Original Scientific Article
Understanding antimicrobial prescription practices: Insights from small animal veterinarians in North Macedonia
Ivana Shikoska * ,
Aleksandar Cvetkovikj ,
Martin Nikolovski ,
Iskra Cvetkovikj

Mac Vet Rev 2024; 47 (2): i - xii

10.2478/macvetrev-2024-0020

Received: 28 May 2024

Received in revised form: 20 June 2024

Accepted: 02 July 2024

Available Online First: 13 July 2024

Published on: 15 October 2024

Correspondence: Ivana Shikoska, ivana@fvm.ukim.edu.mk
PDF

Abstract

Antimicrobial resistance (AMR) is an increasing global concern in small animal veterinary practices. The overuse and misuse of antimicrobials in companion animals can contribute to the spread of AMR between animals and humans. This study aimed to assess small animal veterinarians’ knowledge, attitudes, and behaviors towards antimicrobial use (AMU) and AMR in North Macedonia. A web-based questionnaire was developed, including questions addressing demographics, owner influence on antibiotic prescription and prescribing practices. The response rate of the small animal veterinarians was 47.50% (57/120), with most of them (84.20%) having 1-15 years of work experience. Pearson’s chi-square test of independence was used for contingency tables that met the chi-square assumption, and Fisher’s exact test was conducted for contingency tables that did not. Most veterinarians responded that they had perceived pressure and direct demands from pet owners to prescribe antimicrobials (35.09% frequently, 45.61% occasionally). In the survey, 50.77% of the veterinarians reported frequently administering antibiotics without conducting bacteriological or antimicrobial susceptibility testing. They typically resorted to these tests in cases with recurrent infections, such as skin infections (19.63%), or when empirical therapy is ineffective (14.72%). Based on the findings, it can be concluded that veterinarians play a crucial role in tackling the AMR in North Macedonia. The lack of stewardship programs or guidelines for responsible antimicrobial use in companion animals is a critical issue that requires urgent attention, emphasizing the vital role of veterinarians in combating AMR.

Keywords: stewardship, companion animals, guidelines, survey, awareness



INTRODUCTION

Antimicrobial resistance (AMR) is becoming a primary concern in small animal practices (1). The overuse and misuse of antimicrobials significantly contribute to the spread of resistant bacteria and resistance genes between animals and humans (2). The antimicrobial use (AMU) in companion animals is often overlooked as a contributing factor to the global AMR challenge, representing a significant gap in the One Health strategy for AMR surveillance (3, 4). Over the past decade, multidrug-resistant (MDR) bacteria have emerged and spread among companion animals worldwide, with the potential for zoonotic transmission (5). The most concerning MDR bacteria isolated in companion animals include methicillin-resistant Staphylococcus spp., vancomycin resistant enterococci, extended-spectrum beta-lactamase (ESBL), AmpC and carbapenemase-producing Gram-negative bacteria (6, 7, 8). All these bacteria have shown resistance to all licensed antimicrobials for animal use, posing a significant threat to animal health by increasing the risk of treatment failure (9).
However, antimicrobial prescribing patterns are highly relevant to the efforts towards controlling AMR, which is an increasingly concerning issue in small animal practice (10). In this context, critically important antimicrobials (CIAs), typically reserved for human medicine, are allowed within veterinary clinics (11). Interestingly, it appears that CIAs are used more frequently in companion animals than farm animals despite the overall antimicrobial use being lower in companion animals (12, 13). Therefore, the European Medicines Agency (EMA) has categorized antimicrobials into four groups based on their impact on public health and the need for use in veterinary medicine. Categories D and C should be used cautiously, whereas Categories B and A should be restricted or not being used in veterinary medicine (12, 14). It is crucial to evaluate the use of these drugs in companion animals due to their impact on public health (9, 10).
Recently, there has been an increasing emphasis worldwide on promoting responsible prescribing practices and reducing the use of antimicrobials in veterinary medicine (7). Antimicrobial stewardship, as defined by the American Veterinary Medical Association (AVMA), is the responsibility of veterinarians to ensure the accessibility and effectiveness of antimicrobials while protecting animal, public, and environmental health (15). Several European countries, including the Czech Republic, Denmark, Finland, France, Germany, Ireland, the Netherlands, Norway, Sweden, and the United Kingdom, have established surveillance programs to monitor AMR in animals. Some of these programs also include specific control measures and antimicrobial stewardship guidelines (ASGs) in animals, including companion animals (16). Twelve European ASGs include statements to reserve high priority-CIAs (HP-CIAs) such as carbapenems and vancomycin exclusively for humans (7). This is to raise awareness among practitioners who may not fully understand the importance of these drugs in combating AMR and the role of protecting public health.
No data is available on the usage of antimicrobials in companion animals treated in veterinary practices in North Macedonia. The antimicrobial resistance of the bacteria isolated from these species has not been thoroughly researched, except for the study of Cvetkovikj et al. (17) which focused on AMR in clinical isolates of Staphylococcus spp. in dogs in North Macedonia. Moreover, the lack of stewardship programs and guidelines for prudent antimicrobial use in companion animals is a serious concern that must be addressed. For this reason, understanding current antimicrobial prescribing practices is crucial for developing accurate stewardship strategies (18). This study is a starting point for developing guidelines for antimicrobial use in companion animals in North Macedonia and presents the findings of a survey conducted among small animal veterinarians. The primary goal was to evaluate the veterinarians’ knowledge, attitudes and behaviors towards AMU and AMR in companion animals.

