Escherichia coli is one of the most important foodborne pathogens. Infections caused by antimicrobial-resistant E. coli are becoming increasingly common worldwide and pose a serious health problem for human medicine (EARSS, 2008; ECDC, 2010). In most countries reporting data to EARSS and its successor EARS-Net, a significant increase in resistance to third-generation cephalosporins was observed from 2005 to 2008. Furthermore, resistance to fluoroquinolones in E. coli from bloodstream infections has increased all over Europe consistently over recent years (ECDC, 2010).
The degree to which animals and humans share or exchange common types of E. coli is currently the subject of active research and debate (EFSA, 2011). Commensal E. coli, present in the intestine of farm animals or on animal products, are considered a potential source of resistant bacteria and resistance genes for humans. The German resistance monitoring programme provides valuable data on the pool of resistance present in bacteria of animal origin. This will contribute to the assessment of their relevance for public health.
The results generated within this first year of active monitoring of resistance in commensal E. coli in Germany reflect that these bacteria show resistance to various antibiotics relevant to human medicine. The results are in line with the resistance situation in the food chain previously described for Germany on the basis of Salmonella isolates submitted to the National Reference Laboratory for Salmonella at the Federal Institute for Risk Assessment between 2000 and 2008. Like in the present study, those data had been analysed on the basis of epidemiological cut-off values (Schroeter and Kaesbohrer, 2011).
A previous German study (1999–2001) on 317 E. coli strains from cattle, swine and poultry showed that resistance was found in 40% and multidrug resistance (2–8 resistance determinants) in 32% of the strains (Guerra et al., 2003). Reported resistance was significantly higher in isolates from poultry (61%) and swine (60%) than from cattle (25%) at that time. Resistance to sulfamethoxazole, tetracycline, streptomycin, ampicillin and spectinomycin (30–15%) predominated. Eleven per cent of the strains were resistant to nalidixic acid. None of the isolates showed resistance to ceftiofur. As clinical break points were applied throughout that study, data are not directly comparable with current results, but relations between different sources of isolates can be compared.
On EU level, in 2009, the occurrence of resistance to tetracyclines, ampicillin, chloramphenicol, streptomycin, ciprofloxacin and nalidixic acid in E. coli isolates from chicken (without detailed specification of the production line) showed considerable variation between reporting Member States, similar to the situation observed in previous years (EFSA, 2011). In a pan-European survey of antimicrobial susceptibility in E. coli from broilers sampled at slaughterhouse carried out in 2002/2003, De Jong et al. (2009) described high resistance rates to ampicillin, chloramphenicol and tetracycline on the basis of clinical break points. The resistance prevalence was higher in older compounds (e.g. ampicillin, tetracycline and trimethoprim/sulfamethoxazole) compared to the newer compounds, for example, cefotaxime and ciprofloxacin (De Jong et al., 2009). The present study confirms this tendency that resistance to sulfamethoxazole, tetracycline, streptomycin and ampicillin is frequent in poultry isolates. Furthermore, highest resistance rates to ciprofloxacin were reported in isolates from broilers (43.1%) and chicken meat (53.1%). This is in line with Dutch (MARAN, 2009) and EU-data (EFSA, 2011). In the Netherlands, resistance rates tended to increase in isolates from broilers and broiler products over time (MARAN, 2009). The respective values for ciprofloxacin in the older pan-European study were 30.4% decreased susceptibility and 5.8% clinical resistance in isolates from broilers (De Jong et al., 2009). Decreased susceptibility to fluoroquinolones has been associated with decreased clinical responses of Salmonella infections to fluoroquinolones in humans (Crump et al., 2003; Helms et al., 2004).
Likewise, in this study, broiler and chicken meat isolates showed the highest resistance rates to cefotaxime (5.4% and 6.2%, respectively). The main cause of cefotaxime resistance is the production of different extended-spectrum beta-lactamases (ESBL) or AmpC beta-lactamases as previously described for Salmonella from animals and food products (Rodriguez et al., 2009). In the pan-European study, similar results were reported for broilers. Whereas 5.4% of the isolates showed decreased susceptibility for cefotaxime on the basis of epidemiological cut-off values, 0.4% were clinically resistant on the basis of the clinical break point according to CLSI (De Jong et al., 2009). In the report on EU level, resistance in E. coli to cefotaxime in chicken ranged in reporting countries from 2% to 26% (EFSA, 2011). In the Netherlands, in E. coli isolates from poultry meat, 21.3% and 18.0% resistance to cefotaxime and ceftazidime was observed (MARAN, 2009).
Within our study population, considerable rates of multidrug resistance (resistance to more than one antimicrobial class) were observed among isolates from broilers, as well as chicken and turkey meat. Highest multidrug resistance rates were observed in turkey meat with 38.4% of the isolates showing resistance to more than four classes. Similarly, in the Netherlands, 27.5% of the isolates from broilers showed resistance to six or more classes of antimicrobials.
