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 Enterococcus faecium 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 Enterococcus 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 E. faecium isolates were identified in close relation to phage therapy and, by using whole-genome sequencing, it was demonstrated that vancomycin-susceptible E. faecium 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.
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Acknowledgments: The authors would like to thank the nurses and the whole medical team for their impressive, persevering professionality with which they provided security and emotional support even in critical situations. We also would like to thank the team from IPATH, which received funding from the Mallory Smith Legacy Fund, for coordinating this world-wide phage hunt. Without that effort, a quick response in such a limited time frame would not have been possible.
Funding: Parts of this work were funded by the US–Israel Binational Science Foundation (grant #2017123), the Israel Science Foundation IPMP (grant #ISF_1349/20), the Rosetrees Trust (grant A2232) and the Milgrom Family Support Program to R.H. and R.N.-P.; S.A. received funding support from the UC San Diego Chancellor’s Innovation Fund.
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
- Biliary atresia
- Critical care
- Enterococcus faecium
- Liver transplantation
- Multi-drug resistance
- multi-drug resistance
- critical care
- biliary atresia
- liver transplantation