Comparative in vitro activities of eravacycline and tigecycline against carbapenem-resistant Acinetobacter baumannii: Insights from whole genome sequencing analysis
ABSTRACT: Objectives: Eravacycline (ERV), a novel tetracycline-class antibiotic, has demonstrated efficacy against carbapenem-resistant Acinetobacter baumannii (CRAB) in Europe and the United States but has not been evaluated in Singapore. The objectives of this study are to evaluate the activity o...
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Elsevier
2025-09-01
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| Series: | Journal of Global Antimicrobial Resistance |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213716525001559 |
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| author | Yang Zhong Jocelyn Qi Min Teo Hong Yi Chang Jiahao Yeo Shuhua Thong Sihui Tan Nurhayati Binte Monhamed Yusoff Tze Peng Lim Andrea Lay Hoon Kwa |
| author_facet | Yang Zhong Jocelyn Qi Min Teo Hong Yi Chang Jiahao Yeo Shuhua Thong Sihui Tan Nurhayati Binte Monhamed Yusoff Tze Peng Lim Andrea Lay Hoon Kwa |
| author_sort | Yang Zhong |
| collection | DOAJ |
| description | ABSTRACT: Objectives: Eravacycline (ERV), a novel tetracycline-class antibiotic, has demonstrated efficacy against carbapenem-resistant Acinetobacter baumannii (CRAB) in Europe and the United States but has not been evaluated in Singapore. The objectives of this study are to evaluate the activity of ERV against CRAB clinical isolates from Singapore and to investigate the genetic profiles of these isolates, exploring novel potential ERV resistance mechanisms through whole genome sequencing (WGS) analysis. Methods: Three hundred CRAB clinical isolates collected from Singapore General Hospital (SGH) between 2012 and 2021 were tested for their susceptibility to ERV and other antibiotics. The genomic profile, including sequence type (ST), antimicrobial resistance, and virulence factor (VF) genes of these isolates, was determined. Isolates exhibiting high ERV minimum inhibitory concentrations (MICs) were further analysed to identify potential genetic mutations associated with reducing ERV susceptibility. Results: ERV demonstrated strong in vitro activity against CRAB, with an MIC90 of 2 µg/mL. WGS analysis revealed that the 300 CRAB isolates belonged to 23 STs, with ST2 being the predominant population and frequently harbouring intrinsic blaOXA-type β-lactamases and tetracycline-class efflux pumps (tet(B)). VF analysis shows extensive genetic diversity, with variations beyond simple presence/absence patterns. Notably, the emergence of ERV resistance (elevated MIC, and MIC > MIC90) was detected, and genetic analysis of high-MIC isolates identified novel mutations in the resistance-nodulation-cell division (RND) efflux pump genes (adeABC, adeFGH, and adeIJK) and their regulatory elements (adeS/R and adeL/N). Conclusions: ERV is a promising therapeutic option for managing CRAB infections in Singapore. However, the emergence of resistance mediated by novel genetic mutations highlights the need for continuous surveillance and further investigation.© 2025 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy. |
| format | Article |
| id | doaj-art-b9ebeb498cd14ddd9aacb11d546b5926 |
| institution | Kabale University |
| issn | 2213-7165 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Global Antimicrobial Resistance |
| spelling | doaj-art-b9ebeb498cd14ddd9aacb11d546b59262025-08-20T04:02:50ZengElsevierJournal of Global Antimicrobial Resistance2213-71652025-09-014434034610.1016/j.jgar.2025.06.021Comparative in vitro activities of eravacycline and tigecycline against carbapenem-resistant Acinetobacter baumannii: Insights from whole genome sequencing analysisYang Zhong0Jocelyn Qi Min Teo1Hong Yi Chang2Jiahao Yeo3Shuhua Thong4Sihui Tan5Nurhayati Binte Monhamed Yusoff6Tze Peng Lim7Andrea Lay Hoon Kwa8Department of Clinical Translational Research, Singapore General Hospital, Singapore; Pharmacy, Singapore General Hospital, SingaporePharmacy, Singapore General Hospital, SingaporeDepartment of Clinical Translational Research, Singapore General Hospital, Singapore; Pharmacy, Singapore General Hospital, SingaporePharmacy, Singapore General Hospital, SingaporePharmacy, Singapore General Hospital, SingaporePharmacy, Singapore General Hospital, SingaporePharmacy, Singapore General