Prolonged mechanical ventilation assistance interacts synergistically with carbapenem for clostridium difficile infection in critically Ill patients

Objectives: Interactions between mechanical ventilation (MV) and carbapenem interventions were investigated for the risk of Clostridium difficile infection (CDI) in critically ill patients undergoing concurrent carbapenem therapy. Methods: Taiwan’s National Intensive Care Unit Database (NICUD) was used in this analytical, observational, and retrospective study. We analyzed 267,871 intubated patients in subgroups based on the duration of MV support: 7–14 days (n = 97,525), 15–21 days (n = 52,068), 22–28 days (n = 35,264), and 29–60 days (n = 70,021). The primary outcome was CDI. Results: Age (>75 years old), prolonged MV assistance (>21 days), carbapenem therapy (>15 days), and high comorbidity scores were identified as independent risk factors for developing CDI. CDI risk increased with longer MV support. The highest rate of CDI was in the MV 29–60 days subgroup (adjusted hazard ratio (AHR) = 2.85; 95% confidence interval (CI) = 1.46–5.58; p < 0.02). Moreover, higher CDI rates correlated with the interaction between MV and carbapenem interventions; these CDI risks were increased in the MV 15–21 days (AHR = 2.58; 95% CI = 1.12–5.91) and MV 29–60 days (AHR = 4.63; 95% CI = 1.14–10.03) subgroups than in the non-MV and non-carbapenem subgroups. Conclusions: Both MV support and carbapenem interventions significantly increase the risk that critically ill patients will develop CDI. Moreover, prolonged MV support and carbapenem therapy synergistically induce CDI. These findings provide new insights into the role of MV support in the development of CDI.