A plenty of patients in the Intensive Care Unit (ICU) have a multi-drug resistant bacteria infection risk due to the abuse of antibiotics and the increase of invasive procedures, especially the carbapenem-resistant K. pneumoniae and other carbapenem-resistant Enterobacteriaceae[11, 12]. It was reported that the donors could be infected by multi-drug resistant nosocomial bacteria in two days, and spread those bacteria to recipients. Most of donor organs are donated by brain-dead patients from the ICU, it is common that the donor lungs had been infected and colonized by bacteria, leading to an increase in donor-derived infections. In the United States, the total number of donor-derived disease transmission events on the Organs Access and Transplant Network is also increasing year by year, with donor-derived infections accounting for 71%. And the probability of different diseases is transmitted from the donor to the recipient is different. The probability of malignant tumors, viruses, bacteria, fungi, and parasites caused by donor organs is 67%, 46%, 34%, 29%, and 17%. Compared with other organ transplantation, there are 80% of lung transplant recipients were infected when they received an organ from a same donor who had communicable disease.One research had reported that 18 (10.5%) donors were fixed or infected by carbapenem resistant Gram-negative bacteria in 170 donors who met the transplant criteria in 10 hospitals in Italy during January 1, 2012 to December 31, 2013, but those bacteria were not found during donation of organs and transplantation. Therefore, the screening for colonized bacteria or infected pathogens in donor lungs is particularly important.
In this study, we currently receive donor lungs in accordance with the donor lung selection criteria of National Lung Transplantation Data Center, based on medical history, chest X-ray or chest CT, fiberoptic bronchoscopy, and blood cell counter, C-reactive protein, procalcitonin and other tests to comprehensively assess the infection of the lungs, and exclude the lungs when it was infected. However, we can still detect pathogenic microorganisms from the lungs that meet the standards for lung utilization. We define them as colonized bacteria. Traditional methods for detecting colonized bacteria include bronchial secretions or alveolar lavage fluid. In this study, we not only used bronchial secretions but also lung tissue pathogenic microbial gene detection technology to detect lung-fixing bacteria, we hope to comprehensively evaluate the different distribution of colonized bacteria of the donor lungs and the prognosis of recipient.
It is still unclear whether the pathogenic microorganisms in the donor lungs affect the prognosis of lung transplant recipients. Bonde had reported that 57 of the 64 donors (89%) had positive bacteria for bronchial secretion culture, the study had shown that the colonization of pathogenic microorganisms in donor lungs is common. And multi-factor analysis of pneumonia after lung transplantation found that there is no significant correlation between the culture results of bronchial secretions and pneumonia after lung transplantation. Even more most clinical infections of the recipients were not directly related to the presence of donor organisms. It appears to be no correlation between organisms identified on donor cultures and pathogenic organisms infected with receptors. Ahmad’s study showed that 32 lung transplant recipients, of which 20 (63%) were positive for bronchial secretion culture, 12 (37%) were culture-negative, and the bronchial secretion positive group had a longer mechanical ventilation time than the negative group. But there was no significant difference of the 30-day survival rate and the incidence of grade 3 preimplantation genetic diagnosis (PGD) between the two groups. A study by Avlonitis retrospectively analyzed the culture of lung alveolar lavage fluid in 115 lung transplant recipients, including 53 positive (46%) and negative 62 (54%) for pulmonary alveolar lavage fluid. In the culture-positive recipients, the average tracheal intubation time and ICU intensive time were higher than the negative group, and the 6-month, 1-year, and 2-year survival rates were lower than the negative group.
In this study, the lung colonized bacteria were detected by NGS of lung tissue and bronchial secretion culture. The results of the two methods were not identical may due to different sample. More pathogenic microorganisms could be detected in the NGS group than traditional culture group, and the precise method of gene detection could reflect the distribution of bacteria for donor lung more comprehensive. Although the patients were grouped according to NGS test results or bronchial secretion culture results, the results showed that there was no difference in extracorporeal membrane oxygenation (ECMO) support time, mechanical ventilation time, intensive care unit (ICU) stay time, duration of fever and the number of days in hospital between positive group and negative group. This indicate that neither the bronchial colonized bacteria nor the lung tissue colonized bacteria in donor lungs has affected the early prognosis of lung transplant recipients.
Due to the shortage of standard donor lungs, the use of expanded standard donor lungs was increased in recent years, it was defined as expanded standard donor lungs when bronchoscopy revealed purulent secretion or sputum culture found bacteria[19, 20]. However, whether the expansion of the standard for donor lungs has an impact on the prognosis of recipients is still inconclusive[20, 21]. In fact, positive sputum bacteria culture results could be caused by lung infection or colonized bacteria. This study shows that the donor lungs which had colonized bacteria can also be used for lung transplantation. If there is no clear evidence for lung infection, pathogenic microorganisms in sputum or bronchial secretions should be defined as colonized bacteria. There is no significant correlation between the presence of colonized bacteria in donor lungs and the short-term prognosis of the patients. It is significant for further research on the stratification and definition of donor lung expansion criteria.
In our research, the colonized bacteria in donor lungs did not cause postoperative pulmonary infection in lung transplant recipients, it may due to the prophylactic application of antibiotics. Researches have shown that postoperative targeted antibacterial agents could prevent recipient infections which caused by multidrug-resistant Gram-negative bacilli in lungs[22, 23]. In this study, the pathogenic microorganisms of the recipients were mainly common with the bacteria in the ICU of our center, and there was no correlation with the colonized bacteria of the donor lungs. This may be due to colonized bacteria of the donor lungs causing subclinical infection and lung injury, making the lung susceptible to infection by different pathogenic microorganisms of the recipient[24, 25].
There are also some shortcomings in this research. Such as the number of study cases is not enough, the follow-up time is relatively short, the effect of lung colonization on long-term prognosis of lung transplant recipients has not been observed. Further confirmation is needed for large sample sizes and long-term follow-up studies.