1887

Abstract

Azithromycin is increasingly being used for the treatment of shigellosis despite a lack of interpretative guidelines and with limited clinical evidence. The present study determined azithromycin susceptibility and correlated this with macrolide-resistance genes in spp. isolated from stool specimens in Vellore, India. The susceptibility of 332 isolates to azithromycin was determined using the disc diffusion method. Of these, 31 isolates were found to be azithromycin resistant. The azithromycin minimum inhibitory concentration (MIC) was determined using the broth microdilution method. In addition, isolates were screened for and genes using conventional PCR. Furthermore, an isolate that was positive for resistance genes was subjected to complete genome analysis, and was analysed for mobile genetic elements. The azithromycin MIC for the 31 resistant isolates ranged between 2 and 16 mg l. PCR results showed that a single isolate of carried a gene. Complete genome analysis revealed integration of an IncFII plasmid into the chromosome of , which was also found to carry the following resistance genes: 1, , B4, A, . Mutations in the quinolone-resistance-determining region (QRDR) were also observed. Additionally, prophages, insertion sequences and integrons were identified. The novel finding of IncFII plasmid integration into the chromosome of highlights the potential risk of spp. becoming resistance to azithromycin in the future. These suggests that it is imperative to monitor susceptibility and to study the resistance mechanism of to azithromycin considering the limited treatment choices for shigellosis.

Funding
This study was supported by the:
  • Indian Council of Medical Research (Award AMR/TF/55/13ECDII)
    • Principle Award Recipient: BalajiVeeraraghavan
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Loading

Article metrics loading...

/content/journal/acmi/10.1099/acmi.0.000189
2020-12-09
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/acmi/3/2/acmi000189.html?itemId=/content/journal/acmi/10.1099/acmi.0.000189&mimeType=html&fmt=ahah

References

  1. Kotloff KL, Riddle MS, Platts-Mills JA, Pavlinac P, Zaidi AKM. Shigellosis. Lancet 2018; 391:801–812 [View Article][PubMed]
    [Google Scholar]
  2. Darton TC, Tuyen HT, The HC, Newton PN, Dance DAB et al. Azithromycin resistance in Shigella spp. in Southeast Asia. Antimicrob Agents Chemother 2018; 62:e01748-17 [View Article][PubMed]
    [Google Scholar]
  3. Salah M, Shtayeh I, Ghneim R, Al-Qass R, Sabateen A et al. Evaluation of Shigella species azithromycin CLSI epidemiological cutoff values and macrolide resistance genes. J Clin Microbiol 2019; 57:e01422-18 [View Article][PubMed]
    [Google Scholar]
  4. Boumghar-Bourtchai L, Mariani-Kurkdjian P, Bingen E, Filliol I, Dhalluin A et al. Macrolide-resistant Shigella sonnei . Emerg Infect Dis 2008; 14:1297–1299 [View Article][PubMed]
    [Google Scholar]
  5. Nguyen MCP, Woerther PL, Bouvet M, Andremont A, Leclercq R et al. Escherichia coli as reservoir for macrolide resistance genes. Emerg Infect Dis 2009; 15:1648–1650 [View Article][PubMed]
    [Google Scholar]
  6. Gomes C, Ruiz-Roldán L, Mateu J, Ochoa TJ, Ruiz J. Azithromycin resistance levels and mechanisms in Escherichia coli . Sci Rep 2019; 9:6089 [View Article]
    [Google Scholar]
  7. Sethuvel DP, Perumalla S, Anandan S, Michael JS, Ragupathi NKD et al. Antimicrobial resistance, virulence & plasmid profiles among clinical isolates of Shigella serogroups. Indian J Med Res 2019; 149:247–256 [View Article][PubMed]
    [Google Scholar]
  8. Bopp CA, Brenner FW, Fields PL. Escherichia, Shigella, and Salmonella . In Murray PR, Baron EJ, Jorgensen J, Pfaller MA, Yolken RH. eds Manual of Clinical Microbiology, 8th edn. Washington, DC: American Society for Microbiology; 2003 pp 654–671
    [Google Scholar]
  9. Clinical and Laboratory Standards Institute Performance Standards for Antimicrobial Susceptibility Testing, document M100, 27th edn. Wayne, PA: CLSI; 2017
    [Google Scholar]
  10. Vasudevan K, Devanga Ragupathi NK, Jacob JJ, Veeraraghavan B. Highly accurate-single chromosomal complete genomes using IonTorrent and MinION sequencing of clinical pathogens. Genomics 2020; 112:545–551 [View Article][PubMed]
    [Google Scholar]
  11. Zankari E, Hasman H, Cosentino S, Vestergaard M, Rasmussen S et al. Identification of acquired antimicrobial resistance genes. J Antimicrob Chemother 2012; 67:2640–2644 [View Article][PubMed]
    [Google Scholar]
  12. Carattoli A, Zankari E, García-Fernández A, Voldby Larsen M, Lund O et al. In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob Agents Chemother 2014; 58:3895–3903 [View Article][PubMed]
    [Google Scholar]
  13. Stothard P, Wishart DS. Circular genome visualization and exploration using CGView. Bioinformatics 2005; 21:537–539 [View Article][PubMed]
    [Google Scholar]
  14. Petkau A, Stuart-Edwards M, Stothard P, Van Domselaar G. Interactive microbial genome visualization with GView. Bioinformatics 2010; 26:3125–3126 [View Article][PubMed]
    [Google Scholar]
  15. Zhou Y, Liang Y, Lynch KH, Dennis JJ, Wishart DS. PHAST: a fast phage search tool. Nucleic Acids Res 2011; 39:W347–W352 [View Article][PubMed]
    [Google Scholar]
  16. Varani AM, Siguier P, Gourbeyre E, Charneau V, Chandler M. ISsaga is an ensemble of web-based methods for high throughput identification and semi-automatic annotation of insertion sequences in prokaryotic genomes. Genome Biol 2011; 12:R30 [View Article][PubMed]
    [Google Scholar]
  17. Heiman KE, Grass JE, Sjölund-Karlsson M, Bowen A. Shigellosis with decreased susceptibility to azithromycin. Pediatr Infect Dis J 2014; 33:1204–1205 [View Article][PubMed]
    [Google Scholar]
  18. Ezernitchi AV, Sirotkin E, Danino D, Agmon V, Valinsky L et al. Azithromycin non-susceptible Shigella circulating in Israel, 2014-2016. PLoS One 2019; 14:e0221458 [View Article][PubMed]
    [Google Scholar]
  19. Hassing R-J, Melles DC, Goessens WHF, Rijnders BJA. Case of Shigella flexneri infection with treatment failure due to azithromycin resistance in an HIV-positive patient. Infection 2014; 42:789–790 [View Article][PubMed]
    [Google Scholar]
  20. Benz F, Huisman JS, Bakkeren E, Herter JA, Stadler T. Clinical extended-spectrum beta-lactamase antibiotic resistance plasmids have diverse transfer rates and can spread in the absence of antibiotic selection. bioRxiv 2019796243
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/acmi/10.1099/acmi.0.000189
Loading
/content/journal/acmi/10.1099/acmi.0.000189
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error