Clostridioides difficile (formerly Clostridium difficile) is an anaerobic, gram-positive, spore-forming bacillus capable of producing toxins that cause intestinal inflammation and damage [1]. Clostridioides difficile infection (CDI) has become one of the most common healthcare-associated infections worldwide, with increasing incidence, severity and healthcare costs over the past two decades [2]. The clinical manifestations of CDI range from asymptomatic colonisation and mild diarrhoea to severe pseudomembranous colitis, toxic megacolon and even death [3]. The estimated attributable mortality for CDI ranges from 5 % to 10 %, reaching up to 15 %–25 % in vulnerable populations [4].

Patients with cancer represent a particularly high-risk population for CDI due to multiple predisposing factors. Studies have reported that the incidence of CDI in patients with cancer is 4–7 times higher than in the general hospitalised population [5]. The overall incidence of CDI in patients with cancer ranges from 4 % to 7 %, with considerable variation based on cancer type, treatment modality and comorbidities [6]. Patients with haematological malignancies appear to be at particularly high risk, with reported CDI rates of 7 %–9 %, compared with 3 %–5 % in patients with solid tumours [7].

Several factors contribute to the increased susceptibility of patients with cancer to CDI. First, these patients frequently receive broad-spectrum antibiotics for prophylaxis or treatment of infections related to chemotherapy-induced neutropenia, which disrupts the normal gut microbiota that typically provides colonisation resistance against C. difficile [8]. The duration and spectrum of antibiotic exposure have been consistently identified as key risk factors for CDI development [9].

Second, many patients with cancer receive chemotherapeutic agents and immunosuppressive medications that not only alter gut microbiota but also impair mucosal immunity, further compromising defence mechanisms against C. difficile [10]. Certain chemotherapeutic agents, particularly platinum compounds and antimetabolites, have been associated with higher CDI risk, potentially due to their direct effects on intestinal mucosa and immune function [11].

Third, hospitalisation itself exposes patients with cancer to potential C. difficile spores in healthcare environments, with longer hospital stays increasing exposure risk [12]. Additionally, these patients often have multiple comorbidities, poor nutritional status and altered immune function, which further predispose them to CDI [13].

The clinical implications of CDI in patients with cancer are substantial. Clostridioides difficile infection may lead to treatment delays, increased healthcare costs, longer hospital stays and, in severe cases, increased mortality [14]. Moreover, the management of CDI in patients with cancer presents unique challenges, as the underlying immunosuppression may attenuate typical inflammatory responses, potentially masking classical CDI symptoms and complicating diagnosis [15].

Although the impact of CDI in patients with cancer has been widely recognised, current studies on risk factors for CDI are mostly focused on the general hospitalised population or specific cancer subtypes, particularly patients with haematologic malignancies. The limitations of these studies lie in their failure to fully cover the complex and diverse group of patients with cancer, especially those with solid tumours. Comprehensive analyses of risk factors across various malignancies are limited, and there is a lack of predictive models specifically designed for patients with cancer. Moreover, the relative contributions of different risk factors and their interactions in the context of malignancies remain unclear. For instance, Raeisi et al. [16] reviewed common risk factors associated with CDI in patients with colorectal cancer, such as gut microbiota dysbiosis, colorectal surgery, chemotherapy, prolonged hospitalisation and antimicrobial therapy, but the specific roles and interactions of these factors across different cancer types have not been fully elucidated. Francisco et al. [17] explored the correlation between prior antibiotic classes and CDI, microbiome composition and disease severity in 200 patients with cancer during their first episode or first recurrence of CDI. They found that the use of metronidazole within 90 days prior to diagnosis and the presence of toxin A/B in stools were considerably associated with severe CDI. However, the study only examined the impact of antibiotic classes and microbiome composition. Sahu et al. [4] investigated factors affecting CDI in 59 patients with solid tumour hospitalised with CDI and found that a high qSOFA score (≥2) and a white blood cell count >15 × 109/L were substantially associated with higher in-hospital mortality. Nevertheless, this study mainly focuses on patients with solid tumours; it does not conduct a comprehensive analysis of risk factors across various malignancies or develop predictive models specifically for patients with cancer.

The identification of specific risk factors for CDI in patients with cancer could facilitate the development of targeted preventive strategies and early interventions. Risk stratification tools could help identify patients at high risk who might benefit from enhanced surveillance, antimicrobial stewardship or prophylactic measures. Given the considerable morbidity and mortality associated with CDI in patients with cancer, such approaches could have a substantial clinical impact.

Therefore, this study aims to comprehensively analyse risk factors for CDI in patients with malignant tumours and develop a predictive model to identify patients at high risk. We hypothesise that although certain risk factors are similar to those in the general population (e.g. antibiotic exposure), others might be unique to or more pronounced in patients with cancer (e.g. chemotherapy, immunosuppression, nutritional status). By elucidating these factors and their relative importance, we seek to provide a foundation for evidence-based preventive strategies tailored to patients with cancer.