Hospital, SingaporePharmacy, Singapore General Hospital, SingaporePharmacy, Singapore General Hospital, Singapore; SingHealth Duke-NUS Medicine Academic Clinical Programme, Duke-NUS Medical School, Singapore; Emerging Infectious Diseases, Duke-NUS Medicine School, Singapore; Corresponding author. Mailing address: SingHealth Duke-NUS Medicine Academic Clinical Programme, Duke-NUS Medical School, Singapore.ABSTRACT: Objectives: Eravacycline (ERV), a novel tetracycline-class antibiotic, has demonstrated efficacy against carbapenem-resistant Acinetobacter baumannii (CRAB) in Europe and the United States but has not been evaluated in Singapore. The objectives of this study are to evaluate the activity of ERV against CRAB clinical isolates from Singapore and to investigate the genetic profiles of these isolates, exploring novel potential ERV resistance mechanisms through whole genome sequencing (WGS) analysis. Methods: Three hundred CRAB clinical isolates collected from Singapore General Hospital (SGH) between 2012 and 2021 were tested for their susceptibility to ERV and other antibiotics. The genomic profile, including sequence type (ST), antimicrobial resistance, and virulence factor (VF) genes of these isolates, was determined. Isolates exhibiting high ERV minimum inhibitory concentrations (MICs) were further analysed to identify potential genetic mutations associated with reducing ERV susceptibility. Results: ERV demonstrated strong in vitro activity against CRAB, with an MIC90 of 2 µg/mL. WGS analysis revealed that the 300 CRAB isolates belonged to 23 STs, with ST2 being the predominant population and frequently harbouring intrinsic blaOXA-type β-lactamases and tetracycline-class efflux pumps (tet(B)). VF analysis shows extensive genetic diversity, with variations beyond simple presence/absence patterns. Notably, the emergence of ERV resistance (elevated MIC, and MIC > MIC90) was detected, and genetic analysis of high-MIC isolates identified novel mutations in the resistance-nodulation-cell division (RND) efflux pump genes (adeABC, adeFGH, and adeIJK) and their regulatory elements (adeS/R and adeL/N). Conclusions: ERV is a promising therapeutic option for managing CRAB infections in Singapore. However, the emergence of resistance mediated by novel genetic mutations highlights the need for continuous surveillance and further investigation.© 2025 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.http://www.sciencedirect.com/science/article/pii/S2213716525001559Eravacycline activitiesCarbapenem-resistant Acinetobacter baumanniiWhole genome sequencing |
| spellingShingle | Yang Zhong Jocelyn Qi Min Teo Hong Yi Chang Jiahao Yeo Shuhua Thong Sihui Tan Nurhayati Binte Monhamed Yusoff Tze Peng Lim Andrea Lay Hoon Kwa Comparative in vitro activities of eravacycline and tigecycline against carbapenem-resistant Acinetobacter baumannii: Insights from whole genome sequencing analysis Journal of Global Antimicrobial Resistance Eravacycline activities Carbapenem-resistant Acinetobacter baumannii Whole genome sequencing |
| title | Comparative in vitro activities of eravacycline and tigecycline against carbapenem-resistant Acinetobacter baumannii: Insights from whole genome sequencing analysis |
| title_full | Comparative in vitro activities of eravacycline and tigecycline against carbapenem-resistant Acinetobacter baumannii: Insights from whole genome sequencing analysis |
| title_fullStr | Comparative in vitro activities of eravacycline and tigecycline against carbapenem-resistant Acinetobacter baumannii: Insights from whole genome sequencing analysis |
| title_full_unstemmed | Comparative in vitro activities of eravacycline and tigecycline against carbapenem-resistant Acinetobacter baumannii: Insights from whole genome sequencing analysis |
| title_short | Comparative in vitro activities of eravacycline and tigecycline against carbapenem-resistant Acinetobacter baumannii: Insights from whole genome sequencing analysis |
| title_sort | comparative in vitro activities of eravacycline and tigecycline against carbapenem resistant acinetobacter baumannii insights from whole genome sequencing analysis |
| topic | Eravacycline activities Carbapenem-resistant Acinetobacter baumannii Whole genome sequencing |
| url | http://www.sciencedirect.com/science/article/pii/S2213716525001559 |
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