MATERIAL AND METHODS 

A survey was conducted to investigate the antimicrobial usage patterns among veterinarians who work in small animal practices. A questionnaire was designed and tested on ten small animal clinicians to evaluate its utility and identify potential issues. The pilot study was successful, and no changes were made to the questionnaire. The questionnaire and a cover letter detailing the study’s purpose were sent to 120 small animal veterinarians. The qualified participants received an email containing a link to the web-based questionnaire that was accessible for two weeks. The survey had five parts: demographics, owner influence on antibiotic prescription, prescribing practices and behavior, surgical prescribing practices, and antibiotics for specific/ systemic infections. It consisted of 19 questions focused on the veterinarians’ demographics, experiences in practice, current prescribing habits, individual opinions about antimicrobial usage, and bacteriological testing. The questionnaire offered a comprehensive overview of the antibiotics that small animal veterinarians may prescribe for various health conditions of the patients.

Statistics
Fisher exact test was performed for contingency tables that were not fulfilling the chi-square assumption for cell counts n<5. Pearson’s chi square test of independence was performed for the other contingency tables that fulfilled this assumption. The significance level was set at p<0.05. The level of association for the positive responses of each question and the respective response categories was assessed with Cramer V value and the corresponding degrees of freedom (df). All responses were expressed as counts (n) and percentages (%).

RESULTS

Sociodemographic data of the survey participants
In total, 47.50% (57/120) of the invited veterinarians agreed to participate in the study and filled in the questionnaires providing information on AMU and AMR in North Macedonia. Most veterinarians were male, 57.89% (33/57), while 93% (53/57) were in the age category <50 years. 
There was no significant difference in the gender of the participants. They were mainly in the age range between 25-30 years (n=31, 54.39%) and 36-50 years (n=22, 38.60%). The association level of these age groups with the acceptance to participate in the survey was high (V=0.42, df=2). A significantly higher number of participants (n=54, 83.08%) had between 1 and 15 years of work experience. This was highly associated with the acceptance to participate in the survey (V=0.75, df=2). Table 1 depicts the sociodemographic data distribution.





The influence of pet owners on the antibiotic prescription practice of veterinarians
A significantly higher number of veterinarians answered that pet owners occasionally (n=31, 54.39%) or frequently (n=22, 38.61%) give antibiotic therapy before seeking professional veterinary care compared to responses as ‘always’ (n=3, 5.26%) and 'never’ (n=1, 1.75%). The level of association was high (V=0.51, df=3).
A significantly higher number of veterinarians answered that pet owners occasionally (n=26, 45.61%) or frequently (n=20, 35.09%) request antibiotic treatment for their pets compared to those who responded ‘always’ (n=8, 14.04%) and ‘never’ (n=3, 5.26%). The level of association was high (V=0.38, df=3).
The highest number (n=34, 59.65%) of veterinarians answered that pet owners occasionally demand bacteriological testing. The number of veterinarians (n=22, 38.60%) who answered that pet owners have never demanded this type of testing was significantly lower compared to the previous group of veterinarians, but still significantly higher compared to the veterinarians who have responded “frequently” (n=1, 1.75%). There were no answers with “always.” The level of association was high (V=0.38, df=3).
The detailed distribution of the responses is shown in Table 2.



