Elimination kinetics of chlorhexidine in milk following intramammary infusion to stop lactation in mastitic mammary gland quarters of cows

OBJECTIVE: To evaluate the elimination kinetics of chlorhexidine in milk when used as an intramammary infusion to stop lactation in cows. DESIGN: Prospective study. ANIMALS: 6 cows. PROCEDURE: The study was performed in 2 phases. Three cows were studied in each phase. All cows were treated with chlorhexidine suspension by infusion into a mastitic mammary gland quarter after 2 milkings 24 hours apart. Foremilk samples (100 mL) were collected from treated and untreated (controls) mammary gland quarters of each cow. Chlorhexidine was extracted from raw milk, and residue concentrations were quantified by use of high-performance liquid chromatography. Foremilk samples from days 2, 5, and 8 were analyzed in phase I, and samples from time 0 and days 3, 7, 14, 21, 28, 35, and 42 were analyzed in phase II. RESULTS: In phases I and II, there was no quantifiable transference of chlorhexidine to milk in untreated mammary gland quarters. Measurable chlorhexidine residues were found in milk from treated mammary gland quarters of 2 cows throughout the 42-day sample period in phase II. Estimated mean elimination half-life for chlorhexidine in milk was 11.5 days. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of the long elimination half-life of chlorhexidine in milk from treated mammary gland quarters, the lack of human dietary exposure data to suggest a food tolerance for chlorhexidine in food products, and the Food and Drug Administration's published zero tolerance for chlorhexidine in uncooked edible calf tissues, we do not recommend extralabel use of chlorhexidine suspension as a treatment to stop lactation in mastitic mammary gland quarters of cows.     

Elimination kinetics of ceftiofur hydrochloride after intramammary administration in lactating dairy cows

OBJECTIVE: To determine the elimination kinetics of ceftiofur hydrochloride in milk after intramammary administration in lactating dairy cows. DESIGN: Prospective study. ANIMALS: 5 lactating dairy cows. PROCEDURE: After collection of baseline milk samples, 300 mg (6 mL) of ceftiofur was infused into the left front and right rear mammary gland quarters of each cow. Approximately 12 hours later, an additional 300 mg of ceftiofur was administered into the same mammary gland quarters after milking. Milk samples were collected from each mammary gland quarter every 12 hours for 10 days. Concentrations of ceftiofur and its metabolites in each milk sample were determined to assess the rate of ceftiofur elimination. RESULTS: Although there were considerable variations among mammary gland quarters and individual cows, ceftiofur concentrations in milk from all treated mammary gland quarters were less than the tolerance (0.1 microg/mL) set by the FDA by 168 hours (7 days) after the last intramammary administration of ceftiofur. No drug concentrations were detected in milk samples beyond this period. Ceftiofur was not detected in any milk samples from nontreated mammary gland quarters throughout the study. CONCLUSIONS AND CLINICAL RELEVANCE: Ceftiofur administered by the intramammary route as an extra-label treatment for mastitis in dairy cows reaches concentrations in milk greater than the tolerance set by the FDA. Results indicated that milk from treated mammary gland quarters should be discarded for a minimum of 7 days after intramammary administration of ceftiofur. Elimination of ceftiofur may be correlated with milk production, and cows producing smaller volumes of milk may have prolonged withdrawal times.     

Persistence of antibiotics in bovine mammary secretions following intramammary infusion at cessation of milking

