Higher third-generation cephalosporin prescription proportion is associated with lower probability of reducing carbapenem use: a nationwide retrospective study
Authors: Muller Allison , Bertrand Xavier , Rogues Anne-Marie , Péfau Muriel , Alfandari Serge , Gauzit Rémy , Dumartin Catherine , Gbaguidi-Haore Houssein ,   on behalf of the ATB-RAISIN network steering committee, Alfandari Serge , Berger-Carbonne Anne , Bertrand Xavier , Boussat Sandrine , Crémieux Anne-Claude , Dumartin Catherine , Fascia Pascal , Gauzit Rémy , Giard Marine , Ingels Anne , L’Hériteau François , Lacavé Ludivine , Le Gonidec Patricia , Machut Anaïs , Maugat Sylvie , Mouchot Lory , Péfau Muriel , Rogues Anne-Marie , Schlemmer Benoît , Sénéchal Hélène , Touratier Sophie 
Published: January 2018

Abstract
Background
The ongoing extended spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) pandemic has led to an increasing carbapenem use, requiring release of guidelines for carbapenem usage in France in late 2010. We sought to determine factors associated with changes in carbapenem use in intensive care units (ICUs), medical and surgical wards between 2009 and 2013.

Methods
This ward-level multicentre retrospective study was based on data from French antibiotic and multidrug-resistant bacteria surveillance networks in healthcare facilities. Antibiotic use was expressed in defined daily doses per 1000 patient-days. Factors associated with the reduction in carbapenem use (yes/no) over the study period were determined from random-effects logistic regression model (493 wards nested within 259 healthcare facilities): ward characteristics (type, size…), ward antibiotic use (initial antibiotic use [i.e., consumption of a given antibiotic in 2009], initial antibiotic prescribing profile [i.e., proportion of a given antibiotic in the overall antibiotic consumption in 2009] and reduction in the use of a given antibiotic between 2009 and 2013) and regional ESBL-PE incidence rate in acute care settings in 2011.

Results
Over the study period, carbapenem consumption in ICUs (n = 85), medical (n = 227) and surgical wards (n = 181) was equal to 73.4, 6.2 and 5.4 defined daily doses per 1000 patient-days, respectively. Release of guidelines was followed by a significant decrease in carbapenem use within ICUs and medical wards, and a slowdown in use within surgical wards. The following factors were independently associated with a higher probability of reducing carbapenem use: location in Eastern France, higher initial carbapenem prescribing profile and reductions in consumption of fluoroquinolones, glycopeptides and piperacillin/tazobactam. In parallel, factors independently associated with a lower probability of reducing carbapenem use were ICUs, ward size increase, wards of cancer centres, higher initial third-generation cephalosporin (3GC) prescribing profile and location in high-risk regions for ESBL-PE.

Conclusions
Our study suggests that a decrease in 3GCs in the overall antibiotic use and the continuation of reduction in fluoroquinolone use, could allow reducing carbapenem use, given the well-demonstrated role of 3GCs and fluoroquinolones in the occurrence of ESBL-PE. Thus, antibiotic stewardship programs should target wards with higher 3GC prescription proportions to reduce them.