Mastitis in Cattle
Almost any microbe that can opportunistically invade tissue and cause infection can cause mastitis. However, most infections are caused by various species of streptococci, staphylococci, and gram-negative rods, especially lactose-fermenting organisms of enteric origin, commonly termed coliforms. From an epidemiologic standpoint, the primary sources of infection for most pathogens may be regarded as contagious or environmental.
Except for Mycoplasma spp, which may spread from cow to cow through aerosol transmission and invade the udder subsequent to bacteremia, contagious pathogens are spread during milking by milkers’ hands or the liners of the milking unit. Species that use this mode of transmission include Staphylococcus aureus, Streptococcus agalactiae, and Corynebacterium bovis. Most other species are opportunistic invaders from the cow’s environment, although some other streptococci and staphylococci may also have a contagious component. Additionally, contagious transmission infrequently occurs for pathogens typically associated with environmental reservoirs, eg, through the development of host-adapted virulence factors (Escherichia coli) or by shedding of overwhelming numbers of bacteria from infected udders (Trueperella [formerly Arcanobacterium] pyogenes).
The bedding used to house cattle is the primary source of environmental pathogens, but contaminated teat dips, intramammary infusions, water used for udder preparation before milking, water ponds or mud holes, skin lesions, teat trauma, and flies have all been incriminated as sources of infection.
Intramammary infections are often described as subclinical or clinical mastitis. Subclinical mastitis is the presence of an infection without apparent signs of local inflammation or systemic involvement. Although transient episodes of abnormal milk or udder inflammation may appear, these infections are for the most part asymptomatic and, if the infection persists for at least 2 mo, are termed chronic. Once established, many of these infections persist for entire lactations or the life of the cow. Detection is best done by examination of milk for somatic cell counts (SCCs) (predominantly neutrophils) using either the California Mastitis Test or automated methods provided by dairy herd improvement organizations. SCCs are positively correlated with the presence of infection. Inflammatory changes and decreases in milk quality may start with SCCs as low as 100,000 cells/mL. Although variable (especially if determined on a single analysis), an SCC of ≥280,000 cells/mL in a cow indicates a >85% chance of being infected. Likewise, the higher the SCC in a herd bulk tank, the higher the prevalence of infection in the herd. Herd SCCs <200,000 cells/mL are considered desirable, and lower counts can be attained. Causative agents must be identified by bacterial culture of milk.
Clinical mastitis is an inflammatory response to infection causing visibly abnormal milk (eg, color, fibrin clots). As the extent of the inflammation increases, changes in the udder (swelling, heat, pain, redness) may also be apparent. Clinical cases that include only local signs are referred to as mild or moderate. If the inflammatory response includes systemic involvement (fever, anorexia, shock), the case is termed severe. If the onset is very rapid, as often occurs with severe clinical cases, it is termed an acute case of severe mastitis. More severely affected cows tend to have more serous secretions in the affected quarter.
Although any number of quarters can be infected simultaneously in subclinical mastitis, typically only one quarter at a time will display clinical mastitis. However, it is not uncommon for clinical episodes caused by Mycoplasma to affect multiple quarters. Gangrenous mastitis can also occur, particularly when subclinical, chronic infections of S aureus become severe at times of immunosuppression (eg, at parturition). As with subclinical mastitis, culture of milk samples collected from affected quarters is the only reliable method to determine the etiology of clinical cases.
All dairy herds have cows with subclinical mastitis; however, the prevalence of infected cows varies from 5%–75%, and quarters from 2%–40%. Many different pathogens can establish a chronic infection in which clinical signs of mastitis will manifest only occasionally. The primary focus of most subclinical mastitis programs is to reduce the prevalence of the contagious pathogens S agalactiae and S aureus, as well as other gram-positive cocci, most notably Streptococcus dysgalactiae (which may also be contagious or an environmental pathogen), Streptococcus uberis, enterococci, and numerous other coagulase-negative staphylococci, including Staphylococcus hyicus, Staphylococcus epidermidis, Staphylococcus xylosus, and Staphylococcus intermedius. Herds have been identified that have considerable subclinical mastitis caused by gram-negative rods such as Klebsiella sp, Serratia marcescens, Pseudomonas aeruginosa, and other atypical pathogens such as mycotic and algal microbes.