A study was conducted to determine the persistence of antibiotic preparations for use in nonlactating cows in bovine mammary secretions following intramammary infusion at cessation of milking. Five commercially available antibiotic formulations were evaluated using 311 cows. All quarters of each cow were sampled once only during the nonlactating period and most cows were sampled at or near parturition. Antibiotic residues were detected qualitatively by the Bacillus stearothermophilus disc assay. Great variation between different antibiotics in persistence in mammary secretion was observed. In general, mammary secretions from most mammary glands infused with cloxacillin or penicillin-dihydrostreptomycin were positive at 28–35 days after infusion and some were positive at 42–49 days after infusion. On the other hand, <13% of mammary secretions at 7 days after infusion of novobiocin and 50% of mammary secretions at 14 days after infusion of penicillin-novobiocin were positive for antibiotics. Cephapirin benzathine persisted for about 21 days after infusion. Some samples that were positive for antibiotics after initial testing were negative following heating of samples, suggesting that component(s) of dry secretion can inhibit growth of B. stearothermophilus and influence the interpretation of results. Colostrum samples from all quarters except one were negative for antibiotics. These data suggest that nonlactating-cow antibiotic formulations persist primarily during the early to mid-nonlactating period. Based upon present methods of formulation, it would appear that antibiotic preparations for use in nonlactating cows most likely provide little protection during the periparturient period, at a time when mammary glands are highly susceptible to new intramammary infections.     

Efficacy of using an internal teat sealer to prevent new intramammary infections in nonlactating dairy cattle

OBJECTIVE: To determine whether insertion of an internal teat sealer (ITS) at the end of lactation would prevent development of new intramammary infections (IMIs) during the nonlactating period. DESIGN: Controlled clinical trial. ANIMALS: 939 Holstein-Friesian dairy cows from 16 herds. PROCEDURES: Results of bacteriologic culture of milk samples collected 14 days prior to the end of lactation were used to assign cows to groups (group 1 = negative results for all quarters; group 2 = positive results for > or = 1 quarter). Quarters of cows in group 1 were treated with an ITS or a single intramammary dose of cloxacillin; quarters of cows in group 2 were treated with cloxacillin in conjunction with an ITS or with cloxacillin alone. Milk samples were collected at the end of lactation and within 8 days after calving. RESULTS: Regardless of whether the outcome of interest was new IMIs caused by any pathogens, major pathogens, environmental pathogens, or streptococci other than Streptococcus agalactiae, quarters in group 2 treated with both cloxacillin and an ITS were less likely to develop a new IMI than were quarters treated with cloxacillin alone. For cows in group 1, no significant difference in risk of new IMIs was found between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that for dairy cattle with an IMI late in the lactation period, intramammary administration of cloxacillin at the end of lactation followed by insertion of an ITS enhanced protection against development of new IMIs, compared with use of cloxacillin alone.     

奶牛临床型乳房炎Nisin抗菌肽治疗后日产奶量及主要乳成分的变化

选取临床型乳房炎自然发病病例9头,乳房内灌注乳酸链球菌素(Nisin)进行治疗,通过检测日产奶量以及停药后2,7,14,21 d的主要乳成分指标,确定Nisin乳房灌注剂对临床型乳房炎病例泌乳性能的影响情况。结果显示,乳房内灌注Nisin后患病乳区乳腺组织得到一定程度的修复,日产奶量逐渐恢复,停药后8 d的日产奶量与发病前6 d相比,平均降幅2.5 kg。治愈后患病乳区牛奶乳脂肪、乳蛋白、乳糖和非脂乳固体含量都呈现上升趋势,但与同期相比,略低于非用药乳区混合牛奶;其中,乳糖含量增加幅度较快,除停药后2 d的治疗乳区外,乳糖含量均在4.7%以上,提示奶牛乳房炎病例经Nisin乳房灌注治疗后,受损乳腺组织修复较快,乳腺上皮细胞合成乳成分的能力大幅度提高。由此可见,Nisin对奶牛临床型乳房炎具有良好的治疗作用。     

奶牛乳房内灌注头孢噻呋钠的消除动力学研究

在奶牛乳房内灌注头孢噻呋钠后,采用超高效液相色谱一串联质谱法测定牛乳中头孢噻呋的浓度,对其消除动力学进行了研究。3头实验奶牛按每个乳房0．3g头孢噻呋灌注,牛乳中药物达到的最高浓度Cmax=107．89μg／mL,达峰时间Tmax=8h,药物半衰期T1/2=13．97h。在乳房内用药后的最初56h内,头孢噻呋浓度快速下降;最后一次给药88h后,所有乳腺中头孢噻呋的浓度都低于允许限量（0．1μg／mL）。故建议头孢噻呋在牛奶中的休药期为4d。     

