Treatment Methods for Clinical Mastitis in Lactation
Spain: In Spain, treatment decisions are mostly made by farm personnel. They decide which cow needs to be treated, but the veterinarian decides which antibiotic to use. On large dairy farms that employ their own veterinarian, however, the veterinarian decides both. Clinical mastitis cases are often cultured by farmers to detect which group of bacteria is present on the dairy farm and for generating antibiograms.
There has been a change in the way antibiotics are administered in recent years in Spain. Only 10 years ago, mastitis was mainly treated intramammarily. In 2021, however, 55% of all cases were treated parenterally, 40% intramammarily, and in 5% of all cases, those two routes were combined. The duration of treatment is based on the label instructions, so intramammary treatments usually last 2–3 days and parenteral treatments 3–5 days. In some cases in which Strep. uberis or Staph. aureus is involved and the cure rate is low, an extended therapy of up to 5 days is recommended. However, a longer period is very uncommon. Antibiotic treatment is often supported by the administration of non-steroidal anti-inflammatory drugs (NSAIDs) (especially ketoprofen or carprofen). Here, a new trend can be seen, as some farmers who use on-farm culture tend to use NSAIDs as their first treatment choice when the major group of bacteria is Gram-negative. If clinical symptoms persist after 2–3 days, antibiotic treatment is administered. With this approach, only 20–30% of mastitis cases are treated with AMs without observing a worsening of udder health. However, the implementation of on-farm culture is quite slow, as it involves a considerable increase in effort for the farmers.
As far as critical antibiotics are concerned, a promising change has occurred. In the last decade, Category B antibiotics, like fluoroquinolones and third- and fourth-generation cephalosporins, were the first-choice treatment on many dairy farms. Due to pressure from the authorities and scientists with regards to AMR, a dramatic drop in the application of these treatments is visible. Electronic prescriptions have become mandatory, making it easier to track critically important antibiotic treatments. The National Plan Against Resistance to Antibiotics (PRAN) aims to raise awareness of the imprudent use of antibiotics and has established major guidelines for their usage. In consequence, nowadays Category B antibiotics are only used for hyperacute mastitis caused by Gram-negative bacteria such as Escherichia coli or Klebsiella subspecies, and only when diagnostic and antibiograms are performed. The most commonly used antibiotics today are penicillins and sulfonamides.
The Netherlands: In The Netherlands, a one-to-one relationship between the veterinarian and the dairy farmer is implemented. Politically enforced results of this relationship have to be farm-specific health and treatment plans. The veterinarian is responsible for making treatment decisions, whereas the farmer and/or the farm personnel carry out the administration based on the treatment plan. This approach has led to an improvement in dairy cow health and animal health in general. An official list created by the Veterinary Antimicrobial Policy Working Group (WVAB) of the Royal Dutch Veterinary Association (KNMvD) details prescribable medicine for dairy cows for a specific indication, and classifies veterinary AMs into first, second, and third choice for use in the existing veterinary treatment guidelines. This dairy formulary represents a guideline for AM use, and with the right veterinary practice directs the focus at deciding which cases of mastitis are worth treating and which are not.
AMs are commonly administered intramammarily (about 70%) in The Netherlands only for proven bacterial intramammary infections, since the Dutch government banned the preventive use of all AMs in animals [17
]. The average duration of treatment is, depending on the label, 4 days, and supportive therapy is also common practice. In parallel with the NSAIDs, however, an increase in non-evidence-based mastitis treatments, like the use of natural remedies such as phytotherapeutics, can be observed. The Dutch government aims to spread knowledge of natural remedies and good animal management to support animal health [18
In the last 10–15 years, political pressure to reduce AM use has increased in The Netherlands. Both farmers and veterinarians are obliged to contribute to a substantial reduction in antibiotic usage. This includes the obligation to make the use of antibiotics transparent using the annual animal-defined daily dose per herd (ADDD). This provides a benchmark for comparing different farms within a country based on AM prescription numbers. The Netherlands Veterinary Medicines Institute (SDa) sets the benchmarks, and monitors and evaluates the national trends to identify problem herds. This process of comparison and benchmarking motivates both farmers and veterinarians to further reduce antibiotic use. Furthermore, a restriction on the use of CIAs was introduced in 2011 and, consequently, the use was limited enormously [19
]. In addition, the preventive use of AMs was banned, which especially impacts dry cow therapy and has led to an increase in selective dry cow therapy since 2014. All these requirements resulted in a considerable decrease in antibiotic usage, up to 64%, in the dairy industry in The Netherlands, including CIAs, without deterioration of udder health. Recent years have seen an increase in preventive thinking. Both farmers and veterinarians have become more aware of the selection criteria for cows to be treated during lactation and in the dry period. Therefore, diagnostic testing in a veterinary practice or laboratory (and to some extent on-farm) has been expanded.
