Clostridioides Difficile Infection (CDI) further harms critically ill patients by increasing 28-day mortality and in case of prolonged diarrhoea the length of their hospital stay.

Appropriate therapy should be initiated promptly to shorten duration of diarrhoea.

Our data point to the fact that metronidazole IV as a single agent might not represent an efficient initial monotherapy.

Future studies should address the evaluation of combination therapy in critically ill patients with CDI.

Since immunosuppressive therapy was identified as an independent predictor of increased 28-day mortality, patients should be carefully evaluated whether immunosuppressive therapy is indicated in case of concurrent CDI.

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