Antibiotic Resistance Of Bacteria A Growing Threat For Animals And Public Health

The occurrence of resistant bacteria in animals usually arouses interest and even provokes anxiety, mainly due to the potential risk to people or to the public health [3, 45]. Bacteria living in animals do not live in isolation and remain in close relationships with other microorganisms, as well as the host itself, or microorganisms of other living organisms and ecosystems. This may result in the mutual transfer of genes and the acquisition of new features by the recipients, which determine their pathogenic nature and allow survival in extreme conditions. Comparison of the antibiotic resistance genes found in the microorganisms living in humans and animals indicates that many of them are identical and only few are present exclusively in bacteria that live in humans or certain species of animals [51]. In recent decades, the number of companion animals, i. e. dogs, cats or horses, has increased significantly. The social function of these animals has also changed and they have often been promoted to the role of family members, which resulted in the improvement of their welfare and closer relationships with their owners. On the other hand, close contact between human and companion or food-producing animals, promotes mutual exchange of microbionts through direct contact, as a result of coming into contact with excretions and secretions and as a consequence of animals sneezing, coughing or licking. Pollution of the natural environment will additionally contribute to the spread of microorganisms in the immediate environment of people and animals. Concurrently, the ongoing exchange of genetic material between the close and further related microorganisms, including genes located in bacterial chromosomes and plasmids, especially those located in mobile structures such as transposons, integrons, cassettes etc., will contribute to the formation of cultures adapted to survive in unfavorable conditions, as well as interactions within the network of interdependence with host cells on the host themselves [40, 51]. Concerns about the impact of microorganisms living in animals on the human health, including the spread of antibiotic resistance, are therefore justified, although such risk should be reviewed in terms of the species of the animal, its type of use, living conditions or care. One must also consider that the direction of transfer of bacteria resistant to antibiotics, including multidrug resistant strains, may be reversed, i.e. from human to animal. A common risk factor is the acquisition of resistance by bacteria living in human and animals as a result of the use of antibiotics, especially in unjustified situations, incorrect selection or dosing [27, 35, 45].

The aim of this study is to draw attention to the phenomenon of bacterial resistance in animals, which is as common as in human medicine, and to the resulting consequences in terms of therapy, animal welfare and threats to humans. Selected data on genes and their clusters encoding antibiotic resistance are also presented, as well as resistance spreading mechanisms among animal reservoir bacteria, in particular staphylococci and Gram-negative rods with zoonotic potential. General information on the resistance of zoonotic and indicator bacteria found in food-producing animals is presented on the basis of the European Food Safety Authority (EFSA) report.

