Tsai-Wen Wan , Yu-Tsung Huang , Jian-Hong Lai , Qiao-Ting Chao , Hui-Hui Yeo , Tai-Fen Lee , Yung-Chi Chang , Hao-Chieh Chiu
{"title":"The emergence of transposon-driven multidrug resistance in invasive nontypeable Haemophilus influenzae over the last decade","authors":"Tsai-Wen Wan , Yu-Tsung Huang , Jian-Hong Lai , Qiao-Ting Chao , Hui-Hui Yeo , Tai-Fen Lee , Yung-Chi Chang , Hao-Chieh Chiu","doi":"10.1016/j.ijantimicag.2024.107319","DOIUrl":null,"url":null,"abstract":"<div><div>Nontypeable <em>Haemophilus influenzae</em> (NTHi), once considered a harmless commensal, has emerged as a significant concern due to the increased prevalence of multidrug-resistant (MDR) strains and their association with invasive infections. This study aimed to explore the epidemiology and molecular resistance mechanisms of 51 NTHi isolates collected from patients with invasive infections in northern Taiwan between 2011 and 2020. This investigation revealed substantial genetic diversity, encompassing 29 distinct sequence types and 18 clonal complexes. Notably, 68.6% of the isolates exhibited ampicillin resistance, with 28 categorised as MDR and four isolates were even resistant to up to six antibiotic classes. Among the MDR isolates, 18 pulsotypes were identified, indicating diverse genetic lineages. Elucidation of their resistance mechanisms revealed 18 β-lactamase-producing amoxicillin–clavulanate-resistant (BLPACR) isolates, 12 β-lactamase-producing ampicillin-resistant (BLPAR) isolates, and 5 β-lactamase-nonproducing ampicillin-resistant (BLNAR) isolates. PBP3 analysis revealed 22 unique substitutions in BLPACR and BLNAR, potentially contributing to cephem resistance. Notably, novel transposons, Tn<em>7736</em>-Tn<em>7739</em>, which contain critical resistance genes, were discovered. Three strains harboured Tn<em>7739</em>, containing seven resistance genes [<em>aph(3′)-Ia, bla</em><sub>TEM-1</sub>, <em>catA, sul2, strA, strB</em>, and <em>tet</em>(B)], while four other strains carried Tn<em>7736</em>, Tn<em>7737</em>, and Tn<em>7738</em>, each containing three resistance genes [<em>bla</em><sub>TEM-1</sub>, <em>catA</em>, and <em>tet</em>(B)]. The emergence of these novel transposons underscores the alarming threat posed by highly resistant NTHi strains. Our findings indicated that robust surveillance and comprehensive genomic studies are needed to address this growing public health challenge.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 4","pages":"Article 107319"},"PeriodicalIF":4.9000,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Antimicrobial Agents","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0924857924002358","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
Abstract
Nontypeable Haemophilus influenzae (NTHi), once considered a harmless commensal, has emerged as a significant concern due to the increased prevalence of multidrug-resistant (MDR) strains and their association with invasive infections. This study aimed to explore the epidemiology and molecular resistance mechanisms of 51 NTHi isolates collected from patients with invasive infections in northern Taiwan between 2011 and 2020. This investigation revealed substantial genetic diversity, encompassing 29 distinct sequence types and 18 clonal complexes. Notably, 68.6% of the isolates exhibited ampicillin resistance, with 28 categorised as MDR and four isolates were even resistant to up to six antibiotic classes. Among the MDR isolates, 18 pulsotypes were identified, indicating diverse genetic lineages. Elucidation of their resistance mechanisms revealed 18 β-lactamase-producing amoxicillin–clavulanate-resistant (BLPACR) isolates, 12 β-lactamase-producing ampicillin-resistant (BLPAR) isolates, and 5 β-lactamase-nonproducing ampicillin-resistant (BLNAR) isolates. PBP3 analysis revealed 22 unique substitutions in BLPACR and BLNAR, potentially contributing to cephem resistance. Notably, novel transposons, Tn7736-Tn7739, which contain critical resistance genes, were discovered. Three strains harboured Tn7739, containing seven resistance genes [aph(3′)-Ia, blaTEM-1, catA, sul2, strA, strB, and tet(B)], while four other strains carried Tn7736, Tn7737, and Tn7738, each containing three resistance genes [blaTEM-1, catA, and tet(B)]. The emergence of these novel transposons underscores the alarming threat posed by highly resistant NTHi strains. Our findings indicated that robust surveillance and comprehensive genomic studies are needed to address this growing public health challenge.
期刊介绍:
The International Journal of Antimicrobial Agents is a peer-reviewed publication offering comprehensive and current reference information on the physical, pharmacological, in vitro, and clinical properties of individual antimicrobial agents, covering antiviral, antiparasitic, antibacterial, and antifungal agents. The journal not only communicates new trends and developments through authoritative review articles but also addresses the critical issue of antimicrobial resistance, both in hospital and community settings. Published content includes solicited reviews by leading experts and high-quality original research papers in the specified fields.