Veterinarians’ antibiotic prescribing practices
A significantly higher number of veterinarians (n=33, 50.77%) have declared that they frequently administer antibiotics without conducting bacteriological testing or AST compared to veterinarians answering ‘always’ (n=14, 21.54%), ‘occasionally’ (n=11, 16.92%), and ‘never’ (n=7, 10.77%). The level of association was high (χ2=32.72, V=0.35, df=3).
A significantly higher number of veterinarians have declared that the duration of the prescribed antibiotic therapy was between 3-5 days (n=22, 38.60%) and within 5-10 days (n=31, 54.39%), compared to veterinarians answering ‘based on the diagnosis’ (n=2, 3.51%), ‘within three days’ (n=1, 1.75%), and ‘more than ten days’ (n=1, 1.75). The level of association was high (V=0.55, df=4).
Most of the veterinarians have answered that they require bacteriological testing and AST in recurrent skin infections (n=32, 19.63%), systemic infections (n=30, 18.40%), recurrent urinary infections (n=30, 18.40%), ineffective empirical therapy (n=24, 14.72%), and recurrent respiratory infections (n=24, 14.72%). They were non significantly different (χ2=12.77, V=0.13, df=6) and the level of association was medium.
There was no significant difference in the responses regarding how often the antibiotic therapy was applied while awaiting the laboratory results. They ranged between 15.79% (n=9) for ‘never’ and 33.33% (n=19) for ‘frequently’. The level of association was low (χ2=4.75, V=0.14, df=3).
The antibiotic therapy selection based on the scientific literature was used ‘always’ (n=26, 45.61%) and ‘frequently’ (n=16, 28.07%) by a significantly higher number of veterinarians. A significantly lower number of veterinarians answered ‘occasionally’ (n=12, 21.05%) and ‘never’ (n=3, 5.26%). The association level was high (χ2=25.52, V=0.33, df=3).
The antibiotic therapy selection based on own experience was answered ‘always’ (n=25, 43.86%) and ‘occasionally’ (n=22, 38.60%) in significantly high number of veterinarians. The response for ‘frequently’ (n=9, 15.79%) and ‘never’ (n=1, 1.75%) was given by a significantly lower number of veterinarians compared to the first response. The level of association was high (V=0.39, df=3).
The antibiotic therapy selection based on bacteriological testing/AST was answered with ‘occasionally’ (n=23, 39.66%) and ‘always’ (n=17, 29.31%) in significantly higher number of veterinarians compared to ‘frequently’ (n=8, 13.79%) and ‘never’ (n=9, 15.52%). The level of association was high (χ2=55.46, V=0.49, df=3).
The antibiotic therapy selection based on a colleague’s opinion was answered ‘occasionally’ (n=35, 61.40%) in a significantly high number of veterinarians compared to ‘never’ (n=10, 17.54%), ‘frequently’ (n=8, 14.04%), and ‘always’ (n=4, 7.02%). The level of association was high (χ2=55.46, V=0.49, df=3).
The antibiotic therapy selection based on the manufacturer’s manual was answered ‘occasionally’ (n=18, 31.58%) and was non-significantly higher than ‘frequently’ (n=16, 28.07%), ‘always’ (n=15, 26.32%), and ‘never’ (n=8, 14.04%). The level of association was low (χ2=5.31, V=0.15, df=3).
To the question ‘How frequently do you prescribe a combination of antibiotics?’, significantly higher number of answers were ‘occasionally’ (n=43, 75.44%) compared to ‘frequently’ (n=11, 19.30%), ‘never’ (n=2, 3.51%), and ‘always’ (n=1, 1.75%). The level of association was high (V=0.29, df=3).
To the question ‘Do you keep a record of the antibiotics prescribed for the patient?’, significantly higher number of answers were ‘always’ (n=33, 57.89%) compared to ‘occasionally’ (n=11, 19.30%), frequently (n=9, 15.79%), and ‘never’ (n=4, 7.02%). The level of association was high (χ2=46.29, V=0.45, df=3).
To the question ‘How frequently do you weigh patients before giving antibiotics?’, significantly higher number of answers were ‘always’ (n=37, 64.91%) compared to ‘frequently’ (n=10, 17.54%), ‘occasionally’ (n=5, 8.77%), and never (n=5, 8.77%). The level of association was high (χ2=66.13, V=0.54, df=3).
To the question ‘How frequently do empirical antibiotic treatments fail?’, significantly higher number of answers were ‘occasionally’ (n=50, 87.72%), frequently (n=4, 7.02%), and ‘never’ (n=3, 5.26%). There were no answers ‘always’. The level of association was high (V=0.84, df=3).
To the question ‘How often are antibiotic treatments unsuccessful after bacteriological testing and AST?’, a significantly higher number of answers were ‘occasionally’ (n=39, 68.42%)  compared to ‘never’ (n=18, 31.58%). There were no answers ‘always’ and ‘frequently’. The level of association was high (V=0.65, df=3).
More detailed description of the response’sdistribution can be found in Table 3.




Antibiotic prescribing practices in surgical procedures
To the question ‘How frequently do you prescribe antibiotics after elective surgery?’, significantly higher number of veterinarians have answered ‘>90%’ (n=26, 45.61%) compared to ‘1-10%’ (n=9, 15.79%) and ‘0%’ (n=8, 14.04%), but non-significantly different compared to ’11-50%’ (n=14, 24.56%). The level of association was medium (χ2=19.16, V=0.23, df=3).
To the question ‘On what occasion do you administer antibiotics after surgery?’, significantly higher number of veterinarians have answered ‘When surgeries are contaminated or dirty’ (n=36, 25.35%), ‘When I expect that there will be a leakage from the aseptic area’ (n=32, 22.54%), and ‘Surgeries that last longer than 90 minutes’ (n=23, 16.20%), ‘Prescribing antibiotics after surgery is a common practice’ (n=14, 9.86%), and ‘I have experience with infections after surgery’ (n=11, 7.75%) compared to ‘Depending on the place of living’ (n=1, 0.70%). The level of association was high (χ2=54.42, V=0.23, df=6).
More detailed description on the responses can be found in Table 4.

