Impact of enhanced infection control and antimicrobial stewardship on infections by Clostridioides difficile, vancomycin-resistant enterococci, and third-generation cephalosporin-resistant Enterobacterales: a stepped-wedge cluster intervention study

Objectives Infection prevention and control (IPC) and antimicrobial stewardship (AMS) measures are critical to reducing transmission and infection by Clostridioides difficile (CDI) and other enteric pathogens. This study evaluated the impact of enhanced IPC and AMS on CDI and bloodstream infections (BSIs) caused by vancomycin-resistant enterococci (VRE) and third-generation cephalosporin-resistant Enterobacterales (3GCREB). Methods The study was conducted in five German university hospitals from January 2016 to July 2019. IPC and AMS interventions were sequentially enhanced in three departments with high-incidence CDI at baseline using a stepped-wedge cluster intervention approach. Main outcome measures were incidence densities of CDI and BSI caused by VRE and 3GCREB. An interrupted time series analysis was performed to assess the intervention effects during a normalized study period. Results Across 15 departments, >384,000 patient days were included. Incidence density of target infections was low (CDI, 0.77; VRE BSI, 0.07; and 3GCREB BSI, 0.09 per 1000 patient days). Pooled interrupted time series analysis results showed a significant reduction in CDI incidence density following the enhancement of AMS measures (AMS period regression slopes difference, −0.089; F[ p ] = 5.400 [0.037]). Regarding the incidence density of VRE/3GCREB BSI, no relevant changes could be observed (regression slopes difference, −0.19; F [p] = 0.667 [0.429]). A subgroup analysis focusing on haematological and oncological departments showed that AMS influenced prescription behaviour according to implemented AMS strategies, but not clinical outcomes. Discussion Combined with IPC enhanced short-term AMS measures led to a significant reduction in the incidence of CDI, whereas the incidence of BSI by VRE and 3GCREB remained unchanged in sites with well-established baseline IPC and AMS programmes and low incidence of hospital-associated infections.