Abstract
We evaluated the pet food contained in 30 packages as a potential origin of extended-spectrum cephalosporin-resistant Gram-negative organisms and β-lactamase genes (bla). Live bacteria were not detected by selective culture. However, PCR investigations on food DNA extracts indicated that samples harbored the blaCTX-M-15 (53.3%), blaCMY-4 (20%), and blaVEB-4-like (6.7%) genes. Particularly worrisome was the presence of blaOXA-48-like carbapenemases (13.3%). The original pet food ingredients and/or the production processes were highly contaminated with bacteria carrying clinically relevant acquired bla genes.
TEXT
Enterobacteriaceae possessing β-lactamase genes (bla) encoding extended-spectrum β-lactamase (ESBL) (e.g., CTX-Ms, VEBs), plasmid-mediated AmpC (pAmpC) (e.g., CMYs), and carbapenemase (e.g., Klebsiella pneumoniae carbapenemases [KPCs], OXA-48-like, NDMs) enzymes have become a major threat to public health (1–4). Pets and food-producing animals may be colonized or even infected with these drug-resistant bacteria, possibly acting as a potential reservoir for their spread to humans (5–9).
In line with analyses performed on food products for humans (e.g., retail meat, vegetables) (9–12), this study investigated pet food as a potential source of genes conferring resistance to extended-spectrum cephalosporins (ESCs). For this purpose, we analyzed the presence of ESC-resistant Enterobacteriaceae (ESC-R-Ent), bla genes, and plasmid-specific markers in retail pet food.
In September 2013, 30 pet food (for cats and dogs) packages containing 50 g to 1 kg of mixed wet food with different flavors were purchased from three stores in Bern, Switzerland. The advertised ingredients (content declaration), the brands, and the manufacturers, as indicated on the package labels, are listed in Table 1. For most of the packages, only a minor proportion of the component(s) constituting the overall product was declared in detail. For 73% of the food samples, meat from chicken, duck, and/or turkey was advertised on the label, but this component contributed just 4% to 18% of the final composition. Declarations of the remaining compounds (72% to 96%) were missing. Furthermore, a large proportion of the food mixtures also contained an additional compound(s), like grains, plant-derived products, and fish by-products, that were “not promoted” but listed in the declaration of the composition (data not shown).
TABLE 1.
Epidemiological characteristics and DNA amplicons of relevant antibiotic resistance and plasmid traits from 30 pet food samples
| Sample no. | Pet type | Food component(s) (% declared on label) | Countrya | Store | Brandb | Manufacturerb |
bla gene(s) found |
IncL/M plasmid typingf |
IncF, repFII plasmid typingf | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OXA-48c | CTX-M-1 groupd | CMYe | VEB | TEMf | SHVf | TraU | ParA | RepA | ||||||||
| 101 | Cat | Beef (4), chicken (4) | GER | A | 1 | I | − | ISEcp1-CTX-M-15, CTX-M-3 | − | VEB-4-like | + | + | − | − | + | + |
| 102 | Cat | Veal (4), poultry (4) | GER | A | 1 | I | − | ISEcp1-CTX-M-15, CTX-M-3 | CMY-4 | − | + | + | − | − | + | + |
| 103 | Cat | Salmon (4), trout (4) | GER | A | 1 | I | − | − | − | − | − | − | + | + | + | + |
| 104 | Cat | Poultry (4), liver (4) | GER | A | 1 | I | − | ISEcp1-CTX-M-15, CTX-M-3 | − | − | + | + | − | − | + | + |
