The Burkholderia cepacia complex (Bcc), a group of metabolically versatile Gram-negative bacteria, is recognized as an opportunistic pathogen notorious for its intrinsic multidrug resistance (Gautam et al., 2011). While historically linked to chronic respiratory infections in patients with cystic fibrosis (Kenna et al., 2017; Mahenthiralingam and Vandamme, 2005), Bcc has emerged as a growing cause of nosocomial outbreaks (Angrup et al., 2022; Shen et al., 2023; Sinha et al., 2023; Viderman et al., 2020), posing a significant threat to immunocompromised individuals (Ho et al., 2021; Paes Leme et al., 2022; Siddiqui et al., 2022). Patients with hematologic malignancies represent a uniquely vulnerable cohort due to profound therapy-induced immunosuppression, prolonged neutropenia, and frequent breaches of mucocutaneous barriers via indwelling catheters. Despite this heightened susceptibility, the clinical course and prognostic determinants specifically associated with Bcc colonization and subsequent infection in this population remain inadequately characterized. This study aimed to bridge this knowledge gap by analyzing one of the largest single-center cohorts to date, with a focus on identifying risk factors for mortality and the critical transition from colonization to active infection.

The Burkholderia cepacia complex represents a group of metabolically versatile, gram-negative bacteria that are widely distributed in the environment and recognized as opportunistic pathogens in immunocompromised hosts, including plant pathogens and human pathogens (Sawana et al., 2014). Among them, human pathogens can be divided into two categories. One is Burkholderia pseudomallei complex organisms (Bpc), which can cause glanders, including Burkholderia pseudomallei and Burkholderia pseudomallei; Another type is Burkholderia cepacia complex (Bcc), which belongs to environmental saprophytic bacteria and is also an important pathogen causing nosocomial infections (Sawana et al., 2014). If not controlled in a timely manner, Bcc infection can not only lead to severe pneumonia, but sometimes even progress to “onion syndrome”, which is characterized by fever, rapidly progressing necrotic pneumonia, and bacteremia, with a high mortality rate (Frost et al., 2019). In the past, research on infections caused by Bcc mainly focused on patients with cystic fibrosis (Lord et al., 2020), and in recent years, there have also been related studies on patients in intensive care units (Karakoc Parlayan et al., 2025). However, its role in patients with hematologic malignancies—a population characterized by profound immunosuppression—remains inadequately characterized (Jia et al., 2022).Our study demonstrates that progression from Burkholderia cepacia complex colonization to active infection is a pivotal clinical event, independently associated with increased mortality in patients with hematologic malignancies. This risk is profoundly amplified in the setting of hematopoietic stem cell transplantation. These findings underscore the critical need to distinguish between mere colonization and invasive disease in the management of this immunocompromised population.

Future research should also focus on the prognostic implications of Bcc species-level differentiation. The majority of bacterial strains in our study population were Burkholderia cepacia. Most patients had essentially used third-generation cephalosporin or even carbapenem antibiotics during their treatment. So, our study did not stratify outcomes by specific Bcc species, which may vary in virulence, and antibiotic resistance profiles. A study found that antibiotic sensitivity varies among different species and between cystic fibrosis and non-cystic fibrosis isolates. However, patients carrying B. cenocepacia, B. multivorans, and other Bcc species did not exhibit significant differences in lung function (Kenna et al., 2017). Another study on clinical isolates of Bcc also found that the distribution of Bcc isolates varies among different specimen types, and different Bcc isolates exhibit differences in their antibacterial susceptibility in vitro (Li et al., 2025). Therefore, the impact of different Bcc strains on the prognosis of patients with hematological malignancies remains unclear. Applying molecular typing techniques such as whole-genome sequencing to future research can clarify whether specific bacterial species independently lead to progression from colonization to infection, drug resistance, or death (Sawana et al., 2014).

The vulnerability of hematologic malignancy patients to Bcc is multifaceted. Patients with hematologic malignancies belong to immunocompromised populations who receive cytotoxic drugs, targeted therapies, and immunosuppressants during treatment, which can lead to neutropenia or even neutropenic conditions. Additionally, prophylactic antimicrobial therapy is required during the treatment period. This may be attributed to severe immunesuppression that is almost universally present in patients when treating hematological malignancies. The use of hormones, high-dose chemotherapy, pre-treatment regimens for HSCT, and disease targeted therapy can all lead to severe neutropenia and mucosal barrier damage - the main risk factors for opportunistic infections. Furthermore, patients with hematologic malignancies often require peripherally inserted central catheters (PICCs), ports, or other indwelling catheters during therapy (Abdallah et al., 2018), all of which increase the risk of Bcc colonization or infection. It seems that the high prevalence of indwelling devices provides a surface for Bcc biofilm formation, a key virulence trait that confers protection from both host defenses and antimicrobial agents (Liu et al., 2024; Magizhvannan and Veerappapillai, 2025).Therefore, studies have found that Bcc bacteremia in non-cystic fibrosis patients is mostly related to central venous catheter, and early removal of the catheter is crucial in treatment (Lee et al., 2020; Chang et al., 2022). In our center, almost everyone are PICCs, chosen specifically for this patient population due to their relative safety profile and ease of removal if infection is suspected, which is a critical management step. More importantly, PICC insertion and maintenance follow a strict, protocol-driven care bundle (including maximal sterile barrier at insertion, dedicated line care teams, and standardized dressing changes). This standardization, recommended by recent guidelines to minimize central line-associated bloodstream infections (CLABSIs) (Lebeaux et al., 2014), significantly reduces variability in nursing measures.