In Germany, sales data for antimicrobials used in veterinary medicine are only available for the year 2005. Sales and consumption data on antimicrobials specific for each individual animal species are not available. In the Netherlands, it is reported that the average broiler chicken receives 37 daily doses per year, which means that an individual broiler is treated with antibiotics during 4 days in the 42 days from hatching until slaughter (MARAN, 2009). Quinolones accounted for 18% of total antibiotic use in broiler farms, which was only exceeded by the usage of penicillin. Fluoroquinolone use was 1.4% of total use. This may explain to some extent the resistance rates observed. In a recent review, the relationship between antimicrobial usage and prevalence of antimicrobial-resistant bacteria from food-producing animals was confirmed in Japan (Harada and Asai, 2010). It was concluded that trends in antimicrobial resistance are closely related to the use of antimicrobial agents in veterinary medicine (Aarestrup, 1999; Asai et al. 2005; Harada and Asai, 2010). In contrast, cephalosporins are not licensed for usage in poultry. Therefore, the reason for the presence of resistance to cephalosporins in poultry, as observed in this and several other recent studies, is unclear. For example, in a study on the occurrence of ESBL-producing E. coli in flocks of laying hens reared in Danish organic systems, the factors leading to the origin and persistence of cephalosporin resistance remained unknown (Bortolaia et al., 2010a). In the Netherlands, resistance to cephalosporins could be linked to usage in hatcheries. Similarly, in Quebec, changes of ceftiofur resistance in chicken Salmonella Heidelberg and E. coli isolates were clearly related to changing levels of ceftiofur use in hatcheries (Dutil et al., 2010).
The levels of resistance to all of the antimicrobials in isolates of E. coli from cattle were consistently lower compared to the levels in indicator E. coli from Gallus gallus and pigs from the same Member States (Guerra et al., 2003; EFSA, 2011; MARAN, 2009; De Jong et al., 2009). Detailed analysis of data collected in the present study confirms that resistance level in dairy cattle is low, whereas resistance level in veal calves is higher (MARAN, 2009; De Jong et al., 2009). In Germany, 5 (1.4%) of the E. coli isolates from veal calves were resistant against cefotaxime, whereas 11 isolates (3.0%) were resistant to ceftazidime. In the Netherlands, resistance in veal calves to third-generation cephalosporins was comparable to the German situation, ranging between 1.8% and 2.3% (MARAN, 2009).
Differences in resistance to quinolones between veal calves and beef cattle were also observed. In the Netherlands, 18.1% of isolates from veal calves showed reduced susceptibility, and 6.5% were considered clinically resistant (MIC > 1 mg/l) against ciprofloxacin. In the present study, 13.3% of the isolates from veal calves showed resistance to ciprofloxacin. In Italy, 5.3% of the cattle isolates showed clinical resistance against ciprofloxacin. In contrast, during the EASSA study in 2002/2003, lower resistance rates for fluoroquinolones had been reported for beef cattle, and no clinical resistance against ciprofloxacin was observed for fluoroquinolones in four of five countries (De Jong et al., 2009).
Among the bovine isolates, multidrug resistance was most frequent in veal calf isolates with 22.2%, showing resistance to more than four classes. Similarly, among E. coli collected in the Netherlands from veal calves, multidrug resistance was also widespread with 11.1% of the isolates resistant to six or more classes of antimicrobials (MARAN, 2009). In contrast, within our study, 2.2% of isolates from dairy cattle showed resistance to more than four classes. Differences observed may be correlated with differences in usage patterns. Whereas in dairy cattle, all antimicrobials are applied parenteral or intramammary, oral use is the typical route of application in calves (Merle et al., 2011).
In the EFSA report 2011, the resistance rate of E. coli from pork to tetracyclines was 41% for all reporting countries. The corresponding figures for ampicillin were 27%, for chloramphenicol 6%, for sulphonamides 35% and for streptomycin 41% (EFSA, 2011). In Germany, the observed level of resistance for all these antimicrobials was lower compared to the EU average, except for chloramphenicol, where similar rates were detected. Rates of resistance in E. coli from pork to nalidixic acid remained at low or moderate levels in all reporting countries throughout 2005–2009. Our results from Germany are comparable to EU average data for ciprofloxacin and nalidixic acid, where resistance rates in E. coli isolates from pork were 6% (both antimicrobials).
Resistance to cephalosporins seems to increase in E. coli from pork. In 2009, all countries reporting to EFSA detected cefotaxime resistance in E. coli isolates from pork. The EU average rate for cefotaxime resistance was 3%. In the previous year, only France reported cefotaxime resistance in one of 102 E. coli isolates from pork (EFSA, 2011).