High-Risk International Clones of Carbapenem-Nonsusceptible Pseudomonas aeruginosa Endemic to Indonesian Intensive Care Units: Impact of a Multifaceted Infection Control Intervention Analyzed at the Genomic Level
High-Risk International Clones of Carbapenem-Nonsusceptible Pseudomonas aeruginosa Endemic to Indonesian Intensive Care Units: Impact of a Multifaceted Infection Control Intervention Analyzed at the Genomic Level
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DOI：
10.1128/mbio.02384-19
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发表时间：
2019-11-01
期刊：
影响因子：
6.4
通讯作者：
Severin, Juliette A.
中科院分区：
文献类型：
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作者：
Pelegrin, Andreu Coello;Saharman, Yulia Rosa;Severin, Juliette A.
感染控制有效性评估需要详细的流行病学和微生物学数据。我们分析了从印度尼西亚雅加达国家转诊医院的两个重症监护室 (ICU) 收集的碳青霉烯类不敏感铜绿假单胞菌 (CNPA) 菌株的基因组谱，该医院采用了多方面的感染控制干预措施。我们利用临床数据结合系统收集的 CNPA 的全基因组测序 (WGS) 来推断 CNPA 菌株的传播动态并表征其耐药组。我们发现，随着时间的推移，患者传播和获得 CNPA 的数量变化很大，但总体而言，干预措施并未显着降低传播率。这些传输和获取涉及环境来源。四种高危国际 CNPA 克隆（ST235、ST823、ST375 和 ST446）占主导地位，但干预实施后这些克隆的分布发生了显着变化。使用抗性组分析，碳青霉烯类抗性可以通过多种碳青霉烯酶编码基因（bla(GES-5)、bla(VIM-2-8) 和 bla(IMP-1-7-43)）的存在以及孔蛋白 OprD 内的突变来解释。我们的结果首次揭示了印度尼西亚铜绿假单胞菌抗菌素耐药性 (AMR) 概况的动态，并且还显示了 WGS 与临床数据相结合的效用，以评估感染控制干预措施的影响。 （本研究已在 www.Trialregister.nl 上注册，注册号为 NTR5541）。 重要性 在印度尼西亚等中低收入国家，重症监护病房 (ICU) 的工作可能会因缺乏资源而受到阻碍。在这种情况下使用基因组工具进行大型流行病学研究相当具有挑战性。尽管如此，我们仍然能够系统地研究感染控制干预前后碳青霉烯类不敏感铜绿假单胞菌菌株 (CNPA) 在 ICU 内和之间的传播情况。我们的数据显示了广泛传播国际公认的 CNPA 克隆的重要性、环境储存库的相关性以及所实施干预措施的混合效应；它导致 CNPA 克隆组成发生深刻变化，但并没有降低患者感染 CNPA 的风险。因此，印度尼西亚 ICU 中的 CNPA 流行病学是多个 CNPA 克隆全球扩张的一部分，这些克隆仍然难以通过感染预防措施进行控制。
Infection control effectiveness evaluations require detailed epidemiological and microbiological data. We analyzed the genomic profiles of carbapenem-nonsusceptible Pseudomonas aeruginosa (CNPA) strains collected from two intensive care units (ICUs) in the national referral hospital in Jakarta, Indonesia, where a multifaceted infection control intervention was applied. We used clinical data combined with whole-genome sequencing (WGS) of systematically collected CNPA to infer the transmission dynamics of CNPA strains and to characterize their resistome. We found that the number of CNPA transmissions and acquisitions by patients was highly variable over time but that, overall, the rates were not significantly reduced by the intervention. Environmental sources were involved in these transmissions and acquisitions. Four high-risk international CNPA clones (ST235, ST823, ST375, and ST446) dominated, but the distribution of these clones changed significantly after the intervention was implemented. Using resistome analysis, carbapenem resistance was explained by the presence of various carbapenemase-encoding genes (bla(GES-5), bla(VIM-2-8), and bla(IMP-1-7-43)) and by mutations within the porin OprD. Our results reveal for the first time the dynamics of P. aeruginosa antimicrobial resistance (AMR) profiles in Indonesia and additionally show the utility of WGS in combination with clinical data to evaluate the impact of an infection control intervention. (This study has been registered at www.trialregister.nl under registration no. NTR5541).IMPORTANCE In low-to-middle-income countries such as Indonesia, work in intensive care units (ICUs) can be hampered by lack of resources. Conducting large epidemiological studies in such settings using genomic tools is rather challenging. Still, we were able to systematically study the transmissions of carbapenem-nonsusceptible strains of P. aeruginosa (CNPA) within and between ICUs, before and after an infection control intervention. Our data show the importance of the broad dissemination of the internationally recognized CNPA clones, the relevance of environmental reservoirs, and the mixed effects of the implemented intervention; it led to a profound change in the clonal make-up of CNPA, but it did not reduce the patients' risk of CNPA acquisitions. Thus, CNPA epidemiology in Indonesian ICUs is part of a global expansion of multiple CNPA clones that remains difficult to control by infection prevention measures.