Continued Outbreak of Ceftriaxone-Resistant Salmonella enterica Serotype Typhi across Pakistan and Assessment of Knowledge and Practices among Healthcare Workers

Abstract

Pakistan is experiencing the first known outbreak of extensively drug-resistant (XDR) Salmonella enterica serotype Typhi (resistant to third-generation cephalosporins). The outbreak originated in Hyderabad in 2016 and spread throughout the Sindh Province. Whereas focus has remained on Sindh, the burden of XDR typhoid in Punjab, the most populous province, and the rest of the country is understudied. Using laboratory data from Shaukat Khanum Memorial Cancer Hospital and Research Centre in Lahore (Punjab Province) and its network of more than 100 collection centers across the country, we determined the frequency of blood culture–confirmed XDR typhoid cases from 2017 to 2019. We observed an increase in XDR typhoid cases in Punjab, with the percent of ceftriaxone resistance among Salmonella Typhi cases increasing from no cases in 2017, to 30% in 2018, and to 50% in 2019, with children bearing the largest burden. We also observed spread of XDR typhoid to the two other provinces in Pakistan. To assess prevailing knowledge and practices on XDR typhoid, we surveyed 321 frontline healthcare workers. Survey results suggested that inappropriate diagnostic tests and antibiotic practices may lead to underdiagnosis of XDR typhoid cases, and potentially drive resistance development and spread. Of those surveyed, only 43.6% had heard of XDR typhoid. Currently, serological tests are more routinely used over blood culture tests even though blood culture is imperative for a definitive diagnosis of typhoid fever. We recommend stronger liaisons between healthcare providers and diagnostic laboratories, and increased promotion of typhoid vaccination among healthcare workers and the general population.

Characterization of a P1-bacteriophage-like plasmid (phage-plasmid) harbouring bla CTX-M-15 in Salmonella enterica serovar Typhi

“…Third-generation cephalosporins (extended spectrum β-lactams) are frequently used in the treatment of typhoid fever. The emergence and spread of extensively drug-resistant (XDR) S. enterica Typhi in Pakistan, and now globally, is a publichealth concern as it has left azithromycin (one of the last oral antibiotics available) and meropenem (carbapenem) as the only options available for treatment [2][3][4][5][6][7][8] (https://emergency.cdc.gov/han/2021/han00439.asp).…”

Identification of Multiple Variant Extensively Drug-Resistant Typhoid Infections across Pakistan

“…4 The XDR typhoid outbreak in Pakistan was first observed in the Sindh Province in 2016, with infections clustered around sewage lines in the city of Hyderabad. 10 Previously, we observed 2 an increase in XDR typhoid cases in the Punjab Province of Pakistan, with children bearing the greatest burden. This indicated that XDR typhoid had spread beyond the southern Sindh Province.…”

“…Recent and continued outbreaks of multidrug resistant (MDR) and extensively drug resistant (XDR) typhoid demonstrate the difficulty in containing this infectious disease. [1][2][3] According to the WHO, MDR S. Typhi are defined as resistant to the first-line recommended drugs for treatment, which include chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole. 4 XDR S. Typhi are defined as resistant to all recommended antibiotics for typhoid fever, which include third-generation cephalosporins and fluoroquinolones.…”

Antimicrobial-resistant bacteria in international travelers

“…There were 68 reported cases of imported ESBL Salmonella Typhi and Salmonella Paratyphi in the UK between 2017 and 2020 [ 56 ▪ ]. The majority of cases were associated with travel to Pakistan, where there is an ongoing outbreak of extremely drug-resistant S. Typhi in the Sindh province [ 57 , 58 ]. A separate multisite study of travelers with enteric fever found that 65% of S. Typhi isolates were resistant to multiple classes of antimicrobials [ 50 ▪▪ ].…”