For contagious pathogens, adult lactating cattle are most at risk of infection, either while lactating or during the dry period. The primary reservoir of infection is the mammary gland; transmission occurs at milking with either milkers’ hands or milking equipment acting as fomites. Primiparous heifers have been reported to be infected with staphylococci and streptococci before calving, although the prevalence varies greatly among herds and geographic regions. Teat-end dermatitis caused by the horn fly, Haematobia irritans, which can harbor S aureus, has been associated with increased risk of infection in heifers, especially in warmer climates.
For the contagious pathogens and coagulase-negative staphylococci, there is little or no seasonal variation in incidence of infection.
Therapy is given on the premise that treatment costs will be outweighed by production gains after elimination of infection. In the case of contagious pathogens, elimination may also result in a decrease of the reservoir of infection for previously noninfected cows. No significant economic losses will occur as a result of delaying therapy until bacterial culture can be completed. However, many subclinical cases selected as potential therapy candidates have chronic infections; particularly in the case of S aureus, prediction of therapeutic outcome by in vitro testing is unreliable. Drug distribution after intramammary administration may not be adequate because of extensive fibrosis and microabscess formation in the gland; it is critical to assess the cow’s immune status from a perspective of duration of infection, number of quarters infected, and other variables.
Prevalence of S agalactiae infection can be rapidly reduced by treating an entire herd—or more economically, all the infected cows in a herd—with antibacterials. All four quarters of infected cows should be treated to ensure elimination of the pathogen and to prevent possible cross-infection of a noninfected quarter. Cure rates can often be 75%–90%. Labeled use of commercial intramammary products that contain amoxicillin, penicillin, and erythromycin are as efficacious as procaine penicillin G infusions derived from multiple-dose vials. Consequently, use of drugs originating from multiple-dose vials (labeled for systemic therapy) should not be used for intramammary therapy, because commercial intramammary preparations have superior quality control standards for sterility and better reliability to predict withholding periods for milk and meat after treatment. It is critical to apply strict aseptic techniques (use of alcohol swabs for teat-end preparation) whenever any intramammary infusion product is administered.
Herds undergoing extensive therapy for S agalactiae must be monitored by SCCs and bacteriology to further identify and treat cows not identified or cured during the initial therapy. Usually, 30-day monitoring intervals are successful. A small percentage of cows will not respond to therapy and are best segregated or culled. In addition, failure to use postmilking teat dipping and total dry cow treatment to prevent new infections during the treatment period will ultimately result in reinfection of the herd. Parenteral therapy is not likely to offer any benefit over intramammary therapy.
Most other streptococci also display in vitro susceptibility to numerous antibacterials, especially β-lactam drugs. Despite this apparent susceptibility, many streptococcal infections are not as easily cured as those caused by S agalactiae. Generally, subclinical infections caused by S uberis and S dysgalactiae should be preferentially treated at the end of lactation with intramammary infusions of commercial dry cow products. Cure rates at this time may exceed 75%.
S aureus intramammary infections often result in deep-seated abscesses. Therapy is difficult, because resistance to antibacterials (particularly β-lactams) is more common than with streptococcal infections, and S aureus may survive intracellularly after phagocytosis when antibacterial concentrations are reduced. Intramammary infusions may cure only 35%–40% of infections; however, this number will be substantially lower for chronic infections.
The success rate of therapy for chronic subclinical intramammary infections caused by S aureus may be increased by using both parenteral and intramammary therapy. However, systemic therapy involves extra-label drug use, and milk and meat withholding periods must be determined judiciously. Therapy should be administered for periods long enough (7–10 days) to allow effective killing of the pathogen. It is most economical and least likely to result in residues in milk if this therapy is applied to dry cows. Depending on susceptibility testing, lipophilic antibacterial drugs that distribute well into mammary tissue, such as oxytetracycline (11 mg/kg/day) are the best candidates for systemic administration, although several studies have found oxytetracycline (administered for 4 days or less) to be ineffective. Cure rates may not be much better than those attained from spontaneous cure, and cure must be defined critically. Affected quarters should be monitored bacteriologically for ≥30 days to encompass the refractory period when bacteria may not be isolated.
