Journal article icon

Journal article

Tebipenem as an oral alternative for the treatment of typhoid caused by XDR Salmonella Typhi

Abstract:
Background Antimicrobial therapy is essential for the treatment of enteric fever, the infection caused by Salmonella serovars Typhi and Paratyphi A. However, an increase in resistance to key antimicrobials and the emergence of MDR and XDR in Salmonella Typhi poses a major threat for efficacious outpatient treatments.
Objectives We recently identified tebipenem, an oral carbapenem licensed for use for respiratory tract infections in Japan, as a potential alternative treatment for MDR/XDR Shigella spp. Here, we aimed to test the in vitro antibacterial efficacy of this drug against MDR and XDR typhoidal Salmonella.
Methods We determined the in vitro activity of tebipenem in time–kill assays against a collection of non-XDR and XDR Salmonella Typhi and Salmonella Paratyphi A (non-XDR) isolated in Nepal and Bangladesh. We also tested the efficacy of tebipenem in combination with other antimicrobials.
Results We found that both XDR and non-XDR Salmonella Typhi and Salmonella Paratyphi A are susceptible to tebipenem, exhibiting low MICs, and were killed within 8–24 h at 2–4×MIC. Additionally, tebipenem demonstrated synergy with two other antimicrobials and could efficiently induce bacterial killing.
Conclusions Salmonella Paratyphi A and XDR Salmonella Typhi display in vitro susceptibility to the oral carbapenem tebipenem, while synergistic activity with other antimicrobials may limit the emergence of resistance. The broad-spectrum activity of this drug against MDR/XDR organisms renders tebipenem a good candidate for clinical trials.
Publication status:
Published
Peer review status:
Peer reviewed

Actions

Access Document

Files:
Publisher copy:
10.1093/jac/dkab326

Authors

More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Tropical Medicine
Role:
Author
ORCID:
0000-0002-5179-650X


Publisher:
British Society for Antimicrobial Chemotherapy
Journal:
Journal of Antimicrobial Chemotherapy More from this journal
Volume:
76
Issue:
12
Pages:
3197-3200
Publication date:
2021-09-17
Acceptance date:
2021-08-05
DOI:
EISSN:
1460-2091
ISSN:
0305-7453
Pmid:
34534310


Language:
English
Keywords:
Pubs id:
1195354
Local pid:
pubs:1195354
Deposit date:
2021-12-21
ARK identifier:

Terms of use


Views and Downloads






If you are the owner of this record, you can report an update to it here: Report update to this record

TO TOP