Our results corroborate and extend previous findings. The association between organ dysfunction (respiratory, hepatic, renal) and poor prognosis is consistent with studies of Bcc bacteremia in other settings (Lee et al., 2020).Previous studies have shown that advanced age, steroid use, immunosuppressive drugs, chemotherapy, higher antibiotic usage, type 2 diabetes, and invasive procedures are potential risk factors for bloodstream infections caused by Burkholderia cenocepacia (Chang et al., 2022; Siddiqui et al., 2022). A Korean retrospective study (1997–2016) found that most cases of Bcc bacteremia were nosocomial infections, with central venous catheter-related infections accounting for nearly half of the cases. Female gender, liver cirrhosis, septic shock, and catheter-related infections were independent risk factors for 30-day mortality; notably, liver cirrhosis significantly worsened prognosis in cases of Bcc bacteremia (Lee et al., 2020). This may be due to impaired antibiotic clearance rates and increased toxicity risks associated with liver metabolic dysfunction. In our study, hepatic insufficiency was associated with an eightfold increase in mortality risk (P < 0.001), reinforcing the importance of organ function in sepsis outcomes.

For HSCT recipients, Bcc post-colonization infection conferred a particularly grave prognosis. This is consistent with a 2022 study by Jia et al., which reported that Bcc-infected HSCT patients had significantly higher mortality, with septic shock and procalcitonin >10 µg/L identified as independent death predictors (Jia et al., 2022). Our subgroup analysis further validates that HSCT status amplifies the risk of Bcc-related mortality, highlighting a critical subpopulation for intensified surveillance.

This study indicates that when patients are found to be colonized with Bcc, healthcare workers need to assist in strengthening patients’ personal hygiene management, particularly oral hygiene. The study statistics reveal that 58.9% (33/56) of patients initially tested positive for Bcc in throat swabs, followed by detection in relatively cleaner specimens such as sputum, blood, bronchoalveolar lavage fluid, or wound secretions, marking a transition from Bcc colonization to infection. The study found that patients with Bcc colonization followed by infection have a poorer prognosis. However, different scholars have different opinions on targeted decolonization strategies for carriers of multidrug-resistant Gram negative bacteria (MDR-GNB), and their data is insufficient to provide strong recommendations for decolonization. (Tacconelli et al., 2019) Our findings highlight that progression from colonization to infection significantly increases mortality, particularly in HSCT recipients, raising the possibility that preemptive antimicrobial intervention might be beneficial in high-risk subgroups. Indiscriminate antibiotic use may promote further resistance without clear survival benefit. Instead, we advocate for a risk-stratified approach: for highest-risk patients (e.g., post-HSCT, prolonged neutropenia), targeted prophylaxis guided by local susceptibility patterns could be considered, while emphasizing non-pharmacological measures—enhanced surveillance, strict catheter care, and environmental control. (Kalil et al., 2016; Tacconelli et al., 2019).

To synthesize our findings into a clinically actionable framework, we have summarized the key risk factors, their underlying mechanisms, and proposed management strategies in Table 5. This synthesis emphasizes that prevention and early intervention are paramount.

Based on our findings and existing evidence, we propose a pragmatic infection control bundle for high-risk hematology units: (1) Education of the staff for environmental cleaning and disinfection. Perform weekly hand hygiene audits. (2) Rigorous management of aqueous environments and medical devices(Such as ultrasound gel) (Angrup et al., 2022). Sterile covers were used for the ultrasound probes to prevent the gel touching the patient’s skin. (3) At least once a week surveillance with throat swabs in HSCT recipients and patients with profound neutropenia (Jia et al., 2022). (4)Enhanced source control including mupirocin nasal drop and chlorhexidine mouthwash care for colonized patients. (Ghaffary et al., 2024) (5)Pre-emptive contact isolation for colonized patients to limit potential transmission (Baker and Satlin, 2016). (6)Prompt diagnostic escalation upon symptom development, with expedited culture from sterile sites. Removal of central venous catheter in time (Lee et al., 2020).

Several limitations of our study warrant consideration. Our study is a single-center retrospective design with a limited sample size, especially in the subgroup undergoing hematopoietic stem cell transplantation, which may affect statistical power and limit the generalizability of the results. Multi-center, large-sample prospective studies are needed to further validate these findings and explore more accurate risk prediction models. Detailed antibiotic exposure and catheter parameters need be included. Furthermore, we will continue to study the relationship between the identification of Bcc species and patient prognosis in the future.

In conclusion, this study establishes Bcc post-colonization infection as a life-threatening complication in hematologic malignancy patients. Vigilant surveillance, strict infection control, and pre-emptive strategies are essential for high-risk individuals, particularly HSCT recipients. Future prospective, multicenter studies incorporating molecular typing and correlative microbiome analyses are needed to validate these findings and to develop more precise risk prediction models and targeted interventions.