In affluent societies, many species of companion animals are maintained, both for social reasons and for sport purposes. In the European Union, dogs are present in 25% of households, often with the rights of a family member. Many people have horses, which are particularly liked by humans and are often worshipped [40]. Consequently, owners of companion animals also expect high standards of veterinary care for their pupils, including the therapies using most advanced medical achievements, both on an outpatient and inpatient level. These animals are therefore subjected to intensive veterinary care. Advanced surgical procedures are also carried out on them, which are accompanied by frequent administration of antibiotics. The observed consequences are identical to those found in human medicine, such as the growing problem of hospital-acquired infections, the selection of epidemic multidrug-resistant strains or the exhaustion of therapeutic options [6, 17, 51]. This is confirmed by the growing number of reports on environmental and hospital-acquired Staphylococcus aureus (MRSA) infections, infections by Gram-negative strains resistant to the third generation of cephalosporins, or even carbapenems in dogs and horses and methicillin-resistant Staphylococcus psudintermedius (MRSP) infections in dogs [6, 17, 36, 50, 53]. Deep, systemic and postoperative wound infections with the aforementioned microorganisms pose a direct threat to animal life and give veterinarians a moral choice whether to euthanise the animal or use an inadvisable alternative, which are antibiotics such as glycopeptides, oxazolidinones or carbapenems, critical for the treatment of diseases caused by multidrug-resistant bacteria in humans. On one hand, the introduction of these drugs to animal therapy may contribute to the growth and spread of antibiotic resistance; however, on the other hand, we face the dilemma of euthanising an animal when there is a possibility of effective treatment. As mentioned earlier, many animal owners treat them as family members, for others they are necessary for the day-to-day functioning, e.g. for disabled people; therefore, losing an animal is a serious emotional experience [1]. Resistance of bacteria, which cause infections in companion animals also significantly increases the cost of treatment. For example, in a dog, treatment of bacteremia caused by MRSP with linezolid generated costs of SEK 176,000 just for the medicine alone, which is approximately USD 25,600 [18]. In the case of contamination of clinics and animal hospitals with multidrug-resistant bacteria, the costs related to periodic closure of buildings, sometimes new investments and structural alterations, decontamination of rooms, introduction of asanitary regime and advanced methods of preventing the spread of infections, as well as costs of laboratory tests should be added to this. One should also keep in mind the possible loss of trust in doctors by the clients, etc. [3]. There is also a risk of transmission of the infection from animals to humans, e.g. as in the case of MRSA, including carers working with them, or veterinarians and auxiliary personnel [6]. The problem of using antibiotics in the rearing and therapy of food-producing animals is slightly different. This issue is varies significantly depending on the part of the world and the country. Most of it comes down to the treatment of infectious diseases caused by bacteria to ensure the economic viability of animal production. Depending on the species of food-producing animals, the medicines are administered on an outpatient basis – individually as well as en masse to every animal in the herd, most often orally with food or drinking water [32]. Old first-line drugs, such as penicillin commonly used for the treatment of mastitis in cows, penicillin and tetracycline for the treatment of shipping fever, or trimethoprim-sulfonamide used to treat diarrhea in piglets, are displaced by newer chemotherapeutics, such as fluoroquinolones, third and fourth generation cephalosporins, or new generation macrolides and lincosamides. As a consequence, the above contributes to a broader selective pressure and the spread of antibiotic resistance. Just as in the treatment of companion animals, there is very little difference in the medicines used for treating people and livestock [32, 33, 57]. Recommendations regarding the selection of antimicrobial drugs intended for various animal species are issued in the form of EU documents, as well as by European and national government administration organisations and veterinary medicine associations [10, 16, 19].

The consequences of antibiotic resistance of infection causing bacteria in animals remain the same as in human medicine. Ineffective treatment, regardless of whether it affects a person or an animal, results in patient’s suffering, an increase in medical costs and general social costs resulting from the loss of a ‘family member, low productivity, incapacity to work, etc. Moreover, the increase and spread of antibiotic resistance limits or even eliminates the available treatment options [3, 14, 66].

Staphylococci are a part of physiological microbiota and are commonly found on the skin and mucous membranes of humans and animals. Their relationships with many other components of various ecosystems are close and manifold. As a result, they can acquire genes, including those responsible for multiple drug resistance, even without the direct selective pressure of a particular antibiotic [51]. The presence of plasmids (Table I) carrying different resistance genes was confirmed in bacteria in many ecosystems [51, 66, 70, 72, 73]. The lsa(E) gene, which determines cross-resistance to pleuromutilins, lincosamides and streptogramin A occurs in Enterococcus spp. In turn, in Lactobacillus spp. and Streptococcus spp., the erm(T) gene was detected, which encodes resistance to macrolides, lincosamides and streptogramin B, whereas the cfr gene, responsible for the cross-resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins and streptogramins, occurs in Bacillales. Therefore, the use of antibiotics against one type of bacteria may lead to a selection of strains resistant to the given drug, but also result in strains that carry genes encoding resistance to other antimicrobial drugs, i.e. to co-selection of multidrug-resistant strains [27].

