Department of Pediatrics, Kinder-UKE, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Burn Centre, Laboratory for Molecular and Cellular Technology (LabMCT), Queen Astrid Military Hospital, B-1120 Brussels, Belgium.
Viruses. 2021 Sep 7;13(9):1785. doi: 10.3390/v13091785.
Phage therapy is an experimental therapeutic approach used to target multidrug-resistant bacterial infections. A lack of reliable data with regard to its efficacy and regulatory hurdles hinders a broad application. Here we report, for the first time, a case of vancomycin-resistant abdominal infection in a one-year-old, critically ill, and three times liver transplanted girl, which was successfully treated with intravenous injections (twice per day for 20 days) of a magistral preparation containing two phages. This correlated with a reduction in baseline C-reactive protein (CRP), successful weaning from mechanical ventilation and without associated clinical adverse events. Prior to clinical use, phage genome was sequenced to confirm the absence of genetic determinants conferring lysogeny, virulence or antibiotic resistance, and thus their safety. Using a phage neutralization assay, no neutralizing anti-phage antibodies in the patient's serum could be detected. Vancomycin-susceptible isolates were identified in close relation to phage therapy and, by using whole-genome sequencing, it was demonstrated that vancomycin-susceptible emerged from vancomycin-resistant progenitors. Covering a one year follow up, we provide further evidence for the feasibility of bacteriophage therapy that can serve as a basis for urgently needed controlled clinical trials.
噬菌体疗法是一种用于治疗多重耐药菌感染的实验性治疗方法。由于缺乏关于其疗效和监管障碍的可靠数据，限制了其广泛应用。在这里，我们首次报告了一例一岁危重症、三次肝移植的女孩，因万古霉素耐药性腹部感染，通过静脉注射（每天两次，共 20 天）含有两种噬菌体的自制制剂成功治疗。这与基线 C 反应蛋白（CRP）降低、成功脱离机械通气以及无相关临床不良事件相关。在临床应用之前，对噬菌体基因组进行测序以确认不存在赋予溶原性、毒性或抗生素耐药性的遗传决定因素，从而确保其安全性。使用噬菌体中和测定法，未在患者血清中检测到中和噬菌体的抗体。在噬菌体治疗期间，鉴定出与噬菌体治疗密切相关的万古霉素敏感分离株，通过全基因组测序，证实了万古霉素敏感分离株是从万古霉素耐药的前体中产生的。在为期一年的随访中，我们提供了噬菌体治疗可行性的进一步证据，可为急需的对照临床试验提供依据。