Occasionally, premature agalactia will occur in chronically infected quarters, particularly quarters infected with resistant pathogens. Culling may be a practical option for these cows. Alternatively, it is common to dry off the infected quarter and continue to milk the cow. This may have some benefit for genetically superior animals within a herd or for cows that are to be maintained until calving. Anecdotally, the overall milk production from such cows may remain the same. The goal is to eliminate the infection by causing fibrosis of the affected quarter, thus reducing the risk of further pathogenic change or systemic effects on the cow, as well as reducing risk of infection for other cows.
The dry period of the lactation cycle is a critical time for the udder health of dairy cows. The mammary gland undergoes marked biochemical, cellular, and immunologic changes. Involution of the mammary parenchyma begins 1–2 days after the end of lactation and continues for 10–14 days. During this time, the gland is particularly vulnerable to new intramammary infections. However, the involuted mammary gland offers the most hostile immune environment for bacterial pathogens. Consequently, the dry period is an ideal time to attain synergy between antibacterial therapy and immune function, without incurring the extensive costs typical of lactating cow therapy. Intramammary administration of antibacterials at the end of lactation has been a standard of dairy mastitis management for 30 yr and continues to help reduce the prevalence of mastitis in most dairy herds.
Numerous commercial products are available and include penicillin, cloxacillin, cephapirin, ceftiofur, or novobiocin. One tube per quarter is sufficient and should be administered immediately after the last milking of lactation. Therapy should not be repeated by intramammary infusion; if there is a need to extend therapy, systemic administration should be used as an adjunct to the intramammary infusion. In addition to eliminating existing subclinical infections, one of the most critical roles of dry cow therapy is to prevent new infections. However, most commercial dry cow products have little or no activity against gram-negative pathogens, and their administration at the start of the dry period will not be effective against new infections that begin during the periparturient period. The antimicrobial therapy can be supplemented by subsequent infusion of internal teat sealants that serve as a barrier to help reduce new infections.
Many infections in calving heifers are caused by staphylococcal species other than S aureus, which have a high rate of spontaneous cure. However, under some herd conditions, a substantial portion of heifers are infected at calving; some of these infections are caused by pathogens such as S aureus. Potential sources include milk (fed to calves) and body sites such as tonsils and skin. There is also a geographic risk factor: fly bite dermatitis of the teat end, which compromises this important physical barrier to infection, may play a role in the pathogenesis.
Intramammary infusions of β-lactam antibacterial drugs 7–14 days before expected calving dates have been reported to reduce the rate of intramammary infections at calving. However, longterm benefits on SCCs, milk production, and incidence of clinical mastitis during lactation were found to be highly herd variable and not consistent. Strict teat-end antisepsis should be followed before infusion to prevent contamination; thus, labor to handle animals for treatment can be extensive. This is not a recommended management program for many dairies. However, if herd records indicate that an undesirable proportion of first-lactation animals are infected at calving, particularly with staphylococci, this regimen may be considered.
New infections caused by S agalactiae and S aureus can be prevented by focusing management efforts on milking technique and hygiene. Clean and dry bedding, clean and dry udders at the time of milking, and lack of teat-end lesions all have a positive effect on control. The single most important management practice to prevent transmission of new infections is the use of an effective germicide as a postmilking teat dip. These products should be applied as a dip (rather than a spray) immediately after milking. Other practices that augment teat dipping include use of individual towels for drying teats, gloves for milkers’ hands, use of a premilking germicide (spray or dip), attachment of units at the proper time after teat stimulation (60–120 sec), cleaning milking units after an infected cow has been milked, or segregation of infected cows into a separate milk group. This last option may be unrealistic for cattle in free housing that are normally segregated for nutritional or reproductive reasons. Routine milking equipment evaluations should be conducted to ensure that the teat-end vacuum is operating at a proper level and remains stable during milking. Proper pulsator function should be maintained, and liners and rubber air hoses should be replaced as needed.