The resistance to methicillin (which means resistance to all β-lactam antibiotics) associated with the mecA gene has been detected initially in S. aureus strains found in humans and cattle. At present, it is also detected in strains isolated from companion animals, free-living animals and many species of farm animals [6, 25, 29, 41]. The mecA homolog, referred to as mecC, is a fragment of the mec class E gene complex blaZ-mecC-mecR1-mecI, which is a part of the mobile genomic island called staphylococcal cassette chromosome mec (SCCmec). The aforementioned gene is usually found in the type XI of the SCCmec [68]. Currently, three new mecC allotypes are known, i.e. mecC1, mecC2 and mecC3, which display over 92% homology. The gene occurs in S. aureus and coagulase-negative Staphylococcus spp. (CoNS), isolated from humans and animals [30]. In recent years, the mecB gene has been detected in a cefoxitin-resistant S. aureus strain isolated from a human. It is a part of the methicillin resistance gene complex located on the Tn6045 transposon, originally occurring in Macrococcus caseolyticus [2]. Staphylococcus aureus in companion animals occurs relatively infrequently (in dogs and cats from 0 to 6%, in horses from 0 to 7%) and is responsible for a number of disease processes affecting the skin and soft tissues. It is often the cause of postoperative complications, as well as urinary tract infections, pulmonary infections, etc. It can also be a cause of hospital-acquired infections, as well as infections acquired in places where animals are farmed [23, 31, 56, 58, 63]. The majority of MRSA strains isolated from small animals are identical to the human strains, healthcare-associated (HA-MRSA) strains classified to sequence types such as ST254, ST8 or ST22 [65]. MRSA ST398, known as the livestock-associated clone (LA-MRSA), was also found. It is usually characterised by a multiple drug-resistant phenotype. In addition to resistance to β-lactams, it displays resistance to tetracyclines, macrolides, lincosamides and streptogramins [21, 59]. Detection of the so-called “human” clones in animals and “animal” clones in humans may indicate the mutual exchange of said staphylococci between different animal species and humans. However, the transmission of ST225, ST22 and other “human” sequence types generally occurs from humans to animals. These staphylococci do not usually adapt to animals, but their temporary presence makes them a potential reservoir of the aforementioned bacteria [6, 38, 64].

Methicillin-resistant S. pseudintermedius (MRSP) strains are more relevant in veterinary medicine than MRSA, because as an opportunistic microbiota, this species of staphylococci is commonly found on the skin and the mucous membranes of cats and dogs. MRSP is a good example of how drug resistance contributes to the failure of antibiotic therapy in the treatment of small animals. Staphylococcus pseudintermedius is usually responsible for many lesions (frequency of infections ranges from 8.7 to 28%), including purulent lesions on the skin, otitis externa, wounds infections, urinary tract, respiratory system, joints, oral cavity, peritoneum, hospital-acquired nosocomial infections or sepsis [7]. Similarly to S. aureus, methicillin-resistant strains of S. pseudintermedius appeared very quickly. They were phenotypically identified for the first time in the mid-1980’s. The strains bearing the mecA gene, which determines the above-mentioned characteristic were isolated in the USA in 1999, and in Europe only in 2005 [20, 28]. Since then, the methicillin-resistant S. pseudintermedius strains have become a serious problem in the antibiotic therapy of diseases caused by these bacteria in dogs [8, 36]. MLST (Multilocus Sequence Typing) has revealed the global domination of several multiple drug-resistant clonal complexes (CC), which include several sequence types (ST). Previously, CC71 and CC258 represented by sequence type 71 (ST71) and 258 (ST258) dominated in Europe, CC68 represented by ST68 in the US, and CC45 and CC112 represented by ST45 and ST112 in Asia. CC71 strains are characterised by nearly 100% resistance to enrofloxacin and nearly 100% resistance to erythromycin and clindamycin. Approximately 70% of the strains show no sensitivity to trimethoprim + sufonamide and almost 50% of them show no sensitivity to chloramphenicol. In contrast, the sensitivity to amikacin is found in about 90% of strains. CC258 is usually characterised by resistance to tetracycline, trimethoprim + sufonamide, clindamycin and erythromycin (90% of strains). Only a few per percent of strains display resistance to enrofloxacin, amikacin and gentamycin. CC45 is characterised by 100% resistance to enrofloxacin and erythromycin and nearly 100% resistance to clindamycin, tetracycline, chloramphenicol and gentamicin. Furthermore, approximately 80% of the strains do not show any sensitivity to trimethoprim + sufonamide. Similarly to CC71, it is sensitive to amikacin (approximately 2% of resistant strains) [42]. Currently, a greater diversity in the occurrence of MRSP clonal complexes in a given area of the world can be observed and similarly to the USA, both CC68 and CC71, as well as CC84 are found. However, different profiles of antibiotic resistance of the strains of a given clonal complex found on different continents are noticed [11, 42, 60, 68]. In Poland, the research conducted by Kizerwetter-Świda et al. demonstrated that among the MRSP, ST71 strains with type II–III SCCmec dominated up to 2015. However, in recent years, strains of the new clonal complex – CC551 represented by ST551 with SCCmec, have appeared and seem to be displacing the earlier clones [26].

