Special Factors to Consider When Designing a Protocol for Mastitis Therapy

 

Mastitis therapy demands decision-making regarding whether to use and how to use antimicrobial drugs. As with other diseases of farm animals, the goal of mastitis therapy is to design an efficacious treatment regimen that is reasonable in cost and does not result in a violative drug residue. In addition to the issues confronted when designing any antimicrobial regimen, factors not involved in other diseases can complicate mastitis therapy. The nature of the mammary gland’s response to infection and inflammation, along with the fact that mastitis is the only disease where a drug is expected to act in milk (instead of plasma or intercellular fluid, for example), create unique therapeutic considerations and difficulties. Some of these are listed below:

 

1)    Whether or not to use antimicrobial drugs

Unlike most other bacterial infections of farm animals, there has been ongoing discussion and research focused on whether or not antimicrobial drugs are warranted in the course of mastitis therapy, particularly when the causative agent is a gram-negative organism. Recent research has suggested that for most cases of clinical mastitis, regardless of the bacteria causing the infection, therapy with an antimicrobial increases the likelihood of a bacterial cure and decreases the likelihood of a clinical relapse. The notable exception to this tenet is a chronic infection that has been previously treated and no longer has assistance from an effective immune system.

 

2) Unsusceptible microbes

Despite the fact that antimicrobial therapy is generally beneficial, there are a number of bacteria that are not susceptible to the mechanisms of action of available antibiotic drugs. Yeasts, Nocardia and Pseudomonas also have constitutive resistance to many antimicrobial drugs. Other bacteria, such as Staphylococcus aureus  frequently acquire resistance to antimicrobial drugs, for example by acquiring a gene that codes for drug-destroying enzyme, or by changing to a cell-wall free “L form” to evade drugs that act by destroying the bacterial cell wall.

 

3)    Bacterial behavior in the mammary gland

In addition to the intrinsic properties of the bacteria, the reaction of the mammary gland to a particular bacterial species may also render therapy difficult. For example, Arcanobacterium pyogenes creates abscesses, which are unlikely to be penetrated and resolved by any antibiotic given by any route. Staphylococcus aureus creates “microabscesses” which make therapy difficult, and it may also survive inside phagocytic cells and thus be inaccessible to antimicrobial drugs.

 

4)    When to treat the cow

Many mastitis infections are more effectively treated during the dry period. Chronic infections or infections that are difficult to resolve, such as mastitis due to infection with Staphyloccocus aureus, may be more likely to be resolved by a long-acting dry cow antibiotic preparation. Off-label uses of drugs with extended withholding times may be more practical and cause reduced loss of salable milk and less risk of accidental contamination of milk for sale when used during the dry period. Depending on the type of bacteria and the stage of lactation of the cow, it may be best financially and therapeutically to delay treatment until the cow is dried off.

 

5)    Number of Quarters Infected

This should always be considered when deciding whether or not to treat mastitis. Expenses rise and prognosis usually worsens when more than one quarter is affected.

 

6)    Intramammary vs. Systemic Therapy

In addition to the other aspects of designing a therapeutic regimen (drug choice, frequency of administration, duration of therapy), route of administration is an important consideration in choosing a mastitis drug. Systemic therapy is warranted when a cow is at risk for bacteremia. Even when treating a strictly intramammary infection, however, other issues arise. Not all drugs penetrate well into the mammary gland when administered systemically. Drugs with good lipid solubility are more likely to achieve therapeutic concentrations in milk. Even intrammammary therapy will not penetrate well into abscessed areas of the gland or into milk ducts blocked by the products of inflammation or necrosis.

 

7)    Applicability of lab sensitivity results

Milk cultures are an invaluable tool in the diagnosis, therapy and control of mastitis. However, it must always be kept in mind that an “S”, “I” or “R” on the laboratory report may not translate directly into an accurate prediction of therapeutic success or failure with a particular drug. Sensitivity testing is done using cultures grown on agar gel or in broth. Therapeutic agents used for mastitis are carried in, and must act in, milk. Research using E. coli has shown up to a four-fold higher MIC50* for the same bacteria in milk as compared to broth. As mentioned above, there may also be factors in the mammary gland which decrease the expected penetration of the drug to the site of action.

 

*Concentration of drug required to inhibit growth in 50% of bacterial isolates.

 

 

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