Proper milking hygiene also reduces the new infection rate of noncontagious pathogens. More importantly for environmental pathogens, cows should be provided dry, clean housing. Emphasis should be placed on bedding and any other practices that reduce the exposure of the teat end to bacteria. Inorganic bedding supports less bacterial growth than cellulose-based material; thus, sand is preferred over sawdust, straw, recycled paper, or manure. In particular, higher incidence of infections caused by Klebsiella has been associated with sawdust bedding. Similarly, a higher incidence of infections caused by environmental streptococci has been associated with straw bedding. However, the concentrations of bacteria can vary greatly depending on moisture and presence of organic matter (such as in sand after recycling). Thus, identification of reservoirs of infection should not be based solely on the choice of bedding material. Regular cleaning or changing of bedding, reducing heat stress, removing udder hair, preventing teat trauma, reducing udder edema in periparturient cows by nutritional management of potassium and sodium intake, and preventing frostbite and fly exposure all have a positive impact on environmental mastitis control.
When the balance between host defenses and invading pathogens causes a marked inflammatory response, clinical signs become apparent. Infections from any pathogen can be clinical or subclinical, depending on the duration of infection, host immune status, and pathogen virulence. Control of clinical mastitis usually focuses on prevention and elimination of pathogens that arise from an environmental reservoir. Thus, the epidemiology and prevention of clinical mastitis is similar to previously discussed concepts regarding control of subclinical mastitis.
Except for outbreaks of Mycoplasma, clinical mastitis in most dairy herds is caused by environmental pathogens. In addition, many clinical mastitis cases are transient, especially those that are initial episodes for a cow and quarter. Thus, from an epidemiologic perspective, assessment of clinical mastitis is based on incidence and not prevalence.
The standard methods to monitor subclinical mastitis, ie, routine somatic cell counts (SCCs) and culture of cows with increased SCCs, are poor predictors of herd clinical mastitis episodes. Cows with high SCCs caused by chronic infections may occasionally display clinical mastitis, although it is usually mild. However, cows with low SCCs are also prone to develop clinical mastitis. Herds with low SCCs may actually have a higher incidence of clinical cases caused by environmental organisms (as high as 30–50 cases/100 cows/yr) than herds with higher SCCs. Similarly, routine culture of milk samples from a cow with a low SCC is a poor indicator of the probability of developing clinical mastitis, especially if the culture yielded no organisms.
Thus, the incidence of clinical cases, and data from each case that may determine risk factors (eg, season, age, stage of lactation, and previous episodes), should be recorded as part of a mastitis control program. Milk samples should be collected from affected quarters and, when feasible, antibacterial susceptibility testing performed. For well-managed herds in which mastitis caused by contagious pathogens has been controlled, a goal for the incidence of clinical mastitis should be 1–2 cases/100 cows milking/mo. Severe mastitis cases should be in the range of 1–2 cases/100 cows milking/yr.
Typically, 3%–40% of milk samples collected from clinical mastitis cases yield no organisms on culture. However, of the samples that do yield organisms, 90%–95% of the isolated bacteria include a wide variety of streptococci, staphylococci, or coliforms. If this is not the case, especially if a single pathogen such as a noncoliform gram-negative rod or a mycotic or algal (Prototheca sp) predominates, a point source of infection should be considered.
Coliforms (lactose-fermenting gram-negative rods of the family Enterobacteriaceae) are the most common cause of this form of mastitis. After infection, coliform numbers in milk increase rapidly, often attaining peak bacterial concentrations within a few hours. A subsequent decline (rapid in most cases but may take several days in truly severe mastitis) in bacterial concentration follows neutrophil migration into the gland. Most coliform infections are cleared from the gland with few or mild clinical signs. However, if bacterial concentrations are increased enough to elicit an acute inflammatory response, systemic involvement is a frequent consequence.
Mastitis caused by coliforms results in a higher incidence of cow death or agalactia-related culling (30%–40%) than mastitis caused by other pathogens (2%). Prognosis for cases of Klebsiella infection should be particularly guarded, because these cows are twice as likely to be culled or die than those infected by other coliforms. Thus, primary therapy for severe clinical mastitis should be directed against coliform organisms, although secondary consideration must be given for other causative agents. Supportive care, including fluids, is indicated, and in the case of coliform mastitis, may be the most beneficial component of the therapeutic regimen. Antibacterial therapy is ideally based on identification of the causative pathogen; however, this is not attainable for some hours after initial case recognition. In addition, most antibacterial therapeutic regimens currently used for severe clinical mastitis in the USA are not approved by the FDA.