| 106 | Cat | Turkey (14), rabbit (8) | GER/NED | A | 2 | I, II | − | ISEcp1-CTX-M-15, CTX-M-3 | − | − | + | + | − | − | + | − |
| 107 | Cat | Beef (14), turkey hearts (8) | GER/NED | A | 2 | I, II | − | − | − | − | − | − | + | − | + | + |
| 109 | Cat | Salmon (4), chicken (4) | EU | A | 3 | III | − | ISEcp1-CTX-M-15, CTX-M-3 | − | − | + | − | + | − | + | + |
| 1010 | Cat | Beef (4) | EU | A | 3 | III | − | ISEcp1-CTX-M-15 | − | − | + | − | − | − | + | + |
| 1011 | Cat | Turkey (4), duck (4) | EU | A | 3 | III | − | − | CMY-4 | − | + | − | + | + | + | + |
| 1013 | Dog | Beef (4) | EU | A | 4 | IV | − | ISEcp1-CTX-M-15, CTX-M-3 | − | − | + | + | + | − | + | + |
| 1014 | Dog | Lamb (4) | EU | A | 4 | IV | − | − | − | − | + | + | + | + | + | + |
| 1015 | Dog | Rabbit (4) | EU | A | 4 | IV | OXA-48 | − | − | VEB-4-like | + | + | − | − | + | + |
| 1016 | Dog | Turkey (4), peas (2)/carrots (2) | LIE | A | 5 | V | − | − | − | − | + | + | + | + | + | + |
| 1017 | Cat | Poultry (4) | DEN | B | 6 | VI | − | − | − | − | − | − | + | − | + | + |
| 1018 | Cat | Chicken (8), green beans (5) | EU | B | 7 | VII | − | − | − | − | + | + | + | + | + | + |
| 1020 | Cat | Turkey (4) | EU | B | 8 | VIII | − | − | − | − | + | + | + | − | + | + |
| 1021 | Cat | Poultry (4) | EU | B | 8 | VIII | − | ISEcp1-CTX-M-15 | − | − | + | + | + | − | − | − |
| 1023 | Dog | Beef (4), chicken (4) | NED | B | 9 | IX | OXA-48 | ISEcp1-CTX-M-15 | − | − | + | − | − | − | + | + |
| 1024 | Dog | Turkey (4), chicken (4) | EU | B | 10 | IV | − | ISEcp1-CTX-M-15 | CMY-4 | − | + | + | + | − | + | + |
| 1025 | Dog | Beef (4), liver (4) | EU | B | 10 | IV | − | ISEcp1-CTX-M-15, CTX-M-3 | CMY-4 | − | + | + | + | − | + | + |
| 1026 | Dog | Poultry (4) | FRA | B | 11 | X | − | ISEcp1-CTX-M-15 | CMY-4 | − | + | + | - | − | + | + |
| 1027 | Cat | Chicken (4) | EU | C | 12 | VIII | − | ISEcp1-CTX-M-15 | − | − | + | + | + | − | + | + |
| 1028 | Cat | Poultry (4) | EU | C | 12 | VIII | − | ISEcp1-CTX-M-15 | − | − | + | + | + | − | + | + |
| 1029 | Cat | Chicken (4), turkey (4) | LIE | C | 13 | V | − | − | − | − | + | + | − | − | + | + |
| 1030 | Cat | Beef (4) | LIE | C | 14 | V | − | − | − | − | + | + | − | − | + | + |
| 1031 | Cat | Poultry (4) | LIE | C | 14 | V | OXA-48-likec | CTX-M-15 | CMY-4 | − | + | − | − | − | + | + |
| 1032 | Cat | Poultry (4) | EU | C | 15 | NA | − | CTX-M-15 | − | − | + | + | + | − | + | + |
| 1033 | Dog | Beef (4) | NED | C | 16 | XI | − | − | − | − | + | − | − | − | + | + |
| 1034 | Dog | Chicken (14), rice (4) | GER/NED | C | 17 | I, II | − | − | − | − | + | − | + | − | + | + |
| 1035 | Dog | Turkey (14), rice (4) | GER/NED | C | 17 | I, II | OXA-48 | − | − | − | + | + | − | − | + | + |
GER, Germany; NED, The Netherlands; FRA, France; LIE, Liechtenstein; DEN, Denmark; EU, European Union (the specific country was not declared).
Brands and manufacturers are coded with 1 through 17 and I through VIII, respectively. These data are given as an indication of brands produced at the same factory (i.e., manufacturer VIII produces for brands 8 and 12) or brands receiving products from more than one manufacturer (i.e., brand 2 has manufacturers I and II). NA, not available due to unreadable labeling.
OXA-48-like sequence contains the following amino acid changes compared to OXA-48 (Trp25Leu, Gln41Leu, Thr99Met, Glu168Gln, and Ser171Ala) or OXA-181 (Trp25Leu, Gln41Leu, Thr99Met, Ala104Thr, and Asp110Asn).
