Resistance to sulbactam/durlobactam in carbapenem-resistant Acinetobacter baumannii in treatment-naive setting: In vitro data and genomic insights from Italian bloodstream isolates

IF 5 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents Pub Date : 2026-03-01 Epub Date: 2026-01-16 DOI:10.1016/j.ijantimicag.2026.107718

Gabriele Bianco , Gherard Batisti Biffignandi , Matteo Boattini , Sara Comini , Cristina Costa , Michela Vumbaca , Paolo Gaibani

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引用次数: 0

Abstract

Objective

This study evaluated the in vitro activity of sulbactam/durlobactam and comparators against carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream isolates from Italy and investigated genomic mechanisms underlying resistance.

Methods

A total of 110 consecutive CRAB isolates (2021–2023) were tested for susceptibility to sulbactam/durlobactam, cefiderocol, colistin, and comparators. Whole-genome sequencing (WGS) was performed on sulbactam/durlobactam-resistant isolates to characterise β-lactamase genes, outbreak dynamics, and mutations in penicillin-binding proteins (PBPs).

Results

Sulbactam/durlobactam inhibited 87.3% of isolates (MIC₅₀ = 2 mg/L; MIC₉₀ > 64 mg/L), while 12.7% were resistant. Cefiderocol and colistin showed 91.8% and 96.4% susceptibility rates, respectively. All resistant isolates carried bla_OXA-23, and three also harbored bla_NDM-1. WGS revealed close clonal relationships (average nucleotide identity > 99%) among bla_NDM-1 positive isolates (ST231) and among OXA-23-only isolates (ST837/ST369), indicating local outbreak dynamics. Comparative PBP analysis identified recurrent substitutions P112S and G137R (PBP1b), N392T and A515V (PBP3), and S329N (PBP5). Structural correlation suggests these mutations reduce β-lactam binding and may contribute to resistance, particularly when combined with NDM-1.

Conclusions

This study provides early evidence of sulbactam/durlobactam resistance in treatment-naïve CRAB from Italy, driven by NDM-1 co-production and PBP alterations. The coexistence of epidemic ST231 and ST837/ST369 clones highlights the need for continuous genomic surveillance and prudent antibiotic stewardship to prevent dissemination of resistant A. baumannii lineages.

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未经治疗的耐碳青霉烯鲍曼不动杆菌对舒巴坦/杜氯巴坦的耐药性：来自意大利血液分离株的体外数据和基因组见解

目的：本研究评估舒巴坦/杜氯巴坦及其比较物对意大利碳青霉烯耐药鲍曼不动杆菌（CRAB）血液分离株的体外活性，并探讨其耐药的基因组机制。方法：对2021-2023年连续分离的110株螃蟹进行舒巴坦/杜氯巴坦、头孢地罗、粘菌素及比较物的敏感性检测。对舒巴坦/杜氯巴坦耐药菌株进行全基因组测序（WGS），以表征β-内酰胺酶基因、爆发动态和青霉素结合蛋白（PBPs）突变。结果：舒巴坦/杜氯巴坦抑制了88.7%的分离株（MIC₅₀ = 2 mg/L; MIC₉₀> 64 mg/L）， 12.7%的分离株耐药。头孢地洛和粘菌素的易感率分别为91.8%和96.4%。所有耐药菌株都携带blaOXA-23，其中3株也携带blaNDM-1。WGS结果显示，blaNDM-1阳性分离株（ST231）和oxa -23阳性分离株（ST837/ST369）之间的克隆关系密切（平均核苷酸同一性bbbb99 %），表明当地爆发动态。对比PBP分析发现，P112S和G137R （PBP1b）、N392T和A515V （PBP3）、S329N （PBP5）是反复出现的替代基因。结构相关性表明，这些突变减少β-内酰胺结合，并可能导致耐药性，特别是当与NDM-1结合时。结论：该研究提供了意大利treatment-naïve CRAB耐药的早期证据，由NDM-1联合生产和PBP改变驱动。流行病ST231和ST837/ST369克隆的共存突出了需要持续的基因组监测和谨慎的抗生素管理，以防止耐药鲍曼不雅杆菌谱系的传播。

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来源期刊

International Journal of Antimicrobial Agents 医学-传染病学

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.