Genomic investigation of Staphylococcus aureus recovered from Gambian women and newborns following an oral dose of intra-partum azithromycin
Genomic investigation of Staphylococcus aureus recovered from Gambian women and newborns following an oral dose of intra-partum azithromycin
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DOI：
10.1093/jac/dkz341
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发表时间：
2019-11-01
影响因子：
5.2
通讯作者：
Howden, Benjamin P.
中科院分区：
文献类型：
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作者：
Bojang, Abdoulie;Baines, Sarah L.;Howden, Benjamin P.
背景：分娩时口服阿奇霉素可减少导致新生儿败血症的细菌携带，包括金黄色葡萄球菌。然而，有人担心这可能会促进耐药性。 目的：在这里，我们结合了一项随机产时阿奇霉素试验 (PregnAnZI) 中从母亲和婴儿身上分离出的金黄色葡萄球菌的基因组和流行病学数据，以描述细菌种群动态和耐药机制。 方法：来自试验两组的参与者均被纳入其中，他们在干预后第 3 天和第 28 天的样本中携带金黄色葡萄球菌。对 66 株金黄色葡萄球菌分离株（来自 7 名母亲和 10 名婴儿）进行了比较基因组分析，然后将数据与流行病学数据相结合。试验注册（主要试验）：ClinicalTrials.gov 标识符 NCT01800942。 结果：鉴定出 7 个金黄色葡萄球菌 ST，其中 ST5 占主导地位（n=40，61.0%），其次是 ST15（n=11，17.0%）。 ST5 在安慰剂组中占主导地位（73.0% 对 49.0%，P=0.039），在阿奇霉素组中 ST15 占主导地位（27.0% 对 6.0%，P=0.022）。在阿奇霉素耐药菌株中，msr(A) 是主要的大环内酯类耐药基因（n=36，80%）。来自两个试验组的 10 名研究参与者在最初携带易感菌株后，感染了阿奇霉素耐药金黄色葡萄球菌。在其中九个 (90%) 病例中，获得的克隆是包含 msr(A) 的 ST5 金黄色葡萄球菌。长读长测序表明，在 ST5 中，在 MDR 质粒上发现了 msr(A)。 结论：我们的数据揭示了冈比亚人群中存在具有质粒编码的阿奇霉素抗性的金黄色葡萄球菌显性克隆，该克隆由研究的两个组的参与者获得。了解这些耐药动态对于确定非洲分娩期间预防使用阿奇霉素对公共卫生耐药性的影响至关重要。
Background: Oral azithromycin given during labour reduces carriage of bacteria responsible for neonatal sepsis, including Staphylococcus aureus. However, there is concern that this may promote drug resistance.Objectives: Here, we combine genomic and epidemiological data on S. aureus isolated from mothers and babies in a randomized intra-partum azithromycin trial (PregnAnZI) to describe bacterial population dynamics and resistance mechanisms.Methods: Participants from both arms of the trial, who carried S. aureus in day 3 and day 28 samples post-intervention, were included. Sixty-six S. aureus isolates (from 7 mothers and 10 babies) underwent comparative genome analyses and the data were then combined with epidemiological data. Trial registration (main trial): ClinicalTrials.gov Identifier NCT01800942.Results: Seven S. aureus STs were identified, with ST5 dominant (n=40, 61.0%), followed by ST15 (n=11, 17.0%). ST5 predominated in the placebo arm (73.0% versus 49.0%, P=0.039) and ST15 in the azithromycin arm (27.0% versus 6.0%, P=0.022). In azithromycin-resistant isolates, msr(A) was the main macrolide resistance gene (n=36, 80%). Ten study participants, from both trial arms, acquired azithromycin-resistant S. aureus after initially harbouring a susceptible isolate. In nine (90%) of these cases, the acquired clone was an msr(A)-containing ST5 S. aureus. Long-read sequencing demonstrated that in ST5, msr(A) was found on an MDR plasmid.Conclusions: Our data reveal in this Gambian population the presence of a dominant clone of S. aureus harbouring plasmid-encoded azithromycin resistance, which was acquired by participants in both arms of the study. Understanding these resistance dynamics is crucial to defining the public health drug resistance impacts of azithromycin prophylaxis given during labour in Africa.