Staphylococcus aureus and Staphylococcus pseudintermedius isolated from humans and pets – a comparison of drug resistance and risk factors associated with colonisation

Staphylococci are ubiquitous, Gram-positive bacteria, most of which are opportunistic components of the microbiota that inhabit the skin and mucous membranes of various mammalian species (10, 30, 41). The presence or absence of the free coagulase enzyme and possession or lack of the ability to clot plasma divide staphylococci into coagulase-negative (CoNS) and coagulase-positive (CoPS), the latter of which are considered more pathogenic (10, 36, 39). Among the group of coagulasepositive staphylococci, the most important are S. aureus and S. pseudintermedius. It is believed that the greatest staphylococcal threats to humans are methicillin-resistant and multidrug-resistant S. aureus (MRSA and MDRSA). They may be carried by dogs and cats, and the increasing prevalence and drug resistance of S. pseudintermedius isolated from these companion animals seems equally alarming (20). Until now, it was believed that S. pseudintermedius was a typical animal species with marginal importance for humans (9). However, the incidence of this Staphylococcus species in humans is probably underestimated because of the misidentification of S. pseudintermedius strains as S. aureus (41). It is indicated that the pathogenic potential of S. pseudintermedius in humans is high and comparable to that of S. aureus (9). In addition to the ability to colonise human tissues, this species can also limit the growth of bacteria that are the natural microbiota of humans and animals (18).

If S. pseudintermedius merits attention, it does not imply that MRSA no longer does; this is considered one of the most dangerous human pathogens (11, 14, 31, 38). The global importance of the threat is also emphasised by the 2017 decision by the World Health Organization to include MRSA on the list of the 12 most dangerous pathogens posing a threat to public health (38). In people with reduced immunity, staphylococci may cause endogenous infections ranging from skin inflammation even to life-threatening conditions such as congestive heart failure, diabetes, lung diseases, kidney damage or bacteraemia (27, 30, 33, 39, 40, 41). The course of an infection may be determined by the drug resistance and other virulence factors characterising the infecting strain. The problem of increasing antimicrobial resistance and the occurrence of strains resistant to all or almost all commonly used classes of antimicrobials have a significant impact on the course of therapy for infections and can bring on complications of patients’ pre-existing diseases (6). The zoonotic potential of S. aureus and S. pseudintermedius has not yet been fully elucidated. Certain groups of people are at greater risk of S. aureus colonisation, namely people who spend time in hospital rooms and with patients or their sampled material because of their professions, such as doctors, nurses, midwives, paramedics, medical students and laboratory diagnosticians (38). Animals were more likely to be sick and under the care of medical professionals if they were detected to be carriers of coagulase-positive staphylococci. In relation to sick animals, S. aureus was most often isolated from cases of wound infection (including postoperative ones), skin infections, ear inflammation, septic arthritis, upper respiratory tract inflammation, pneumonia, urinary tract infections and endocarditis (4, 13, 27, 35).

