The emergence of transposon-driven multidrug resistance in invasive nontypeable Haemophilus influenzae over the last decade

IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES International Journal of Antimicrobial Agents Pub Date : 2024-09-02 DOI:10.1016/j.ijantimicag.2024.107319
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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.

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过去十年中,侵袭性非类型流感嗜血杆菌出现了转座子驱动的多药耐药性。
非耐药型流感嗜血杆菌(NTHi)曾被认为是一种无害的共生菌,但由于耐多药(MDR)菌株的流行率增加及其与侵袭性感染的关联,NTHi已成为一个备受关注的问题。本研究旨在探索 2011 年至 2020 年间从台湾北部侵袭性感染患者中采集的 51 株 NTHi 分离物的流行病学和分子耐药机制。调查发现了大量遗传多样性,包括 29 种不同的序列类型和 18 个克隆复合体。值得注意的是,68.6%的分离株表现出氨苄西林耐药性,其中28株被归类为MDR,4株分离株甚至对多达6种抗生素产生耐药性。在 MDR 分离物中,发现了 18 个脉冲型,表明了不同的基因系。对其耐药机制的阐明发现了 18 个产生阿莫西林-克拉维酸的β-内酰胺酶耐药(BLPACR)分离株、12 个产生氨苄西林的β-内酰胺酶耐药(BLPAR)分离株和 5 个不产氨苄西林的β-内酰胺酶耐药(BLNAR)分离株。PBP3 分析揭示了 BLPACR 和 BLNAR 中的 22 个独特取代,这可能是导致头孢菌素耐药性的原因。值得注意的是,发现了包含关键抗性基因的新型转座子 Tn7736-Tn7739。三个菌株携带 Tn7739,其中含有七个抗性基因[aph(3')-Ia、blaTEM-1、catA、sul2、strA、strB 和 tet(B)],另外四个菌株携带 Tn7736、Tn7737 和 Tn7738,每个菌株含有三个抗性基因[blaTEM-1、catA 和 tet(B)]。这些新型转座子的出现凸显了高抗性 NTHi 菌株所带来的令人担忧的威胁。我们的研究结果表明,要应对这一日益严峻的公共卫生挑战,需要进行强有力的监测和全面的基因组研究。
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来源期刊
CiteScore
21.60
自引率
0.90%
发文量
176
审稿时长
36 days
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.
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