26 Mar 2024
Nim Panesar
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Mastitis is the most common disease of dairy cattle, causing economic losses through reduced yield and poor quality of milk (Cheng et al, 2020). In the UK it is also the most common reason for administering antibiotics to dairy cows.
The epidemiology of mastitis has evolved over the years, with shifts in pathogen type, herd structure and approaches to prevention and treatment. As vets, our role in antimicrobial stewardship and addressing public concerns about antibiotic usage has also become increasingly important (Ruegg, 2018).
The aim of this article is to provide an update on mastitis pathogen prevalence and antimicrobial usage and monitoring, and to summarise the latest literature on treatment and prevention strategies for mastitis.
An extensive amount of fresh literature on mastitis pathogen prevalence from UK dairy farms is not available. Surveys by Bradley et al (2007) and Payne et al (2013) found Streptococcus uberis and Escherichia coli were the most frequently isolated pathogens from clinical mastitis (CM) cases, and concluded that environmental pathogens predominated, although in some herds contagious pathogens remained an issue. This is a clear shift from the picture in the UK 50 years ago (Bradley et al, 2007). A more detailed look at the aetiology of mastitis is beyond the scope of this article, but can be found in a previous article in Vet Times (Neale, 2022).
Latest mastitis bacteriology data can be found in the Veterinary Antimicrobial Resistance and Sales Surveillance Report (UK-VARSS, 2022), which shows results from bovine mastitis samples submitted to APHA. Although the sample size was much smaller, S uberis was the most frequently isolated pathogen in 2021, followed by E coli and S aureus.
The report also showed results of antibiotic sensitivity testing of key bovine mastitis pathogens: resistance to beta-lactams was low/not detected for all pathogens except E coli, which showed moderate/high resistance to beta-lactams. One E coli isolate was found to be resistant to a highest priority critically important antibiotic (HP-CIA), and penicillin resistance was not detected in streptococci.
This data was from a collaboration project between the VMD and APHA to collect and analyse samples from private veterinary laboratories to enhance routine antimicrobial resistance (AMR) surveillance in animals (VMD, 2023a; 2023b). A summary of the results of this project can be found in Swinson et al (2023).
As one of the most prevalent diseases in UK dairy farms, mastitis contributes a significant proportion to the industry’s medicines and antibiotics usage. Yearly updates on antibiotic sales, use and AMR across all food-producing species are published in UK-VARSS.
In the dairy sector, trends in use of intramammary tubes are monitored by looking at total sales across a rolling three-year period (UK-VARSS, 2023). The key findings from the report published in September 2023 from available antibiotic use data in cattle are shown in Panel 1.
Definitions of the antimicrobial use metrics used in the aforementioned report are summarised in Panel 2. The update shows UK antibiotic sales and usage is on track to meet the RUMA Task Force Targets set out to be achieved by 2024 (RUMA, 2020), which are shown in Panel 3.
Also published in 2023 was the RUMA Targets Task Force 2: 3 Years On (TTF) report, which summarised the progress made against antibiotic use since the Targets Task Force was launched in 2020. To examine antibiotic use in the dairy sector, clinical and subclinical mastitis data was monitored from 81 “sentinel” herds across the UK (Panel 4).
These findings were from a study carried out by Leach et al (2023) as part of a project funded by AHDB Dairy looking at individual somatic cell counts (SCC) and CM records from a cohort of milk recording herds between 2012 and 2020. They concluded the encouraging progress in mammary gland health was likely a result of implementation of a national Mastitis Control Plan (MCP) and QuarterPRO initiatives to tackle problems at individual farm level. Other factors that have contributed are pressure to reduce antimicrobial use from the industry and financial implications such as bonus and penalty payments for bulk milk SCC and targets for CM imposed by some milk buyers (Leach et al, 2023).
Medicine Hub was launched by the Agriculture and Horticulture Development Board (AHDB) in 2021 and is a centralised national database aiming to improve antibiotic use data collection from dairy, sheep and beef enterprises. Figures presented in the latest RUMA TTF report using data from Medicine Hub only represent a low proportion of the dairy sector (28%) compared to other livestock sectors’ medicine use data (more than 90% coverage), highlighting the importance of vets and producers to participate in more active engagement with Medicine Hub as a crucial part of the drive to encourage responsible use.
Another update due this year is from the VMD-led PATH-SAFE project, which is looking at the levels of AMR bacteria in healthy ruminants. Previously, the only two livestock sectors routinely monitored for AMR in the UK were pigs and poultry, results of which are published yearly within the VARRS reports. The PATH-SAFE project is conducting four pilot surveys to bridge this knowledge gap to produce baseline ruminant-specific AMR data through surveillance in bulk milk, sheep, livestock feed and in beef cattle (Kirby, 2023). Since the majority of AMR and mastitis pathogen prevalence data is currently sourced from private laboratories, it will be interesting to see the findings, which are due to be published in 2024 (VMD, 2023).
Treatment of mastitis revolves around the use of lactating and dry cow intramammary antibiotics, NSAIDs and, in some cases, injectable antibiotics. However, sector-specific recommendations set out in the RUMA TTF2 (RUMA, 2020) contained targets to reduce HP-CIA use, lactating and dry cow intramammary tubes and increase sealant usage, highlighting that mastitis treatment is a key industry focus. Use of farm-specific control plans, modifying existing approaches to mastitis treatment to reduce unnecessary antibiotic use, and on-farm culture (OFC) are approaches through which improved mastitis control can be achieved (Breen, 2021).