Staphylococcus pseudintermedius is a species typically found in dogs, and up to 92% of healthy individuals are carriers of it (23). This Staphylococcus species can be isolated from many anatomical sites of healthy animals, including the ears, conjunctival sacs, nostrils, oral cavity, groin skin and perineum (23). The carriage of S. pseudintermedius in cats is reported less frequently than it is in dogs (15). According to some authors, felines (Felidae) are not natural hosts of S. pseudintermedius (17). There are more and more reports of the isolation of S. pseudintermedius from humans, but infections are rarely reported (23, 39, 40). Colonisation of people in contact with dogs or cats is more often described and affects 0.4–8.9⁰%; of owners or people professionally dealing with animals (23). The prevailing opinion is that human colonisation with this Staphylococcus species is transient and infections mainly affect immunosuppressed or elderly people (23). The issue of staphylococcal transmission between humans and animals deserves attention, especially because of the possibility of resistance genes being transferred to antimicrobial chemotherapeutics. Bacterial transmission between humans and animals and the exchange of genetic information between different microbial species are means for animal and human bacterial strains to acquire antimicrobial resistance genes through horizontal gene transfer and become more virulent (42). A microorganism’s resistance to antimicrobials is of interest not only to scientists, but also to clinicians. It may result in prolongation of treatment time, additional burden on the patient’s body, side effects, technical difficulties in conducting therapy or even complete therapy failure and the death of the patient (11, 14). Infections with drug-resistant staphylococcal strains also cost heavily in treatment (infection with MRSA needs treatment approximately 1.5–3 times more expensive than the treatment for susceptible strains), incur losses in patients of working age because of the absence or lower productivity of the employee, and pose a significant threat to public health (14, 43). It is estimated that if the current epidemiological situation is left unchecked, bacterial drug resistance may become the main cause of patient mortality by 2050 and cost approximately USD 100 trillion (43). Resistance is also particularly problematic in the case of veterinary medicine because the number of available preparations is more limited than it is in human medicine. This is because certain groups of antimicrobials in veterinary medicine were restricted in use under Commission Implementing Regulation (EU) 2022/1255 of 19 July 2022 specifying antimicrobials or groups of antimicrobials reserved for the treatment of certain infections in humans in accordance with Regulation (EU) 2019/6 of the European Parliament and of the Council. In the light of these facts, and taking into account the frequency and proximity of contact between people and their pets (23), a study was considered worthwhile to specify the prevalence of S. aureus and S. pseudintermedius strains isolated from humans, dogs and cats and to determine and compare their drug resistance. An additional goal was to determine risk factors that may be related to the more frequent isolation of methicillin-resistant strains in selected people and animals.

The presence of S. aureus was most often found in the nasal vestibule in humans, cats and dogs, and also in the oral cavity in cats. In all study groups, it was also the nasal vestibule where S. pseudintermedius was most often detected, and additionally the skin in the elbow crease in humans, the conjunctival sac in cats and the oral cavity and anus in dogs. The nasal vestibule is one of the anatomical locations most frequently verified to harbour staphylococci in humans and animals. It is therefore not surprising that the results for this swabbing location are reflected in the literature on the subject (1, 9). The skin and external auditory canal are also frequently reported sites of colonisation, especially when inflammation is present (24).

The growing antibiotic resistance of bacteria is a threat to human and veterinary medicine. In this study, the highest percentages of resistant S. pseudintermedius strains were recorded for penicillin (71.5%), ampicillin (63.6%), clindamycin (41.2%) and erythromycin (41.2%). There were no strains resistant to mupirocin, linezolid, rifampicin or tigecycline. At the genetic level, the most abundant gene were blaZ, tet[M] and ermB, but no strain had the mupA gene. Methicillin-resistant S. pseudintermedius isolates were most frequently isolated from the nose and oral cavity. Similar results in terms of high resistance of strains to penicillin and ampicillin were described by Liang et al. (19), Naziri and Majlesi (26) and Scott et al. (34). Numerous strains resistant to clindamycin and erythromycin were observed by Naziri and Majlesi (26) and Rynhoud et al. (32). A very high percentage of tetracycline resistance was obtained by Liang et al. (19), for whom resistant strains of S. pseudintermedius accounted for as much as 96.6%. In the same study, almost 80% of isolates showed resistance to erythromycin. Researchers have also indicated frequent resistance of S. pseudintermedius strains to potentised sulfonamides, which was not confirmed in our study (26, 32). Non-susceptible strains of S. aureus were detected to a tested antibiotic in every case. The highest resistance of S. aureus isolates was demonstrated for ampicillin (62.4%), penicillin (61.4%), erythromycin (29.2%) and amoxicillin with clavulanic acid (28.2%). At the genetic level of S. aureus, the blaZ, tet[M] and ermA genes were most frequently found, but the tet[L] and mupA genes were not detected. In a review of publications from around the world by Abdullahi et al. (1), S. aureus isolates from dogs showed resistance most often to tetracyclines, aminoglycosides, rifampicin and potentised sulfonamides, while those from cats showed resistance to potentised sulfonamides, ciprofloxacin, erythromycin, clindamycin, amikacin, enrofloxacin and tetracyclines. Similar results were obtained by Liang et al. (19) in humans in China. It seems that regardless of the region or host species, the most frequently isolated staphylococcal strains are characterised by resistance, mostly to the same groups of antimicrobial chemotherapeutics, differing only in the percentage of isolated bacteria. In some studies a more frequent occurrence of strains insensitive to selected classes of active substances has been observed, but there is a consistent, disturbing trend in the development of drug resistance, which is progressing so rapidly that some researchers have already isolated S. aureus strains resistant to all verified active substances (34). Such cases highlight the need to monitor resistance in this bacterial species to protect human and animal health.