The copresence of CTX-M-3 and CTX-M-15 is suggested by a double pick in the DNA sequence of the CTX-M-1 group amplicon, corresponding to amino acid position 242, discriminating between the CTX-M-3 and CTX-M-15 variants (Asp242 in CTX-M-3 and Gly242 in CTX-M-15 [GenBank accession no. Y10278 and AY044436, respectively]). By PCR analysis, most of the blaCTX-M-15 genes were associated with ISEcp1.
By PCR analysis, no blaCMY-4 genes were associated with an upstream ISEcp1 element.
+, PCR-positive amplicon; −, PCR-negative amplicon. Amplicons were not sequenced.
A portion of the food content (about 10 g each) was enriched in Luria-Bertani broth plus 20 μg/ml ampicillin (Sigma-Aldrich) at 37°C overnight. From there, an aliquot of 50 μl was streaked out on MacConkey, Drigalski plus cefotaxime (1.5 μg/ml), and MacConkey plus ceftazidime (2 μg/ml) agar plates (bioMérieux). ESC-R-Ent or other cephalosporin-resistant bacteria were not detected by selective cultivation in any of the 30 samples.
DNA isolation was performed with the QIAamp DNA minikit (Qiagen) using about 10 g of food from each package. Each sample was examined as previously described by standard PCR and DNA sequencing for the presence of bla genes (blaTEM, blaSHV, blaCTX-M-1 group, blaCTX-M-9 group, blaVEB, blaCMY, blaOXA-48-like, blaIMP, blaVIM, blaNDM), insertion sequence ISEcp1, and plasmid types (IncA/C, IncN, IncI1, IncF, and IncL/M and the genes parA, repA, and traU) (1, 13–16).
As shown in Table 1, 16 samples were positive for blaESBL genes: 14 samples harbored blaCTX-M-1 group, one was positive for blaCTX-M-1 group and blaVEB, and one had only blaVEB. In seven samples, the DNA sequence of the blaCTX-M-1 group amplicon led us to suspect the presence of both the blaCTX-M-3 and the blaCTX-M-15 genes. This was due to the observation of a double peak in the DNA sequence corresponding to amino acid position 242, discriminating between the CTX-M-3 (Asp242) and CTX-M-15 (Gly242) variants.
It was not possible to determine the complete genetic environments of the amplified genes because the pet food processing and heat treatment steps used to sterilize the food likely caused a partial fragmentation of the bacterial DNA, and it was therefore not possible to amplify targets larger than 800 to 1,000 bp. However, for many samples, a positive amplification was detected for the ISEcp1-blaCTX-M intergenic region (Table 1), with the expected distance of 48 bp from the start codon of the blaCTX-M-15 gene (17). This result demonstrates that blaCTX-M-15 was an acquired, presumably plasmid-located resistance gene. Conversely, the blaCTX-M-3 gene may be presumably derived from pet food contaminated with Kluyvera species progenitors, where it is intrinsic (18).
The two blaVEB-positive amplicons were blaVEB-4-like and were very likely acquired resistance genes, since this gene has never been described in a progenitor species. We recently identified blaVEB-6, a blaVEB-4-like variant, in a Proteus mirabilis isolate from poultry meat in Switzerland (10).
Six samples (20%) were positive for blaCMY-4 (Table 1). Sequencing analyses indicate that blaCMY-4 cannot be attributed to the chromosomal gene found in the ancestral species (Citrobacter freundii) generating this family of pAmpCs (i.e., no 100% DNA homology) (19). Conversely, it has always been identified on plasmids and is usually found in Enterobacteriaceae isolates of human origin (3) and in retailed chicken meat (20, 21).
Three food samples were contaminated with blaOXA-48 (Table 1). In particular, DNA sequences of the amplicons revealed that they were 100% identical to the plasmid-mediated blaOXA-48 genes usually identified on IncL/M plasmids circulating in Enterobacteriaceae (13). These sequences showed three nucleotides of difference with the intrinsic blaOXA-48-like genes identified in Shewanella species progenitors. Therefore, the genes found in the food samples were likely acquired resistance genes. Conversely, in a fourth sample, a novel blaOXA-48-like variant was identified (see Table 1 footnotes), and this might have derived from an unknown progenitor contaminating the food. Unfortunately, because of the fragmentation of the bacterial DNA, it was not possible to determine the genetic environments (e.g., Tn1999-like) of the four blaOXA-48-like genes (13). In particular, no amplification was detected when a primer lending into the blaOXA-48-like gene (OXA-48RVout [5′-TCATACGTGCCTCGCCAATT-3′]) was combined with a primer specific for the genetic vicinity of its 5′ end (IS1999RVout [5′-GGATATTGGCTTCGCGCATC-3′]).
