Tigecycline combination therapy for fulminant Clostridioides difficile infection: an Australian experience

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Abstract
Background: Recent European Society of Clinical Microbiology and Infection and Australasian Society of Infectious Diseases Clostridioides difficile infection (CDI) management guidelines endorse the addition of intravenous tigecycline in patients who are progressing to fulminant infection. However, there are very limited data regarding clinical outcomes with this approach. Aims: We aimed to evaluate mortality and adverse outcomes after tigecycline combination therapy was commenced at the time of fulminant CDI. Methods: This retrospective single‐site observational study included patients between January 2018 and December 2022 treated with adjunctive intravenous tigecycline for fulminant CDI in addition to oral vancomycin and intravenous metronidazole. The primary outcome was all‐cause mortality at 30 days. Secondary outcomes included clinical cure, partial response, in‐hospital CDI‐attributable and 90‐day all‐cause mortality, colectomy and adverse events. Results: Eighteen patient episodes occurred, with median age 67.5 years, requiring intensive care admission and inotropic support in 66.7% and 50% of episodes respectively. All‐cause mortality at 30 days was 22.2%. Clinical cure occurred at 14 days in 16.7% of cases and partial response requiring further oral therapy in 55.6%. There was one colectomy and two serious adverse events, including a hyperkalaemic cardiac arrest in a haemodialysis patient and one significant intra‐abdominal bleeding episode requiring surgery. Conclusions: Tigecycline combination therapy resulted in improved all‐cause 30‐day mortality in high‐risk CDI patients versus historical data, without the use of faecal microbiota transplantation. Poor outcomes were seen in three patients with pre‐existing renal failure, and we question the efficacy and safety of tigecycline in this group. This is a useful salvage strategy, but monitoring for toxicity is essential.

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