Mastitis Therapy: Antimicrobial Drugs
General Concepts
Mastitis remains the most common cause of antimicrobial drug therapy for cows on U.S. dairy farms. In 2014, 21.7% of cows were treated for mastitis using antimicrobial drugs.21 If this use represents the majority of all U.S.
dairy herds, with approximately 9 million dairy cows, then nearly 1.9 million mastitis cases are treated annually. Surveys from Wisconsin and Canada estimated that between two and four doses of intramammary infusions are used per cow per year; this means that on a 1000-cow dairy, an average of 5 to 10 doses of intramammary antimicrobials would be administered daily.398,399 Antimicrobial therapy benefits animal health and well-being, but economic losses associated with antimicrobial therapy of mastitis include drug and veterinary expenses, extended labor, and most importantly, discarded milk.400 Unwarranted antimicrobial use in dairy cattle can result in residue violations in milk and meat and erode consumer confidence in the safety of dairy foods.To date, the risk of emerging antimicrobial resistance among bovine mastitis pathogens has been low, particularly for drugs with high therapeutic value in human medicine.401-403 Nonetheless, prudent administration of antimicrobials is needed on dairy farms, similar to stewardship of antimicrobial resources as advocated in human medicine. Responsible antimicrobial stewardship minimizes the emergence and dissemination of antimicrobial resistance among pathogens and preserves the therapeutic integrity of the drugs.
Mastitis therapy is often initiated empirically, without consideration of case risk factors for efficacy, and as a substitute for an integrated mastitis control program.140,404 Standardizing mastitis therapeutic protocols should diminish spontaneous “cow-side” biases and establish uniformity for therapeutic regimens.
However, farmer therapeutic decisions often differ from veterinary recommendations.405 In a Wisconsin study across 51 herds, nearly a quarter of cows treated received an additional secondary treatment because of perceived lack of response to the initial treatment.404 The majority of intramammary treatments were administered to cows with a microbiological diagnosis of no growth or E. coli, two culture outcomes that are not likely to benefit from therapy. In addition, in a survey of more than 600 herds from Michigan, Pennsylvania, and Florida, only about half of the respondents stated that they “frequently or always” record treatments or review treatment records before administering mastitis therapy.406 In addition, more than 80% of the herds reported that they rarely or never use bacteriologic results for mastitis therapy decisions.Risk factors that decrease therapeutic efficacy include increasing (1) age of the cow, (2) preexisting SCC before treatment, (3) duration of infection, (4) number of quarters infected, and (5) S. aureus infections.205,223,407 In particular, chronic infections have poor therapeutic outcomes and may require extended duration of antimicrobial therapy.400 Thus to reduce antimicrobial use associated with mastitis, we need to change behaviors and attitudes of farm personnel to (1) use bacteriology to the best of herd labor abilities, (2) determine the history of the cow and identify cow-level risk factors that may affect the efficacy of therapy, and (3) apply standardized therapy protocols that are based on sound pharmacology.
A small proportion of cows can be responsible for a large proportion of clinical mastitis episodes in a herd. Thus antimicrobial therapy is unlikely to cure infections in glands with repeated bouts of clinical mastitis episodes. Many herds tend to unnecessarily lose time and money by treating “repeat offender” clinical mastitis cases. When coupled with the lack of bacteriologic culture, thus opening the door for treatment of unresponsive pathogens, most clinical mastitis may be treated unnecessarily on many dairy farms.
Veterinarians should not only direct drug selection and protocols for mastitis therapy on dairy farms, but more importantly establish selection criteria for cows to be either included or excluded for treatment. In addition, it is critical to have not only a therapy protocol, but also a protocol to determine efficacy or a “cure” after therapy. Many clinical trials in the literature, or those done on farm, evaluate therapeutic outcome in relatively short periods after treatment is completed (less than 14 days). As many cases of mastitis relapse after this period (up to 30 days is common), practitioners should adopt a long-range view of therapeutic outcomes, including subesquent SCC testing, survival in herd, loss of quarter function, and milk production, in additon to relapses.Alternatives to antibiotic treatment include (1) euthanizing or culling the cow, (2) drying off the cow or gland, (3) administering supportive treatment alone, or (4) doing nothing. The cow's welfare must be considered when choosing among these options, to minimize pain and suffering. If supportive treatment or no treatment is chosen, the cow should be milked after healthy cows and the milk withheld from sale for as long as it is visibly abnormal. If a single gland is dried off, antibiotics should not be infused because this may result in antibiotic residues in milk from the other glands.
LIMITATIONS OF ANTIMICROBIAL SUSCEPTIBILITY TESTING. Antimicrobial susceptibility test results should not be used as the main basis for antibiotic selection. In most cases, susceptibility cut-points for zone diameters (for the disk diffusion test) or minimum inhibitory concentration (MIC) values are based on antibiotic concentrations in serum or interstitial fluid of people after oral or intravenous (IV) dosing; these are not equivalent to concentrations achieved in milk or mammary tissue after intramammary or systemic dosing.408 The absolute MIC value is more useful than a dichotomous result (susceptible or resistant) based on an irrelevant cut-point. However, the reported MIC value may not reflect the MIC in milk because MICs in milk are often higher than in blood, especially for non-β-lactam drugs.393 More recently marketed intramammary antibiotics have MIC or disk diffusion cut-points that are relevant to treatment of mastitis, but the cut-points need to be validated in vivo. Recent studies have determined that susceptibility test results (susceptible versus resistant) had no impact on the outcome (clinical cure, bacteriologic cure) of clinical mastitis episodes. ’ ’ Interestingly, S. aureus isolates that are penicillinase-producing strains are less responsive to treatment even if penicillinase-resistant antibiotics are used.411