Antimicrobial usage for the treatment of different infections
For skin infections treatment, from 257 responses, the most frequently selected antibiotics comprising 56.41% of all responses were amoxicillin (n=27, 10.51%), amoxicillin+clavulanic acid (n=24, 9.34%), marbofloxacin (n=23, 8.95%), penicillin (n=19, 7.39%), clindamycin (n=18, 7.00%), cefalexin (n=17, 6.61%), and chloramphenicol (n=17, 6.61%). For otitis externa treatment, from 220 responses, the most frequently selected antibiotics comprising 59.1% of all responses were tobramycin (n=30, 13.64%), ciprofloxacin (n=22, 10.00%), chloramphenicol (n=21, 9.55%), marbofloxacin (n=16, 7.27%), amoxicillin+clavulanic acid (n=15, 6.82%), amoxicillin (n=13, 5.91%), and enrofloxacin (n=13, 5.91%).
For respiratory symptoms treatment, from 347 responses, the most frequently selected antibiotics comprising 65.71% of all responses were amoxicillin+clavulanic acid (n=41, 11.82%), ceftriaxone (n=34, 9.80%), doxycycline (n=34, 9.80%), amoxicillin (n=33, 9.51%), penicillin (n=21, 6.05%), marbofloxacin (n=17, 4.90%), lincomycin (n=16, 4.61%), and oxytetracycline (n=16, 4.61%).
For urinary infections treatment, from 224 responses, the most frequently selected antibiotics comprising 65.17% of all responses were enrofloxacin (n=34, 15.18%), ciprofloxacin (n=20, 8.93%), marbofloxacin (n=19, 8.48%), ceftriaxone (n=17, 7.59%), doxycycline (n=16, 7.14%), amoxicillin+clavulanic acid (n=16, 7.14%), trimethoprim-sulfamethoxazole (n=13, 5.80%), and penicillin (n=11, 4.91%).





For gastrointestinal infections treatment, from 240 responses, the most frequently selected antibiotics comprising 64.99% of all responses were metronidazole (n=44, 18.33%), trimethoprimsulfamethoxazole (n=42, 17.50%), enrofloxacin (n=20, 8.33%), ceftriaxone (n=18, 7.50%), lincomycin (n=11, 4.58%), doxycycline (n=11, 4.58%), and oxytetracycline (n=10, 4.17%).
According to the median, the most frequently used antibiotics were: ceftriaxone (median 17) for respiratory, urinary, and gastrointestinal infections; marbofloxacin (median 17) for skin, ear, respiratory, and urinary infections; amoxicillin+clavulanic acid (median 16) for skin, ear, respiratory, and urinary infections; enrofloxacin (median 16) for ear, respiratory, urinary, and gastrointestinal infections; amoxicillin (median 13) for skin, ear, and respiratory infections; ciprofloxacin (median 11) for ear and urinary infections; penicillin (median 11) for skin, respiratory, and urinary infections; doxycycline (median 11) for respiratory, urinary, and gastrointestinal infections, and ciprofloxacin (median 11) for ear and urinary infections.
The use of other antibiotics was more selective for treatment of specific infections. Clindamycin (median 10) - skin infections; lincomycin (median 6) - respiratory and gastrointestinal infections; oxytetracycline (median 6) - respiratory and gastrointestinal infections; trimethoprimsulfamethoxazole (median 4) - urinary and gastrointestinal infections; chloramphenicol (median 2) - skin and ear infections; tobramycin (median 2) - ear infections. More detailed description on their use can be found in Table 5.

