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从美国一家中心连续治疗多药耐药细菌感染的首例10例静脉注射噬菌体疗法中吸取的经验教训。

Lessons Learned From the First 10 Consecutive Cases of Intravenous Bacteriophage Therapy to Treat Multidrug-Resistant Bacterial Infections at a Single Center in the United States.

作者信息

Aslam Saima, Lampley Elizabeth, Wooten Darcy, Karris Maile, Benson Constance, Strathdee Steffanie, Schooley Robert T

机构信息

Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, California, USA.

Center for Innovative Phage Applications and Therapeutics, University of California, San Diego, La Jolla, California, USA.

出版信息

Open Forum Infect Dis. 2020 Aug 27;7(9):ofaa389. doi: 10.1093/ofid/ofaa389. eCollection 2020 Sep.

Abstract

BACKGROUND

Due to increasing multidrug-resistant (MDR) infections, there is an interest in assessing the use of bacteriophage therapy (BT) as an antibiotic alternative. After the first successful case of intravenous BT to treat a systemic MDR infection at our institution in 2017, the Center for Innovative Phage Applications and Therapeutics (IPATH) was created at the University of California, San Diego, in June 2018.

METHODS

We reviewed IPATH consult requests from June 1, 2018, to April 30, 2020, and reviewed the regulatory process of initiating BT on a compassionate basis in the United States. We also reviewed outcomes of the first 10 cases at our center treated with intravenous BT (from April 1, 2017, onwards).

RESULTS

Among 785 BT requests to IPATH, BT was administered to 17 of 119 patients in whom it was recommended. One-third of requests were for , , and . Intravenous BT was safe with a successful outcome in 7/10 antibiotic-recalcitrant infections at our center (6 were before IPATH). BT may be safely self-administered by outpatients, used for infection suppression/prophylaxis, and combined successfully with antibiotics despite antibiotic resistance, and phage resistance may be overcome with new phage(s). Failure occurred in 2 cases despite in vitro phage susceptibility.

CONCLUSIONS

We demonstrate the safety and feasibility of intravenous BT for a variety of infections and discuss practical considerations that will be critical for informing future clinical trials.

摘要

背景

由于多重耐药(MDR)感染日益增多,人们对评估噬菌体疗法(BT)作为抗生素替代品的使用产生了兴趣。2017年我们机构首例成功通过静脉注射噬菌体疗法治疗全身性多重耐药感染后,2018年6月,加利福尼亚大学圣地亚哥分校创建了创新噬菌体应用与治疗中心(IPATH)。

方法

我们回顾了2018年6月1日至2020年4月30日期间IPATH的会诊请求,并回顾了在美国基于同情原则启动噬菌体疗法的监管程序。我们还回顾了我们中心首例10例接受静脉注射噬菌体疗法治疗的病例(从2017年4月1日起)的结果。

结果

在向IPATH提出的785项噬菌体疗法请求中,119名被建议接受噬菌体疗法的患者中有17名接受了治疗。三分之一的请求是针对……。在我们中心,静脉注射噬菌体疗法是安全的,在7/10例抗生素难治性感染中取得了成功结果(6例在IPATH成立之前)。噬菌体疗法可由门诊患者安全地自行给药,用于感染抑制/预防,并且尽管存在抗生素耐药性,但仍可与抗生素成功联合使用,新的噬菌体可能会克服噬菌体耐药性。尽管体外噬菌体敏感,但仍有2例治疗失败。

结论

我们证明了静脉注射噬菌体疗法对多种感染的安全性和可行性,并讨论了对未来临床试验至关重要的实际考虑因素。

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