Division of Infectious Diseases and Global Public Health and the Center for Innovative Phage Applications and Therapeutics, University of California San Diego, La Jolla, California, USA.
Department of Biology, San Diego State University, San Diego, California, USA.
Antimicrob Agents Chemother. 2024 Apr 3;68(4):e0172823. doi: 10.1128/aac.01728-23. Epub 2024 Mar 12.
Left ventricular assist devices (LVAD) are increasingly used for management of heart failure; infection remains a frequent complication. Phage therapy has been successful in a variety of antibiotic refractory infections and is of interest in treating LVAD infections. We performed a retrospective review of four patients that underwent five separate courses of intravenous (IV) phage therapy with concomitant antibiotic for treatment of endovascular LVAD infection. We assessed phage susceptibility, bacterial strain sequencing, serum neutralization, biofilm activity, and shelf-life of phage preparations. Five treatments of one to four wild-type virulent phage(s) were administered for 14-51 days after informed consent and regulatory approval. There was no successful outcome. Breakthrough bacteremia occurred in four of five treatments. Two patients died from the underlying infection. We noted a variable decline in phage susceptibility following three of five treatments, four of four tested developed serum neutralization, and prophage presence was confirmed in isolates of two tested patients. Two phage preparations showed an initial titer drop. Phage biofilm activity was confirmed in two. Phage susceptibility alone was not predictive of clinical efficacy in endovascular LVAD infection. IV phage was associated with serum neutralization in most cases though lack of clinical effect may be multifactorial including presence of multiple bacterial isolates with varying phage susceptibility, presence of prophages, decline in phage titers, and possible lack of biofilm activity. Breakthrough bacteremia occurred frequently (while the organism remained susceptible to administered phage) and is an important safety consideration.
左心室辅助装置（LVAD）越来越多地用于心力衰竭的治疗；感染仍然是常见的并发症。噬菌体治疗在各种抗生素难治性感染中已取得成功，因此对治疗 LVAD 感染很有兴趣。我们对四名接受了五次静脉（IV）噬菌体治疗的患者进行了回顾性研究，同时使用抗生素治疗血管内 LVAD 感染。我们评估了噬菌体的敏感性、细菌株测序、血清中和、生物膜活性和噬菌体制剂的保质期。在知情同意和监管批准后，给予了五名患者一到四种野生型毒性噬菌体（s）的治疗，持续时间为 14-51 天。没有成功的结果。在五次治疗中的四次中发生了突破性菌血症。两名患者死于基础感染。我们注意到，在五次治疗中的三次后，噬菌体的敏感性出现了不同程度的下降，四次测试中的四次均产生了血清中和，并且在两名测试患者的分离物中证实了原噬菌体的存在。两种噬菌体制剂最初的滴度有所下降。两种都证实了噬菌体生物膜活性。在血管内 LVAD 感染中，噬菌体的敏感性单独并不能预测临床疗效。尽管缺乏临床效果可能是多因素的，包括存在对给予的噬菌体具有不同敏感性的多种细菌分离株、原噬菌体的存在、噬菌体滴度的下降以及可能缺乏生物膜活性，但 IV 噬菌体在大多数情况下与血清中和有关。经常发生突破性菌血症（而该生物体仍然对给予的噬菌体敏感），这是一个重要的安全考虑因素。