The limitation of therapeutic options associated with the occurrence of methicillin resistance in staphylococci and the accompanying resistance to other classes of antibiotics makes it necessary to search for new chemotherapeutic agents. Enrofloxacin, as well as marbofloxacin and orbifloxacin, are fluoroquinolone drugs approved for use in the veterinary medicine. Pradofloxacin, a new third-generation fluoroquinolone with a broad spectrum of activity against Gram-positive and Gram-negative bacteria, including anaerobic bacteria, has also been approved for treatment of bacterial infections in dogs and cats in Europe. This drug, in contrast to older fluoroquinolones, demonstrates the same affinity for both enzymes involved in the DNA replication, i.e. topoisomerase II (gyrase) and topoisomerase IV. The low value of MIC of pradofloxacin MIC compared to other fluoroquinolones in relation to many veterinary pathogens, including S. pseudintermedius, which indicated a greater effectiveness of this antibiotic in combating infections with the aforementioned species of staphylococci in dogs and cats. However, the research on MRSP susceptibility to pradofloxacin conducted by Kizerwetter-Świda et al. demonstrated that over 94% of the researched strains demonstrated resistance [24]. This is due to a single mutation in the gyrA gene (DNA gyrase) and a single mutation in the grlA gene (topoisomerase IV) resulting in the conversion of serine to leucine at position 84 and serine to isoleucine at position 80 in the encoded proteins, respectively. The results of the cited research demonstrated that only single strains of MRSP can be suscetible to pradofloxacin and consequently to other fluoroquinolones. This practically limits the use of fluoroquinolones in the therapy of diseases caused by methicillin-resistant staphylococci [24].