Efficacy of intramammary infusion of ceftiofur hydrochloride at drying off for treatment and prevention of bovine mastitis during the nonlactating period

This study evaluated the efficacy of intramammary infusion of ceftiofur hydrochloride for the treatment of intramammary infections present at the last milking of lactation and for prevention of new intramammary infections during the nonlactating period. Cows were randomly assigned to five treatments (untreated negative control, 125, 250, and 500 mg of ceftiofur, and a positive control group receiving 300 mg cephapirin benzathine). A dose of 125 mg of ceftiofur per mammary quarter was effective for treatment of existing infections present at the time of milk cessation, but only the 500-mg dose of ceftiofur per mammary quarter was effective for both treatment of existing intramammary infections at the time of milk cessation and for prevention of new intramammary infections during the nonlactating period.     

Depletion study of trimethoprim and sulphadiazine in milk and its relationship with mastitis pathogenic bacteria strains minimum inhibitory concentrations (MICs) in dairy cows

Time-related concentrations in milk of a combination of trimethoprim-sulphadiazine (TMP-SDZ) intramammary formulated infusion and its relationship with pathogenic bacteria strains minimum inhibitory concentrations (MICs) isolated from clinical mastitis cows were analysed. The MICs study was performed for Escherichia coli, Staphylococcus aureus and Streptococcus sp. strains. The SDZ concentrations in milk were analysed using high-performance liquid chromatography (HPLC) and TMP using a microbiological assay. Ten lactating cows milked three times daily were used in the time-concentration studies of TMP-SDZ. Milk samples (approximately 20 mL) from the treated mammary quarters were taken at 6, 12, 24, 30 and 36 h after first administration. In order to define the withdrawal time, milk samples from the treated mammary quarters were taken at 24, 36, 48, 72, 84 and 96 h, after finishing the therapy. The MICs fluctuated between 1 and 8 microg/mL. Effective therapeutic concentrations lasted for 36 h when intramammary infusion was repeated three times every 12 h. No TMP was detected in milk for 24 h after finishing therapy. Milk SDZ concentrations were below 0.1 microg/mL in all treated cows after 84 h finishing therapy. At 96 h after finishing therapy, no SDZ milk concentrations were found in six animals, although four animals of the experimental group still had concentrations of 0.07 microg/mL.     

Efficacy of extended pirlimycin therapy for treatment of experimentally induced Streptococcus uberis intramammary infections in lactating dairy cattle

Streptococcus uberis is an important cause of mastitis in dairy cows throughout the world, particularly during the dry period, around the time of calving, and during early lactation. Strategies for controlling S. uberis mastitis have not received adequate research attention and are therefore poorly defined and inadequate. Objectives of the present study were to evaluate the efficacy of extended therapy regimens with pirlimycin for treatment of experimentally induced S. uberis intramammary infections in lactating dairy cows during early lactation and to evaluate the usefulness of the S. uberis experimental infection model for evaluating antimicrobial efficacy in dairy cows. The efficacy of extended pirlimycin intramammary therapy regimens was investigated in 103 mammary glands of 68 dairy cows that became infected following experimental challenge with S. uberis during early lactation. Cows infected with S. uberis in one or both experimentally challenged mammary glands were randomly allocated to three groups, representing three different treatment regimens with pirlimycin, including 2-day (n = 21 cows, 31 mammary quarters), 5-day (n = 21 cows, 32 quarters), and 8-day (n = 26 cows, 40 quarters). For all groups, pirlimycin was administered at a rate of 50 mg of pirlimycin hydrochloride via intramammary infusion. A cure was defined as an experimentally infected mammary gland that was treated with pirlimycin and was bacteriologically negative for the presence of S. uberis at 7, 14, 21, and 28 days after treatment. Experimental S. uberis intramammary infections were eliminated in 58.1% of the infected quarters treated with the pirlimycin 2-day regimen, 68.8% for the 5-day regimen, and 80.0% for the 8-day regimen. Significant differences (P <.05) in efficacy were observed between the 2-day and 8-day treatment regimens. The number of somatic cells in milk decreased significantly following therapy in quarters for which treatment was successful in eliminating S. uberis. However, there was no evidence to suggest that extended therapy with pirlimycin resulted in a greater reduction in somatic cell counts in milk than the 2-day treatment. The S. uberis experimental infection model was a rapid and effective means of evaluating antimicrobial efficacy during early lactation at a time when mammary glands are highly susceptible to S. uberis intramammary infection.     

