BC is widely found in water, soil and plants in nature. It can survive for a long time and spread through contact or respiratory tract. The main pathogenic factor is adhesin, which is an important pathogen causing nosocomial infection . If not controlled promptly, BC infection can not only cause severe pneumonia (sometimes even develop into “cepacia syndrome” leading to respiratory failure), but also result in systemic infections such as bacteremia and sepsis [21, 22]. In the past, for the infection of patients after HSCT, people might pay more attention to Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, etc. . Here, our survey found that although the detection rate of BC was indeed lower than that of the above-mentioned bacteria—only less than 5%, which is basically consistent with the data reported by Lu et al. . However, the resulting risk of death is greatly increased, thus placing a heavy burden on the life and property safety of patients. Age, ICU stay more than 2 weeks, APACHE II score, and the presence of efflux pump gene were reported to be independent risk factors for developing BC bloodstream infection . A previous study showed that due to the obviously increased mortality in patients with BC infection, in the early days, some medical institutions even held reservations about whether patients with pulmonary cystic fibrosis complicated by BC infection were suitable for lung transplantation [26, 27]. To our knowledge, this is the first retrospective case–control study to specifically investigate the impact of BC on HSCT patients, and proposed that BC infection is associated with septic shock, admission to ICU for intensive care, and renal impairment.
Our study shows that the lung remains the most common site of BC infection. On this basis, pulmonary rejection after HSCT may further increase the likelihood of lung function deterioration and respiratory failure, although we have not found statistical differences in the occurrence of aGVHD between the BC infected group and the matched non-BC infected group. However, it still reminds us of the importance of strengthening the management of respiratory infection during transplantation. In addition, we also found that CMV infection before transplantation may be a related factor to induce BC infection. CMV has been reported to have significant bone marrow suppression . The replication and reactivation of it can initiate systemic inflammatory response, affect hematopoiesis and immune reconstitution, which may create opportunities for BC invasion . The higher frequency of use of anti-CMV immunoglobulin in the BC group after transplantation also supports this view.
Unexpectedly, despite the high mortality rate, BC infection did not show obvious resistance to a variety of commonly used antibiotics, which is similar to the results of multiple previous studies [30, 31]. We speculate that this may be related to the improper selection of antibiotics during empiric anti-infective therapy. For the post-transplant population, considering factors such as immunosuppression, catheter implantation, high venous nutrition and delayed hematopoietic reconstruction, clinicians often choose to “strike hard” at the beginning of infection. In contrast, ceftazidime, levofloxacin, cotrimoxazole and other seemingly “weak” or relatively high resistance antibiotics were excluded. Another possibility is that HSCT patients are usually accompanied by multi-pathogen infection, so even if some patients choose antibiotics sensitive to BC, such as meropenem, cefoperazone sulbactam, etc., they still have poor anti-infection effect and eventually die under the combined action of other drug-resistant bacteria.
Septic shock and PCT > 10 µg/L are independent risk factors associated with death that we obtained in this study. Septic shock is a serious systemic disease in which microorganisms and their metabolites invade the blood circulation, activate the host immune system, produce cytokines and endogenous mediators, and then act on various organs/systems and affect perfusion, eventually leading to cell ischemia and hypoxia, metabolic disorder and multiple organ dysfunction (MODS) . The clinical treatment of sepsis and septic shock is a huge challenge that threatens global health. The World Health Organization (WHO) advocates that governments should make it a “diseases of global medical priority concern”. According to the recommendations of SSC Guide for shork (2021 version), screening and early therapy, hemodynamic management, mechanical ventilation, long-term care and support are treatment priorities . Since septic shock is a complex and changing process of interaction between microorganisms and the body, it is highly heterogeneous from pathogenic bacteria to early systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS). Therefore, individualized intervention at different stages is needed . Patients with BC infection after HSCT, as a special population with severely suppressed immune function, should pay more attention to the clinical management of septic shock. The first is the identification of risk factors, such as older age, malnutrition, hyperthermia or hypothermia, prolonged hospital stay, unstable vital signs (heart rate > 120 beats/min, systolic blood pressure < 110 mmHg or 60–70% below baseline), central venous catheter, long-term use of antibiotics/hormones/chemotherapy drugs, viral infections, etc. The second is the rapid assessment of the shock, that is, according to clinical manifestations to determine the patient’s stage (shock compensation or decompensation). Finally, use antibiotics empirically as soon as possible, and actively identify the type of pathogenic bacteria (blood culture, sputum culture, NGS and other methods). At the same time, based on the analysis of pathophysiology of patients, reduce the inflammatory response and improve organ function, so as to prevent the development of septic shock to MODS.
PCT has been identified as an important biomarker for diagnosing infection (especially excellent in the early diagnosis of infections caused by Gram-negative strains), and PCT > 10 µg/L is more indicative of the severity of bacterial infection or the insufficiency of antibacterial treatment, because a large number of studies have confirmed that the significantly increased PCT is positively correlated with poor prognosis of patients [35,36,37]. For example, as early as 1993 Assicot et al. reported that PCT levels were directly related to the extent and severity of microbial invasion . Later, Dan et al. also found that the PCT of infected patients in the death group was significantly higher than that in the control group . In addition, Muller and Hina et al. also pointed out that elevated levels of PCT were associated with increased infection severity in community-acquired pneumonia [40, 41].
Although our conclusions are preliminary, and limited by retrospective study design and factors such as sample size, completeness of medical record information, selection bias, etc., our study is the first to provide clinicians with useful information on the patterns, characteristics, mortality risk factors and antibiotic susceptibility of BC infection in HSCT patients. Continuing to expand the sample size and combine multi-centers in different regions to conduct prospective studies will be the focus of our next research.