Pitfalls in defining infections and overlooking host immunity: limitations of a study on prophylactic antibiotics in renal cell carcinoma ablation

Dear Editor, We read with great interest the recent article titled “Association between Prophylactic Antibiotics and Post-Ablation Infections in Renal Cell Carcinoma Patients: A Retrospective Multicenter Cohort Study1”. While the study provides valuable insights into the use of prophylactic antibiotics in preventing post-ablation infections in renal cell carcinoma (RCC) patients, there are some design-related concerns that we believe need to be addressed for a more comprehensive understanding of the issue. This correspondence was developed following the TITAN Guidelines 20252 for the declaration and use of artificial intelligence in scholarly publishing. No artificial intelligence tools were employed in the conception, design, analysis, interpretation, or writing of this work. The study defines infection as a broad category, including both localized infections and systemic infections. This wide-ranging definition might be problematic, as it lumps together different types of infections that can vary significantly in severity, treatment response, and clinical implications. For example, a urinary tract infection (UTI) may require different antibiotic regimens and have a vastly different clinical course compared to a renal abscess or urosepsis. By treating all infections equally, the study may obscure important nuances in the effectiveness of prophylactic antibiotics. Previous research has shown that various infection types differ in terms of their pathophysiology and response to treatment, which can affect the efficacy of prophylactic antibiotics3. Thus, the lack of differentiation in infection types could limit the ability to determine the specific role of prophylactic antibiotics in preventing different types of infections, potentially leading to overly simplistic conclusions. We would suggest that future studies clearly categorize infections into subtypes (e.g. UTIs, renal abscesses, urosepsis) and assess the effectiveness of prophylactic antibiotics in each group separately. This approach would provide a more nuanced understanding of the utility of antibiotics in the context of RCC ablation and potentially inform more targeted therapeutic strategies.HIGHLIGHTS The broad definition of “infection” may obscure the nuanced efficacy of prophylactic antibiotics. The study does not account for critical patient factors like immune status and comorbidities. Key subgroups (e.g. diabetic or immunosuppressed patients) warrant specific analysis. Future studies require refined infection categorization and host-factor adjustment. Another critical concern is the lack of consideration for the immune status of patients. The study does not address how factors such as immune function or immunosuppressive therapy might influence infection risk or the effectiveness of prophylactic antibiotics. This oversight is particularly important given that many RCC patients may have co-morbid conditions like diabetes, which can significantly alter immune responses. Diabetic patients, for example, have been shown to have an increased risk of postoperative infections, largely due to impaired immune function and microvascular damage4. Moreover, immunosuppressive therapies, such as corticosteroids, commonly used in RCC patients, can further increase susceptibility to infections. As such, the failure to account for the baseline immune status of patients could lead to an incomplete or inaccurate assessment of the role of prophylactic antibiotics, especially in high-risk subgroups such as those with diabetes, the elderly, or those on immunosuppressive therapy. These patient populations may have different infection risks and responses to antibiotics, which are critical factors that need to be explored in future studies. Incorporating immune status as an important factor in the study design could help identify specific subgroups of patients who may benefit more or less from prophylactic antibiotic treatment. This would enhance the clinical relevance of the findings and provide more personalized treatment recommendations for RCC patients undergoing thermal ablation. In conclusion, while the study contributes valuable information to the field, addressing these design flaws could significantly enhance the quality and applicability of the findings. Specifically, refining the infection definition and considering immune status would lead to a more precise and clinically relevant assessment of prophylactic antibiotic use in RCC ablation. We believe that addressing these issues in future studies will provide clearer guidelines for the use of antibiotics in this patient population.