 (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.

Exploring the potent antimicrobial activity of manuka honey as against clinically isolated multi-drug resistant and ceftriaxone-resistant Salmonella Typhi in septicemia patients: a promising therapeutic option

“…Additionally, the H58 strain co-existed with XDR-S. Typhi, along with the gyrA, gyrB, blaCTX-M-15, and blaTEM-1 genes. A study conducted in Hong Kong found that 30 strains originating from southeast Asia displayed the H58 haplotype in XDR-S. Typhi In addition, a study conducted in Lahore, Pakistan identi ed the presence of the gyrA, gyrB, blaCTX-M-15, blaTEM, and sul1 genes at the molecular level (Jabeen et al 2023). We investigated the antibacterial activity of manuka honey (+ 24UMF) imported from New Zealand against several MDR and XDR strains of S. Typhi.…”

Defying the odds: Determinants of the antimicrobial response of Salmonella Typhi and their interplay

“…Initially, cephalosporin and azithromycin were very effective in reducing the severity of typhoid fever caused by quinolone-resistant MDR-S. Typhi. Fluoroquinolones, third-generation cephalosporins and azithromycin are collectively referred to as the second line of antibiotics for the treatment of typhoid fever (Jabeen et al, 2023;Laghari et al, 2019;Rathod et al, 2016). Prudent administration of azithromycin with ceftriaxone allowed some cure for the infection caused by MDR Salmonella (Girgis et al, 1999;Parry, 2004;Parry et al, 2023;Veeraraghavan et al, 2021).…”

“…TEM, SHV and CTX-M are the three major ESBLs found in Enterobacteriaceae that build resistance to the third-generation cephalosporins. The clinical isolate of XDR S. Typhi reported in Pakistan exhibits an abundance of a plethora of resistance genes for the first (bla TEM-1 , sul1, catA1 and dhfR7) and second line (gyrB, gyrA, parC, parE and qnrS) antibiotics as well as the derivatives ofCTX-M ESBLs such as 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(Jabeen et al, 2023). The experimental evidences showed the presence of two other ESBLs (SHV and TEM) in the clinical isolates of S. Typhi (purified from blood), which are associated with resistance to ceftriaxone, cefixime and ceftazidime(Ahamed Riyaaz et al, 2018).…”

Source tracking of extensively drug resistant Salmonella Typhi in food and raw vegetables using molecular approaches

“…Typhoid is a systemic febrile disease that can be fatal, which necessitates early antibiotic treatment. It is estimated that there are 14.3 million cases of typhoid worldwide with 128,000 to 161,000 deaths annually [1,2]. The incidence rate of typhoid fever is highest in South Asia, followed by Southeast Asia, Western sub-Saharan Africa, Eastern Sub-Saharan Africa, and Oceania [3].…”