Persistent Experimental Salmonella dublin Intramammary Infection in Dairy Cows

Experimental intramammary infections were induced in five post-parturient Holstein cows by inoculation of low numbers (5000 colony forming units) of virulent Salmonella dublin via the teat canal of mammary gland quarters. Rectal temperature, pulse and respiratory rates, milk yield, and milk quality as assessed by the California Mastitis Test (CMT) and somatic cell counts (SCC) were recorded every 12 hours at milking. Bacteriologic cultures of foremilk quarter samples and feces were obtained daily, as were complete blood counts. ELISA titers for IgG and IgM recognizing S. dublin lipopolysaccharide (LPS) were obtained weekly on serum and quarter milk samples. All cows excreted S. dublin intermittently from infected quarters, but no changes were detected in rectal temperature, appearance of the mammary gland or secretions, CBC, milk yield, and pulse and respiratory rates. Somatic cell counts were modestly increased in infected quarters as compared with uninfected quarters (P = .015, paired t test); however, CMT scores after infection remained low, and were not significantly different from pre-infection scores (P greater than .10, sign test). After infection, administration of dexamethasone resulted in signs of clinical mastitis and increased excretion of S. dublin from mammary quarters (P = .0004, paired t test). One cow had necrotizing mastitis and S. dublin septicemia and was euthanatized. In the four surviving cows, clinical improvement was observed after systemic gentamicin therapy and intramammary infusion with polymyxin B, but all cows continued to excrete S. dublin intermittently from one or more quarters and occasionally from feces for the remaining period of observation. All infected cows demonstrated a rise in IgG and IgM ELISA titers recognizing S. dublin LPS in serum and milk. At necropsy (13-25 weeks postinfection), S. dublin was recovered only from the mammary tissue or supramammary lymph nodes in three of four cows. In one cow, mammary gland and lymph-node samples were negative for S. dublin despite positive milk cultures. In all cows, histopathologic examination revealed multifocal areas of chronic active mastitis. These lesions were similar to histopathologic findings from mammary gland carriers with naturally acquired S. dublin infection.     

Tuberculin elicited cellular immune response in the lactating bovine mammary gland vaccinated intramammarily with Mycobacterium bovis

The development of a local antigen-specific sensitivity was monitored histologically and in secretions of the bovine mammary gland. Three cows in mid-lactation were immunized by injecting 50 microliter of a killed Mycobacterium bovis vaccine into the dorsal secretory tissue of the rear mammary glands; two cows served as unvaccinated controls. Ten weeks after vaccination, all cows were challenged by intramammary infusion of 1.0 microgram tuberculin in 5 ml phosphate-buffered saline (PBS). Three quarters of each cow received tuberculin at 72, 48, and 24 hours before slaughter; a control quarter received PBS at 72 hours. Vaccinated cows exhibited an intense, local cellular reaction to tuberculin in teat-end tissues at all times post infusion; PBS-infused glands were normal. A moderate leukocyte response in parenchymal tissues adjacent to the gland cistern of tuberculin-infused quarters was observed, but deep parenchymal tissues were normal; no effect on milk yield was found. Tuberculin-infused quarters exhibited histological responses in teat cisternal tissues similar to those in delayed-type hypersensitivity reactions. Leukocytic accumulation was primarily macrophages and lymphocytes with few neutrophils. Erythema was observed in the distal half of the cistern, and fibrin deposits were found in subepithelial connective tissues. The epithelium, although distended with leukocytes, was intact and numerous mitotic figures were present. Unvaccinated cows showed no response to challenge. Results demonstrated a marked and specific cellular response in sensitized cows to challenge with tuberculin.     

