Antimicrobial use for selected diseases in cats in Switzerland

Mitigation of antimicrobial resistance has been an emerging topic that plays an important role in human and veterinary medicine. Antimicrobial resistance in bacteria is a naturally occurring phenomenon and has been subject to evolution over millions of years [1–5]. The frequent use of antimicrobials in human and veterinary medicine and in agriculture exerts an enormous selection pressure on bacterial populations and promotes the development of multidrug-resistant bacteria that can readily spread their resistance genes by various mechanisms [1–3]. Antibiotic use in veterinary medicine is discussed as one of the main drivers for resistance development. In Europe, around 8000 tons of antibiotics were sold for veterinary use in 2015, with pronounced differences between countries [6]. The amount of antibiotics used in companion animals in Europe in comparison to the amount prescribed in livestock is relatively small [6], but is not to be neglected. The close contact of pets with their owners facilitates the transmission of multidrug-resistant organisms between humans and companion animals [1, 7–14]. Furthermore, the trend for intensive medical care of dogs and cats poses a risk for nosocomial infections [15–18] and is associated with an increasing number of geriatric and immunosuppressed patients that are highly susceptible to infections with multidrug-resistant bacteria.

Based on recent data, Centres for Disease Control and Prevention estimates that approximately 30 ̶50% of antibiotic prescriptions in humans are unnecessary [19, 20]. Surveys describing antimicrobial use in dogs and cats revealed that antibiotics are frequently prescribed, in particular beta-lactam antibiotics [21–30], and that cats are especially exposed to the critically important third generation cephalosporins [21–25, 30–33]. Most previous studies performed in dogs and cats were based on questionnaires presenting hypothetical scenarios that have been sent out to veterinarians [22, 23, 28, 33–37]. These studies are commonly hampered by a selection bias, recall bias and prevarication bias, and the answers given do not necessarily reflect the actual prescribing practice. Some studies analyzed pharmacy records [38, 39] and veterinary or pet insurance databases [21, 22, 24–27, 29, 30, 32] but only few studies evaluated whether prescriptions practice was in accordance with relevant guidelines [24, 26, 27, 33, 34].

The aims of this study were to investigate the antimicrobial prescribing practice in Switzerland for indications in cats with frequent use of antibiotics, i.e., in cases of acute upper respiratory tract disease (aURTD), feline lower urinary tract disease (FLUTD) as well as abscesses, and to evaluate to what extend the prescriptions comply with recently established consensus guidelines [40, 41]. The a priori compliance with the proposed guidelines was evaluated in this study to lay the basis to monitor, in a next step, the impact of these guidelines on antimicrobial prescription patterns in Switzerland.

The results of this study indicate that overprescription of antibiotics in cats in Switzerland with aURTD, FLUTD and abscesses is very common. When prescription was compared to the consensus guidelines, 14–34% of all cases received antibiotics although not indicated; when only the cases were considered for which judgment of prudent use was possible, the rate of antibiotic overprescription was even higher (29–48%). The diagnostic work-up was more elaborate at the university hospitals, and critically important antibiotics were less commonly prescribed at the universities, but the prudent use pattern of prescriptions was not clearly superior when compared to private practices. This was mainly due to the very common use of potentiated aminopenicillins instead of non-potentiated aminopenicillins at the universities. On the other hand, the quality of antimicrobial prescription could often not be judged in the cases from private practices because the diagnostic work-up or the symptoms of the patients were not documented. The common discrepancy of antimicrobial prescription with recently established consensus guidelines [40, 41] at the two university hospitals is surprising considering that senior clinicians of these hospitals were involved in the drafting of the guidelines. The overall frequency of antimicrobial treatment was also not different at the university hospitals compared to private practices. However, our data indicates that the animals presented to the university hospitals were more often pretreated or hospitalized, and could thus have been in a more debilitated condition.

Only 17 ̶24% of the treatment decisions in this study were classified as JS-1 and therefore in complete accordance with the consensus guidelines. Recent studies in dogs and cats have reported an overall agreement of 0–69% with published guidelines [24, 27, 33, 34]. This overall low accordance raises the question of whether the proposed guidelines cannot be implemented in clinical practice, for example, due to poor market availability of appropriate antibiotic formulations, or whether the content is not well disseminated among veterinary practitioners.

