Dramatic increase of third-generation cephalosporin-resistant E. coli in German intensive care units: secular trends in antibiotic drug use and bacterial resistance, 2001 to 2008

Abstract

Introduction: The objective of the present study was to analyse secular trends in antibiotic consumption and resistance data from a network of 53 intensive care units (ICUs).

Methods: The study involved prospective unit and laboratory-based surveillance in 53 German ICUs from 2001 through 2008. Data were calculated on the basis of proportions of nonduplicate resistant isolates, resistance densities (that is, the number of resistant isolates of a species per 1,000 patient-days) and an antimicrobial usage density (AD) expressed as daily defined doses (DDD) and normalised per 1,000 patient-days.

Results: Total mean antibiotic use remained stable over time and amounted to 1,172 DDD/1,000 patient-days (range 531 to 2,471). Carbapenem use almost doubled to an AD of 151 in 2008. Significant increases were also calculated for quinolone (AD of 163 in 2008) and third-generation and fourth-generation cephalosporin use (AD of 117 in 2008). Aminoglycoside consumption decreased substantially (AD of 86 in 2001 and 24 in 2008). Resistance proportions were as follows in 2001 and 2008, respectively: methicillin-resistant Staphylococcus aureus (MRSA) 26% and 20% (P = 0.006; trend test showed a significant decrease), vancomycin-resistant enterococcus (VRE) faecium 2.3% and 8.2% (P = 0.008), third-generation cephalosporin (3GC)-resistant Escherichia. coli 1.2% and 19.7% (P < 0.001), 3GC-resistant Klebsiella pneumoniae 3.8% and 25.5% (P < 0.001), imipenem-resistant Acinetobacter baumannii 1.1% and 4.5% (P = 0.002), and imipenem-resistant K. pneumoniae 0.4% and 1.1%. The resistance densities did not change for MRSA but increased significantly for VRE faecium and 3GC-resistant E. coli and K. pneumoniae. In 2008, the resistance density for MRSA was 3.73, 0.48 for VRE, 1.39 for 3GC-resistant E. coli and 0.82 for K. pneumoniae.

Conclusions: Although total antibiotic use did not change over time in German ICUs, carbapenem use doubled. This is probably due to the rise in 3GC-resistant E. coli and K. pneumoniae. Increased carbapenem consumption was associated with carbapenem-resistant K. pneumoniae carbapenemase-producing bacteria and imipenem-resistant A. baumannii.

Figure 1

Antibiotic consumption in 53 German intensive care units from 2001 to 2008. DDD, defined daily doses; pd, patient-days.

Figure 2

Change in antibiotic consumption in German intensive care units from 2001 to 2008. DDD, defined daily doses; pd, patient-days; 1&2GC, first-generation and second-generation cephalosporins; 3&4GC, third-generation and fourth-generation cephalosporins. P value for the linear regression coefficient and trend (increase, +; decrease, -) in parentheses.

Figure 3

Change in burden of resistance of multidrug-resistant pathogens from 2001 to 2008. MRSA, methicillin-resistant Staphylococcus aureus; Imi R Aci, imipenem-resistant Acinetobacter baumannii; VRE, vancomycin-resistant Enterococcus faecium; 3GC R Kleb, third-generation cephalosporin-resistant Klebsiella pneumoniae; 3GC R Eco, third-generation cephalosporin-resistant Escherichia coli.

Figure 4

Third-generation cephalosporin-resistant Escherichia coli and carbapenem use from 2001 to 2008. (a) Percentage of third-generation cephalosporin-resistant (3GC) Escherichia coli. The pooled mean (solid line) and the median (dotted line) run almost parallel to one another. The sharp increase in 3CG-resistant E. coli starts in 2006 and affects almost all intensive care units (ICUs). The interquartile range (shaded area) shows that 50% of all ICUs had resistance proportions between 5 and 15% in 2008. (b) Carbapenem use. The pooled mean (solid line) and the median (dotted line) run almost parallel to one another. In most ICUs the increase in carbapenem use also starts in 2006. The interquartile range (shaded area) shows that carbapenem use in 50% of all ICUs ranged between 70 and 190 daily defined doses (DDD)/1,000 patient-days (pd) in 2008.