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Azithromycin resistance in Shigella spp. in Southeast Asia

Abstract:
Infection by Shigella spp. is a common cause of dysentery in Southeast Asia. Antimicrobials are thought to be beneficial for treatment, however antimicrobial resistance in Shigella spp. is becoming widespread. We aimed to assess the frequency and mechanisms associated with decreased susceptibility to azithromycin in Southeast Asian Shigella isolates and use these data to assess appropriate susceptibility breakpoints. Shigella isolated in Vietnam and Laos were screened for susceptibility against azithromycin (15μg) by disc diffusion and minimum inhibitory concentration (MIC). Phenotypic resistance was confirmed by PCR amplification of macrolide resistance loci. We compared the genetic relationships and plasmid contents of azithromycin resistant S. sonnei using whole genome sequences. From 475 available Shigella spp. isolated in Vietnam and Laos between 1994 and 2012, 6/181 S. flexneri (3.3%, MIC≥16g/L) and 16/294 S. sonnei (5.4%, MIC≥32g/L) were phenotypically resistant to azithromycin. PCR amplification confirmed a resistance mechanism in 22/475 (4.6%) isolates (19 mphA and 3 ermB). Susceptibility data demonstrated the acceptability of S. flexneri (MIC≥16g/L, zone≤15mm) and S. sonnei (MIC≥32g/L, zone≤11mm) breakpoints with <3% discrepancy. Phylogenetic analysis demonstrated that decreased susceptibility has arisen sporadically in Vietnamese S. sonnei on at least seven occasions between 2000 and 2009, but failed to become established. While the proposed susceptibility breakpoints may allow better recognition of resistant isolates, additional studies are required to assess the impact on clinical outcome. The potential emergence of azithromycin resistance highlights the need for alternative management options for Shigella infections in endemic countries.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1128/aac.01748-17

Authors


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Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM; Tropical Medicine
Role:
Author
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Role:
Author
ORCID:
0000-0001-9189-7244


More from this funder
Funding agency for:
Baker, S
Grant:
Sir Henry Dale 365 Fellowship grant number 10008/Z/12/Z
Sir Henry Dale 365 Fellowship grant number 10008/Z/12/Z to SB
More from this funder
Funding agency for:
Thwaites, G
Baker, S
Newton, P
Grant:
89276/2/09/2
Sir Henry Dale 365 Fellowship grant number 10008/Z/12/Z
106698/Z/14/ZtoDABD,PNN,RP
VD
106698/Z/14/Z
More from this funder
Grant:
Academic Clinical 360 Lectureship grant number 3557 to TCD


Publisher:
American Society for Microbiology
Journal:
Antimicrobial Agents and Chemotherapy More from this journal
Volume:
62
Issue:
4
Pages:
e01748-17
Publication date:
2018-01-29
Acceptance date:
2017-11-02
DOI:
EISSN:
1098-6596
ISSN:
0066-4804
Pmid:
29378707


Language:
English
Keywords:
Pubs id:
pubs:822609
UUID:
uuid:6f1710fd-1f74-4104-be5b-c91a82106fe4
Local pid:
pubs:822609
Source identifiers:
822609
Deposit date:
2018-02-03

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