DISCUSSION

This was the first national survey conducted on AMU in companion animals among the small animal veterinarians in North Macedonia. Assessing the current awareness and knowledge of AMU and AMR is crucial as it provides a foundation for achieving success in reducing AMR in companion animals. We observed varying opinions and perceptions among veterinarians regarding the antimicrobial usage patterns. The total response rate of 47.50% is reasonable, given the busy schedules of small animal veterinarians. As seen in prior studies, the online survey format may have resulted in lower response rates (19, 20). Younger veterinarians were more likely to participate due to the electronic nature of the survey (19).
Veterinarians considered several factors when choosing antimicrobials for their patients, including their perception of the drug’s effectiveness, ease of administration, and personal preferences and experiences (4, 21). Our study revealed that “scientific literature” and “own experience” were the two most influential factors affecting veterinarians’ prescribing behavior, with 45.61% and 43.86%, respectively. Experience plays a crucial role in shaping the prescribing behavior of veterinarians (13, 14). A study on antimicrobial prescribing behavior in Europe (8) suggests that scientific literature and continued education could be influential factors (13, 15). It is important to mention that Hughes et al. (22) conducted a study which revealed that a significant number of practitioners rely on the information provided by the pharmaceutical industry. This may lead to biased information being used in practice due to the promotional influence of this industry (22).
On the other hand, it has been observed that pet owners significantly influence the prescribing practice of veterinarians (23). Based on our survey, a significant number of veterinarians (45.61%) answered that pet owners occasionally demand antimicrobial prescriptions, while 35.09% of veterinarians answered that the owners frequently do. Frey et al. (24) indicate that some pet owners lack awareness of antimicrobial drug side effects and would still want antibiotics for their pets even when the efficacy is uncertain. Moreover, the lack of AMR awareness among pet owners can be a significant obstacle in making decisions regarding the diagnosis and treatment of their pets (25). Our study further supports this because a large proportion of pet owners either do not seek or only occasionally seek bacteriological testing (38.60% and 59.65%, respectively).
The initial choice of an antibiotic is usually made based on empirical evidence (1). Veterinarians need to know the different types of bacteria that cause infections in various organ systems, as this helps in the empirical choice of antibiotics (26). If an infection is causing discomfort or is complex or lifethreatening, antibiotic treatment typically starts before the culture and AST results are received (26). However, these tests are essential tools for antimicrobial stewardship (27). It is concerning to use prophylactic or empirical antimicrobial therapy without testing (28), especially when using fluoroquinolones, macrolides, and third- and fourthgeneration cephalosporins (29). Our findings show that bacteriological testing/AST is not commonly performed before prescribing antimicrobials, which is consistent with other studies that have reported low AST usage in veterinary practice (21, 30). A study by Chipangura et al. (19) reported that 81.22% of patients returned due to ineffective empirical antibiotic therapy. This finding aligns with our results, where a large percentage of veterinarians (87.72%) reported experiencing occasional failure of empirical antibiotic treatment. Moreover, in our study 68.42% reported that even after bacteriological testing and AST, the antibiotic treatment was unsuccessful. Most veterinarians follow the practice of requiring bacteriological testing and AST in cases of recurrent infections like skin (19.63%), urinary (18.40%), and respiratory (14.72%) infections. They also follow the same practice for systemic infections or in cases where empirical therapy has proved to be ineffective.
It has been reported that waiting time for AST results and cost constraints discourage from using these tests (21, 31). Diagnostic cytology is recommended whenever possible, as it can provide valuable information in identifying the specific microorganisms involved and guide the selection of appropriate antibiotics (21). A study conducted in Italy revealed that only 5% of antimicrobial prescriptions in a veterinary teaching hospital were supported by the results of microbial culture and antimicrobial susceptibility testing (32). In our study, 15.52% of the veterinarians rarely or never used bacteriological testing and AST. This lack of confirmed diagnosis can lead to the misuse of antimicrobials, which can have serious consequences (7, 33).
Beside choosing the appropriate antibiotic, it is crucial to consider the dosage and duration of antimicrobial therapy when prescribing medication (7). For example, to optimize treatment outcomes in non-complicated urinary infections, it is generally recommended to prescribe a shorter course of antimicrobial therapy, ideally based on AST, lasting between 3 to 5 days (29). Chronic infections, skin infections (deep pyoderma) and infections with intracellular pathogens often require longer treatment (26). According to our results, 54.39% of veterinarians preferred a longer 5-10 day-course of antimicrobial therapy, which is consistent with the findings of a study conducted by Zhuo et al. (34). In contrast, 38.60% preferred a shorter course of 3-5 days while only 3.51% of veterinarians indicated that their preference depended on the diagnosis. Furthermore, it is recommended to weigh patients before administering antibiotics to discourage under dosing and emphasize the importance of accurate dosing (27). Our survey found that 64.91% of veterinarians complied with this recommendation.
Antimicrobial prophylaxis is a common practice in veterinary surgery, particularly in elective surgeries such as castration/ovariohysterectomy, where the risk of infection is low (27). Although it is generally advised not to use antimicrobials in clean surgical procedures, our study found that a significant number of veterinarians (45.61%) prescribed antibiotics after such surgeries (27). The incidence of surgical site infections (SSIs) in small animal surgery is typically 2-5%, and complications can be affected by factors such as wound type, surgery duration and hospitalization (27). When administered correctly, antimicrobials can diminish the chances of surgical site infections (SSIs) (35). However, if antimicrobials are not selected appropriately or administered incorrectly, it can lead to an increase in SSI cases and the emergence of antimicrobial-resistant bacteria (27). It is important to note that prophylactic antibiotics should not be used as a substitute for surgical asepsis and must be used with caution (27, 36).
Several studies on companion animals have shown significant use of broad-spectrum antimicrobials and a prescription pattern that does not align with current European guidelines (3, 7). Beta lactams, particularly amoxicillin and amoxicillin combined with clavulanic acid, are widely used as antibiotics for cats and dogs in Denmark, Finland, Italy, Sweden, Norway, and the UK (22, 37). Our results support the wide use of amoxicillin and amoxicillin-clavulanic in treating various infections such as skin, otitis externa, respiratory, gastrointestinal, and urinary infections. However, it seems there is a lack of awareness among veterinarians regarding the relevant guidelines and their recommendations for first-choice antibiotics. Clindamycin, for example, is often recommended as the drug of first choice for the treatment of skin infections in dogs (38). Similarly, amoxicillin and trimethoprimsulfamethoxazole are often recommended as first-line antibiotics for the empirical treatment of uncomplicated urinary infections (30). Based on our results, these antibiotics are less frequently used in practice (7%, 3.13% and 5.80% respectively). In contrast, doxycycline (9.80%) and amoxicillin (9.51%) are more commonly used for the treatment of respiratory tract infections, as they are also recommended as the first choice in the international guidelines for the treatment of respiratory diseases in dogs and cats (39). It has been found that among the antimicrobials classified as High Priority-CIAs by the WHO, fluoroquinolones and extendedspectrum cephalosporins are the most commonly prescribed in small animal veterinary practices (9, 33). In our study, enrofloxacin and marbofloxacin are among the most used antibiotics, even though they are categorized in category B, and they should be given after none of the antibiotics of category C or D is effective (14). Hur et al. (40) indicate that dogs are prescribed more antimicrobials than cats. Still, cats receive more high-importance-rated antimicrobials, such as cefovecin, a long-acting third-generation cephalosporin (41). This may be due to the ease of administration and its 14-day activity duration, which is beneficial for practitioners and owners with oral administration (23). However, of the 57 veterinarians, 48 (84.2%) stated that they do not use cefovecin to treat bacterial infections, probably because it is not licensed in our country (42). Our study did not differentiate between the use of antibiotics in dogs and cats. As no data is available to differentiate between antibiotic use in dogs and cats, further research is needed to better understand the antimicrobial use in companion animals in North Macedonia.
The findings of our study can help create the first national guidelines for antimicrobial stewardship in companion animals in North Macedonia. It’s crucial to continue the research and surveillance efforts to monitor and understand the prevalence of antimicrobial resistance (AMR) in companion animals, identify emerging resistance patterns, and develop strategies for prevention and treatment. Other factors should also be considered, such as the availability of licensed medicines in our country, national prescribing policies, and regional differences in diseases and antibiotic resistance (14).