Investigation of the plasmid types showed that most of the samples were contaminated with IncL/M and IncF plasmids, while IncA/C, IncN, and IncI1 plasmids were not present. Remarkably, all the food samples were positive for one or more of the targets of the PCR-typing scheme proposed to detect the IncL/M plasmid pOXA48 (repA, traU, and parA; Table 1) (13, 16). All but two samples were positive for the repFII replicon, suggesting a high prevalence of IncF plasmids, which are widely diffused in Enterobacteriaceae and very often associated with the blaCTX-M-15 gene (22).
Overall, our data indicate that a relevant contamination of bla genes was detected in the pet food, suggesting a reservoir of antibiotic resistance bacteria in the production chain preceding the final packaging. Hence, the source(s) from which the pet food acquired the resistance genes remains to be elucidated. Potential derivations may be the original food components themselves or other ingredients that were added to the mixture, as well as the various steps in the food production process. When looking at the designated ingredients, no clear correlations were detected at the level of the different bla genes to the respective food components. The comparison of the detected resistance genes to the respective countries of production and to the factories that produced the different brands gave no clear correlations. This is partially due to the fact that, for almost half of the packages, it was not stated from which country within the European Union the respective products were manufactured (Table 1).
It is particularly relevant that the resistance genes detected in this study (e.g., blaOXA-48, blaCTX-M-15, blaVEB-4-like, and blaCMY-4) are those typically found in human rather than in animal settings, while it would have been expected to find other gene variants such as blaCTX-M-1 and blaCMY-2 (6). This observation is also supported by the fact that no plasmids demonstrated to be prevalent in food-producing animals and in food of animal origin (e.g., the IncN and IncI1 plasmids associated with blaCTX-M-1 or the IncA/C and IncI1 plasmids associated with blaCMY-2) were found in the food (6, 10, 12, 23, 24). However, we emphasize that the detection of blaOXA-48 is worrisome due to its epidemiological and clinical impact (25). The blaOXA-48 gene is usually detected in humans (3, 26), but blaOXA-48-possessing Enterobacteriaceae isolates were found recently in pets (27).
In conclusion, our data point toward a likely environmental or human-made contamination source(s) that may have taken place during the various steps of the production process of the pet food. Since bacteria were killed during the preservation process (heat treatment step), and contaminating bacterial DNA was highly fragmented, it is unlikely that these resistance genes were transmitted among the bacterial flora in animals fed with this food. However, it is important to trace the source of the drug-resistant bacteria and to prevent the contamination of pet food. These results should raise awareness of the importance of identifying the contamination source(s) because it might be an original niche of clinically important multidrug-resistant bacteria and associated mobile genes.
ACKNOWLEDGMENTS
This work was supported by internal funds of the Institute of Infectious Diseases of Bern (IFIK) and partially by grant 1.12.06 (2012-2014) from the Swiss Veterinary Federal Office (BVET). Salome N. Seiffert is a Ph.D. student supported by the IFIK and the BVET.