Many types of Gram-negative rods are a part of the natural human and animal ecosystems, such as the gastrointestinal tract, the genitourinary tract or the respiratory system. The emergence of multidrug-resistant strains, including opportunistic species, first detected in humans, highlighted the risks associated with the failure of therapy and the spread of resistance. It soon became clear that the resistance of these bacteria is to a large extent determined by the production of β-lactamases, which are often derivatives of TEM-1, TEM-2 or SHV-1, as well as CTX-M, VEB, PER, BES and OXA, characterised by an extended substrate spectrum (extended-spectrum beta-lactamases, ESBL). OXA β-lactamase also has the characteristics of carbapenemases classified as class D, CHDL type (carbapenem-hydrolysing class D β-lactamase) [39, 62]. The first report on the isolation of cefotaxime-resistant E. coli strains producing CTX-M-type ESBL from dog’s faeces took place in Japan in 1986 and the isolation of SHV-12-type producing strains from the urinary tract of this animal species took place in Spain in 1998 [34, 54]. Subsequently, the data on the occurrence of TEM-type and SHV-type β-lactamases producing E. coli strains in healthy dogs and strains with chromosome carrying a gene responsible for the overproduction of AmpC β-lactamase [4, 5] have appeared. Since then, the number of publications on the occurrence of ESBL and AmpC-producing Gram-negative rods in companion animals has increased significantly, and the CTX-M, TEM or SHV enzymes detected in them represent different families within the ESBL group. Some of their clones, however, caused epidemics and even pandemics in humans and animals, such as the multidrug-resistant E. coli ST131 clone [46]. Isolates of these bacteria demonstrated the same virulence genotype, drug resistance pattern, presence of plasmids and PFGE profile [43]. Infections caused by bacteria producing the above-described β-lactamase in dogs and cats were documented considerably late, not until 2009, on the basis of the research on strains from the years 2004–2006, which demonstated resistance to fluoroquinolones. Concurrently, the identity of highly virulent E. coli clones – O25b:H4 ST131 and O25a ST648-D, which are found in poultry and produce the CTX-M-9 β-lactamase, and clinical isolates of these bacteria from humans [37, 61] was confirmed. The E. coli O25b ST131 strain was also found in the faeces of hospitalised dogs [22]. Other sequence types of ESBL producing E. coli, e.g. ST156, ST405, ST410 and the aforementioned ST 648 were found in both companion animals and humans [12].

Publications from 2013 report that companion animals with NDM-1 (New Delhi metallo-beta-lactamase) carbapenemase-producing E. coli strains were found in the US and those with a NDM-5 type were found in Finland [44, 52]. In Europe, OXA-48 carbapenemase-producing E. coli and Klebsiella pneumoniae strains were found in dogs [53]. In 2016, a case of the transmission of CTX-M-15-producing, colistin-resistant E. coli strains from companion animals was described [71]. The research on the occurrence of multidrug-resistant strains of E. coli involved in infections in dogs and cats in Poland was conducted by Rzewuska et al. in 2015 [48]. As a result, it was demonstrated that as much as 66.8% of isolates were multidrug-resistant, and moreover, a statistically significant increase in the resistance took place over the years 2007–2013. However, further research demonstrated that only 3.4% of strains produced ESBL [49]. In these strains bla_SHV12, bla_CTX-M-15 and bla_TEM-116, encoding respectively SHV-12, CTX-M-15 and TEM-116 β-lactamases [49], were found.

Psudomonas spp. and Acinetobacter spp. are Gramnegative rods commonly found as components of microbiota in animals. These bacteria are characterised by multidrug-resistance, have a zoonotic potential, and are also a potential reservoir of resistance genes. Pseudomonas aeruginosa are often responsible for otititis externa and otitis media, pyoderma or nosocomial infections. Multidrug resistance is a characteristic feature of these bacteria, although in contrast to strains found in humans, so far there is no pandrug-resistance (PDR) phenomenon in isolates of animal origin. Approximately 7% of isolates display resistance to gentamycin and 3% of isolates are resistant to amikacin. Resistance to fluoroquinolones includes 16% resistance to ciprofloxacin, 31% to enrofloxacin and 52% to orbifloxacin [47]. Acinetobacter baumannii live on the skin and in the oral mucosa of dogs. Little data on the infection with these bacteria in animals is available, and the existing research refers to nosocomial infections of the renal and respiratory systems or bactermia in dogs, in which the mortality rate reached 47%. A. baumannii isolates from dogs and horses demonstrate phenotypic and genotypic traits identical to those of human isolates [15]. In 2014, a case of a cat with a urinary tract infection caused by a multidrug-resistant A. baumannii strain, which produces OXA-23 β-lactamase responsible for the carbapenem resistance, was described. This strain belonged to the same clonal line (ST-2) as the strains involved in human infections [44].