Many inflammatory and systemic changes seen in severe coliform mastitis result from the effects of release of lipopolysaccharide (LPS) endotoxin from the bacteria and subsequent activation of cytokine and arachidonic acid–derived mediators of inflammation and the acute phase response. By the time therapy is initiated, maximal release of LPS has likely occurred. Thus, the primary therapeutic concern is the treatment of endotoxin-induced shock with fluids, electrolytes, and anti-inflammatory drugs. The IV route is preferred as the initial method of fluid administration. If isotonic saline is administered, 30–40 L are necessary throughout a 4-hr period, which can be difficult under farm conditions. A practical alternative is 2 L of 7% NaCl (hypersaline) administered IV. This induces rapid fluid uptake from the body compartment into the circulation. Cows should then be offered free-choice water to drink, and if at least 10 gal. is not consumed, 5–7 gal. should be pumped into the rumen. Many cows with endotoxic shock are marginally hypocalcemic; thus, 500 mL of calcium borogluconate should be administered SC (to avoid potential complications of IV administration). Alternatively, rapid absorption calcium gels, designed for periparturient hypocalcemia, can be given. If the cow remains in shock, continued fluid therapy should be administered PO or IV as isotonic, not hypertonic, fluids.
If administered early in the course of disease, glucocorticoids may be helpful in cases of mastitis caused by endotoxin-producing coliforms. Administration of dexamethasone (30 mg, IM) to dairy cows immediately after introduction of E coli into the mammary gland has been reported to reduce mammary gland swelling and inhibition of rumen motility. Isoflupredone (10–20 mg, IM) has also been shown to reduce local mammary swelling. Cattle are sensitive to glucocorticoid-induced immune suppression; however, it is unlikely that one-time administration of a glucocorticoid will adversely affect cows with endotoxin-induced severe clinical mastitis. Temporary suppression of inflammation as manifested by reduced neutrophil migration may well be beneficial. Care should be exercised in administering these drugs to pregnant animals; however, severe clinical mastitis in and of itself may cause pregnancy loss in cattle.
There is little published research on the use of glucocorticoids for mastitis caused by gram-positive bacteria. It is reasonable to expect that gram-positive infections would be less likely to benefit from the anti-inflammatory activities of glucocorticoids and may even be adversely affected. Intramammary glucocorticoid administration to reduce local inflammation, without affecting the migration of neutrophils into the gland, is an attractive therapeutic option. Although products that combine antibacterial and glucocorticoid drugs for intramammary administration exist in Europe, it is not clear whether clinical benefit is gained when compared with antibacterial therapy alone. As a general guideline, glucocorticoid treatment should be reserved for severe cases of gram-negative mastitis, with a single dose administered early in the disease course.
NSAIDs are widely used in treatment of acute mastitis. Flunixin meglumine, flurbiprofen, carprofen, ibuprofen, and ketoprofen have been studied as treatments for experimental coliform mastitis or endotoxin-induced mastitis. Systemic use of these drugs is preferred over orally administered aspirin, which is not likely to attain effective concentrations in tissue or lead to beneficial results. Dipyrone use in food animals is specifically prohibited by the FDA. Phenylbutazone is prohibited in dairy cattle >20 mo old; the tolerance level for phenylbutazone is zero, and detection of any concentration is an illegal residue. Thus, these two drugs should not be used for anti-inflammatory therapy for mastitis in cattle.
Treatment with ketoprofen improved recovery of cows with acute clinical mastitis in a blinded, placebo-controlled study. Ketoprofen is available as a veterinary product for use in horses, has a high therapeutic index, has favorable pharmacokinetics for use in lactating dairy cattle, and is approved for use in cattle in France; however, it is not labeled for food animal use in the USA. The Food Animal Residue Avoidance Databank (FARAD) recommends withdrawal intervals of 7 days for slaughter and 24 hr for milk, with IV or IM administration, for dosages up to 3.3 mg/kg/day, for up to 3 days.