Footnotes
Published ahead of print 4 August 2014
REFERENCES
- 1.Seiffert SN, Hilty M, Kronenberg A, Droz S, Perreten V, Endimiani A. 2013. Extended-spectrum cephalosporin-resistant Escherichia coli in community, specialized outpatient clinic and hospital settings in Switzerland. J. Antimicrob. Chemother. 68:2249–2254. 10.1093/jac/dkt208 [DOI] [PubMed] [Google Scholar]
- 2.Pitout JD. 2013. Enterobacteriaceae that produce extended-spectrum β-lactamases and AmpC β-lactamases in the community: the tip of the iceberg? Curr. Pharm. Des. 19:257–263. 10.2174/138161213804070348 [DOI] [PubMed] [Google Scholar]
- 3.Seiffert SN, Perreten V, Johannes S, Droz S, Bodmer T, Endimiani A. 2014. OXA-48 carbapenemase-producing Salmonella enterica serovar Kentucky isolate of sequence type 198 in a patient transferred from Libya to Switzerland. Antimicrob. Agents Chemother. 58:2446–2449. 10.1128/AAC.02417-13 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Nordmann P, Naas T, Poirel L. 2011. Global spread of carbapenemase-producing Enterobacteriaceae. Emerg. Infect. Dis. 17:1791–1798. 10.3201/eid1710.110655 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Verraes C, Van Boxstael S, Van Meervenne E, Van Coillie E, Butaye P, Catry B, de Schaetzen MA, Van Huffel X, Imberechts H, Dierick K, Daube G, Saegerman C, De Block J, Dewulf J, Herman L. 2013. Antimicrobial resistance in the food chain: a review. Int. J. Environ. Res. Public Health 10:2643–2669. 10.3390/ijerph10072643 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Seiffert SN, Hilty M, Perreten V, Endimiani A. 2013. Extended-spectrum cephalosporin-resistant Gram-negative organisms in livestock: an emerging problem for human health? Drug Resist. Updat. 16:22–45. 10.1016/j.drup.2012.12.001 [DOI] [PubMed] [Google Scholar]
- 7.Timofte D, Dandrieux J, Wattret A, Fick J, Williams NJ. 2011. Detection of extended-spectrum-β-lactamase-positive Escherichia coli in bile isolates from two dogs with bacterial cholangiohepatitis. J. Clin. Microbiol. 49:3411–3414. 10.1128/JCM.01045-11 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Sallem RB, Gharsa H, Slama KB, Rojo-Bezares B, Estepa V, Porres-Osante N, Jouini A, Klibi N, Saenz Y, Boudabous A, Torres C. 2013. First detection of CTX-M-1, CMY-2, and QnrB19 resistance mechanisms in fecal Escherichia coli isolates from healthy pets in Tunisia. Vector Borne Zoonotic Dis. 13:98–102. 10.1089/vbz.2012.1047 [DOI] [PubMed] [Google Scholar]
- 9.Donati V, Feltrin F, Hendriksen RS, Svendsen CA, Cordaro G, Garcia-Fernandez A, Lorenzetti S, Lorenzetti R, Battisti A, Franco A. 2014. Extended-spectrum-β-lactamases, AmpC beta-lactamases and plasmid mediated quinolone resistance in Klebsiella spp. from companion animals in Italy. PLoS One 9:e90564. 10.1371/journal.pone.0090564 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Seiffert SN, Tinguely R, Lupo A, Neuwirth C, Perreten V, Endimiani A. 2013. High prevalence of extended-spectrum-cephalosporin-resistant Enterobacteriaceae in poultry meat in Switzerland: emergence of CMY-2- and VEB-6-possessing Proteus mirabilis. Antimicrob. Agents Chemother. 57:6406–6408. 10.1128/AAC.01773-13 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Doi Y, Paterson DL, Egea P, Pascual A, Lopez-Cerero L, Navarro MD, Adams-Haduch JM, Qureshi ZA, Sidjabat HE, Rodriguez-Bano J. 2010. Extended-spectrum and CMY-type β-lactamase-producing Escherichia coli in clinical samples and retail meat from Pittsburgh, USA and Seville. Spain. Clin. Microbiol. Infect. 16:33-38. 10.1111/j.1469-0691.2009.03001.x [DOI] [PubMed] [Google Scholar]
- 12.Voets GM, Fluit AC, Scharringa J, Schapendonk C, van den Munckhof T, Leverstein-van Hall MA, Stuart JC. 2013. Identical plasmid AmpC β-lactamase genes and plasmid types in E. coli isolates from patients and poultry meat in the Netherlands. Int. J. Food Microbiol. 167:359–362. 10.1016/j.ijfoodmicro.2013.10.001 [DOI] [PubMed] [Google Scholar]