The frequency of MRSA and MRSP strains obtained in this research does not differ significantly from the data in the literature, as it remains in the range of 0.8–9% described by other scientists (9, 11, 30, 32, 34). Higher results were described by Saud et al. (33) of as much as 47% in the case of MRSA. Scott et al. (34) observed more frequent isolation of MRSA from dogs than from cats, which was not demonstrated in our study. What is particularly alarming is that the frequency of occurrence of strains with at least one of the genes determining vancomycin resistance (vanA or vanB) in our own analyses was almost 16% for both CoPS species examined. This is quite a high result, considering that vancomycin is one of the last-chance antimicrobials used in human treatment (2). So far, such a high prevalence has been evinced mainly by bacteria of the genus Enterococcus, termed vancomycin-resistant enterococci (3). However, there are reports confirming the presence of these genes in staphylococci, but so far these have been incidental cases (2, 3). Nevertheless, this result is extremely disturbing and indicates that the level of resistance of Staphylococcus spp. should be monitored and the use of antimicrobials should be carefully deliberated on each time in clinical practice to limit the development of drug resistance. The results of phenotypic analysis indicate that MDRSP strains were isolated from the studied humans and animals with a similar frequency (41–47%) without statistically significant host species differences. However, under genotypic analysis, MDRSP were statistically significantly more common in cats than in dogs. Both at the phenotypic and genotypic levels, MDRSA strains occurred with similar frequency – 4–10% in humans and 32–45% in animals. Similar frequencies of MDRSA and MDRSP isolation were described by Abdullahi et al. (1), Cocca et al. (8) and Thomson et al. (39)in canine isolates of S. aureus (41%). However, in the study by Ferradas et al. (12), higher values were found for S. aureus (50%) and much lower ones for S. pseudintermedius (3.3%), while in Saud et al. (33) as many as 74% of S. aureus isolates were classified as MDR. Rana et al. (30) found the range of distribution of MDR bacteria in dogs and cats to start at 2.5% in the UK, increase through approximately 14% in Finland and reach its maximum at 66.5% in Japan. The discrepancies between the reviewed results are probably related to the size of the groups of people and animals tested and, therefore, the pools of tested bacterial isolates.

