To the Editor
This letter is a comment on the recent study by Fischer et al. who found no extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) in the nares of 114 persons exposed to pigs. These results were surprising due to the high prevalence of ESBL-E in livestock [Reference Fischer1]. They detected Enterobacteriaceae in the nares of 76/114 (66·7%) participants, none of which produced ESBL. No association between working hours per week on pig farms and nasal colonization with Enterobacteriaceae could be identified. The authors concluded that nares represent a negligible reservoir for carriage of ESBL-E in persons exposed to pigs.
Interestingly, Dohmen et al. found rectal colonization with ESBL-E in 27% (95% CI 10–44) of humans with daily exposure to ESBL-E-carrying pigs. [Reference Dohmen2]. Genetic similarities of ESBL genes, plasmid types and sequence types (STs) suggested a likely transmission between humans and pigs on the same farms. Further, human colonization with ESBL-E was associated with the number of working hours on a particular farm and with the ESBL carriage of the pigs. Dohmen and colleagues found evidence for transmission of rectal ESBL-E between pig farmers and their livestock. In this context, the rectum and not the nose seems to be the crucial reservoir for colonization of humans with ESBL-E after exposure to pigs.
We feel it necessary to add certain points to the well conducted discussion of Fischer et al. They stated that the northwestern area of Germany is one of the regions with the highest densities of pig production in Europe. Recent data from the German national nosocomial infections surveillance system (KISS) documented the highest – and significantly increasing – incidence of nosocomial infections with ESBL-E in this region [Reference Leistner3]. This observation suggests a relationship between the production farming of pigs and the emergence of ESBL-E infections in the same regions. A Dutch study using whole genome sequencing (WGS) confirmed the similarity of epidemiologically linked strains from humans and pigs of the same farms [Reference de Been4]. Thus, in the case of human and animal contact, our ‘farming theory’ suggests dissemination of ESBL-E between pigs and pig farmers that causes rectal colonization of humans.
Not only contact with farm animals, but also consumption of meat might lead to human ESBL-E carriage. So far, the most often discussed source of ESBL-E from livestock is poultry [Reference Hille5]. Therefore, transmission from poultry to the human consumer was suspected. However, de Been et al. demonstrated by WGS that transmission of ESBL-producing E. coli between humans and poultry via the food chain seems unlikely [Reference de Been4]. They suggested that rather than whole bacteria, ESBL genes are disseminated between animals and humans by ESBL-carrying plasmids. However, it remains unclear how the transmission of these ESBL-carrying plasmids occurs. Consumption of raw contaminated meat might be an important source of transmission since plasmids are most likely destroyed by correct temperature during cooking. To our knowledge, there is no dish containing raw poultry meat in the European culture, but in Germany, for example, there are several dishes that contain raw pork. In 2012, we conducted a case-control study assessing the risk factors for community-associated colonization with ESBL-E in hospital patients [Reference Leistner6]. Among other factors, we found that ESBL-E carriage was associated with frequent consumption of pork. In addition, data from KISS showed high incidences of nosocomial infections with ESBL-E in North Rhine-Westphalia and Thuringia [Reference Leistner3]. Interestingly, these German federal states are associated with high consumption of meat, mainly pork (German National Nutrition Study II, 2008). These findings lead to our ‘food theory’ suggesting that antibiotic resistance might be disseminated by mobile genetic elements following the consumption of raw pork.
Another important issue considered by Fischer et al. is differentiating between colonization and infection. In the literature and in our hospital, CTX-M-15 is described as the most common genotype (58%) in clinical ESBL-E isolates, while CTX-M-1 was found in only 22% of clinical isolates from E. coli bloodstream infections [Reference Leistner7]. The latter ESBL genotype was found by Dohmen et al. in 66% (12/18) of ESBL-E-positive pig-farms [Reference Dohmen2] and was the predominant genotype in patients colonized with ESBL-E (45%, 37/83 patients carrying ESBL-E) [Reference Leistner6]. This leads to the assumption that bacteria with the CTX-M-1 genotype, although found in the community quite frequently, cause infections less frequently. Furthermore, the E. coli ST commonly found in ESBL-E infections is ST131 [Reference Mathers, Peirano and Pitout8]. In the study on rectal colonization with ESBL-E by Dohmen et al., this ST was found in neither pigs nor humans [Reference Dohmen2]. As a consequence, there might be a distinct difference between clinically associated ESBL genotypes and STs and those associated with frequent colonization in the community.
It is still not clear what role animal-to-human-transmission plays in the emergence of ESBL-E infections in humans. By this letter, we hope to stimulate the discussion of three issues. First, close contact with production animals including pigs represents an important risk factor for human ESBL-E carriage in the rectum, not nares. Second, transmission of antibiotic resistance via the food chain is most likely facilitated by ESBL-carrying plasmids and might be more likely for pork than poultry. Third, molecular analyses of ESBL genotypes and STs lead to the hypothesis that ESBL-E, which cause human infections, might originate mainly from sources other than the food chain or production animals. These could presumably include human-to-human-transmission, e.g. in hospitals or by selection after antibiotic consumption.
L.A.D. and R.L. are partially funded by the national interdisciplinary research project RESET financially supported by the German Federal Ministry of Education and Research (BMBF).
Declaration of Interest