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, ST357, 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.

中文翻译：

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印尼重症监护病房特有的碳青霉烯不敏感铜绿假单胞菌的高风险国际克隆：在基因组水平上进行多方面感染控制干预的影响。

感染控制效果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病房（ICU）收集的碳青霉烯类不敏感铜绿假单胞菌铜绿假单胞菌（CNPA）菌株的基因组概况，该实验室采用了多方面的感染控制干预措施。我们将临床数据与系统收集的CNPA的全基因组测序（WGS）相结合，以推断CNPA菌株的传播动态并表征其抗药性。我们发现，患者的CNPA传播和获取次数随时间变化很大，但总体而言，干预并未显着降低发病率。这些传播和获取涉及环境资源。四个高风险国际CNPA克隆（ST235，ST823，ST357和ST446）占主导地位，但是在实施干预后，这些克隆的分布发生了显着变化。使用电阻组分析，碳青霉烯耐药性是由于存在各种碳青霉烯酶编码基因（bla GES-5，bla VIM-2-8和bla IMP-1-7-43）以及孔蛋白OprD中的突变而引起的。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）分布的动态，另外还显示了WGS与临床数据结合使用以评估感染控制干预措施的效果。（此研究已经在www.trialregister.nl进行了注册，注册号为NTR5541。）重要信息在印度尼西亚等中低收入国家，缺乏资源可能会阻碍重症监护病房（ICU）的工作。在这种情况下，使用基因组工具进行大型流行病学研究颇具挑战。尽管如此，在感染控制干预之前和之后，我们仍能够系统地研究ICA内和之间的铜绿假单胞菌铜绿假单胞菌不敏感菌株（CNPA）的传播。我们的数据显示了广泛传播国际认可的CNPA克隆的重要性，环境水库的相关性以及实施的干预措施的混合效应的重要性；它导致了CNPA克隆构成的深刻变化，但并没有降低患者获得CNPA的风险。从而，