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

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.

Ice, ice, maybe? Is it time to ditch the igloo cooler? Benefits of machine perfusion preservation of donor hearts

“…No solution is currently designed for perfusion preservation and typical substrates, such as glucose, may be ineffective to support myocardial metabolism during cold perfusion . Ex vivo perfusion systems for lung transplantation have already been used to treat aspiration pneumonitis, pneumonia, and pulmonary thromboembolic disease . Experimental evidence also suggests delivery of anti‐inflammatory cytokines, gene products, and other therapeutic agents is feasible to repair donor organs or reduce injury sustained by the graft during preservation––thus increasing the donor pool and improving results after transplantation …”

Ex vivo lung perfusion

“…For example, it was shown that donor lungs impaired by aspiration of gastric acid can be treated with lavage and surfactant replacement during EVLP . Similarly, in the case of donor lung infection, antibiotics will be delivered in the EVLP system at high doses to avoid systemic toxicity . Other preclinical studies show that hepatitis C virus can be cleared from donor lungs using a combination of ultraviolet irradiation and photodynamic therapy during EVLP, similar to the means used in blood banks to sterilize donor blood components .…”

“…17 Similarly, in the case of donor lung infection, antibiotics will be delivered in the EVLP system at high doses to avoid systemic toxicity. 18 Other preclinical studies show that hepatitis C virus can be cleared from donor lungs using a combination of ultraviolet irradiation and photodynamic therapy during EVLP, similar to the means used in blood banks to sterilize donor blood components. 19 Moreover, we anticipate that in the long-term future, EVLP will be used to go beyond the treatment of impaired donor lungs to actually enhance the donor lungs beyond their physiological function.…”

Ex vivo limb perfusion for traumatic amputation in military medicine

“…Our hypothetical treatment approach for this obvious military medical challenge is outlined in this paper. Recently, there has been growing evidence for the successful application of ex vivo perfusion in solid organ transplantation [13][14][15][16][17]. Figure 1 shows the basic scheme of a machine perfusion system.…”

“…In addition to the reduction of the cold ischemic time, ex vivo organ perfusion systems can be used for extended criteria donor organs due to an improvement of graft function during machine perfusion. Individualized organ therapy is possible following the reevaluation of the organ [17]. It can be assumed that ex vivo organ perfusion is able to relieve the donor organ shortage.…”