The resistance of selected microorganisms to chemotherapeutics is constantly monitored in the European Union countries, on the basis of the 2003/99/EC directive [13]. It concerns mainly the zoonotic bacteria, other selected microorganisms found in livestock, which contaminate food and feed, as well as indicator bacteria. The results of tests conducted using routine methods and, to a lesser extent, using specific methods, are submitted to the European Food Safety Authorities (EFSA) and the European Center for Disease Prevention and Control (ECDC) by the individual member countries in the form of an annual report. These institutions analyse the data, which is then presented as reports in the EFSA Journal published by John Wiley and Sons Ltd. The latest report was published in 2019 and concerns the data from 2017, which was submitted by the 28 EU member countries and other European countries. In the part of the analysis concerning the resistance, the report mainly refers to campylobacter spp. and Salmonella enterica rods from humans and selected animal species. However, in the section concerning indicator bacteria, it refers to commensal E. coli strains isolated from fattening pigs and calves under 1 year of age, as well as the meat samples obtained from these animals. The data on the occurrence and the antibiotic resistance of methicillin-resistant S. aureus strains were also included to a lesser extent [55].

Based on the analysis of the data contained in the previous and current reports, a steady trend in the increase of resistance of zoonotic bacteria can be observed. The widespread ciprofloxacin resistance exhibited by Campylobacter coli strains isolated from fatteners and Campylobacter jejuni strains isolated from cattle (over 52% of resistant strains), which a drug of critical significance to human health, is alarming, as it is used for the treatment of campylobateriosis. Resistance to erythromycin (the second drug of critical significance for humans due to the above) was maintained at a low level (1.3%) among C. jejuni strains isolated from cattle and C. coli strains found in broilers. Resistance to this drug was found in a higher percentage in C. coli isolated from pigs and turkeys (15.5% of strains). The rapid increase in the resistance of C. jejuni and C. coli to gentamycin, found in up to 65% of C. coli isolates from pigs, is an adverse phenomenon observed in some countries.

Fluoroquinolones resistance of Salmonella rods isolated from pig and bovine carcasses appears to be negligible, although the percentage of resistant strains varies from one country to another, thus 42.3% of strains in Italy and 20.7% in Spain demonstrated resistance to ciprofloxacin. So far, no high degree of fluoroquinolone resistance, i.e. demonstrating MIC ≥ 4 mg/L, has been found among animal isolates of these bacteria. Many strains, in particular ones isolated from pig carcasses and from pigs, are characterised by multi-drug-resistance reaching up to 51.3% of isolates. This state is mainly influenced by the monophasic Salmonella Typhimurium strains, which constitute 56.7% of multidrug-resistant Salmonella isolated from pig carcasses and 52.3% found in pigs. They demonstrate resistance to ampicillin, sulfamethoxazole and tetracycline, typical of this serovar; however, resistance to streptomycin is demonstrated equally as often. In addition, a relationship between certain Salmonella rods serovars and affinity for specific hosts and resistance patterns can be noticed. Certain serovars demonstrated tigecycline resistance, such as Salmonella Typhimurium and less frequently other serovars found in pigs and pig carcasses. The fact that no resistance to carbapenems was found in the tested Salmonella rods, both those isolated from pigs and cattle, as well as those isolated from carcasses of the said animals, can be perceived encouraging.