Intramammary administration of gentamicin as treatment for experimentally induced Escherichia coli mastitis in cows.

In 8 Holstein cows, 50 colony-forming units (CFU) of Escherichia coli was administered into 1 mammary gland. Infections were established in all inoculated glands. In 4 of the 8 cows, 500 mg of gentamicin sulfate was administered by intramammary infusion 14 hours after inoculation; the other 4 cows were untreated controls. Infusions of gentamicin also were given after each of the 3 successive milkings after the initial infusion, so that a total dose of 2 g of gentamicin was given to each of the treated cows. During the 33-hour treatment period and for the first milking after the last infusion of gentamicin, the treated cows had a mean gentamicin concentration of greater than or equal to 31.0 micrograms/ml in milk samples that were collected from inoculated quarters immediately before each milking. Concentrations of 0.34 and 0.69 micrograms of gentamicin/ml were detected in milk from 2 cows at 8 days after inoculation with E coli. Mean serum concentrations of gentamicin were greater than or equal to 0.37 micrograms/ml throughout the treatment period and the first 12 hours after the last infusion, with a mean peak concentration of 0.96 micrograms/ml at 24.4 hours. The range of peak concentration of gentamicin detected in urine from all treated cows was 42 to 74.4 micrograms/ml. Peak concentration of E coli in milk in the treated cows (6.08 +/- 1.02 log10 CFU/ml) did not significantly (P greater than 0.05) differ from that of the control cows (5.26 +/- 1.00 log10 CFU/ml). Similarly, mean duration of infection in the treated cows (54 hours) did not differ significantly from that of the control cows (48 hours).(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of extended pirlimycin hydrochloride therapy for treatment of environmental Streptococcus spp and Staphylococcus aureus intramammary infections in lactating dairy cows

Fifty-one chronically infected lactating dairy cows were used to evaluate the efficacy of extended pirlimycin therapy regimens for treatment of intramammary infections by environmental Streptococcus spp and Staphylococcus aureus. Cows (n = 47) with one or more infected mammary quarters were blocked by parity and randomly allocated to one of three groups for treatment with pirlimycin (50 mg/mammary quarter) as follows: one treatment per day for 2 days (n = 36 infected mammary quarters); one treatment per day for 5 days (n = 36 infected mammary quarters); and one treatment per day for 8 days (n = 20 infected mammary quarters). Four cows with nine infected mammary quarters were included as untreated controls. Milk samples from each mammary quarter were collected 7 days before treatment, immediately before treatment, and weekly for 4 weeks after the final treatment for microbiological evaluation. A bacteriologic cure was defined as a treated, infected quarter that was bacteriologically negative for the presence of previously identified bacteria at weekly intervals after treatment. Efficacy of pirlimycin therapy against intramammary infections caused by environmental Streptococcus spp and S. aureus was 44.4%, 61.1%, and 95.0% for the 2-, 5-, and 8-day treatment regimens, respectively. None of the infections in the untreated control quarters was cured. Significant differences in efficacy were detected between all pirlimycin groups and the untreated control group, between the 8- and 2-day treatment regimens, and between the 8-day and 5-day treatment regimens (P < or = .05). Results of this study indicate that extended pirlimycin therapy was effective in eliminating intramammary infections caused by environmental streptococci and S. aureus in lactating dairy cows.     

Lymphocytes from one side of the bovine mammary gland migrate to the contra lateral gland and lymph node tissue

The four quarters of bovine mammary glands are completely separated and two quarters on each side (right or left) are connected to ipsi lateral supra mammary lymph nodes. It is not clear whether cells infused into the cistern of the mammary gland are capable of migrating to lymph nodes or the general circulation. To examine cell migration, a prescapular lymph node was removed from each of two lactating and three non-lactating dairy cows, and isolated lymphocytes were stained with Hoechst 33342. Autologous stained cells were infused into the mammary gland and then activated by intramammary infusion of zymosan-stimulated serum (source of C5a). After 17 h, Escherichia coli J5 bacterin was infused into the contra lateral mammary gland to mimic infection. After 43 h cows were euthanized and tissue samples (mammary quarters, right and left supra mammary, mesenteric, ileocecal and prescapular lymph nodes, liver and spleen) were collected for microscopic examination as well as flow cytometric analysis. Hoechst stained cells were detected not only in infused quarters, but also in contra lateral quarters as well as in both supra mammary lymph nodes. This indicates that cells infused into the mammary gland migrate to contra lateral tissues and supra mammary lymph nodes.     