CONCLUSION

In conclusion, the survey highlighted concerns about antibiotic prescribing practices among veterinarians in North Macedonia. The most concerning finding is that bacteriological and antimicrobial susceptibility testing is not commonly used before prescribing antibiotics. This, along with the frequent use of critically important antibiotics for humans in companion animals, significantly elevates the risk of antimicrobial resistance. Educational campaigns for veterinarians and pet owners are crucial to promote responsible antibiotic use and address this One Health issue.

CONFLICT OF INTERESTS

The authors declare that they have no known conflict of interest in the conduction of the current study.

ACKNOWLEDGMENTS

This research was supported by the Faculty of Veterinary Medicine - Skopje.

References

1. Marco-Fuertes, A., Marin, C., Lorenzo-Rebenaque, L., Vega, S., Montoro-Dasi, L. (2022). Antimicrobial resistance in companion cnimals: a new challenge for the One Health approach in the European Union. Vet Sci. 9(5): 208. https://doi.org/10.3390/vetsci9050208 PMid:35622736 PMCid:PMC9146952
2. World Health Organization (2021). Global antimicrobial resistance and use surveillance system (GLASS) report: 2021.
3. Joosten, P., Ceccarelli, D., Odent, E., Sarrazin, S., Graveland, H., Van Gompel, L., Battisti, A., et al. (2020). Antimicrobial usage and resistance in companion animals: A cross-sectional study in three european countries. Antibiotics 9(2): 87. https://doi.org/10.3390/antibiotics9020087 PMid:32079072 PMCid:PMC7175148
4. Galarce, N., Arriagada, G., Sánchez, F., Venegas, V., Cornejo, J., Lapierre, L. (2021). Antimicrobial use in companion animals: assessing veterinarians’ prescription patterns through the first national survey in Chile. Animals (Basel). 11(2): 348. https://doi.org/10.3390/ani11020348 PMid:33573203 PMCid:PMC7912091
5. Jin, M., Osman, M., Green, B.A., Yang, Y., Ahuja, A., Lu, Z., Cazer, C.L. (2023). Evidence for the transmission of antimicrobial resistant bacteria between humans and companion animals: a scoping review. One Health 17, 100593. https://doi.org/10.1016/j.onehlt.2023.100593 PMid:37448771 PMCid:PMC10336692
6. Guardabassi, L., Prescott, J.F. (2015). Antimicrobial stewardship in small animal veterinary practice: from theory to practice. Vet Clin North Am Small Anim Pract. 45(2): 361-376. https://doi.org/10.1016/j.cvsm.2014.11.005 PMid:25721619
7. Allerton, F., Prior, C., Bagcigil, A.F., Broens, E., Callens, B., Damborg, P., Dewulf, J., et al. (2021). Overview and evaluation of existing guidelines for rational antimicrobial use in small-animal veterinary practice in europe. Antibiotics 10(4): 409. https://doi.org/10.3390/antibiotics10040409 PMid:33918617 PMCid:PMC8069046
8. Nielsen, S.S., Bicout, D.J., Calistri, P., Canali, E., Drewe, J.A., Garin-Bastuji, B., Gonzales Rojas, J.L., et al. (2021). Assessment of animal diseases caused by bacteria resistant to antimicrobials: dogs and cats. EFSA J. 19(6): e06680. https://doi.org/10.2903/j.efsa.2021.6680 PMid:34194578 PMCid:PMC8237238
9. Lhermie, G., La Ragione, R.M., Weese, J.S., Olsen, J.E., Christensen, J.P., Guardabassi, L. (2020). Indications for the use of highest priority critically important antimicrobials in the veterinary sector. J Antimicrob Chemother. 75(7): 1671-1680. https://doi.org/10.1093/jac/dkaa104 PMid:32240295
10. Pomba, C., Rantala, M., Greko, C., Baptiste, K.E., Catry, B., van Duijkeren, E., Mateus, A., et al. (2017). Public health risk of antimicrobial resistance transfer from companion animals. J Antimicrob Chemother. 72(4): 957-968. https://doi.org/10.1093/jac/dkw481 PMid:27999066
11. Tomanic, D., Stojanovic, D., Belić, B., Davidov, I., Novakov, N., Radinovic, M., Kladar, N., Kovacevic, Z. (2021). Off label use of human approved drugs in treatment of dogs in the Republic of Serbia. Pol J Vet Sci. 24(3): 399-407. https://doi.org/10.24425/pjvs.2021.138731 PMid:34730304
12. European Medicines Agency (EMA). (2017). Sales of veterinary antimicrobial agents in 30 European countries in 2015. Trends from 2010 to 2015. Seventh ESVAC Report. Oj L 135: 1-109.
13. Duarte, A.S.R., Høg, B.B., Korsgaard, H., Attauabi, M., Boel, J., Dalby, T., Hammerum, A.M., et al. (2021). DANMAP 2020 - Use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, food and humans in Denmark. Statens Serum Institut og Technical University of Denmark. DANMAP.