Estonia: In Estonia, the number of dairy cows was about 85,000, with an average herd size of 140 dairy cows. There are two types of veterinary services. Private practitioners provide their service to several dairy farms, whereas farm-specific veterinarians only work for one dairy farm or company. Antibiotics can only be prescribed by veterinarians. In acute mastitis cases, the farm-specific veterinarians do parenteral treatment themselves, while private practitioners usually use veterinary technicians or skilled farm personnel for parenteral treatments. In both cases, intramammary treatments are normally administered by the milkers and/or the farmers following guidelines by the veterinarian. The ratio of intramammary and parenteral therapy is more or less in proportion, with roughly 50% being treated parenterally. Extended therapy is a common practice in Estonia. The average treatment duration is 4 ± 2 days. In about 15% of the cases, treatment is extended to 7–10 days. Supportive treatment with NSAIDs is frequently used in moderate and severe cases, with ketoprofen as the most common remedy. Currently, available data on the sales of veterinary medicines in Estonia are based on wholesalers` reports collected by State Agency of Medicines and include total sales of veterinary medicines to veterinarians and veterinary pharmacies. However, this information is not itemized by animal species.
Instructions for prudent use of AMs and treatment guidelines were already available in 2012. In July 2021, the use of third- and fourth-generation cephalosporins and fluoroquinolones was restricted in Estonia. If the pathogens are resistant to other AMs, a sensitivity testing became mandatory prior to their use [20
]. However, monitoring, general verification, and analysis of the treatments and antibiotic use at farm level are missing. There is also no regulation by the authorities for the milk sample analysis prior to mastitis treatment. Although there are laboratories for testing, and on-farm culture takes place on farms, presumably less than 10% of clinical mastitis cases are analyzed every year in different laboratories.
From 2016–2020, there was a “penicillin promotion campaign.” Together with voluntary national guidelines published in 2017, the aim was to change the attitude and knowledge of both veterinarians and farmers. During this period, educational courses for veterinarians and farmers were organized and many papers were published. As a result, sales of penicillin, especially for intramammary usage, have increased over the years, while those of cephalosporins decreased. However, it is noteworthy that the amount of CIA marbofloxacin has also increased, and thus represents the second most commonly used agent for parenteral treatment, especially for acute cases.
In Estonia, there exists good cooperation with the government, but as there is no restriction at governmental level, voluntary involvement is required. That is why university researchers are trying at an educational level to engage in discourse with both farmers and veterinarians, studying attitudes and behaviors with regards to treatment by participatory epidemiology. They hope that in the near future institutions or the industry itself will start to control the usage of CIAs, and a general database for antibiotic use will be developed.
Ireland: In Ireland, antibiotics can be prescribed from the “attending” veterinarian for a bona fide client, but at the same time also from a “co-op vet.” These are veterinarians employed by the dairy co-op. If milk suppliers have signed up to a co-op Mastitis Control Program, they are entitled to apply for their prescription. A prescription is valid for 12 months (this changed with regulation (EU) 2019/6 which came into force in January 2022), and thus, the prescription from the co-op vet is often based on a forecast of the amount of antibiotics the farmer may need. Thus, the farmer often has intramammary tubes—the primary form of administration in Ireland—in stock for administration when needed. Antibiotic treatment is increasingly supported by the administration of NSAIDs. Severe cases are mainly attended to and treated by the veterinarian. Written treatment plans rarely exist, so treatment decisions are very often guided by experience rather than veterinary input or bacteriological culture. The duration of treatment is 3 days on average. Extended therapy sometimes occurs and if so, generally in consultation with the veterinarian who prescribed the agents.
Ireland has a seasonal calving system with over 70% of calving taking place between February and April. This is a labor-intensive time for farmers, so the practicality of sending samples from clinical cases immediately to the laboratory is difficult. Nevertheless, farmers often take samples from clinical cases and freeze them for later analysis. The intention of this is not usually to influence the decision-making for an individual cow, but rather to extend knowledge of the pathogens present on the farm. They also take samples of chronic cases to decide whether treatment is appropriate or not. The average milk recording participation is about 50% of the herds.
Regarding the availability of antibiotic products, it is noticeable that there are few licensed products in Category D. Due to this circumstance, and aided by the force of habit, the use of Category C products is high. There are also highest priority critically important antibiotics (HPCIAs: third-, fourth-, and fifth-generation cephalosporins, glycopeptides, macrolides, and ketolides, polymyxins, quinolones, [8
]) licensed for both lactation and dry cow therapy. In recent years, almost all in-lactation tubes sold in Ireland have contained a CIA from Category C, and in 2020, 13% of tubes sold contained an HPCIA, an increase of 7% compared to 2019 [21
]. It is also worth noting that many dairy co-ops have stopped stocking HPCIAs since 2019. The quantity of intramammary antibiotics being used, expressed as defined course dose for animals (DCDvet), has decreased since 2012 [21
]. One reason for this was the introduction of the national mastitis control program “CellCheck” in 2011.
