Treatment of infected lungs by ex vivo perfusion with high dose antibiotics and autotransplantation: A pilot study in pigs

PLoS One. 2018 Mar 5;13(3):e0193168. doi: 10.1371/journal.pone.0193168. eCollection 2018.

Abstract

The emergence of multi-drug resistant bacteria threatens to end the era of antibiotics. Drug resistant bacteria have evolved mechanisms to overcome antibiotics at therapeutic doses and further dose increases are not possible due to systemic toxicity. Here we present a pilot study of ex vivo lung perfusion (EVLP) with high dose antibiotic therapy followed by autotransplantation as a new therapy of last resort for otherwise incurable multidrug resistant lung infections. Severe Pseudomonas aeruginosa pneumonia was induced in the lower left lungs (LLL) of 18 Mini-Lewe pigs. Animals in the control group (n = 6) did not receive colistin. Animals in the conventional treatment group (n = 6) received intravenous application of 2 mg/kg body weight colistin daily. Animals in the EVLP group (n = 6) had their LLL explanted and perfused ex vivo with a perfusion solution containing 200 μg/ml colistin. After two hours of ex vivo treatment, autotransplantation of the LLL was performed. All animals were followed for 4 days following the initiation of treatment. In the control and conventional treatment groups, the infection-related mortality rate after five days was 66.7%. In the EVLP group, there was one infection-related mortality and one procedure-related mortality, for an overall mortality rate of 33.3%. Moreover, the clinical symptoms of infection were less severe in the EVLP group than the other groups. Ex vivo lung perfusion with very high dose antibiotics presents a new therapeutic option of last resort for otherwise incurable multidrug resistant pneumonia without toxic side effects on other organs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autografts
  • Colistin / pharmacology*
  • Lung / microbiology*
  • Lung Transplantation*
  • Perfusion
  • Pneumonia, Bacterial / drug therapy*
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas aeruginosa*
  • Swine

Substances

  • Colistin

Associated data

  • figshare/adf47e90e5d1283acc67

Grants and funding

We report grants from German Federal Ministry of Education and Research - DZL German Center for Lung Research (82DZL00201; http://www.dzl.de/index.php/de/), grants from German Science Foundation - REBIRTH Cluster of Excellence (DFG EXC 62; http://www.rebirth-hannover.de/de/home.html), during the conduct of the study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.