Trends in Expanded-Spectrum Cephalosporin-Resistant Escherichia coli and Klebsiella pneumoniae among Dutch Clinical Isolates, from 2008 to 2012

Abstract

We investigated time trends in extended-spectrum cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae isolates from different patient settings in The Netherlands from 2008-2012. E. coli and K. pneumoniae isolates from blood and urine samples of patients > = 18 years were selected from the Dutch Infectious Disease Surveillance System-Antimicrobial Resistance (ISIS-AR) database. We used multivariable Poisson regression to study the rate per year of blood stream infections by susceptible and resistant isolates, and generalized estimating equation (GEE) log-binomial regression for trends in the proportion of extended-spectrum cephalosporin-resistant isolates. Susceptibility data of 197,513 E. coli and 38,244 K. pneumoniae isolates were included. The proportion of extended-spectrum cephalosporin-resistant E. coli and K. pneumoniae isolates from urine and blood samples increased in all patient settings, except for K. pneumoniae isolates from patients admitted to intensive care units. For K. pneumoniae, there was a different time trend between various patient groups (p<0.01), with a significantly higher increase in extended-spectrum cephalosporin-resistant isolates from patients attending a general practitioner than in isolates from hospitalized patients. For E. coli, the increasing time trends did not differ among different patient groups. This nationwide study shows a general increase in extended-spectrum cephalosporin-resistant E. coli and K. pneumoniae isolates. However, differences in trends between E. coli en K. pneumoniae underline the importance of E. coli as a community-pathogen and its subsequent influence on hospital resistance level, while for K. pneumoniae the level of resistance within the hospital seems less influenced by the resistance trends in the community.

Fig 1. The rate of bloodstream infections by Escherichia coli and Klebsiella pneumoniae (A) and the rate of bloodstream infections by extended-spectrum cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae (B) from 2008–2012, ISIS-AR, the Netherlands, adjusted for patient characteristics, including age, gender, patient setting and geographic region.

The plots show the point-estimates and log-linear trends generated by a Poisson regression with robust standard error.

Fig 2. The proportion (in %) of extended-spectrum cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae isolates, for blood isolates (A), male urine isolates (B) and female urine isolates (C) from 2008–2012, ISIS-AR, the Netherlands.

The point-estimates and log-linear trends per year were estimated with a generalized estimation equation (GEE) for log-binominal regression including time in years, and patient characteristics, including age, gender, patient setting and geographic region. The error bars represent the 95% confident intervals of each of the point-estimates.

Fig 3. The proportion (in %) extended-spectrum cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae isolates, for blood isolates (A), male urine isolates (B) and female urine isolates (C), per patient setting (general practitioner [GP], outpatient department [OPD], inpatient department [IPD] and intensive care units [ICU]), from 2008–2012, ISIS-AR, the Netherlands.

The point-estimates are generated with a generalized estimation equation (GEE) for log-binominal regression, including time in years, and patient characteristics, including age, gender, and geographic region. The error bars represent the 95% confident intervals of each of the point-estimates. To produce plots with comparable y-axis, the upper error bar is cut-off for some of the point-estimates.