14. EMA/CVMP/CHMP. (2019). Categorisation of antibiotics in the European Union. Eur Med Agence. 31, 1-73.
15. Frey, E., Costin, M., Granick, J., Kornya, M., Weese, J.S. (2022). 2022 AAFP/AAHA antimicrobial stewardship guidelines. J Am Anim Hosp Assoc. 58(4): 1-5. https://doi.org/10.5326/1547-3317-58.4.1 PMid:35793483
16. Mader, R., Muñoz Madero, C., Aasmäe, B., Bourély, C., Broens, E.M., Busani, L., et al. (2022). Review and analysis of national monitoring systems for antimicrobial resistance in animal bacterial pathogens in Europe: A basis for the development of the European antimicrobial resistance surveillance network in veterinary medicine (EARS-Vet). Front Microbiol. 13, 838490. https://doi.org/10.3389/fmicb.2022.838490 PMid:35464909 PMCid:PMC9023068
17. Cvetkovikj, I., Shikoska, I., Ratkova Manovska, M., Prodanov, M., Rashikj, L., Popova, Z., Djadjovski, I., Cvetkovikj, A. (2022). Antimicrobial resistance in Staphylococci isolated from dogs in the Republic of North Macedonia. Days of Vet Med. September, 22-25, (p. 48), Ohrid, North Macedonia.
18. Van Cleven, A., Sarrazin, S., de Rooster, H., Paepe, D., Van der Meeren, S., Dewulf, J. (2018). Antimicrobial prescribing behaviour in dogs and cats by Belgian veterinarians. Vet Rec. 182(11): 324. https://doi.org/10.1136/vr.104316 PMid:29196488
19. Chipangura, J.K., Eagar, H., Kgoete, M., Abernethy, D., Naidoo, V. (2017). An investigation of antimicrobial usage patterns by small animal veterinarians in South Africa. Prev Vet Med. 136, 29-38. https://doi.org/10.1016/j.prevetmed.2016.11.017 PMid:28010905
20. Hopman, N.E.M., Mughini-Gras, L., Speksnijder, D.C., Wagenaar, J.A., van Geijlswijk, I. M., Broens, E.M. (2019). Attitudes and perceptions of Dutch companion animal veterinarians towards antimicrobial use and antimicrobial resistance. Prev Vet Med. 170, 104717. https://doi.org/10.1016/j.prevetmed.2019.104717 PMid:31421495
21. De Briyne, N., Atkinson, J., Pokludová, L., Borriello, S.P., Price, S. (2013). Factors influencing antibiotic prescribing habits and use of sensitivity testing amongst veterinarians in Europe. Vet Rec. 173(19): 475. https://doi.org/10.1136/vr.101454 PMid:24068699 PMCid:PMC3841786
22. Hughes, L.A., Williams, N., Clegg, P., Callaby, R., Nuttall, T., Coyne, K., Pinchbeck, G., Dawson, S. (2012). Cross-sectional survey of antimicrobial prescribing patterns in UK small animal veterinary practice. Prev Vet Med. 104(3-4): 309-316. https://doi.org/10.1016/j.prevetmed.2011.12.003 PMid:22225772
23. Vandeweerd, J.M., Vandeweerd, S., Gustin, C., Keesemaecker, G., Cambier, C., Clegg, P., Saegerman, C., et al. (2012). Understanding veterinary practitioners’ decision-making process: Implications for veterinary medical education. J Vet Med Educ. 39(2): 142-151. https://doi.org/10.3138/jvme.0911.098R1 PMid:22718001
24. Frey, E., Kedrowicz, A., Hedgpeth, M.W. (2024). Decision making on antimicrobial use: cat and dog owners’ knowledge and preferences for veterinary communication. Vet Rec. 194(5): e3411. https://doi.org/10.1002/vetr.3411 PMid:37691448
25. Scarborough, R., Hardefeldt, L., Browning, G., Bailey, K. (2021). Pet owners and antibiotics: knowledge, opinions, expectations, and communication preferences. Antibiotics (Basel). 10(11): 1326. https://doi.org/10.3390/antibiotics10111326 PMid:34827264 PMCid:PMC8615269
26. Jessen, L.R., Damborg, P., Spohr, A. (2019). Antibiotic use guidelines for companion animal practice, 2nd ed. Danish Small Anim Vet Assoc. SvHKS.
27. Timofte, D., Broens, E.M., Guardabassi, L., Pomba, C., Allerton, F., Ikonomopoulos, J., Overesch, G., Damborg, P. (2021). Driving laboratory standardization of bacterial culture and antimicrobial susceptibility testing in veterinary clinical microbiology in Europe and beyond. J Clin Microbiol. 59(6): e02572-20. https://doi.org/10.1128/JCM.02572-20 PMid:33361339 PMCid:PMC8315970
28. Alcantara, G.L.C., Pinello, K.C., Severo, M., Niza-Ribeiro, J. (2021). Antimicrobial resistance in companion animals - Veterinarians’ attitudes and prescription drivers in Portugal. Comp Immunol Microbiol Infect Dis. 76, 101640. https://doi.org/10.1016/j.cimid.2021.101640 PMid:33684640
29. Weese, J.S., Blondeau, J., Boothe, D., Guardabassi, L.G., Gumley, N., Papich, M., Jessen, L.R., et al. (2019). International society for companion animal infectious diseases (ISCAID) guidelines for the diagnosis and management of bacterial urinary tract infections in dogs and cats. Vet J. 247, 8-25. https://doi.org/10.1016/j.tvjl.2019.02.008 PMid:30971357