The acquisition of antimicrobial resistance by commensal bacteria colonising animals remains in direct dependence on the intensity of their use. Consequently, this leads to the selective pressure of these substances, co-selection and clonal propagation of resistant bacteria, or the transmission of genes encoding resistance between strains through multiple mechanisms. Research on the drug susceptibility of commensal, indicator E. coli strains isolated from the gastrointestinal tract of healthy animals and food of animal origin can provide a lot of valuable information regarding the current state, as well as the tendency in the formation of drug susceptibility of bacteria in the animal reservoir. Through spreading among animals or transmitting to humans, these microorganisms can be a potential threat to both the animal and the public health. The data for 2017 included in the report indicate that E. coli strains isolated from the bowels of fattening pigs and calves under 1 year of age demonstrate resistance to many chemotherapeutic agents (Table II) in a significant proportion. Resistance to tetracycline was found in 52.1% of isolates from pigs and 43.8% of isolates from calves. Resistance to sulphamethoxazole, trimethoprim and ampicillin was also quite high, ranging from 24.7% to 42.4% of strains from both groups of animals. Resistance to ciprofloxacin was observed at an average level, with 10.6% of strains demonstrating resistance; however, it was higher than resistance to nalidixic acid (5.8% of pig isolates and 6.7% of calf isolates). Similarly, resistance to chloramphenicol was at an average level (18% of isolates from pigs and 14.4% of isolates from calves). The low percentage of strains demonstrated resistance to gentamycin, cefotaxime, ceftazidime, azithromycin and a very low percentage to colistin. Meropenem resistance and tigecycline resistance were not detected. Depending on the country, there is an upward or downward trend in the resistance of commensal E. coli strains to these antibiotics. The isolates from pigs demonstrated susceptibility to all classes of chemotherapeutic agents in a lower percentage those from calves (39.2% versus 56.7%). Multidrug-resistance was demonstrated by 34.9% of pig isolates and 27.7% of calf isolates. Most frequently, the resistance concerned tetracycline, ampicillin, sulfamethoxazole and trimethoprim. Resistance to antibiotics, which are of critical significance to human health and are used in the treatment of bacterial diseases in humans, such as ciprofloxacin, cefotaxime, ceftazidime, meropenem, colistin or azithromycin, with the exception of the first one, was demonstrated by a small percentage of E. coli isolated from pigs and calves. Resistance to third generation cephalosporins was confirmed in 1.4% of isolates from pigs and 1.3% of isolates from calves. Similarly, the percentage of azithromycin-resistant strains did not exceed 2%. A small percentage of E. coli indicator strains demonstrated resistance to colistin; 0.3% of pig isolates and 0.8% of calf isolates. No resistance to carbapenems was found, whereas, as mentioned earlier, a relatively high percentage of commensal E. coli demonstrated resistance to ciprofloxacin (> 10%). Moreover, 55–64% of the isolates demonstrated cross-resistance to ciprofloxacin and nalidixic acid.

Considering the fact that the resistance of bacteria present in animals to third generation cephalosporins and carbapenemes constitutes a threat to public health, the European Commission, with the means of the 2013/652/EU decision, introduced the obligation, starting in 2014, to monitor the sensitivity of these antibiotics to Salmonella and indicator E. coli rods [9]. These bacteria, which show resistance to cefotaxime, ceftazidime or meropenem are subjected to further detailed analysis to determine the resistance phenotypes and their mechanisms. In most European countries, animal isolates of Salmonella rods have not shown resistance to cephalosporins. However, on average only 0.8% of them produced ESBL and 0.1% AmpC. In one case, production of VIM-1 by Salmonella Infantis isolates from sick piglets was detected. Similarly, E. coli strains resistant to third generation cephalosporins constituted only a small percentage of the natural microbiota components of the intestines. Strains potentially producing ESBL, AmpC or ESBL+AmpC were found in 1.2% of fattening pigs and 1.4% of calves under one year of age. As a result of an expanded and specific test for the presence of E. coli strains in stool of fattening pigs and calves under 1 year of age, which produce ESBL/AmpC /carbapenemase, data confirming a high percentage of strains potentially producing these β-lactamases were obtained. The enzymes listed above were produced by 43.8% of isolates present in the stool of fattening pigs and the stool of 44.5% of the calves. The percentage of strains producing these enzymes isolated from pork or veal meat was much lower and amounted to 6% and 4.8%, respectively.

