Different European Perspectives on the Treatment of Clinical Mastitis in Lactation.

As part of the European Network for Optimization of Veterinary Antimicrobial Treatment (ENOVAT), a webinar on the topic "Mastitis Treatment in Lactation" was held, in which eight mastitis experts from different European countries (Spain, The Netherlands, Estonia, Ireland, Poland, Finland, Germany, and Italy) presented their treatment approaches for clinical mastitis in lactation. The aim of this study was to compare the therapeutic approaches to identify commonalities and differences. In all eight participating countries, the decision to start treatment is usually made by the veterinarians, while the farm personnel are responsible for treatment administration. Antibiotic treatment is then typically administered intramammarily. The treatment duration often depends on the label instructions and is frequently extended if Staphylococcus aureus or Streptococcus uberis is involved. Administering supportive therapy, especially non-steroidal anti-inflammatory drugs (NSAIDs) is an established practice in all countries. Penicillin is the first-choice drug for the treatment of mastitis in an increasing number of countries. The use of critically important antimicrobials (CIAs) such as quinolones and third- and fourth-generation cephalosporins is at a low level in Finland and The Netherlands. In Estonia, Germany, Italy, and Spain, the use of CIAs is declining and is only allowed if milk samples are analyzed in advance following the legal framework. Systems for monitoring antibiotic use are being introduced in more and more countries. This exchange of different views will help the European countries to move towards a common high standard of antimicrobial stewardship in veterinary medicine.

1. Introduction

The development of antimicrobial resistance (AMR) currently represents one of the most important public health challenges [1]. Any use of antibiotics carries the risk of enhancing the development of AMR [2,3]. The amount of antibiotics used in food-producing animals has recently been below the amount used in human medicine. Nevertheless, it contributes enormously to the overall consumption of antimicrobials (AM) [4]. Both veterinary and human medicine have to address the problem of AMR and promote a more prudent use of antibiotics.

The European Network for Optimization of Veterinary Antimicrobial Treatment (ENOVAT), a COST Action CA 18217, aims to optimize the use of AMs in veterinary medicine, focusing on developing guidelines for AM treatment and improving microbiological diagnostic methods. Members of the project Working Group 4 aim to describe standards for veterinary practice guidelines on the use of AMs, and to establish a priority list of infectious diseases that make up a relatively high proportion of AM consumption in animals [5]. One of them is bovine mastitis. In dairy cows, bovine mastitis represents one of the most common infectious diseases. AM treatment of mastitis remains an important part of mastitis control and represents the main reason for antibiotic treatment in dairy cows [6,7].

To further promote prudent use of antibiotics in Europe in the field of mastitis treatment, it is important to record and understand the current treatment strategies and approaches in the different European countries. On Wednesday, 29 September 2021, a webinar on the topic “Mastitis Treatment in Lactation” was held as part of Working Group 4 of the ENOVAT project. Therein, eight mastitis experts from Spain, The Netherlands, Estonia, Ireland, Poland, Finland, Germany, and Italy described how clinical mastitis in lactation is usually treated in their countries. The aim of this study is to evaluate and compare the different therapeutic approaches and to highlight commonalities and differences. It is intended to help improve understanding of different strategies in European countries and provide a benchmark for comparison between countries. It further aims to help European countries to converge by sharing different views, and thus move towards a common high standard of AM stewardship in veterinary medicine. Finally, it may be possible to come up with urgent research questions that need to be targeted by the scientific community in the near future.

2. Results and Discussion

Looking at the therapeutic approaches for clinical mastitis in lactation in the different European countries of Spain, The Netherlands, Estonia, Ireland, Poland, Finland, Germany, and Italy, both differences and similarities become clear. An overview of the comparison of the therapy methods can be seen in Table 1. A more detailed description of the contents of the individual countries can be found in Appendix A.

Table 1

Comparison of selected aspects from eight European countries concerning the treatment of clinical bovine mastitis in lactation.