Flunixin meglumine is labeled for beef and dairy cattle. It is the only NSAID labeled for use in cattle in the USA and is therefore the most logical choice for treating clinical mastitis. In field studies, increased survival and improved milk production have not been demonstrated after treatment of clinical acute mastitis with flunixin meglumine at a dosage of 1.1 mg/kg. However, in studies of experimental mastitis, flunixin meglumine reduced the severity of clinical signs such as fever, depression, heart and respiratory rates, and udder pain. The FDA-approved withdrawal intervals are 4 days for slaughter and 36 hr for milk when used as labeled by IV administration. Because of extensive and unpredictable withdrawal periods, this drug should not be administered by IM injection. As with the glucocorticoids, NSAIDs may provide symptomatic relief and promote well-being. Administration early in the course of infection is likely to increase clinical benefit.
Antibacterial therapy may be of secondary importance relative to immediate supportive treatment of endotoxic shock, but it remains an integral part of a therapeutic regimen. Occasionally, coliform infections do result in chronic mastitis. Research suggests that bacteremia may occur in >40% of severe coliform cases. In addition, numerous other pathogens, including gram-positive cocci, cause severe clinical mastitis, which can be difficult to distinguish from cases caused by coliforms at initial presentation.
Selection of an appropriate antibacterial for severe coliform mastitis depends primarily on the susceptibility of the organism to the selected drug and the ability to maintain effective concentrations at the primary pharmacologic target (which, in the case of coliform mastitis, is the plasma compartment of the cow).
In one study, IM gentamicin was not more effective in preventing agalactia or death resulting from severe coliform mastitis, or in improving other clinical outcomes, than IM erythromycin or no systemic antibacterials. Cows experimentally challenged with E coli and treated with 500 mg of intramammary gentamicin bid did not have lower peak bacterial concentrations in milk, duration of infection, convalescent SCCs or serum albumin concentrations in milk, or rectal temperatures than untreated challenged cows. In addition, gentamicin readily diffused through the milk-blood barrier, resulting in drug residues in the kidney that could extend beyond 18 mo. Because of zero tolerance for aminogylcoside residues at slaughter, the use of this class of drugs in dairy cattle is not recommended.
Oxytetracycline (11 mg/kg/day, IV) improved outcome of cows with clinical coliform mastitis (not necessarily severe) as compared with cows that did not receive systemic antibacterials. Ceftiofur sodium (2.2 mg/kg/day, IM ) decreased the mortality and cull rates of cows with severe coliform mastitis. This drug distributes poorly to the mammary gland, supporting the emphasis on treating the cow rather than the mammary gland because of the risk of septicemia.
Intramammary infusion of commercial products that have good activity against gram-positive organisms should be administered to any cow with severe clinical mastitis. This treatment is not likely to affect the outcome of a case caused by coliforms but may provide some benefit for cases caused by gram-positive cocci. The need for antibacterial therapy in cows with grossly abnormal milk, but with improved appetite, attitude, and milk production, should be evaluated critically. Unnecessary extension of therapy in these instances results in increased discarded milk expense for the dairy producer and risk of antibacterials in marketed milk.
No microorganisms are isolated from 30%–40% of bacteriologic cultures of milk samples collected from cows with clinical mastitis. Many mild mastitis cases that fail to yield bacteria on culture are coliform intramammary infections that resolve before treatment is necessary. In addition, numerous mild clinical mastitis cases are temporary setbacks in the balance between pathogen and host defenses that occurs in more chronic intramammary infections. A “no antibiotic” approach to mild clinical mastitis cases avoids costs of discarded milk and residue risks inherent in antibacterial therapy.
A comparison of cure rate in treated versus untreated cows in a study of three California dairies found bacteriologic cure assessed at 4 and 20 days after treatment with amoxicillin, cephapirin, or oxytocin (no antibacterial) did not differ for mild clinical mastitis cases caused by streptococci and coliforms. However, the rates of both relapses and recurring cases were higher in untreated cows, especially among streptococcal cases. In a Colorado dairy study, a no-antibiotic approach also increased the rate of relapses, with an increase in the incidence of clinical mastitis, prevalence of intramammary infections, and herd SCCs associated with streptococcal infections. If bacterial culture of affected quarters yields no organisms or coliforms, therapy is not likely to be beneficial, whereas if gram-positive cocci are isolated, therapy is recommended.
