The impact of antibiotic use on the incidence and resistance pattern of extended-spectrum beta-lactamase-producing bacteria in primary and secondary healthcare settings.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: • The emergence and spread of bacteria producing extended-spectrum beta-lactamases (ESBLs) has important therapeutic and epidemiologic implications. • A key target for the establishment of hospital antibiotic stewardship is reducing the occurrence of additional antibiotic resistance. • Further research is needed to accumulate supporting evidence that reducing antibiotic use will result in a parallel reduction in antibiotic resistance. WHAT THIS STUDY ADDS: • Fluoroquinolone restriction reversed ciprofloxacin resistance in primary and secondary healthcare settings. • Fluoroquinolone restriction reduced ESBL-producing bacteria incidence rates in both the primary and secondary healthcare settings. • This study highlights the value of time-series analysis in designing efficient antibiotic stewardship. AIMS: The objective of the present study was to study the relationship between hospital antibiotic use, community antibiotic use and the incidence of extended-spectrum beta-lactamase (ESBL)-producing bacteria in hospitals, while assessing the impact of a fluoroquinolone restriction policy on ESBL-producing bacteria incidence rates.
METHODS: The study was retrospective and ecological in design. A multivariate autoregressive integrated moving average (ARIMA) model was built to relate antibiotic use to ESB-producing bacteria incidence rates and resistance patterns over a 5 year period (January 2005-December 2009).
RESULTS: Analysis showed that the hospital incidence of ESBLs had a positive relationship with the use of fluoroquinolones in the hospital (coefficient = 0.174, P= 0.02), amoxicillin-clavulanic acid in the community (coefficient = 1.03, P= 0.03) and mean co-morbidity scores for hospitalized patients (coefficient = 2.15, P= 0.03) with various time lags. The fluoroquinolone restriction policy was implemented successfully with the mean use of fluoroquinolones (mainly ciprofloxacin) being reduced from 133 to 17 defined daily doses (DDDs)/1000 bed days (P < 0.001) and from 0.65 to 0.54 DDDs/1000 inhabitants/day (P= 0.0007), in both the hospital and its surrounding community, respectively. This was associated with an improved ciprofloxacin susceptibility in both settings [ciprofloxacin susceptibility being improved from 16% to 28% in the community (P < 0.001)] and with a statistically significant reduction in ESBL-producing bacteria incidence rates. DISCUSSION: This study supports the value of restricting the use of certain antimicrobial classes to control ESBL, and demonstrates the feasibility of reversing resistance patterns post successful antibiotic restriction. The study also highlights the potential value of the time-series analysis in designing efficient antibiotic stewardship.