TY - JOUR
T1 - Spontaneous Emergence of Azithromycin Resistance in Independent Lineages of Salmonella Typhi in Northern India
AU - Carey, Megan E.
AU - Jain, Ruby
AU - Yousuf, Mohammad
AU - Maes, Mailis
AU - Dyson, Zoe A.
AU - Thu, Trang Nguyen Hoang
AU - Nguyen Thi Nguyen, To
AU - Ho Ngoc Dan, Thanh
AU - Nhu Pham Nguyen, Quynh
AU - Mahindroo, Jaspreet
AU - Thanh Pham, Duy
AU - Sandha, Kawaljeet Singh
AU - Baker, Stephen
AU - Taneja, Neelam
PY - 2021/3/1
Y1 - 2021/3/1
N2 - BACKGROUND: The emergence and spread of antimicrobial resistance (AMR) pose a major threat to the effective treatment and control of typhoid fever. The ongoing outbreak of extensively drug-resistant Salmonella Typhi (S. Typhi) in Pakistan has left azithromycin as the only remaining broadly efficacious oral antimicrobial for typhoid in South Asia. Ominously, azithromycin-resistant S. Typhi organisms have been subsequently reported in Bangladesh, Pakistan, and Nepal. METHODS: Here, we aimed to understand the molecular basis of AMR in 66 S. Typhi organisms isolated in a cross-sectional study performed in a suburb of Chandigarh in Northern India using whole-genome sequencing and phylogenetic analysis. RESULTS: We identified 7 S. Typhi organisms with the R717Q mutation in the acrB gene that was recently found to confer resistance to azithromycin in Bangladesh. Six out of the seven azithromycin-resistant S. Typhi isolates also exhibited triple mutations in gyrA (S83F and D87N) and parC (S80I) genes and were resistant to ciprofloxacin. These contemporary ciprofloxacin/azithromycin-resistant isolates were phylogenetically distinct from each other and from those reported from Bangladesh, Pakistan, and Nepal. CONCLUSIONS: The independent emergence of azithromycin-resistant typhoid in Northern India reflects an emerging broader problem across South Asia and illustrates the urgent need for the introduction of typhoid conjugate vaccines in the region.
AB - BACKGROUND: The emergence and spread of antimicrobial resistance (AMR) pose a major threat to the effective treatment and control of typhoid fever. The ongoing outbreak of extensively drug-resistant Salmonella Typhi (S. Typhi) in Pakistan has left azithromycin as the only remaining broadly efficacious oral antimicrobial for typhoid in South Asia. Ominously, azithromycin-resistant S. Typhi organisms have been subsequently reported in Bangladesh, Pakistan, and Nepal. METHODS: Here, we aimed to understand the molecular basis of AMR in 66 S. Typhi organisms isolated in a cross-sectional study performed in a suburb of Chandigarh in Northern India using whole-genome sequencing and phylogenetic analysis. RESULTS: We identified 7 S. Typhi organisms with the R717Q mutation in the acrB gene that was recently found to confer resistance to azithromycin in Bangladesh. Six out of the seven azithromycin-resistant S. Typhi isolates also exhibited triple mutations in gyrA (S83F and D87N) and parC (S80I) genes and were resistant to ciprofloxacin. These contemporary ciprofloxacin/azithromycin-resistant isolates were phylogenetically distinct from each other and from those reported from Bangladesh, Pakistan, and Nepal. CONCLUSIONS: The independent emergence of azithromycin-resistant typhoid in Northern India reflects an emerging broader problem across South Asia and illustrates the urgent need for the introduction of typhoid conjugate vaccines in the region.
KW - Salmonella Typhi
KW - antimicrobial resistance
KW - azithromycin resistance
KW - India
KW - typhoid fever
UR - https://www.scopus.com/pages/publications/85102657932
U2 - 10.1093/cid/ciaa1773
DO - 10.1093/cid/ciaa1773
M3 - Article
C2 - 33515460
AN - SCOPUS:85102657932
SN - 1058-4838
VL - 72
SP - e120-e127
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 5
ER -
