Ventilator-associated pneumonia (VAP) is a major infectious complication in the neurologic intensive care unit (NICU). VAP caused by multi-drug resistant (MDR) pathogens is related to poor clinical outcomes. This study investigates the relationship between early plasma cytokine profiles and the development of MDR VAP following neurosurgery. We retrospectively analyzed neurosurgical patients admitted to the NICU who developed VAP between January 2021 and January 2024. A receiver operating characteristic (ROC) curve was used to determine the predictive value of the cytokines. Among 67 VAP patients, MDR VAP cases exhibited lower Glasgow Coma Scale (GCS) scores on admission and a higher incidence of prolonged hospitalization (>5 days) before infection. Significantly elevated levels of IL-2, IL-6, IL-10 and IL-17a were observed in MDR VAP patients, while IL-4, TNFα and IFNγ presented no statistical difference. ROC curves revealed that IL-2 (AUC: 0.722, 95 % CI: 0.599–0.845) and IL-10 (AUC: 0.798, 95 % CI: 0.687–0.909) had the strongest predictive value, with optimal cut-off values of 2.635 pg/mL (IL-2, sensitivity 57.1 %, specificity 84.4 %) and 8.495 pg/mL (IL-10, sensitivity 77.1 %, specificity 84.4 %), respectively. A combined IL-2 + IL-10 model further improved predictive performance (AUC: 0.827, 95 % CI: 0.726–0.927). This was confirmed by a multivariate analysis (OR: 23.1, p = 0.007). In conclusion, early elevations in plasma IL-2, IL-6, IL-10 and IL-17a (at 24 h of admission to the NICU) are associated with MDR VAP in NICU patients. The combined measurement of IL-2 and IL-10 may serve as a useful adjunctive tool for predicting post-neurosurgery MDR VAP risk, aiding in early clinical intervention.
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