The critically important antibiotics used in cats in this study were mostly third generation cephalosporins as well as fluoroquinolones. Third generation cephalosporins were the second most frequently prescribed antibiotic class and were used in 25–28% of the cases. This mirrors the results obtained in previous studies [21–25, 31–33] and could likely be explained by the convenient application (as a single subcutaneous injection) and the long dosing interval (2 weeks) of the authorized product in Switzerland (cefovecin, Convenia®, Zoetis, Delémont, Switzerland). A previous study evaluating electronic health records found that inability to orally medicate the cat was the most common reason given for prescribing cefovecin [42]. An online survey in veterinarians in Switzerland also revealed that the route of application was the most important factor in the choice of antimicrobial therapy in cats [43]. In our study, the prescription of critically important antibiotics was significantly more frequent in private practices compared to the university hospitals. This observation supports the hypothesis that the workplace environment is an important factor determining treatment decisions and antimicrobial use [44]. University hospitals, as training centers, may have stronger restrictions for the use of critically important antibiotics: one of the two university hospitals of this study completely forbids the use of third generation cephalosporins in its patients. On the other hand, the cats at the university hospitals were more commonly hospitalized compared to the cases in private practices, thus allowing for parenteral medication and avoiding the problem of oral application of the antibiotic drug.

Antimicrobial prescription in the absence of proper diagnostic work-up was very common in this study. In only 40% of the FLUTD cases overall, and in only 10% of the FLUTD cases in private practices, bacterial culture and susceptibility testing were carried out. In a previous study based on a questionnaire, 32.5% of companion animal practitioners in Europe reported that they frequently undertake antimicrobial susceptibility testing whereas 9.1% never demand such tests [45]. In another survey from Italy, 91% of the practitioners reported to carry out microbiological analysis, although only 20% reported to do so frequently [35]. Our results indicate that these data based on questionnaires are probably too optimistic and that bacterial culture, an essential diagnostic work-up step for cats with FLUTD, is rarely performed in private practices. In contrast, bacterial culture was performed in 87% of the FLUTD cases presented to the university hospitals, although this did not result in a less frequent prescription of antimicrobials. Interestingly, 56% of the FLUTD cases at the universities received antibiotic therapy despite the absence of bacteria in urine culture. A total of 20% of these cats were pretreated with antibiotics which could have affected the interpretation of a negative bacterial culture result. Also many of these cats suffered from urinary tract obstruction and antibiotic therapy was initiated after removal of the indwelling urinary catheter.

The trend towards more diagnostic testing at the university hospitals is also demonstrated by a more frequent use of PCR for the detection of feline calicivirus (FCV) and feline herpesvirus-1 (FHV) in cases with aURTD. These tests can be useful to support a diagnosis of viral infection and to initiate supportive measures such as the prescription of famciclovir in the case of FHV infection, and thus reduce the use of antibiotics [46]. In this study, the detection of FCV and FHV did not affect the frequency of antibiotic prescription. Overprescription of antibiotics in cats with aURTD was common: although only 29% of the cats showed symptoms that would have justified an antibiotic therapy according to the consensus guidelines, 77% of the cases received antibiotic treatment. Potentiated aminopenicillins were most often prescribed at the university hospitals, while third generation cephalosporins and aminopenicillins were most commonly used in private practices. A study revealed that amoxicillin with clavulanic acid is not superior to doxycycline when treating cats with signs of acute respiratory tract disease [47]. Our data, however, indicate that the cases presented to the university hospitals were in a more debilitated condition, because 72% of the cats with aURTD were hospitalized in comparison to 3% in private practices. Furthermore, 68% of the cats presented to university hospitals had symptoms listed in the guidelines, while at the private practices only 21% of the cats were reported to show a poor general condition, fever, lethargy and/or anorexia. The more compromised clinical condition of the patients at university hospitals could explain the common use of potentiated aminopenicillins instead of doxycycline due to the lack of a licensed injectable doxycycline preparation in Switzerland. However, potentiated instead of non-potentiated aminopenicillins were almost exclusively used at the universities. Non-potentiated and potentiated aminopenicillins are often used interchangeably although it has been shown that the use of clavulanic acid may increase AmpC-mediated resistance causing inducible organisms to become insensitive to 1st to 3rd generation cephalosporins [48, 49]. The frequent use of potentiated aminopenicillins instead of non-potentiated aminopenicillins in this study could also be due to the better availability of these products on the market, since they make up the largest part of antimicrobial compounds licensed for cats in Switzerland [50].

