Fidaxomicin for the treatment of Clostridium difficile infection (CDI) in at-risk patients with inflammatory bowel disease, fulminant CDI, renal impairment or hepatic impairment: a retrospective study of routine clinical use (ANEMONE)

Maria J G T Vehreschild,Florian Thalhammer,Areti Georgopali,Graham Wetherill,Emilio Bouza,Surabhi Taori,Joop Van Oene,Simon D Goldenberg

doi:10.1007/s10096-018-3344-1

Abstract

Information is limited or lacking on fidaxomicin treatment of Clostridium difficile infection (CDI) in patients with inflammatory bowel disease, fulminant or life-threatening CDI, severe renal impairment, moderate-to-severe hepatic impairment and pregnancy. The ANEMONE study investigated fidaxomicin use in a routine clinical setting, focusing on these medical conditions of specific interest (MCSIs). This retrospective, post-authorisation study reviewed hospital records from Austria, Germany, Spain and the UK (June 2012–June 2015), collecting data from hospital admission to 30 days after last fidaxomicin dose. The primary objective was to identify the proportion of fidaxomicin-treated patients with MCSIs. Secondary objectives were to describe 30-day mortality, changes in ECG and laboratory parameters, fidaxomicin exposure and CDI response (resolution of diarrhoea; 30-day recurrence). 45.3% (261/576) of patients had ≥ 1 MCSI. Thirty-day mortality (post-first dose) was 17.0% (98/576) in the total population and slightly higher (24.6–27.6%) in patients with fulminant CDI or severe renal impairment. 29.6% (24/81) deaths of known cause were attributable to CDI. Of changes in laboratory parameters or ECG findings, only a decrease in leucocyte counts appeared associated with fidaxomicin, consistent with a positive treatment response. Diarrhoea resolved in 78.0% (404/518) of treatment episodes; diarrhoea resolution was lowest in patients with fulminant CDI (investigator-defined, 67.5%, 56/88) and severe renal impairment (68.0%, 68/100). Thirty-day recurrence (18.8%, 79/420) was similar across MCSI subgroups. Although almost half of fidaxomicin-treated patients had ≥ 1 MCSI, the majority of patients in all subgroups had positive responses to treatment, and no particular safety concerns were identified.

Highlights

Clostridium difficile is the leading cause of infectious nosocomial diarrhoea in developed countries [1]
Limited data are available on the use of fidaxomicin in patients with C. difficile infection (CDI) who have severe renal impairment and/or moderate-to-severe hepatic impairment, while data in pregnant women are absent [13]
CDI was confirmed in 97.2% (519/534) of treatment episodes for which data were available (Table 2)

Summary

Introduction

Clostridium difficile is the leading cause of infectious nosocomial diarrhoea in developed countries [1]. The incidence and severity of C. difficile infection (CDI) have increased in recent years [2], alongside increased morbidity, mortality and healthcare costs [3]. The mainstays of CDI treatment over the past 30 years have been metronidazole and vancomycin [4, 5]; more recently, the narrow-spectrum macrocyclic antibiotic fidaxomicin [6,7,8] has been approved in the USA [9] and the EU [10] for the treatment of CDI. The ANEMONE study aimed to determine the prevalence of these conditions in patient populations treated with fidaxomicin, assess fidaxomicin use in a routine clinical setting and investigate its safety and effectiveness in these specific patient groups

Objectives

Methods

Results

Conclusion