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鉴定两种猕猴物种中耐甲氧西林的万古霉素耐药性,并对食蟹猴进行去定植和长期预防再定植()。

Identification of Vancomycin Resistance in Methicillin-resistant in two macaque species and decolonization and long-term prevention of recolonization in Cynomolgus Macaques ().

机构信息

Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United States.

Division of Pathobiology and Immunology, Oregon National Primate Research Center, Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United States.

出版信息

Front Immunol. 2023 Aug 22;14:1244637. doi: 10.3389/fimmu.2023.1244637. eCollection 2023.

Abstract

Methicillin-resistant (MRSA) is a strain with resistance to beta-lactam antibiotics, making it a global human and veterinary health concern. Specifically, immunosuppressed patients have a remarkably higher risk of clinical MRSA infections with significantly increased rates of prolonged clinical recovery, morbidity, and mortality. The current treatment of choice for MRSA is vancomycin. Importantly, we report the first known vancomycin-resistant (VRSA) carriers in a cohort of Mauritian cynomolgus macaques (CM) imported to the Oregon National Primate Research Center (ONPRC), with a MRSA carrier rate of 76.9% (10/13 animals). All MRSA isolates also demonstrated resistance to vancomycin with prevalence of vancomycin-intermediate (VISA) at 30% (3/10 MRSA-positive CMs) and VRSA at 70% (7/10 MRSA-positive CMs). Additionally, we identified VRSA in a rhesus macaque (RM) housed within the same room as the VRSA-positive CMs and identified a MRSA/VISA carrier rate of 18.8% in RMs (3/16 positive for both MRSA and VISA) in unexposed recently assigned animals directly from the ONPRC RM breeding colony. Considering that the MRSA and VRSA/VISA-positive CMs future study aims included significant immunosuppression, MRSA/VRSA/VISA decolonization treatment and expanded "MRSA-free" practices were employed to maintain this status. We report the first controlled study using in-depth analyses with appropriate diagnostic serial testing to definitively show an MRSA decolonization therapy (90% success rate) and expanded barrier practice techniques to successfully prevent recolonization (100%) of a cohort of CMs MRSA-free (up to 529 days with a total of 4,806 MRSA-free NHP days).

摘要

耐甲氧西林金黄色葡萄球菌(MRSA)是一种对β-内酰胺类抗生素具有耐药性的菌株,这是一个全球性的人类和兽医健康关注点。具体来说,免疫功能低下的患者患有临床耐甲氧西林金黄色葡萄球菌感染的风险显著增加,临床康复时间延长、发病率和死亡率显著增加。目前治疗耐甲氧西林金黄色葡萄球菌的首选药物是万古霉素。重要的是,我们报告了首例在毛里求斯食蟹猴(CM)队列中发现的万古霉素耐药(VRSA)携带者,这些 CM 被进口到俄勒冈国家灵长类动物研究中心(ONPRC),其中 MRSA 携带者率为 76.9%(13 只动物中有 10 只)。所有耐甲氧西林金黄色葡萄球菌分离株也对万古霉素表现出耐药性,其中万古霉素中介(VISA)的流行率为 30%(10 株耐甲氧西林金黄色葡萄球菌阳性 CM 中有 3 株),VRSA 的流行率为 70%(10 株耐甲氧西林金黄色葡萄球菌阳性 CM 中有 7 株)。此外,我们在与 VRSA 阳性 CM 同住一个房间的恒河猴(RM)中发现了 VRSA,并在来自 ONPRC RM 繁殖群的未接触的最近分配的动物中发现了 RM 的 MRSA/VISA 携带者率为 18.8%(MRSA 和 VISA 均为阳性的动物有 3/16)。考虑到 MRSA 和 VRSA/VISA 阳性 CM 的未来研究目的包括显著的免疫抑制,因此采用了 MRSA/VRSA/VISA 去定植治疗和扩大“MRSA 阴性”实践,以维持这一状态。我们报告了首例使用深入分析和适当的诊断性连续检测的对照研究,明确显示了 MRSA 去定植治疗(成功率为 90%)和扩大的屏障实践技术的成功,成功地使 CM 队列保持了无 MRSA(最长 529 天,共 4806 天无 MRSA 的非人灵长类动物)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87a1/10477669/561c4a75d0ed/fimmu-14-1244637-g001.jpg

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