1a. Treatment Decision	Mostly Farm Personnel	Veterinarian	Veterinarian and Farm Personnel
	ESP1, IRL2	NLD3, FIN4, EST5, GER6	POL7 ITA8
1b. Treatmentadministration	Mostly farm personnel	Veterinarian and farm personnel
	ESP, NLD, IRL, GER, ITA	EST, POL, FIN
2a. Diagnostic	All: Clinical symptoms, elevated cell count, etc.
2b. Bacteriologicalanalysis	Often	Sometimes	Rarely	Not specified
	FIN, GER, ESP	IRL, ITA	EST, POL	NLD
3. Legislative requirements for analysis of milk samples	Existing	Not existing	Not specified
	For CIAs9: ESP, GER, ITA, ESTRegularly: FIN	POL, IRL10	NLD
5. Way of treatment	Mostly parenterally	Mostly intramammarily	Equally often	Others
	ESP	NLD, IRL, POL, GER, ITA	EST	FIN11
6. Treatment duration	Following label instructions12	Extended	Others
	ESP, IRL, POL	ITA (3–5d imm)EST (4d ± 2d; up to 7–10d)NLD (circa 4d)ESP, POL, FIN, GER (Staph. aureus, Strep. uberis)	FIN (depends on pathogen)GER (depends on treatment protocol)
7. Supportivetreatment	NSAIDs13 used commonly	Other supportivetreatment
	All	NLD (natural remedies)
9. Use of CIAs	High use	Medium use	Low use
	POL (esp. fluoroquinolones)EST14 (esp. marbofloxacin)ITA14, ESP14	GER, IRL	FIN, NLD

1 Spain, 2 Ireland, 3 The Netherlands, 4 Finland, 5 Estonia, 6 Germany, 7 Poland, 8 Italy, 9 critically important antimicrobials, 10 guidelines for highest priority critically important antimicrobials (HPCIAs) existent, 11 depends on the pathogen, 12 2–3d intramammary (imm), 3–5d (parenteral), 13 non-steroidal anti-inflammatory drugs, 14 drop in the recent time.

The testing of milk samples is handled quite differently in the evaluated countries. On the one hand, in countries like Finland, Germany, and Spain, milk samples are often used to detect the pathogen and for the preparation of antibiograms. In Finland, polymerase chain reaction (PCR) is the most common method used in milk sample testing, while in Germany, cultural detection is predominant. In Ireland, farmers often take samples of clinical cases but, due to time constraints, freeze them first and have those analyzed later on. The frequency of the use of milk samples often also depends on the preference of the veterinarian, as is the case in Italy, Poland, and Estonia. Basically, however, little attention is paid to this diagnostic device in Estonia and Poland. Interest in on-farm culture is noticeable in almost all countries. This diagnostic tool is already widely used in some countries like Germany or The Netherlands. In other countries, its use is still in the initial stage, but young veterinarians in particular are interested in it being used more readily.

Regarding the legislative framework for the analysis of milk samples in the individual countries, there is a consensus in Spain, Germany, and Italy. In all three countries, milk samples need to be analyzed when critically important antimicrobials (CIAs) are about to be used. In July 2021, sensitivity testing prior to their use became mandatory in Estonia as well. In Ireland, to date, sampling to justify the use of highest priority critically important antimicrobials (HPCIAs) is only recommended. Finnish legislation requires milk samples to be analyzed regularly, whereas there are no legislative requirements in Poland.

Two different AM classification systems were taken into consideration. The WHO CIA list demonstrates the importance of various AM groups to human medicine: important AM, highly important AM, critically important AM (CIA, with prioritization to high priority and highest priority (HPCIA)) [8]. The European Medicines Agency (EMA) categorization classifies the AMs for prudent and responsible use in animals into four different groups: Category A (“Avoid”), Category B (“Restrict), Category C (“Caution”), Category D (“Prudence”) [9].

In Spain, The Netherlands, Italy and Germany, the use of CIAs has decreased in recent years. Due to fewer licensed Category D products, and aided by the force of habit, in Ireland, almost all tubes contain a CIA, and in 2020, 13% of tubes sold contained an HPCIA. However, the development is positive there, as many co-ops stopped stocking HPCIAs. The use of CIAs can be improved in Poland and Estonia because the use of CIAs is very popular there. In Poland, there is a lack of legal regulations, and the use of antibiotics has even increased over the last years. In Estonia, there have nevertheless been positive developments as well, through voluntary engagement on the part of the scientific community. This has increased the use of penicillin and decreased the use of cephalosporins.

The administration of supportive therapy is an established procedure in more or less all countries, with the use of non-steroidal anti-inflammatory drugs (NSAIDs) predominating. It should be noted that the use also often depends on the preference of the veterinarian, e.g., in Germany and Poland. In The Netherlands, there has been an increase in non-evidence-based mastitis therapy. The Dutch government is promoting the use of natural remedies such as phytotherapeutics to further reduce antibiotic usage.

Furthermore, there are differences in the application of treatment plans. The Netherlands has a model role in this respect, as the 1:1 relationship between veterinarians and farmers, enforced by political pressure, results in herd-based health and treatment plans. In Finland, the preparation of treatment plans and an official herd health contract between a farmer and a veterinarian with regularly scheduled herd visits are prerequisites for leaving antibiotics on the farm in advance for certain commonly occurring diseases. There also exist treatment plans in Germany, but only approximately 30% of them are written down [10]. In most cases, treatment instructions are communicated verbally with the farmer. The Estonian farmers are educated by the veterinarians and also administer antibiotics according to their instructions. In Ireland, there are only a few written treatment plans at all. One reason for this may be the fact that antibiotics for one farm may be prescribed by more than one veterinarian.

