TAILΦR Labs, Molecular Virology and Microbiology Department, Baylor College of Medicine, Houston, TX 77030, USA.
Center for Innovative Phage Applications and Therapeutics, Division of Infectious Diseases and Global Public Health, University of California, San Diego, CA 92093, USA.
Viruses. 2021 Oct 12;13(10):2049. doi: 10.3390/v13102049.
We rationally designed a bacteriophage cocktail to treat a 56-year-old male liver transplant patient with complex, recurrent prostate and urinary tract infections caused by an extended-spectrum beta-lactamase (ESBL)-producing () (UCS1). We screened our library for phages that killed UCS1, with four promising candidates chosen for their virulence, mucolytic properties, and ability to reduce bacterial resistance. The patient received 2 weeks of intravenous phage cocktail with concomitant ertapenem for 6 weeks. Weekly serum and urine samples were collected to track the patient's response. The patient tolerated the phage therapy without any adverse events with symptom resolution. The neutralization of the phage activity occurred with sera collected 1 to 4 weeks after the first phage treatment. This was consistent with immunoassays that detected the upregulation of immune stimulatory analytes. The patient developed asymptomatic recurrent bacteriuria 6 and 11 weeks following the end of phage therapy-a condition that did not require antibiotic treatment. The bacteriuria was caused by a sister strain of (UCS1.1) that remained susceptible to the original phage cocktail and possessed putative mutations in the proteins involved in adhesion and invasion compared to UCS1. This study highlights the utility of rationally designed phage cocktails with antibiotics at controlling infection and suggests that microbial succession, without complete eradication, may produce desirable clinical outcomes.
我们合理设计了一种噬菌体鸡尾酒疗法，用于治疗一名 56 岁的男性肝移植患者，该患者患有由产超广谱β-内酰胺酶（ESBL）的 ()（UCS1）引起的复杂、复发性前列腺和尿路感染。我们筛选了我们的噬菌体文库，以寻找能杀死 UCS1 的噬菌体，其中有四个有前途的候选噬菌体因其毒力、黏液溶解特性以及降低细菌耐药性的能力而被选中。患者接受了 2 周的静脉内噬菌体鸡尾酒治疗，并同时接受了 6 周的厄他培南治疗。每周收集血清和尿液样本以跟踪患者的反应。患者耐受噬菌体治疗，无任何不良反应，症状缓解。在第一次噬菌体治疗后 1 至 4 周采集的血清中中和了噬菌体活性。这与免疫测定结果一致，免疫测定结果检测到免疫刺激分析物的上调。在噬菌体治疗结束后 6 周和 11 周，患者出现无症状复发性菌尿症-无需抗生素治疗的情况。菌尿症是由 UCS1 的姐妹株 (UCS1.1) 引起的，该菌株仍对原始噬菌体鸡尾酒敏感，并且与 UCS1 相比，参与粘附和入侵的蛋白质存在假定突变。这项研究强调了合理设计的噬菌体鸡尾酒与抗生素联合使用控制感染的效用，并表明微生物演替，即使未完全根除，也可能产生理想的临床结果。