As the literature indicates, some groups of people and animals are more exposed to colonisation and infections caused by staphylococci. High risk is described in newborns and children up to 6 months of age and those who have been hospitalised or have had invasive medical procedures performed (17). Children are also exposed to infection because they have not fully developed good hygiene habits, are liable to have close contact with animals and playground equipment (organoleptic exploration) and are suboptimally protected by an immune system still in development. Adults’ risk factors include immunosuppression, the occurrence of atopy, working in a hospital environment and being hospitalised and taking antibiotics (9, 11, 12, 37). Authors have concluded that people who have contact with animals, especially dogs but also cats, are significantly more likely to be infected (23). In people who have close contact with dogs, which are natural carriers of S. pseudintermedius, cases of colonisation and infections caused by this species are increasingly reported (18, 23). An association between close contact with humans and a higher risk of S. aureus colonisation of cats has also been observed (23). Therefore, humans and dogs or cats sharing a place of residence and maintaining close physical contact (e.g. by petting, hugging, kissing or sleeping in the same bed) create the possibility of pathogen transmission between organisms (10, 13, 23, 30). Currently, particular attention is being paid to the potential transmission of virulent pathogens between humans and the animals perceived as their reservoirs (10, 13, 23, 24, 25, 43). It is suspected that humans may be the primary source of MRSA isolated from pets and may act as another reservoir of these bacteria (16). It has been shown that the clonal complexes of S. aureus previously observed in hospital-acquired MRSA cases in humans also circulate in the dog and cat population (16, 37). In our study, some of the risk factors explored – treatment of the examined people in the year up to examination or the need for antibiotics during that time (whether therapy was once with one or on different occasions with varied antimicrobials) – were associated with sixfold more frequent isolation of MRSP. With respect to S. aureus, risk factors such as the animal’s treatment under a veterinarian in the past year and antibiotic use during that time were associated with increased MRSA isolation. The analyses also showed that the greater the number of cats in the house, the greater the chances of MRSP occurrence. This may be the result of horizontal gene transfer between strains, which may occur more often in large animal populations than in small ones. The co-habitation of humans and larger animal populations poses a risk of spreading virulence factors bidirectionally between humans and animals. The issue of staphylococci being transferred from the zoonotic reservoir of pets to their owners is particularly important, taking into account the marked change in people’s approach to companion animals in recent years (42). The number of animals cohabiting with people has been estimated in recent years at up to 124 million, depending on the country, and in Poland in 2021 it was over 20 million (9, 16). Caregivers more and more often declare not only keeping a dog or cat in their home but also expressing emotional attachment to the animal and treating it as an equal member of the family (11). Therefore, many of them (up to 82%) have close daily physical contact with the animal (5, 43). People who come into close contact with animals because of their occupations, such as veterinary doctors and students, veterinary support staff, zootechnicians, groomers and animal behaviourists, also have frequent contact with pathogens originating from animals (10, 35, 39). Work involving contact with animals has been reported in recent years to be an important risk factor for colonisation by S. aureus. Researchers have pointed out that veterinarians and other staff of veterinary clinics are more exposed to infection than animal owners (10, 24, 25, 28, 35). Interestingly, the results of this study showed that studying medicine was associated with an 84% lower chance of MRSP isolation compared with those studying in a field related to contact with animals (e.g. veterinary medicine, animal science and others). This suggests that the MRSP strains found in these people came from animals they had come into contact with during their studies. With regard to MRSA strains, it has not been confirmed that people engaged in professions involving contact with animals are colonised more often than others. However, in the case of MDRSA isolates, the chances of their occurrence increased if any household member worked in direct contact with animals. The presented data suggest that the presence of animals in people’s lives, their sharing owners’ home spaces, and owners’ maintaining close and frequent physical contact with animals may constitute important risk factors for human colonisation by zoonotic pathogens, including S. aureus and S. pseudintermedius. Exposure to opportunistic bacteria was also increased among people working in the healthcare sector, including doctors, nurses, healthcare assistants and hospital porters (33, 35, 38). However, this tendency described in the literature was not reflected in the results of our research.

Staphylococcal infections are a serious problem around the world; therefore, they are monitored by international organisations. According to international statistics, 5-10% of hospitalised patients suffer from nosocomial infections, which in relation to Poland may constitute several hundred thousand people per year. In the USA, out of 94,000 cases of MRSA infections, as many as 18,650 were fatal. The highest incidence of nosocomial MRSA infections was recorded in Asia, reaching as much as 70% (14). Based on data from the European Union, the authors estimate that MRSA causes 150,000 infections annually and 7,000 related deaths (31). The One Health approach links the health of humans and domestic animals closely and regards the welfare of one group and that of the other as interdependent. Regular, close contact between people and animals in professional and private life promotes the transmission of microorganisms and, with them, virulence determinants. Monitoring the epidemiological patterns of strains and knowing the prevalence of resistant isolates is necessary to human and veterinary medicine to facilitate preventive programmes, appropriate therapeutic decisions and sound strategic choices to combat the phenomenon of methicillin resistance (2, 11, 37). Contributing to the amassed knowledge on the resistance of CoPS may provide useful guidance to clinicians, especially in cases where it is not possible to perform an antibiogram or wait for its result before administering antimicrobial chemotherapy. This time-pressured situation may occur when it is necessary to implement treatment immediately because the patient’s condition does not allow waiting several days for the result. Then, knowledge of the scale of resistance of these bacteria to commonly used first-choice antimicrobials will allow clinicians to assess which medication will be appropriate in a given situation. At the same time, the authors would like to emphasise the role of reliable antibiogram performance, especially in the face of the increasing antibiotic resistance of staphylococci, the scope of which is presented in this article.