Using OFC aims to minimise the use of antibiotic based on the likely causal pathogen, which guides the strategic treatment of mild-moderate cases of CM. Lago et al (2011) showed use of OFC reduced intramammary antibiotic use by 50% and decreased milk withhold time by one day without sacrificing treatment efficacy. Farms could also incur considerable savings on treatment-related costs (Lago et al, 2018). However, appropriate herd selection is important: it is suitable for low SCC herds with a low prevalence of Gram-positive pathogens such as S uberis, as randomised clinical trials suggest that the impact of deferring treatment and using an OFC approach may result in a poorer chance of cure for Gram-positive pathogens – and it may not be cost-effective in herds where the prevalence of Gram-positive pathogens is greater than 20% (Breen, 2021). A more detailed look at OFC can be found in a previous article in Vet Times (Plate and Hayton, 2021).
It is worth noting that, in contrast to OFC findings by Lago et al (2018), Bruno et al (2023) showed significant benefits were achieved in treating non-severe clinical Gram-negative mastitis with antibiotics compared with not treating these cases. Similarly, Fuenzalida et al (2019) showed improved bacteriological cure rates in Gram-negative infections caused by Klebsiella pneumoniae when treated with intramammary antibiotics. However, the study also found treatment of non-severe E coli mastitis with intramammary antibiotics had no economic benefit.
Some evidence suggests that extended duration intramammary therapy can increase the bacterial cure of invasive pathogens such as S aureus (Barkema et al, 2006), but no evidence exists to show it improves clinical outcomes for non-invasive pathogens such as E coli, which infect superficial mucosal surfaces (Ruegg, 2018).
Administration of parenteral antibiotics for the treatment of CM does not provide significant benefit over intramammary antibiotics, because it is difficult to attain and maintain therapeutic concentrations in milk or udder tissue following systemic administration (Pyörälä, 2009). The exceptions would be severe or toxic coliform mastitis where parenteral administration has been suggested to combat bacteraemia (Pyörälä, 2009) and mastitis caused by S aureus (Barkema et al, 2006).
NSAIDs have an important role in mastitis treatment to help reduce inflammation and, most importantly, for cow welfare and pain relief (Breen, 2017). Evidence is well-established for use of NSAIDs in treatment of severe CM, including mediating endotoxin-induced effects in acute coliform mastitis. Some evidence suggests the addition of NSAIDs to antibiotic therapy for the treatment of CM can reduce quarter-level SCC and risk of culling (McDougall et al, 2009), and that NSAID use in conjunction with intramammary antibiotics resulted in a higher probability of bacteriological cure for mild-moderate cases of CM (McDougall et al, 2016).
Use of NSAIDs without antibiotics in treatment of CM is an important area of further research, especially with increasing use of OFC. Only one study was found showing that NSAIDs as a sole treatment for OFC-negative, mild CM did not reduce time to clinical cure compared with untreated controls (Latosinski et al, 2020).
Finally, the prognosis and likely outcome of treatment, as well as cow welfare, are important when making mastitis treatment decisions. Appropriate usage guidelines infer the cow is healthy enough to respond, and treatment protocols should include a review of the cow’s medical history before a decision is made to give antibiotics (Ruegg, 2018). Glover et al (2021) proposed the concept of “treatment worthiness” as a framework for determining which cows receive antimicrobial therapy for CM and showed that use of statistical models that evaluate cow and herd level factors with the probability of cure could be used to inform decision-making with regards to CM treatment.
Prevention of new infections to avoid the need for antibiotic treatment is also an important way through which improved mastitis control, and therefore reduced antibiotic use, may be achieved (Breen, 2021). Prevention was historically focused on reducing the risk of contagious mastitis through implementation of a five-point plan, and more recently environmental control through farm-specific risk factor control such as the MCP. Other areas of focus should include strategies to optimise mammary gland defences, which are an effective way to prevent the establishment of new infections and limit the use of antimicrobials needed to treat them (Sordillo, 2018).
Vaccination can augment a herd mastitis control plan under certain circumstances. Two commercial mastitis vaccines are available in the UK; Startvac and Ubac (both Hipra UK). A meta-analysis conducted by Mata et al (2023) looking at the efficacy of mastitis vaccination concluded that while full clarification of efficacy was not shown, vaccination had demonstrated a reduction of the severity in clinical cases, rate of culling and had increased the production of milk and milk solids.
If vaccination is used, the data sheet protocol should be followed. Importantly, vaccination should only be applied as part of a comprehensive mastitis prevention programme, and not as a proxy for inadequate management (Erskine, 2012).
Nutritional status is directly related to the efficiency of the immune response; a balanced macronutrient supply has an essential role in optimising immune response and increasing disease resistance, and of these, vitamin E and selenium have an important role in supporting aspects of innate and adaptive immunity that can influence mastitis susceptibility (Sordillo, 2018). Dietary deficiency of vitamin E and selenium can increase incidence and duration of CM (Ruegg, 2017), although it is important to note dairy cows in the UK are unlikely to be deficient in macronutrients except in extensive grazing systems.
Coagulase-negative staphylococci (CNS) are a predominant cause of intramammary infection and subclinical mastitis in heifers. Mastitis in heifers can be costly especially due to increased risk of premature culling and lost future milk yield. A review by De Vliegher et al (2012) recommended fly control, avoidance of inter-sucking, and hygienic and comfortable housing as important for prevention of heifer mastitis. However, this is an area where future research is needed to help us better understand the epidemiology and effect of CNS infections (Ruegg, 2017).
In summary, the current picture of mastitis control shows a declining trend in mean CM rate, SCC and dry period new infection rate (Leach et al, 2023). Sales of intramammary antibiotic tubes have also fallen to below the targets set by the RUMA TTF (2020). However, there is still considerable opportunity to improve antimicrobial usage on dairy farms by adopting measures to prevent new infections and possibly using culture-based treatment protocols that limit antimicrobial usage to cases that will benefit (Ruegg, 2018).
