Impact of a restrictive antibiotic policy on the acquisition of extended-spectrum beta-lactamase-producing Enterobacteriaceae in an endemic region: a quasi-experimental, before-and-after, propensity-matched cohort study in a Caribbean intensive care unit

Abstract

Background: High-level antibiotic consumption plays a critical role in the selection and spread of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in ICU. Implementation of a stewardship program including a restrictive antibiotic policy was evaluated with respect to the ESBL-E acquisition (carriage and infection).Methods: We implemented a two-years, quasi-experimental, before-and-after intervention study with all consecutive adult patients admitted for >48 h in the medical-surgical 26-bed ICU of Guadeloupe University Hospital (French West Indies). A conventional strategy period (CSP), including a broad-spectrum antibiotic as initial empirical treatment, followed by de-escalation (period before) was compared to a restrictive strategy period (RSP) limiting broad-spectrum antibiotics and shortening their duration. Antibiotic therapy was delayed and initiated only after microbiological identification, except for septic shock, severe acute respiratory distress syndrome and meningitis (period after). A multivariate Cox proportional hazard regression model adjusted on propensity score values was performed. The main outcome was the median time of being free of ESBL-E in the ICU. Secondary outcome included all-cause ICU mortality.Results: The study included 1,541 patients, for a total of 738 in the CSP and 803 in the RSP. During the RSP, less patients were treated with antibiotics (46.8% vs 57.9%; p<0.01), treatment duration was shorter (5 vs 6 days; p<0.01), administration of antibiotics targeting anaerobic pathogens significantly decreased (65.3% vs 33.5%; p<0.01) compared to the CSP. The incidence of ICU-acquired ESBL-E was lower (12.1% vs 19%; p<0.01) during the RSP. The median time of being free of ESBL-E was 22 days (95% confidence interval, 16-NA days) in the RSP and 18 days (95% CI, 16-21 days) in the CSP. After propensity score weighting and adjusted analysis, the median time of being free of ESBL-E was independently associated with the RSP (hazard ratio, 0.746 [95% CI, 0.575-0.968]; p=0.02, and hazard ratio 0.751 [95% CI 0.578-0.977]; p=0.03, respectively). All-cause ICU mortality were lower in the RSP than in the CSP (22.5% vs 28.6%; p<0.01).Conclusions: Implementation of a program including a restrictive antibiotic strategy is feasible and is associated with less ESBL-E acquisition in the ICU without any worsening of patient outcome.