As an upcoming tendency, there will be changes in the area of dry cow therapy with the regulation (EU) 2019/6 [11
]. At the moment, there is a high rate of blanket dry cow therapy. It would also be a good opportunity to redefine who is authorized to prescribe antibiotics and what the required thresholds of knowledge for prescribing should be. For this purpose, the introduction of herd-specific treatment plans would also be beneficial. Further trends are the implementation of an electronic National Veterinary Prescribing System during this year, and an increased availability of licensed narrow-spectrum products for treating bovine mastitis.
Poland: Polish dairy herds are relatively small, with an average herd size of less than 20 cows. The stables are often old, manure is usually removed only once a day, and the straw, as bedding material as well as the feed, can be of poor quality. In addition, the milking hygiene is often inadequate. These are the main reasons for bacterial infections of the udder, especially with environmental pathogens.
General treatment decisions are made by veterinarians who are also responsible for the first administration, especially in acute mastitis cases. The following treatments are determined by farmers, zootechnicians or other farm personnel. However, farmers can obtain any antibiotic tube from veterinary clinics at any time without a veterinarian paying them a visit. Antibiotics are commonly administered intramammarily. For specific cases in which Staph. aureus or Streptococcus agalactiae are involved, parenteral treatments are also used. The average duration of treatment is 2–3 days, with an extended therapy of 5–7 days in cases in which Strep. uberis or Staph. aureus is the causative pathogen. In acute cases, supportive treatment with antioxidants, selenium, and immunomodulators is given. The use of NSAIDs depends on the attending veterinarian.
Legislative requirements are generally missing in Poland. That is why each veterinarian makes treatment decisions at his or her discretion and without a set procedure. This also influences the usage of antibiotics, which has increased over the years. The use of CIAs is not restricted and, consequently, both quinolones and third- and fourth-generation cephalosporins are quite popular. The analysis of milk samples is not obligatory, so few farmers use this diagnostic tool. All these factors seem to culminate in high AMR rates in Poland.
However, during the last few years, some improvements have been made. Young farmers, in particular, are becoming more interested in the prevention of mastitis as well as in bacteriological examinations. Changing the mentality of both farmers and veterinarians towards putting prophylaxis of mastitis in the foreground, and thus reducing the use of antibiotics in the long term, is viewed as a crucial point.
Finland (and other Nordic countries)
: A network of mastitis researchers in the Nordic countries of Denmark, Finland, Norway, and Sweden, has jointly developed Nordic Guidelines for Mastitis Therapy (https://www.sva.se/media/qsljw2yb/nordic-guidelines-for-mastitis-therapy.pdf
, accessed on 15 October 2021). Practices and legislation differ to some degree between those countries, but the general approach is similar [22
In Finland, farmers do not have access to veterinary drugs, such as antibiotics, without a veterinary prescription. Farmers detect sick cows and call a veterinarian if required, and veterinarians make treatment decisions and initiate the treatments. Veterinarians can leave drugs on the farm so that farmers can continue the treatment of a specific animal according to veterinary advice. Most farms belong to the national herd health program, and, in that context, a veterinarian and a farmer can make an official contract, whereby the veterinarian visits the farm at regular intervals. In such cases, the veterinarian can leave antibiotics on the farm in advance for the treatment of commonly occurring diseases such as mastitis. This, however, requires detailed written instructions, careful electronic record keeping on the farm, and regular monitoring by the veterinarian that the instructions are followed. Only the amount of medicines that is expected to be needed in between two herd visits can be left on the farm. All veterinarians and farmers are required to keep records of all drugs they administer to food-producing animals.
Initiation of antibiotic treatment for intramammary infections is expected to be based on a microbiologic diagnosis. Milk samples are taken frequently to ensure the most appropriate and targeted treatment, but also to find out whether antibiotics could be omitted. Legislation requires regular bacteriologic analysis, so that etiologic agents of intramammary infections and their AMR profiles in the herd are known, even if not all mastitis cases were sampled. Which antibiotic is used depends on the type of pathogen causing the disease (Gram-positive, Gram-negative, β-lactamase−, β-lactamase+), but in general, penicillin is the drug of choice. As far as CIAs are concerned, it can be noted that no cephalosporin products are licensed and on the market for intramammary treatments. Fluoroquinolones are licensed for parenteral treatment of severe infections caused by Gram-negative bacteria. For such intramammary infections cases, however, the first choice for treatment is no antibiotics, but only supportive therapy. Recommendations for the route of administration and length of antibiotic treatments of intramammary infections depend on the etiologic agent and vary between the Nordic countries. In Finland, a 3-day intramammary treatment for mild and moderate clinical cases caused by most Gram-positive bacteria is used. Treatments of Staph. aureus and Strep. uberis intramammary infections are extended to 5 days, often using a combination of parenteral and intramammary therapy. Supportive treatment, such as fluid therapy or anti-inflammatories, is used in all severe cases.
