Stéphane FLOCH – DVM – International Medical Manager Udder Health
Vetoquinol SA, 37 Rue de la Victoire, Paris, France
In the last decade, regulatory bodies have taken actions to encourage reduction of antimicrobial use (AMU) in both livestock and companion animals, especially at EU level. This has resulted in a tremendous reduction of 47% of AMU in 10 years! Then came the New Veterinary Regulation, going further, but all restrictions being still managed at Member State level. Looking at DCT, selective treatment has been promoted and implemented for about more than a decade now. In this newsletter, Dr. Stéphane Floch of Vetoquinol elaborates on another approach to further reduce the use of antimicrobials on dairy farms.
1. Context
There is a strong association between antimicrobial consumption in livestock with antimicrobial resistance (AMR) in consumers’ and politicians’ mind leading to an incredible societal pressure. But the potential impact of restricting the use of antibiotics in animal production on the development of antibiotic resistance is not yet clearly defined (Ruegg – 2022).
In the last decade, regulatory bodies have taken actions to encourage reduction of antimicrobial use (AMU) in both livestock and companion animals, especially at EU level. This has resulted in a tremendous reduction of 47% of AMU in 10 years! Then came the New Veterinary Regulation, going further, but all restrictions being still managed at Member State level.
Looking at dairy, 70% of AMU sits in udder health management: treatment of clinical mastitis (CM) where some % could be avoided due to self-cure of some infections, and dry cow therapy (DCT) where more than 50% of cows are not infected at that time. This is coming from plans and procedures that have been established 50 years ago, and usages transmitted from one generation of farmers to another.
Looking at DCT,
selective treatment has been promoted and implemented for about more than a
decade now, and we see that in countries where regulation bodies have not
established it as mandatory, there is still an important part of dairy cows
that receive antibiotics at dry off whether they require it or not. This is a
slow adoption as farmers still see DCT as an important asset in mastitis
prevention, and most of them hold strong negative beliefs about the
consequences of SDCT.
2. PRINCIPLE
The main principle of selective antimicrobial treatment of non-severe cases of CM is to treat only cases with a high probability to be responsive to antimicrobials (e.g., Gram-positive CM).
Avoiding
routinely treating all CM cases with antimicrobials is possible due to reduced
incidence and prevalence of CM caused by contagious pathogens, improvements in
udder health management practices, and advancements in diagnostic technologies
during recent decades.
In many regions we saw a shift towards environmental bacteria and farmers and veterinarians have gained access to several rapid diagnostic test options.
3. OBJECTIVE
The
objective of selective CM treatment sits in treating only CM cases with
substantially higher odds of bacteriological cure when treated with
antimicrobials and not treating CM cases that will (likely) not benefit from
antimicrobial treatment. This will be achieved by considering clinical signs
of CM cases excluding severe cases, potential causal agent especially those with high spontaneous cure rate (e.g., culture negative and
most of Gram-negative cases) (Suojala et al., 2013).
It is then crucial
when using selective CM treatment to have an accurate identification available
within 24 h after detecting the CM case. Several commercial rapid diagnostic
tests are now available that can identify causal agent up to at least Gram
staining. These systems are predominantly based on culture and identification
of mastitis-causing pathogens via selective media on plates or in tubes. Sensitivity
to identify Gram-positive bacteria ranges from 59 to 98%, and specificity
ranges from 48 to 97% (Malcata et al., 2020).
Expected probability of cure: cow SCC level and CM history can be used to identify CM cases with high probability of cure (Ruegg, 2018). Therefore, when possible, with available SCC data and CM record keeping, an evaluation should be made on a per-case basis of SCC history, CM history and the results of rapid diagnostic tests (Gram-positive or Gram-negative) to predict the likelihood of clinical cure for the current CM case.
Susceptibility profiles: Identifying whether causal bacteria of a CM case are Gram-positive or -negative is key in a selective treatment strategy. Examples of commercially available rapid on-farm systems that offer crude sensitivity testing are displayed in the table below.
Test name
Turnout time
Information displayed
Reference
Mastatest
24 h
MICS for 3 major antibiotics.
Jones et al., 2019
MastDecide Plus
12-14 h
1 point MIC for penicillin
Leimbach and Kromker, 2018
Speed Mam Color
48 h
Antibiogram for 14 antibiotics
Manner, 2001
PathoProof
4 h
Gene coding for beta lactamase by PCR
Supportive
treatments: In
addition to treating pain, for mild and moderate cases, NSAIDs can have other
benefits: lower rectal temperatures, lower heart rate, and improvements in
rumen motility and clinical signs (Anderson et al., 1986;
Anderson and Hunt, 1989; Lohuis et al., 1991; Wagner and Apley, 2004;
Vangroenweghe et al., 2005; Banting et al., 2008; Zimov et al., 2011; Yeiser et
al., 2012; Chapinal et al., 2013).