Common sense and individual herd history should determine the course of therapy for mild clinical mastitis cases in dairy herds. Use of approved commercial intramammary infusions is likely to be the best option. Assessment of success should be based on bacteriologic cure but will be more practically based on return to normal milk. However, the frequency of relapsed cases should be monitored as the best means to determine cures, because many cases will be deemed to have been successfully treated initially but relapse later in lactation. If mastitis recurs regularly in affected quarters in the absence of systemic signs, repeated treatment of what now has become chronic intramammary infection is not warranted. Additionally, augmentation with parenteral therapy for these cases has not been demonstrated to be effective and will not likely overcome the expense of discarded milk, other related treatment costs, and the increased risk of residues in milk and meat. Previous history of clinical cases ("repeat offenders"), long duration of infection (as exhibited by high individual SCCs or extended periods of increased SCCs), and infections caused by nonresponsive pathogens are the greatest risk factors for poor therapeutic outcome. Practitioners should develop a protocol with dairy clients to reduce unnecessary treatment of poor risk cases as listed above and not rely on continued unsuccessful therapy or seeking a "better drug."
If standard regimens achieve less than desired results, it would be better to extend initial therapy for a prolonged period rather than to change to other antibacterial drugs or increase the amount of each dose. Studies have demonstrated improved cure rates for gram-positive cocci, especially coagulase-negative staphylococci and streptococci, when infected quarters were treated with intramammary infusions for up to 8 days as compared with 2 or 5 days. Care should be especially exercised in teat asepsis for extended therapy because of the increased risk of nosocomial infections.
Pseudomonas aeruginosa may cause outbreaks of clinical mastitis. Generally, a persistent infection occurs, which may be characterized by intermittent acute or subacute exacerbations. The organism is found in soil-water environments common to dairy farms. Herd infections have been reported after extensive exposure to contaminated wash water, teat cup liners, or intramammary treatments administered by milkers. Failure to use aseptic techniques for udder therapy or use of contaminated milking equipment may lead to establishment of P aeruginosa infections within the mammary glands. Severe peracute mastitis with toxemia and high mortality may follow immediately in some cows, whereas subclinical infections may occur in others. The organism has persisted in a gland for as long as five lactations, but spontaneous recovery may occur. Other than supportive care for severe episodes, therapy is of little value. Culling is recommended for cows.
Trueperella (formerly Arcanobacterium) pyogenes is common in suppurative processes of cattle and pigs and produces a characteristic mastitis in heifers and dry cows. It is occasionally seen in mastitis of lactating udders after teat injury, and it may be a secondary invader. The inflammation is typified by the formation of profuse, foul-smelling, purulent exudate. Mastitis due to T pyogenes is common among dry cows and heifers that are pastured during the summer months on fields and that have access to ponds or wet areas. The vector for animal-to-animal spread is the fly Hydrotaea irritans. Control of infections is by limiting the ability to stand udder-deep in water and by controlling flies. Preventive treatment of heifers and dry cows in susceptible areas with long-acting penicillin preparations has effectively reduced infections. Therapy is rarely successful, and the infected quarter is usually lost to production. Infected cows may be systemically ill, and cows with abscesses usually should be slaughtered. (Also see Actinomycosis.)
Mycoplasma spp can cause a severe form of mastitis that may spread rapidly through a herd with serious consequences. M bovis is the most common cause. Other significant species include M californicum, M canadense, and M bovigenitalium. Onset is rapid, and the source of infection is believed to be endogenous after outbreaks of respiratory disease in heifers or cows. The disease is often seen in herds undergoing expansion in which animals from outside sources have been added. Typically, introduced animals will be asymptomatic carriers and then shed the organism via respiratory or intramammary transmission. Some or all quarters become involved. Loss of production is often dramatic, and the secretion is soon replaced by a serous or purulent exudate. Initially, a characteristic, fine granular or flaky sediment may be seen in the material removed from infected glands. Despite the severe local effects on udder tissue, cows usually do not manifest signs of systemic involvement. The infection may persist through the dry period. Identification of infected cows can be difficult because of the frequent propensity of these cows to become asymptomatic carriers and intermittently shed the organism in milk.