An investigation of mastitis due to S agalactiae, S uberis and M smegmatis in a dairy herd

Subclinical mastitis caused by streptococcal infections affected 27 of 83 cows in a commercial dairy herd. Between three and six weeks after intramammary treatment of these cows with cloxacillin, 16 (59 per cent) of the treated cows developed acute clinical mastitis associated with Mycobacterium smegmatis. None of the untreated cows was affected. Infected quarters were moderately hypertrophied and fine clots were present in the milk for three to four weeks. No cows showed systemic signs of illness. Studies carried out over 12 months showed that infected cows shed M smegmatis for three to four months and affected quarters remained hypertrophied in all but one cow after 12 months. The mean milk cell count of affected quarters fell slowly from 4,850,000/ml in the acute stage to 810,000/ml five months later and 620,000/ml 12 months later, suggesting that the organism persisted in the udder. The estimated mean loss in lactation yield for cows with M smegmatis mastitis was 10.8 per cent. Losses were greatest when the hind quarters were involved (mean 28 per cent for cows with both hind quarters affected). Ten of the 16 affected cows were ultimately culled owing to serious reductions in yield.     

Response of lactating dairy cows fed different supplemental zinc sources with and without evaporative cooling to intramammary lipopolysaccharide infusion: metabolite and mineral profiles in blood and milk

The objective of this study was to determine the effect of evaporative cooling and dietary supplemental Zn source on blood metabolites, insulin and mineral concentrations, and milk mineral concentrations following intramammary lipopolysaccharide (LPS) infusion. Seventy-two multiparous Holstein cows were assigned to one of four treatments with a 2 × 2 factorial arrangement. Treatments included two environments: with or without evaporative cooling using fans and misters over the freestall and feedbunk, and two dietary sources of supplemental Zn: 75 mg/kg of dry matter (DM) supplied by Zn hydroxychloride (inorganic Zn; IOZ) or Zn hydroxychloride (35 mg of Zn/kg of DM) + Zn–Met complex (ZMC; 40 mg of Zn/kg of DM). A subset of cows (n = 16; 263 ± 63 d in milk) was infused with 10 μg of LPS or a saline control in the left or right rear quarters on day 34 of the environmental treatment. Individual milk samples collected from LPS-infused quarters at −4, 0, 6, 12, 24, 48, 72, 96, and 144 h relative to infusion were analyzed for minerals. Blood samples were collected at the same time with an additional sample collected at 3 h post-infusion to analyze glucose, nonesterified fatty acids (NEFA), insulin, and minerals. Cooling by time interactions (P ≤ 0.07) were observed for plasma glucose, NEFA, and serum insulin. Compared with cooled cows, non-cooled cows had lower concentrations of plasma glucose except at 3 h following intramammary LPS infusion, greater serum insulin at 3 and 12 h, and lower plasma NEFA at 24 and 48 h after infusion. Relative to cooled cows, non-cooled cows tended (P = 0.07) to have lower serum K concentration and had lower (P < 0.01) serum Zn 6 h following infusion (cooling by time interaction: P < 0.01). Relative to ZMC cows, IOZ cows had greater (P ≤ 0.09) concentrations of plasma Se, skim milk Na and Se, and skim milk Na to K ratio. Regardless of treatment, intramammary LPS infusion reduced (P < 0.01) serum or plasma concentrations of Ca, Mg, Zn, Fe, and Se, but increased (P < 0.01) their concentration in skim milk. In conclusion, deprivation of cooling resulted in more rapid and prolonged insulin release and influenced the systemic and mammary mineral metabolism during mammary inflammation induced by LPS of lactating dairy cows. Dietary supplementation of Zn–Met complex reduced blood and milk Se concentrations compared with cows fed Zn from an inorganic source.     