Other types
of supportive treatments (including rehydration fluids, frequent milk-out,
oxytocin, calcium, hypertonic saline and corticosteroids) are sometimes
considered in CM treatment protocols (Roberson,
2012; Oliveira and Ruegg, 2014; Persson Waller et al., 2016). However, there are insufficient
studies to evaluate their effectiveness (Leslie and
Petersson-Wolfe, 2012; Francoz et al., 2017).
4. Cow and farm outcomes
Cow and farm outcomes of implementing a selective CM treatment protocol, the mains aspects to look at are udder health, antimicrobial use, economic consequences.
Udder health: a recent systematic review and meta-analysis, that reviewed 13 studies comparing selective CM treatment protocol impacts on udder health parameters to a blanket CM treatment protocol (De Jong et al., 2023), concluded that for bacteriological cure, a selective CM protocol was not inferior to a blanket CM protocol.
Furthermore,
the review found no evidence to assume a difference between cases treated
according to a blanket or selective CM protocol in terms of new IMI risk, recurrence of CM later in lactation, return of SCC to baseline, average
lactational milk yield, and risk of culling (see table below).
Non-inferiority of selective over blanket treatment
Superiority of blanket over selective treatment
High level of evidence
Bacteriological cure (at 21 days past case)
High iSCC (14 to 21 days post case)
Culling rate (21 to 305 days post case)
Moderate level of evidence
New infections (at 21 days post case)
High iSCC (21 to 305 days post case)
Milk yield (150 to 305 days post case)
% new cases (60 to 305 days post case)
Poor level of evidence
Clinical cure (5 to 14 days post case)
Slight reduction in time to clinical cure
Antimicrobial use: the same review reported variable AMU reduction. The only explanatory variable was proportion of cases identified as Gram-negative or culture-negative.
Results of
the linear model are displayed in Figure 1: The fitted model could be denoted
as y = 0.06 + 0.91 x, meaning that for a 10 percent point increase in
proportion of cases identified as Gram-negative or culture- negative, proportion
AMU reduced increased by 9.1 percent point (95% CI: 0.4 – 14.1%).
Economic consequences
Direct
costs associated with the selective treatment protocols included costs for analysing
milk samples (labour and costs of the plates). Potential benefits to
selectively treating CM cases were described as reduced treatment costs and
reduced days out of the tank.
Indirect costs included production losses because of CM and potential culling and replacement costs.
A selective treatment protocol based on on-farm culture results was still beneficial if < 50% CM cases were Gram-positive, with a difference in bacteriological cure of up to 5% between the group of cows treated immediately and the group of cows treated after 24 hours (Figure 2, Down et al., 2017).
Most
important factors influencing costs were differences in days out of the bulk
tank, costs of antimicrobial treatment (Down et al.,
2017), and assumed milk price (Pinzón-Sánchez
et al., 2011).
5. PROSPECTIVE
Adoption of selective clinical mastitis treatment protocols: the % of farm implementing this varies among countries in EU where use of bacterial aetiology and sensitivity to inform treatment is widely encouraged.
Increasing uptake of selective CM treatment protocols without legislation requires recognizing that implementation of on-farm rapid diagnostic tests require substantial motivation and dedication from producers and their staff. Properly using and interpreting on-farm testing systems are essential and require training and frequent practice, a sufficiently high number of CM cases per month may be necessary to maintain knowledge.
Knowledge
and technology gaps:
Investigating
the potential for NSAIDs to replace antimicrobial treatment for mild and
moderate cases could refine the proposed selective CM treatment protocol and
augment AMU reduction, while having a positive impact on animal well-being.
Diagnostic
accuracy of several
on-farm rapid diagnostic tests is not optimal. Comparing outcomes of on-farm
tests with conventional laboratory analyses: from 14% to 22% of CM should have
received a treatment (Lago et al., 2011a and McDougall et
al. 2018 respectively).
Polymerase
chain reaction (PCR) technology can be used as an alternative rapid diagnostic test to
culture-based methods. PCR tests can provide results quicker and detect smaller
bacterial quantities.
Although there is consensus on the predictive ability of SCC and CM history to identify CM cases with a low probability of clinical cure, more evidence regarding specific thresholds is lacking.
As no studies
evaluating selective versus blanket CM treatment protocols have been conducted
on farms with automated milking systems, it is impossible to make any
decision.
To promote selective CM antimicrobial treatments and subsequently reduce AMU on farms, it is important that protocols are easy to understand and tailored to the farm-specific context. This will also need an understanding of the target group’s motivations, opportunities, and social influences (Lam et al., 2017).
TAKE HOME MESSAGES
Not all CM cases benefit from antimicrobial treatment, therefore identifying cases who do benefit is key to supporting judicious AMU in dairy.
Characteristic and history of the herd and individual cow and fast basic identification of causative pathogen are needed for treatment decision.
Literature did not report any negative udder health consequences and adding NSAID improved outcomes.
No negative economic consequences.
Uptake depends on legislation, management systems and adoption of control programs.
Level of AMU reduction depends on pathogens responsible for CM.
References upon request