Systems and procedures for monitoring antibiotic use are being introduced in more and more countries. In The Netherlands, The Netherlands Veterinary Medicines Institute (SDa) monitors antibiotic use at farm level and thus evaluates national trends. In Finland, all treatments given to food-producing animals must be recorded, which is monitored by the Finnish Food Authority. With the introduction of the electronic prescription system “ricetta elettronica” in 2019 and the database “ClassyFarm,” Italy also started monitoring the use of antibiotics. Electronic prescription of medicines was introduced in Ireland in 2022. With the National Veterinary Prescription System (NVPS), they aim to meet certain requirements within the new EU veterinary medicines regulation 2019/6 [11]. In Spain, electronic prescription became mandatory in 2018, with the result that the use of CIAs, in particular, has dropped. There also exists the National Plan Against Resistance to Antibiotics (PRAN) in Spain which established guidelines to monitor the consumption of antibiotics, control antibacterial resistance, and promote preventive measures. Furthermore, there are regulations for the recording of antibiotic use in Germany, but these currently only apply to meat producers [12]. Monitoring and general analysis of treatments and antibiotic use at farm level are missing in Estonia. There are available data on the sales of veterinary medicines based on wholesalers’ reports, but these data are not divided by species.

With the enforcement of the new EU veterinary medicines regulation 2019/6, a veterinary prescription is mandatory when antibiotics are used in all European countries [11]. However, in Poland, farmers can obtain any antibiotic tube from veterinary clinics at any time without paying a veterinarian a visit. In Ireland, more than one veterinarian can prescribe drugs for a farm, which is a controversial issue as not all veterinarians involved know the farm and/or the farmer well.

The contents of this study need to be viewed within the usual limitations of expert opinions [13]. Due to different mindsets and experiences, there may have been differences in the interpretation of various aspects of the therapy by the speakers. Since the information of the presentation often came from personal experiences or from exchanges with other veterinarians working in the cattle sector, it must be taken into account that these could be anecdotal to some extent. Nevertheless, it can be stated that expert opinions are an important addition, alongside scientific papers, to provide evidence, especially in the practical field of mastitis therapy and its consequences. They help to overcome the gap between clinical research and practical clinical medicine. Thus, they complement empirical evidence and make an overall critical contribution in the context of clinical research. Expert opinion should always be based on clinical experience [14,15]. The experts who participated in this webinar and presented treatment approaches from their respective countries were all veterinarians working in the field of bovine medicine. In addition to their experiences, scientific literature from the respective country was used as a source of information when available. This shows that the information presented is based on both clinical experience and scientific work and can therefore be considered meaningful.

In addition, it should be briefly mentioned that webinars are a relevant platform for knowledge exchange, allowing experts from a wide range of countries to participate and share their knowledge [16]. However, since the length of this webinar and thus the number of participating countries was limited, only a selection of representative European countries could be considered in this study. Therefore, expert opinions from other countries (e.g., United Kingdom, France, and Belgium) are missing. Nevertheless, in selecting the participating countries, emphasis was placed on presenting as broad a picture as possible of European treatment practices for clinical mastitis in lactation. Thematically, the subject area addressed in this webinar was the treatment of clinical mastitis in lactation. To achieve a complete representation of the mastitis treatment of European countries, such as treatment practices of subclinical mastitis and dry cow therapy, further webinars or similar are necessary.

The identified differences between the participating countries in how clinical mastitis in lactation is treated in their respective countries give rise to some research questions that need to be targeted by the scientific community in the near future:

Systemic treatment versus local treatment: Which treatment method is more effective?

What is the sufficient treatment duration and how can it be determined?

Do we need critically important antibiotics in mastitis treatment?

How much diagnostics is really needed?

Do different initial situations (like pathogens, AMR, etc.) represent a cause for the described differences?

3. Materials and Methods

To reach the goal of optimizing the use of AMs in veterinary medicine, members of the ENOVAT project aim to generate an overview of the current state of microbiological diagnostic procedures and veterinary treatment in Europe. To gain an understanding of the current treatment methods for clinical mastitis in lactation in Europe, an international webinar was scheduled. Various mastitis experts from several European countries were contacted via email and asked to participate in the webinar. They were each requested to prepare a 10 min presentation on their treatment approaches for clinical mastitis in lactation. To give some orientation, a list of possible aspects that they could focus on in their presentations was prepared in advance. The list included the following:

Who is responsible for making treatment decisions and for treatment administration in general with regards to bovine clinical mastitis/therapy of high cell count cows in lactation?