Because there is no satisfactory treatment, affected cows should be segregated during active outbreaks. Routine screening of the bulk tank and milk strings may help identify the presence of infected cows. However, culture of the mammary secretion of cows with clinical mastitis, or recently calved cows, is the most reliable surveillance method. If cows continue to display clinical mastitis or systemic signs, they should be culled. Sanitary measures should be strictly enforced, especially at milking and in hospital/treatment areas. Milk from Mycoplasma-infected cows should not be fed to calves, because this may result in respiratory and inner ear infections. Milk replacer or pasteurized milk, rather than discarded milk, should be fed to calves in herds with Mycoplasma.
Nocardia asteroides causes a destructive mastitis characterized by acute onset, high temperature, anorexia, rapid wasting, and marked swelling of the udder. Response in the udder is typical of a granulomatous inflammation and leads to extensive fibrosis and formation of palpable nodules. Herd histories suggest that infection of the udder may be associated with failure to ensure asepsis in intramammary treatment of the common forms of mastitis. Slaughter is recommended for infected cows.
Serratia mastitis may arise from contamination of milk hoses, teat dips, water supply, or other equipment used in the milking process. The organism is resistant to disinfectants. Cows with this form of mastitis that continue to display clinical signs should be culled.
Mastitis due to various mycotic organisms (yeasts) has appeared in dairy herds, especially after the use of penicillin in association with prolonged repetitive use of antibiotic infusions in individual cows. Yeasts grow well in the presence of penicillin and some other antibiotics; they may be introduced during udder infusions of antibiotics, multiply, and cause mastitis. Yet, heifers that have never received intramammary infusions may develop yeast mastitis. Signs may be severe, with a fever followed either by spontaneous recovery in ~2 wk or, more rarely, by a chronic destructive mastitis. Other yeast infections cause minimal inflammation and are self-limiting. If mastitis due to yeast is suspected, antibiotic therapy should be stopped immediately. Yeast or other mastitis infections can be reduced if the tip of the plastic infusion tube is only partially (rather than completely) inserted through the teat canal during intramammary therapy.
A chronic, indurative mastitis similar to that caused by the tubercle bacillus has been reported to be caused by acid-fast Mycobacterium spp derived from the soil, such as M fortuitum, M smegmatis, M vaccae, and M phlei when such organisms are introduced into the gland along with antibiotics (especially penicillin) in oil or ointment vehicles. The oil apparently enhances the invasiveness of these organisms, and such therapy is contraindicated. These organisms otherwise tend to be saprophytic and to disappear from infected quarters, at least by the next lactation. In the meantime, mastitis is usually moderate. Distinct outbreaks do occur and several have been reported, especially with M fortuitum and M smegmatis.
Prototheca sp are nonpigmented unicellular algae commonly found in wet environments such as streams, stagnant ponds, and marine waters, particularly in humid habitats with organic matter in the soil. In dairy farm environments, they are especially abundant in muddy or wet outdoor runs or lots, resting areas, paths where animals are driven, and pastures contaminated with slurry. Protothecal mastitis in dairy cattle is often chronic and asymptomatic with increased SCCs, although sporadic severe infections occur. Although some infections may spontaneously resolve, longterm carriage with intermittent shedding is common. After initially causing clinical mastitis, infections may be undetectable by culture of milk for several months, only to recur during the subsequent lactation, particularly soon after calving. Therapeutic interventions are unrewarding. Thus, dairy producers have limited ability to predict the progression or affect the outcome of protothecal mastitis and are constrained to management options similar to those used to manage chronic mastitis caused by other pathogens. Therefore, the primary management focus is prevention rather than mitigation of infections. To reduce pathogen exposure to other noninfected cows in the herd, chronic mastitic cows are often culled. The primary causative agent of protothecal mastitis in cattle has been identified as P zopfii. Other reports have challenged the absolute exclusivity of P zopfii as the etiologic agent of protothecal mastitis, but on a practical basis cows identified as having mastitis caused by Prototheca sp are managed in similar fashion, regardless of species or genotype.
Bacterins made using core-antigen technology based on J5 mutant E coli can help reduce the severity of clinical mastitis caused by coliforms. Vaccination programs using these bacterins should minimally include multiple administration during the dry period to reduce the incidence of clinical coliform mastitis frequently associated with early lactation. Protocols for extended numbers of immunizations of these bacterins may be warranted in herds with high rates of severe mastitis beyond 60 days in milk, because protection often wanes 50–60 days after the last immunization.