Although the Nordic countries already have followed the prudent use of antibiotics guidelines, and thus have low antibiotic consumption rates, there is still interest in further reduction by focusing on prevention [22
: Regarding antibiotic therapy, a clinical examination of the sick animal by the veterinarian is required [23
]. Antibiotics are then prescribed by the veterinarian for that specific animal. A veterinarian may dispense prescription drugs for food-producing animals in an amount intended for use within the following 31 days. Medicinal products containing AM agents that are not exclusively applied locally may only be dispensed for the following 7 days [12
]. The administration of treatment is mostly done by milkers or the herdsman [10
]. Normally, farmers have a few udder tubes on the farm to start treatment according to treatment instructions made by the veterinarian. Accordingly, antibiotics are mostly administered intramammarily. Additional systemic AM treatment depends on the veterinarian and is mostly given in severe cases. Many farmers finish therapy after completing the instructions on the treatment protocol for mastitis, others stop when flakes are no longer detected in the milk [10
]. If clinical signs persist, or Strep. uberis
or Staph. aureus
is detected, therapy is sometimes extended. Supportive treatment, such as the use of NSAIDs, is used commonly but always depends on the preference of the treating veterinarian.
Although farmers are not legally obliged to have milk samples bacteriologically tested, about 70% of farmers do so regularly. The most common methods here are cultural detection and resistance tests. When it comes to the use of CIAs, a resistance test has been mandatory since the Amendment of Veterinary Pharmacy Regulation in 2018 [23
]. As a result, many veterinarians stopped using CIAs and farmers started to realize that it is important to use fewer CIAs in the future. In a survey conducted in 2019, only 17% of the farms mentioned using CIAs at all, and then, only used them in severe cases [24
Notably, a targeted therapy concept, serving as a guideline for more evidence-based therapy decisions, is gradually being adopted, especially in northern and central Germany. It can be used by both farmers and veterinarians. This procedure is based on an on-farm test in combination with the identification of animals worthy of treatment. Using this therapy concept, 73% of intramammary antibiotic doses and 65% of systemic antibiotics could be reduced [25
Italy: In Italy, there have recently been major changes. Monitoring of the use of antibiotics started with the introduction of an electronic prescription (“ricetta elettronica”) in 2019. With this implementation, and the fact that veterinarians in Italy do not sell drugs, farmers can buy all medicines indicated in the veterinary prescription from an external pharmacy. The treatment decision thus lies with the veterinarian today, whereas until 2019, the situation was quite similar to Spain, with mostly farmers and/or milkers making treatment decisions. The milkers then initiate the treatments based on veterinary protocols. Furthermore, “ClassyFarm,” a database collecting drug prescriptions, animal welfare, and production data from Italian farms, was introduced, which allows the analysis of antibiotic use for each farm.
Antibiotics are generally administered intramammarily based on label recommendations. Supportive treatment with anti-inflammatories has started to be part of the protocol in most clinical mastitis cases, also presenting a major change. In Italy, a specific length of treatment based on the etiology of the mastitis case does not exist, except for the herds where on-farm culture is performed. Important factors in this context are the level of experience of the veterinarian as well as the label instructions on the product. In some cases, therapy is extended for 5–7 days, with an increase in antibiotic withdrawal times. The veterinarian is also the decision-maker when it comes to cultural testing of milk samples. On-farm tests are only used on about 6% of farms, usually on large ones that are supervised by young veterinarians interested in milk quality. Other veterinarians collect clinical mastitis cases every month and send them to the laboratory to detect any change in epidemiology and to carry out resistance tests. Conversely, however, there are also farms performing no culture tests at all. Nonetheless, when a CIA is about to be used, legislation requires cultural analysis and resistance tests. In 2004, cephalosporins were the first choice of treatment, followed by fluoroquinolones [26
]. Today, influenced by the implementation of electronic prescriptions, the use of third- and fourth-generation cephalosporins has decreased, and first-generation cephalosporins and penicillin are experiencing more widespread application.
As an upcoming tendency, there is a discussion whether milk payment will not only be based on yield, butter fat, protein, and SCC, but also on the basis of welfare and reduction in the use of antibiotics. Furthermore, sharing information and the promotion of collaborations, both at a national level between different institutions and at an international level, is viewed as an important task to aid udder health.