Baseline Neutrophil-Lymphocyte Ratio Combined with Mean Corpuscular Volume in Predicting Catheter-Related Bloodstream Infection: A Retrospective Case-Control Study

Technical Summary: Baseline Neutrophil-Lymphocyte Ratio Combined with Mean Corpuscular Volume in Predicting Catheter-Related Bloodstream Infection

Problem Statement
Central line-associated bloodstream infection (CLABSI) remains a critical complication of indwelling central venous catheters, significantly increasing patient mortality, hospital length of stay, and healthcare burdens. While previous research has identified macro-level risk factors (e.g., catheter dwell time, multilumen catheters) and biological markers (e.g., white blood cell count, procalcitonin), there is a gap in prospective risk stratification tools. Existing studies often focus on diagnostic markers after infection onset rather than predictive indicators available prior to catheterization. Furthermore, the independence and interactive effects of routine hematological markers, specifically the Neutrophil-Lymphocyte Ratio (NLR) and Mean Corpuscular Volume (MCV), on CLABSI risk have not been systematically elucidated.

Methodology
The study employed a retrospective case-control design involving 81 patients from The First Affiliated Hospital of Fujian Medical University between January 2022 and December 2023.

• Participants: The case group consisted of 27 patients diagnosed with CLABSI. The control group comprised 54 patients with central venous catheters but no CLABSI, matched 1:2 with cases based on age (±5 years), gender, and underlying diseases (traumatic, hematologic, cerebrovascular, and tumors).
• Data Collection: Baseline laboratory data were extracted from routine blood tests performed within 24–48 hours prior to catheter insertion. Key variables included NLR and MCV, alongside demographic and clinical confounders (e.g., ICU admission, diabetes, catheter type, intravenous nutrition).
• Diagnostic Criteria: CLABSI diagnosis adhered to the 2011 CDC/NHSN Surveillance Definition, requiring bacteremia during catheter dwell time or within 48 hours of removal, accompanied by systemic signs of infection, with microbiological confirmation.
• Statistical Analysis:
  • Regression: Multivariate logistic regression was used to identify independent risk factors, adjusting for clinical confounders.
  • Predictive Performance: Receiver Operating Characteristic (ROC) curve analysis evaluated the Area Under the Curve (AUC) for NLR and MCV individually.
  • Interaction Analysis: Multifactor Dimensionality Reduction (MDR) was utilized to detect non-linear interactions between MCV and NLR.
  • Validation: A prediction model based on the identified interaction was validated using ten-fold cross-validation.

Key Results

• Independent Predictors: Multivariate analysis identified baseline NLR as an independent risk factor for CLABSI (OR = 1.081, P = 0.033) and MCV as a protective factor (OR = 0.934, P = 0.038).
• Predictive Accuracy: ROC analysis demonstrated that MCV (AUC = 0.706) had superior predictive performance compared to NLR (AUC = 0.635). The optimal cutoff for MCV was determined to be 91.5 fL.
• Non-linear Associations: Restricted cubic spline models confirmed a significant non-linear relationship between MCV and CLABSI risk (P = 0.039 for non-linearity), whereas the non-linear association for NLR did not reach statistical significance.
• Interaction and Risk Stratification: MDR analysis revealed a significant interaction between MCV and NLR (P < 0.001).
  • High-Risk Combination: Patients with MCV < 91.5 fL** and **NLR > 8 exhibited the highest risk, with a relative risk of 9.375 and an infection risk ratio of 0.75 (indicating a strong protective effect when these factors are absent).
  • Model Performance: A prediction model constructed based on this interaction achieved an accuracy of 76.7% with a 10/10 consistency in ten-fold cross-validation, indicating robustness without overfitting.
• Subgroup Findings: The association between NLR and CLABSI was more pronounced in patients >65 years and non-diabetic patients. In diabetic patients, the predictive power of NLR was not significant, likely due to pre-existing chronic inflammatory states masking the marker's utility.

Key Contributions

1. Novel Predictive Combination: The study is the first to systematically evaluate the combined predictive value of pre-catheterization NLR and MCV for CLABSI, moving beyond single-marker analysis.
2. Identification of Interaction: It demonstrates that the interaction between elevated NLR (reflecting systemic inflammation/immune suppression) and decreased MCV (reflecting compromised bone marrow reserve/nutritional status) creates a synergistic risk ("1+1>2") that is more predictive than either marker alone.
3. Clinical Utility of Routine Data: The findings suggest that widely accessible, low-cost routine blood test parameters can be leveraged to construct a risk stratification tool for early identification of high-risk patients before catheterization.

Significance and Claims
The paper claims that the interaction between elevated pre-catheterization NLR and decreased MCV serves as a combined predictor for CLABSI. This approach facilitates the early identification of high-risk patients, potentially guiding the implementation of targeted preventive strategies in clinical practice.

The authors position this work as a step toward shifting from "passive diagnosis" to "active prevention." They propose that integrating these indicators into hospital information systems could enable automated pre-catheterization risk assessment. However, the authors maintain a modest stance regarding clinical application, acknowledging that while the model shows promise as a decision support system (76.7% accuracy), it is not yet a standalone diagnostic tool. They emphasize that the current findings are preliminary and require validation through larger-scale, prospective, multi-center cohort studies to confirm causal inference and generalizability, particularly given the single-center nature and small sample size of the current study.