- 13.Poirel L, Bonnin RA, Nordmann P. 2012. Genetic features of the widespread plasmid coding for the carbapenemase OXA-48. Antimicrob. Agents Chemother. 56:559–562. 10.1128/AAC.05289-11 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Bonnin RA, Nordmann P, Carattoli A, Poirel L. 2013. Comparative genomics of IncL/M-type plasmids: evolution by acquisition of resistance genes and insertion sequences. Antimicrob. Agents Chemother. 57:674–676. 10.1128/AAC.01086-12 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Dallenne C, Da Costa A, Decre D, Favier C, Arlet G. 2010. Development of a set of multiplex PCR assays for the detection of genes encoding important β-lactamases in Enterobacteriaceae. J. Antimicrob. Chemother. 65:490–495. 10.1093/jac/dkp498 [DOI] [PubMed] [Google Scholar]
- 16.Carattoli A, Bertini A, Villa L, Falbo V, Hopkins KL, Threlfall EJ. 2005. Identification of plasmids by PCR-based replicon typing. J. Microbiol. Methods 63:219–228. 10.1016/j.mimet.2005.03.018 [DOI] [PubMed] [Google Scholar]
- 17.Lartigue MF, Poirel L, Nordmann P. 2004. Diversity of genetic environment of bla(CTX-M) genes. FEMS Microbiol. Lett. 234:201–207. 10.1111/j.1574-6968.2004.tb09534.x [DOI] [PubMed] [Google Scholar]
- 18.Rodriguez MM, Power P, Radice M, Vay C, Famiglietti A, Galleni M, Ayala JA, Gutkind G. 2004. Chromosome-encoded CTX-M-3 from Kluyvera ascorbata: a possible origin of plasmid-borne CTX-M-1-derived cefotaximases. Antimicrob. Agents Chemother. 48:4895–4897. 10.1128/AAC.48.12.4895-4897.2004 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Jacoby GA. 2009. AmpC beta-lactamases. Clin. Microbiol. Rev. 22:161–182. 10.1128/CMR.00036-08 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Zhao S, White DG, McDermott PF, Friedman S, English L, Ayers S, Meng J, Maurer JJ, Holland R, Walker RD. 2001. Identification and expression of cephamycinase blaCMY genes in Escherichia coli and Salmonella isolates from food animals and ground meat. Antimicrob. Agents Chemother. 45:3647–3650. 10.1128/AAC.45.12.3647-3650.2001 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Vogt D, Overesch G, Endimiani A, Collaud A, Thomann A, Perreten V. 28 April 2014. Occurrence and genetic characteristics of third-generation cephalosporin-resistant Escherichia coli in Swiss retail meat. Microb. Drug Resist. 10.1089/mdr.2013.0210 [DOI] [PubMed] [Google Scholar]
- 22.Villa L, Garcia-Fernandez A, Fortini D, Carattoli A. 2010. Replicon sequence typing of IncF plasmids carrying virulence and resistance determinants. J. Antimicrob. Chemother. 65:2518–2529. 10.1093/jac/dkq347 [DOI] [PubMed] [Google Scholar]
- 23.Endimiani A, Rossano A, Kunz D, Overesch G, Perreten V. 2012. First countrywide survey of third-generation cephalosporin-resistant Escherichia coli from broilers, swine, and cattle in Switzerland. Diagn. Microbiol. Infect. Dis. 73:31–38. 10.1016/j.diagmicrobio.2012.01.004 [DOI] [PubMed] [Google Scholar]
- 24.Leverstein-van Hall MA, Dierikx CM, Cohen Stuart J, Voets GM, van den Munckhof MP, van Essen-Zandbergen A, Platteel T, Fluit AC, van de Sande-Bruinsma N, Scharinga J, Bonten MJ, Mevius DJ, National ESBL Surveillance Group 2011. Dutch patients, retail chicken meat and poultry share the same ESBL genes, plasmids and strains. Clin. Microbiol. Infect. 17:873–880. 10.1111/j.1469-0691.2011.03497.x [DOI] [PubMed] [Google Scholar]
- 25.Guerra B, Fischer J, Helmuth R. 2014. An emerging public health problem: acquired carbapenemase-producing microorganisms are present in food-producing animals, their environment, companion animals and wild birds. Vet. Microbiol. 171:290–297. 10.1016/j.vetmic.2014.02.001 [DOI] [PubMed] [Google Scholar]
- 26.Poirel L, Potron A, Nordmann P. 2012. OXA-48-like carbapenemases: the phantom menace. J. Antimicrob. Chemother. 67:1597–1606. 10.1093/jac/dks121 [DOI] [PubMed] [Google Scholar]
- 27.Stolle I, Prenger-Berninghoff E, Stamm I, Scheufen S, Hassdenteufel E, Guenther S, Bethe A, Pfeifer Y, Ewers C. 2013. Emergence of OXA-48 carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in dogs. J. Antimicrob. Chemother. 68:2802–2808. 10.1093/jac/dkt259 [DOI] [PubMed] [Google Scholar]