In a routine study carried out in 2017, no carbapenemase-producing Salmonella strains and indicator E. coli were detected, although in the specific study investigating the presence of E. coli stains producing ESBL/AmpC/carbapenemase, one case of a VIM-1-positive strain in the stool of slaughter pigs was detected.

Research into the occurrence of MRSA in animals and in food as well as into the characteristics of isolated strains has shown that these bacteria frequently contaminate food, including meat from cattle, pigs and rabbits. The typing of the spa confirmed that the vast maj ority of MRSA strains found in pork meat belonged to the t011, t034C, and t108 types, and were associated with a dominant CC398 clone in livestock (LA-MRSA). Few other types of spa, such as t002, usually included in ST5 (CC5), have been classified as hospital-acquired strains (HA-MRSA). The aforementioned sequential type, in addition to resistance to β-lactam antibiotics, exhibits additional resistance to gentamycin and kanamycin. Other types of spa, outside the LA-MRSA line, include t091, t109, t127 and t6292, representing mainly community-associated MRSA (CA-MRSA) strains. Data from Sweden, which refers to MRSA in dogs, show that isolated staphylococci belonged to all three categories. The spa t034 type is associated with CC398, and the t2734 type with Cc97, and both belong to the LA-MRSA category. In turn, t127 and t891 are representatives of the CA-MRSA. Although the first type does not produce PLV toxin, its status as a CA-MRSA representative is sustained. Other spa types, such as t008, t022, t032 and t5634, represented the HA-MRSA category. Data from the report also revealed novel spa types of MRSA found in farm animals (pigs, calves), such as t17061, t17304, t17339, or 17627 included in the LA-MRSA category.

The data presented show that resistant and multi-resistant bacteria are present both in humans and in animals, and contaminate food products of animal origin. Similarly, genes coding for antimicrobial resistance are mostly identical in the microorganisms found in both hosts. It is possible to colonise humans by bacterial species that live in animals, as well as animals by “human” microorganisms. The direction of this transmission is not always possible to prove. Also, its risk has not been estimated yet. The widespread and unjustified use of antibiotics favour the selection of resistant strains, co-selection of multi-resistant strains, maintenance of genes that determine resistance, and the spread of resistance, which are significant threats to public health.

It should be emphasised that it is not always possible to draw a linear correlation between the use of a particular antibiotic and bacterial resistance, or the presence of the genes conditioning this resistance. An example here is the occurrence of genes conditioning resistance to florfenicol or apramycin in Staphylococcus spp. These antibiotics are not used to treat infections with the mentioned bacteria; however, are used to control other bacteria that cause respiratory and digestive diseases in livestock. In case of the selective pressure of these antibiotics, staphylococci occurring in, for example, the skin or mucous membranes, must obtain genes coding for the mechanisms of resistance to the above antibiotics in order to survive. This phenomenon is an example of the transfer of such genes between the microorganisms of indigenous communities. To understand the phenomena of co-selection or persistent resistance, it is necessary to know the physical connection of some resistance genes with others, or groups of genes transferred together (Table I.) [51, 66, 67, 72, 73].

Problems resulting from infections caused by multi-resistant bacteria in hospitalised companion animals are an exact reflection of the issues affecting hospitalised people. Both places are high-risk environments resulting from the intensive use of antibiotics, advanced therapies and a greater concentration of patients. Bacteria isolated from healthy animals, which are not given antibiotic treatment, unlike those from hospital environments, are characterised by high sensitivity to antimicrobial agents, which confirms the importance of selection pressure in the induction of resistance and its spread. Resistance and multi-resistance of zoonotic bacteria and indicator strains found in livestock, as well as in food products of animal origin may pose a potential threat to the public health. Limiting the use of antibiotics to absolutely necessary cases, and therefore rational antibiotic therapy, consistent with treatment recommendations including the initiation and implementation of drug management policy, other optional treatments, prophylaxis and biosecurity may be potential solutions to reduce the problem [3].