A total of 96% of the cats with abscesses received antibiotic treatment but only 30% of the cats presented symptoms that, according to the guidelines, would justify an antibiotic therapy. Our findings are in line with results from previous studies where frequency of antibiotic prescriptions for skin diseases such as wounds or abscesses ranged from 90 to 97% [24, 32]. In children, antibiotics might sometimes be applied instead of local wound drainage to avoid anesthesia or sedation [51]. However, 72% of the cats in this study received local wound treatment and passive drains were placed in 15% of the cats. It can be assumed that, in many of these cases, antibiotics were supplemented as a preventative measure. Studies from human medicine showed that appropriate drainage of the abscess is important and that antibiotic treatment may not be necessary [52–55]. Several guidelines for small animals state that an antibiotic treatment is not indicated if the abscess is well-defined and the animal is in a good general condition [56–58].

The present study has some limitations. The insufficient documentation in the databases limited the information available for review. The presence of bacteria in urine sediment analysis of an aseptically collected urine sample was considered appropriate to confirm a bacterial etiology in cases with FLUTD, although this is considered insufficient diagnostic work-up according to some guidelines due to the variable quality of interpretation, the risk of stain contamination as well as the possibility of false positive results [57, 59]. In a recent study, overall accuracy of in-house microscopic evaluation for bacteriuria in primary practice was only 64.5% when comparing results to reference bacterial cultures [60]. We decided to consider these results since former studies have reported accuracies of urine sediment analysis of 97–98% when performed by experienced laboratory personal [61–64]. Furthermore, the generally low prevalence of bacterial cystitis in cats should not result in many false positive results [65–67].

The assessment score used in this study leaves a margin of interpretation and the justification of antimicrobial prescription was based on consensus guidelines released in Switzerland. Results could differ to some extent when comparing prescription to guidelines from other countries. Furthermore, the limited number of cases included per practice did also not allow for a statistical analysis at a single practice level. Also, there could be a selection bias since the participation in this study was on a voluntary basis and the enrolled practices might have been more aware of antimicrobial resistance and more likely to prescribe antibiotics prudently.

The present study highlights the need to promote antimicrobial stewardship in small animal medicine and to implement effective intervention strategies. Particular attention should be paid to the education of veterinarians, the propagation of diagnostic work-up and the need for proper documentation to justify antibiotic treatment. Antimicrobial stewardship at universities should be urgently advanced as they serve as role models for veterinary practice. Developments on the market to provide small spectrum antibiotics for convenient application would be of particular importance in cats since the route of application is a major factor in the choice of antimicrobials in this species. Such new products will contribute to ensure that effective antimicrobials remain available in the future to combat bacterial infections in human and veterinary medicine.

For statistical analysis, the commercially available SPSS® software (SPSS Inc., IL, USA) was used. Descriptive statistics and comparisons of groups were conducted. Because the continuous variables were not normally distributed, the Mann Whitney U Test was used to compare the median age as well as the duration of therapy between the university hospitals and private practices. For the median age, 95% confidence intervals (CI) were calculated. The Chi square test was performed for comparison of categorical variables (case characteristics, diagnostic work-up, hospitalization, antibiotic pretreatment and antibiotic prescription) between university hospitals and private practices; frequency of antibiotic therapy between the indications; association of symptoms listed in the guidelines (for aURTD and abscesses) or the presence of bacteriuria (for FLUTD) with antibiotic therapy. The level of significance was set at p < 0.05. For the comparison of the justification scores between university hospitals and private practices the Chi square test was performed and the significance level was adapted for multiple tests using the Bonferroni correction.