Use of intravenous tigecycline in patients with severe Clostridium difficile infection: a retrospective observational cohort study

Abstract

There are only a limited number of antimicrobials for treating severe Clostridium difficile infection (sCDI). Tigecycline shows significant in vitro effect against C. difficile and is approved for management of complicated intra-abdominal infections. Our aim was to analyse the efficacy of tigecycline compared with standard therapy (oral vancomycin plus intravenous metronidazole) in adults treated for sCDI. A retrospective cohort study of such patients hospitalized at our department from January 2014 to December 2015 was performed. Patients receiving tigecycline monotherapy were compared with patients treated with standard therapy alone. Diagnosis and severity of CDI were determined according to guidelines of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Primary outcome was clinical recovery, secondary outcomes were in-hospital and 90-day all-cause mortality and relapse, colectomy, and complication rates. Of the 359 patients hospitalized for sCDI, 90 (25.0%) were included, 45 in each group. Patients treated with tigecycline had significantly better outcomes of clinical cure (34/45, 75.6% vs. 24/45, 53.3%; p 0.02), less complicated disease course (13/45, 28.9% vs. 24/45, 53.3%; p 0.02), and less CDI sepsis (7/45, 15.6% vs. 18/45, 40.0%; p 0.009) compared with patients receiving standard therapy. Tigecycline usage was not associated with adverse drug reactions or need for colectomy. Rates of ileus, toxic megacolon, mortality, and relapse were similar between the two groups. Favourable outcomes suggest that tigecycline might be considered as a potential candidate for therapeutic use in cases of sCDI refractory to standard treatment.

The outcome of patients with severe and severe‐complicated Clostridium difficile infection treated with tigecycline combination therapy: a retrospective observational study

“…Our severe group included five immunocompromised patients and two aged >80 years, known risk groups for higher mortality . We also found an overall 90 day all‐cause mortality rate of 23% (3/13), which compares favourably with the 37.8 and 46.7% respectively seen in the tigecycline monotherapy and the standard therapy arms in the study by Gergely Szabo et al …”

“…In our study, combination therapy was associated with clinical cure in 89% (8/9) of severe CDI cases with no 30‐day mortality or colectomies (Table ). This is notable, given that clinical cure rates for the standard therapy with oral vancomycin and intravenous metronidazole in severe CDI have been reported at 53.3–65.1% and Bass et al . reported mortality within 30 days of treatment and colectomy rates of 23.3 and 9.3% respectively.…”

“…We utilised tigecycline combination therapy in two key scenarios: first, for patients with severe CDI who required abdominal sepsis cover or needed ongoing antimicrobials for systemic infections; and second, for patients with severe‐complicated disease admitted to ICU. Monotherapy was not used, given the lack of prospective RCT data . Also, similarly to LaSalvia et al ., we commenced using this regimen several years ago, before any monotherapy data emerged .…”

“…These studies identified no mortality benefit, but they were not adequately powered and could not fully exclude that sicker patients had received adjunctive therapy. Other investigators retrospectively evaluated tigecycline monotherapy, tigecycline with oral vancomcyin or mixed regimens, including patients with non‐refractory disease and utilising tigecycline's provision of abdominal sepsis cover while simultaneously treating CDI. Results were mixed, but Gergely Szabo et al .…”

Does Adjunctive Tigecycline Improve Outcomes in Severe-Complicated, Nonoperative Clostridium difficile Infection?

“…In this population, few case reports suggest a role [13, 14, 18, 19]. A recent retrospective cohort study investigating tigecycline for severe CDI found higher rates of clinical cure, less complicated courses, and a reduction in CDI sepsis in patients who received tigecycline monotherapy versus standard treatments [20]. Our study expands upon this concept by evaluating the impact of tigecycline in a small cohort of patients with severe, complicated disease who were nonsurgical candidates.…”