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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 isolates recovered in Vietnam and Laos were screened for susceptibility to azithromycin (15 μg) by disc diffusion and MIC. Phenotypic resistance was confirmed by PCR amplification of macrolide resistance loci. We compared the genetic relationships and plasmid contents of azithromycin-resistant Shigella sonnei isolates using whole-genome sequences. From 475 available Shigella spp. isolated in Vietnam and Laos between 1994 and 2012, 6/181 S. flexneri isolates (3.3%, MIC ≥ 16 g/liter) and 16/294 S. sonnei isolates (5.4%, MIC ≥ 32 g/liter) were phenotypically resistant to azithromycin. PCR amplification confirmed a resistance mechanism in 22/475 (4.6%) isolates (mphA in 19 isolates and ermB in 3 isolates). The susceptibility data demonstrated the acceptability of the S. flexneri (MIC ≥ 16 g/liter, zone diameter ≤ 15 mm) and S. sonnei (MIC ≥ 32 g/liter, zone diameter ≤ 11 mm) breakpoints with a <3% discrepancy. Phylogenetic analysis demonstrated that decreased susceptibility has arisen sporadically in Vietnamese S. sonnei isolates 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 the clinical outcome. The potential emergence of azithromycin resistance highlights the need for alternative options for management of Shigella infections in countries where Shigella is endemic.

Authors+Show Affiliations

The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School, Sheffield, United Kingdom.The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Vientiane, Laos. Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, United Kingdom.Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Vientiane, Laos. Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, United Kingdom. Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Vientiane, Laos.Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Vientiane, Laos.The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, United Kingdom.Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom. School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan.The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam sbaker@oucru.org. Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, United Kingdom. Department of Medicine, University of Cambridge, Cambridge, United Kingdom.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29378707

Citation

Darton, Thomas C., et al. "Azithromycin Resistance in Shigella Spp. in Southeast Asia." Antimicrobial Agents and Chemotherapy, vol. 62, no. 4, 2018.
Darton TC, Tuyen HT, The HC, et al. Azithromycin Resistance in Shigella spp. in Southeast Asia. Antimicrob Agents Chemother. 2018;62(4).
Darton, T. C., Tuyen, H. T., The, H. C., Newton, P. N., Dance, D. A. B., Phetsouvanh, R., ... Baker, S. (2018). Azithromycin Resistance in Shigella spp. in Southeast Asia. Antimicrobial Agents and Chemotherapy, 62(4), doi:10.1128/AAC.01748-17.
Darton TC, et al. Azithromycin Resistance in Shigella Spp. in Southeast Asia. Antimicrob Agents Chemother. 2018;62(4) PubMed PMID: 29378707.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Azithromycin Resistance in Shigella spp. in Southeast Asia. AU - Darton,Thomas C, AU - Tuyen,Ha Thanh, AU - The,Hao Chung, AU - Newton,Paul N, AU - Dance,David A B, AU - Phetsouvanh,Rattanaphone, AU - Davong,Viengmon, AU - Campbell,James I, AU - Hoang,Nguyen Van Minh, AU - Thwaites,Guy E, AU - Parry,Christopher M, AU - Thanh,Duy Pham, AU - Baker,Stephen, Y1 - 2018/03/27/ PY - 2017/08/23/received PY - 2017/11/02/accepted PY - 2018/1/31/pubmed PY - 2019/4/20/medline PY - 2018/1/31/entrez KW - Shigella KW - Southeast Asia KW - azithromycin KW - breakpoints KW - genome analysis KW - resistance JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 62 IS - 4 N2 - 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 isolates recovered in Vietnam and Laos were screened for susceptibility to azithromycin (15 μg) by disc diffusion and MIC. Phenotypic resistance was confirmed by PCR amplification of macrolide resistance loci. We compared the genetic relationships and plasmid contents of azithromycin-resistant Shigella sonnei isolates using whole-genome sequences. From 475 available Shigella spp. isolated in Vietnam and Laos between 1994 and 2012, 6/181 S. flexneri isolates (3.3%, MIC ≥ 16 g/liter) and 16/294 S. sonnei isolates (5.4%, MIC ≥ 32 g/liter) were phenotypically resistant to azithromycin. PCR amplification confirmed a resistance mechanism in 22/475 (4.6%) isolates (mphA in 19 isolates and ermB in 3 isolates). The susceptibility data demonstrated the acceptability of the S. flexneri (MIC ≥ 16 g/liter, zone diameter ≤ 15 mm) and S. sonnei (MIC ≥ 32 g/liter, zone diameter ≤ 11 mm) breakpoints with a <3% discrepancy. Phylogenetic analysis demonstrated that decreased susceptibility has arisen sporadically in Vietnamese S. sonnei isolates 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 the clinical outcome. The potential emergence of azithromycin resistance highlights the need for alternative options for management of Shigella infections in countries where Shigella is endemic. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/29378707/Azithromycin_Resistance_in_Shigella_spp__in_Southeast_Asia_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&amp;pmid=29378707 DB - PRIME DP - Unbound Medicine ER -