Evaluation of an extracorporeal ozone-based bactericide system for the treatment of Escherichia coli sepsis

Paul Skorup; Anette Fransson; Jenny Gustavsson; Johan Sjöholm; Henrik Rundgren; Volkan Özenci; Alicia Y W Wong; Tomas Karlsson; Christer Svensén; Mattias Günther

doi:10.1186/s40635-022-00443-w

Evaluation of an extracorporeal ozone-based bactericide system for the treatment of Escherichia coli sepsis

Intensive Care Med Exp. 2022 Apr 25;10(1):14. doi: 10.1186/s40635-022-00443-w.

Authors

Affiliations

¹ Section of Infectious Diseases, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
² Section for Experimental Traumatology, Department of Neuroscience, Karolinska Institutet, Biomedicum - 8B, 171 77, Stockholm, Sweden.
³ Sangair AB, Stockholm, Sweden.
⁴ Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.
⁵ Department of Clinical Microbiology, Karolinska University Hospital, Huddinge, Sweden.
⁶ Department of Clinical Science at Education Södersjukhuset, Unit of Anesthesiology and Intensive Care, Karolinska Institutet, Stockholm, Sweden.
⁷ Section for Experimental Traumatology, Department of Neuroscience, Karolinska Institutet, Biomedicum - 8B, 171 77, Stockholm, Sweden. mattias.gunther@ki.se.
⁸ Department of Clinical Science at Education Södersjukhuset, Unit of Anesthesiology and Intensive Care, Karolinska Institutet, Stockholm, Sweden. mattias.gunther@ki.se.

Abstract

Background: Sepsis is associated with substantial mortality rates. Antibiotic treatment is crucial, but global antibiotic resistance is now classified as one of the top ten global public health risks facing humanity. Ozone (O₃) is an inorganic molecule with no evident function in the body. We investigated the bactericide properties of ozone, using a novel system of extracorporeal ozone blood treatment. We hypothesized that ozone would decrease the concentration of viable Escherichia coli (E. coli) in human whole blood and that the system would be technically feasible and physiologically tolerable in a clinically relevant model of E. coli sepsis in swine.

Methods: The E. coli strain B09-11822, a clinical isolate from a patient with septic shock was used. The in vitro study treated E. coli infected human whole blood (n = 6) with ozone. The in vivo 3.5-h sepsis model randomized swine to E. coli infusion and ozone treatment (n = 5) or E. coli infusion and no ozone treatment (n = 5). Live E. coli, 5 × 10⁷ colony-forming units (CFU/mL) was infused in a peripheral vein. Ozone treatment was initiated with a duration of 30 min after 1.5 h.

Results: The single pass in vitro treatment decreased E. coli by 27%, mean 1941 to 1422 CFU/mL, mean of differences - 519.0 (95% CI - 955.0 to - 82.98, P = 0.0281). pO₂ increased (95% CI 31.35 to 48.80, P = 0.0007), pCO₂ decreased (95% CI - 3.203 to - 1.134, P = 0.0069), oxyhemoglobin increased (95% CI 1.010 to 3.669, P = 0.0113). Methemoglobin was not affected. In the sepsis model, 9/10 swine survived. One swine randomized to ozone treatment died from septic shock before initiation of the treatment. Circulatory, respiratory, and metabolic parameters were not affected by the ozone treatment. E. coli in arterial blood, in organs and in aerobic and anaerobic blood cultures did not differ. Hemoglobin, leucocytes, and methemoglobin were not affected by the treatment.

Conclusions: Ozone decreased the concentration of viable E. coli in human whole blood. The system was technically feasible and physiologically tolerable in porcine sepsis/septic shock and should be considered for further studies towards clinical applications.

Keywords: Antibiotic resistance; E. coli; Intensive care; Ozone; Porcine sepsis model.