30. Carmo, L.P., Nielsen, L.R., Alban, L., da Costa, P.M., Schüpbach-Regula, G., Magouras, I. (2018). Veterinary expert opinion on potential drivers and opportunities for changing antimicrobial usage practices in livestock in Denmark, Portugal, and Switzerland. Front Vet Sci. 5, 29. https://doi.org/10.3389/fvets.2018.00029 PMid:29546044 PMCid:PMC5837977
31. Chirollo, C., Nocera, F.P., Piantedosi, D., Fatone, G., Della Valle, G., De Martino, L., Cortese, L. (2021). Data on before and after the traceability system of veterinary antimicrobial prescriptions in small animals at the university veterinary teaching hospital of Naples. Animals 11(3): 913. https://doi.org/10.3390/ani11030913 PMid:33806745 PMCid:PMC8005210
32. Escher, M., Vanni, M., Intorre, L., Caprioli, A., Tognetti, R., Scavia, G. (2011). Use of antimicrobials in companion animal practice: A retrospective study in a veterinary teaching hospital in Italy. J Antimicrob Chemother. 66(4): 920-927. https://doi.org/10.1093/jac/dkq543 PMid:21393194
33. EMA. (2013). Reflection paper on the risk of antimicrobial resistance transfer from companion animals Summary. Ema/Cvmp/Awp/401740/2013. 44, 1-27.
34. Zhuo, A., Labbate, M., Norris, J.M., Gilbert, G.L., Ward, M.P., Bajorek, B.V., Degeling, C., et al. (2018). Opportunities and challenges to improving antibiotic prescribing practices through a One Health approach: results of a comparative survey of doctors, dentists and veterinarians in Australia. BMJ Open 8(3): e020439. https://doi.org/10.1136/bmjopen-2017-020439 PMid:29602857 PMCid:PMC5884343
35. Holloway, S., Trott, D., Shipstone, M., Barrs, V., Malik, R., Burrows, M., Norris, J., et al. (2022). AIDAP Antibiotic prescribing guidelines-companion animals. Aust Infect Dis Advis Painel. 2, 205.
36. Williams, J. (2018). Antimicrobial prophylaxis: the why and how of antimicrobial prophylaxis. BSAVA Companion 11, 4-7. https://doi.org/10.22233/20412495.1118.4 
37. Attauabi, M., Høg, B. B., Müller-Pebody, B. (2021). Summary Danmap 2020: use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, food and humans in Denmark. Statens Serum Institut og Technical University of Denmark. DANMAP
38. Hillier, A., Lloyd, D.H., Weese, J.S., Blondeau, J.M., Boothe, D., Breitschwerdt, E., Guardabassi, L., et al. (2014). Guidelines for the diagnosis and antimicrobial therapy of canine superficial bacterial folliculitis (antimicrobial guidelines working group of the international society for companion animal infectious diseases). Vet Dermatol. 25(3): 163-e43.
39. Lappin, M.R., Blondeau, J., Boothe, D., Breitschwerdt, E.B., Guardabassi, L., Lloyd, D.H., Papich, M.G., et al. (2017). Antimicrobial use guidelines for treatment of respiratory tract disease in dogs and cats: antimicrobial guidelines working group of the international society for companion animal infectious diseases. J Vet Intern Med. 31(2): 279-294. https://doi.org/10.1111/jvim.14627 PMid:28185306 PMCid:PMC5354050
40. Hur, B.A., Hardefeldt, L.Y., Verspoor, K.M., Baldwin, T., Gilkerson, J.R. (2020). Describing the antimicrobial usage patterns of companion animal veterinary practices; free text analysis of more than 4.4 million consultation records. PLoS One 15(3): e0230049. https://doi.org/10.1371/journal.pone.0230049 PMid:32168354 PMCid:PMC7069610
41. Burke, S., Black, V., Sánchez-Vizcaíno, F., Radford, A., Hibbert, A., Tasker, S. (2017). Use of cefovecin in a UK population of cats attending first-opinion practices as recorded in electronic health records. J Feline Med Surg. 19(6): 687-692. https://doi.org/10.1177/1098612X16656706 PMid:27507842 PMCid:PMC11128814
42. Food and Veterinary Agency of Republic of North Macedonia. (2024). List of veterinary medicinal products that have a marketing authorization, i.e. for which the approval has been cancelled, i.e. for which a change has been made during the validity of the authorization. Official Gazette of Republic of North Macedonia No.111/2024 [in Macedonian].


Copyright

© 2024 Shikoska I. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Conflict of Interest Statement

The authors declared that they have no potential lict of interest with respect to the authorship and/or publication of this article.

Citation Information

Macedonian Veterinary Review. Volume 47, Issue 2, Pages i-xii, e-ISSN 1857-7415, p-ISSN 1409-7621, DOI: 10.2478/macvetrev-2024-0020