How does the underlying diagnostic for justification of treatment work?

What are the legislative requirements for analyzing milk samples?

Are there noteworthy differences in the treatment practice of mastitis based on different production systems?

How is an antibiotic treatment commonly administered?

How long is antibiotic therapy usually given for, and what criteria are used to assess this?

Is supportive treatment commonly used? If yes, what kind, and for which indication?

Are broad-spectrum antibiotics used in mastitis treatment? If yes, for which indication?

Are critically important antibiotics (CIAs) used in mastitis treatment? If yes, for which indication?

Have there been any significant changes in the development of mastitis treatment in your country in the last 10 years?

Are there any upcoming tendencies that you would expect to change mastitis treatment practices in your country in the near future?

Eight mastitis experts from Spain, The Netherlands, Estonia, Ireland, Poland, Finland, Germany, and Italy participated in the webinar, all of whom are veterinarians active in a wide variety of fields related to cattle health (Table 2). The speakers were free to choose whether to address the topics of all the points on the orientation list in their presentation, or to pick out a few points that they felt were particularly relevant. Around 200 listeners followed the webinar and actively participated via chat. The webinar took place within the framework of a virtual mobility grant from the ENOVAT project to strengthen existing networks, share knowledge, and learn new techniques. It was held online via a platform of Copenhagen University, Denmark and was recorded for subsequent editing.

Table 2

The eight speakers of the webinar “Mastitis Treatment in Lactation”.

Mastitis Expert	Country	Field of Expertise
Demetrio Herrera	Spain	Cofounder of international company Q-Llet
Christian Scherpenzeel	The Netherlands	Dairy veterinary specialist at Royal GD Animal Health
Piret Kalmus	Estonia	Associate Professor at Estonian University of Life Sciences, Institute of Veterinary Medicine and Animal Sciences
Finola McCoy	Ireland	CellCheck Program Manager
Sebastian Smulski	Poland	Veterinary laboratory manager, Assistant Professor at Poznan University of Life Sciences
Päivi Rajala-Schultz	Finland	Professor of Milk Hygiene and Cattle Health at University of Helsinki
Anne Schmenger	Germany	Postdoc at Hannover University of Applied Sciences and Arts
Paolo Moroni	Italy	Professor at University of Milan at the Department of Veterinary Medicine; Director of Quality Milk Production Services Program (QMPS)

4. Conclusions

The treatment of intramammary infections represents the main reason for the use of antibiotics in dairy cows. That is why changes are needed in the way clinical mastitis in lactation is treated, not only in individual countries, but across all European countries. To this end, it is necessary to exchange information, views, and approaches, and to promote cooperation at both national and international levels.

There are promising trends in many of the participating European countries. The use of CIAs is already declining in many countries due to pressure from the authorities. In some countries, such as Spain, Germany, Italy, and Estonia, testing of milk samples is mandatory if critical antibiotics are to be used. As already mentioned above, antibiotic use is directly related to the development of AMR [2,3]. That is why the recording and monitoring of antibiotic use is crucial. Fortunately, systems and procedures for recording are being introduced in more and more countries.

In the area of lactational mastitis treatment, increased diagnostic efforts will be necessary in the future to be able to use antibiotics in a more targeted manner. One possible way is the use of rapid on-farm tests, which can often avoid unnecessary use of antibiotics. In addition, a change in drug selection towards narrow-spectrum antibiotics is an important lever for future improvements in antibiotic use. To implement and establish improvement measures, legislative requirements are crucial. Many of the participating countries already have strict legal requirements at the national level that restrict, for example, the use of CIAs. For further Europe-wide improvement of antibiotic use, legal regulations in all European countries are essential. An important contribution has only recently been made at the European level by regulation (EU) 2019/6, which created further legal framework conditions for the best possible use of antibiotics in livestock farming. However, in addition to legal requirements, the willingness of all stakeholders to cooperate, both between countries and at the national level, is key to implementing change. Cooperation between countries allows for the exchange of ideas and learning from each other’s successes and failures. At the farm level, close collaboration between veterinarians and farmers promotes understanding of the benefits of new requirements and ensures their conscientious implementation. For this reason, collaboration at all levels must be promoted in the future, for example, through more webinars like this one.

In the end, it became clear that overall, European countries have a common basis to jointly address the problem of AMR. And since this webinar had about 200 listeners, with some even attending from countries outside Europe, it is clear that the subjects of antibiotics in dairy farming and the related development of resistance in bacteria are topics of global interest.