Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Sep 1;8(9):1336.
doi: 10.3390/microorganisms8091336.

Emergence of Resistance to Fluoroquinolones and Third-Generation Cephalosporins in Salmonella Typhi in Lahore, Pakistan

Farhan Rasheed  1 , Muhammad Saeed  2 , Nabil-Fareed Alikhan  3 , David Baker  3 , Mohsin Khurshid  2 , Emma V Ainsworth  3 , A Keith Turner  3 , Ambereen Anwar Imran  1 , Muhammad Hidayat Rasool  2 , Muhammad Saqalein  2 , Muhammad Atif Nisar  2 , Muhammad Fayyaz Ur Rehman  4 , John Wain  3   5 , Muhammad Yasir  3 , Gemma C Langridge  3 , Aamer Ikram  6
Affiliations

Emergence of Resistance to Fluoroquinolones and Third-Generation Cephalosporins in Salmonella Typhi in Lahore, Pakistan

Farhan Rasheed et al. Microorganisms. .

Abstract

Extensively drug-resistant (XDR) Salmonella Typhi has been reported in Sindh province of Pakistan since 2016. The potential for further spread is of serious concern as remaining treatment options are severely limited. We report the phenotypic and genotypic characterization of 27 XDR S. Typhi isolated from patients attending Jinnah Hospital, Lahore, Pakistan. Isolates were identified by biochemical profiling; antimicrobial susceptibility was determined by a modified Kirby-Bauer method. These findings were confirmed using Illumina whole genome nucleotide sequence data. All sequences were compared to the outbreak strain from Southern Pakistan and typed using the S. Typhi genotyping scheme. All isolates were confirmed by a sequence analysis to harbor an IncY plasmid and the CTX-M-15 ceftriaxone resistance determinant. All isolates were of the same genotypic background as the outbreak strain from Sindh province. We report the first emergence of XDR S. Typhi in Punjab province of Pakistan confirmed by whole genome sequencing.

Keywords: Lahore; Salmonella Typhi; XDR; cephalosporin resistance; typhoid fever.

PubMed Disclaimer

Conflict of interest statement

G.C.L. has received fees from RevoluGen for consultancy work. The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Phylogenetic tree of XDR S. Typhi. Radial phylogram of maximum-likelihood phylogeny (RaxML) rooted to S. Typhi ERL12148 (accession LT883153.1). PAK strain numbers in black are from [5] and XDR strain numbers (red) are from Lahore (this study). Black bar labeled MDR, indicates MDR strains and green arrow indicates that all strains from PAK0022 clockwise to XDR24 are XDR.
Figure 2
Figure 2
CTX-M-15 located on the IncY plasmid. The inner circle represents the reference plasmid sequence p60006. Concentric rings indicate BLAST identity between reference and strains sequenced as part of this study. BLASTn matches between 90% and 100% nucleotide identity are colored from lightest to darkest shade, respectively. Matches with less than 80% identity, or plasmid regions with no BLAST matches, appear as blank spaces in each ring. Inner most rings plot GC Skew and GC content. Outermost ring shows locations of coding sequences (red—sense; blue—antisense) and gene names are labeled where known. The CTX-M-15 gene is labeled in black.
See this image and copyright information in PMC

References

    1. Buckle G.C., Walker C.L., Black R.E. Typhoid fever and paratyphoid fever: Systematic review to estimate global morbidity and mortality for 2010. J. Glob. Health. 2012;2:010401. doi: 10.7189/jogh.01.010401. - DOI - PMC - PubMed
    1. Mogasale V., Maskery B., Ochiai R.L., Lee J.S., Mogasale V.V., Ramani E., Kim Y.E., Park J.K., Wierzba T.F. Burden of typhoid fever in low-income and middle-income countries: A systematic, literature-based update with risk-factor adjustment. Lancet Glob. Health. 2014;2:e570–e580. doi: 10.1016/S2214-109X(14)70301-8. - DOI - PubMed
    1. Wain J., Kidgell C. The emergence of multidrug resistance to antimicrobial agents for the treatment of typhoid fever. Tans. R. Soc. Trop. Med. Hyg. 2004;98:423–430. doi: 10.1016/j.trstmh.2003.10.015. - DOI - PubMed
    1. Bhutta Z.A. Current concepts in the diagnosis and treatment of typhoid fever. Br. Med. J. 2006;333:78–82. doi: 10.1136/bmj.333.7558.78. - DOI - PMC - PubMed
    1. Klemm E.J., Shakoor S., Page A.J., Qamar F.N., Judge K., Saeed D.K., Wong V.K., Dallman T.J., Nair S., Baker S., et al. Emergence of an Extensively Drug-Resistant Salmonella enterica Serovar Typhi Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins. MBio. 2018;9 doi: 10.1128/mBio.00105-18. - DOI - PMC - PubMed

LinkOut - more resources