Pseudomonas aeruginosa ventricular assist device infections: findings from ineffective phage therapies in five cases

Saima Aslam*, Dwayne Roach, Mikeljon P. Nikolich, Biswajit Biswas, Robert T. Schooley, Kimberley A. Lilly-Bishop, Gregory K. Rice, Regina Z. Cer, Theron Hamilton, Matthew Henry, Tiffany Luong, Ann Charlott Salabarria, Laura Sisk-Hackworth, Andrey A. Filippov, Francois Lebreton, Lindsey Hall, Ran Nir-Paz, Hadil Onallah, Gilat Livni, Eran ShostakAnat Wieder-Finesod, Dafna Yahav, Ortal Yerushalmy, Sivan Alkalay-Oren, Ron Braunstein, Leron Khalifa, Amit Rimon, Daniel Gelman, Ronen Hazan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 Pseudomonas aeruginosa 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 P. aeruginosa 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.

Original languageAmerican English
JournalAntimicrobial Agents and Chemotherapy
Volume68
Issue number4
DOIs
StatePublished - Apr 2024

Bibliographical note

Publisher Copyright:
Copyright © 2024 American Society for Microbiology. All Rights Reserved.

Keywords

  • LVAD
  • MDRO
  • Pseudomonas aeruginosa
  • device-related infection
  • phage therapy

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