Pharmacological aspects of chloramphenicol administration by the intramammary route to lactating dairy cows

Concentrations of chloramphenicol (C M) were determined, by microbiological assay, in the milk and blood serum of 17 culled dairy cows after intramammary infusion of an approved parenteral CM product (Gloveticol) and in the milk of 16 lactating cows after treatment with two approved CM products for intramammary infusion, at dosages ranging from 1 to 30 g/cow. C M was quickly absorbed from the udder into the blood circulation; the doses of 12.5 and 25 g/cow were almost completely absorbed within 20 hours. Absorption half-life (t1/2ab) from fully functioning quarters was 57+/-18 minutes, and the t1/2ab from partially functioning quarters was 125+/-37 minutes. Mean peak serum C M concentrations were 6.1, 16.2, and 37.4 microg/ml after the cows had been infused with 5, 12.5, and 25 g, respectively. These values were considerably higher than the corresponding peak serum C M concentrations reported following intramuscular injection of equivalent doses of the drug. C M residues were not detectible microbiologically in milk from treated quarters 20 hours after treatment with 5 g or 6.25 g, and 36 hours after treatment with 15 g. Drug concentrations in the milk from the non-treated quarters were approximately 70 per cent of the corresponding serum drug levels. Serum CM concentrations of potential therapeutic value in the treatment of gram-negative bacterial infections, i.e. > 5 microg/ml, were maintained for 8 hours after cows had been infused with 12.5 g, and for 12 hours after infusion with 25 g. The implications of the improved systemic availability of C M infused by the intramammary route over the intramuscular route are discussed in terms of potential therapeutic efficacy, local irritation, and duration of drug residues.     

Intramammary infusion of an Enterococcus faecium SF68 preparation promoted the involution of drying off Holstein cows partly related to neutrophil‐associated matrix metalloproteinase 9

A problem for dairy cows following milk stasis is to cope with a high risk of intramammary infection and there is a need to initiate an extensive renewal of secretory modules in mammary glands so that milk production in next lactation may be optimized. We recently reported that ultrasonicated Enterococcus faecium SF68 (SF68) is compatible with cow mammary glands and an enhancer of innate immunity during the immediate post‐milk stasis period. The current study further examines the concomitant effect of ultrasonicated SF68 on mammary tissue remodeling. Four Holstein cows each received intramammary infusions of regular antibiotic dry‐cow formula (positive control) and two different doses of SF68 in different quarters. Analyses of individual quarter secretion samples showed faster neutrophil infiltration, earlier modifications in protein composition, including caseins and lactoferrins, as well as more prompt elevation of the specific unit of 92‐kDa matrix metalloproteinase 9 (MMP9) in SF68‐infused quarters compared to the positive controls. Intramammary infusion of ultrasonicated SF68 seems able to accelerate the regression of mammary synthetic capacity and potentiate the breakdown of glandular extracellular matrix, indicating a more efficient mammary gland involution. Correlation analyses imply that the ability of ultrasonicated SF68 to induce faster neutrophil chemotaxis and the associated MMP9 release is partly responsible.     

Accelerated bovine mammary involution induced by infusion of concanavalin A or phytohemagglutinin

Right mammary quarters of dairy cows were infused with concanavalin A (conA) or phytohemagglutinin (PHA) near drying off. Significant changes in milk yield and composition were observed by 24 hours after infusion. In general, conA or PHA treatment resulted in significantly greater compositional changes earlier in the dry period compared with control quarters. As involution progressed, lactoferrin, serum albumin, immunoglobulin G, pH, and numbers of somatic cells increased, whereas citrate and the molar ratio of citrate:lactoferrin decreased. Mammary secretion accumulation at 7 days of involution was significantly lower in treated compared with control quarters. The data indicated that intramammary infusion of conA or PHA near drying off accelerates bovine mammary involution, resulting in elevated levels of natural protective factors.     

Effects of dry cow intramammary therapy on quarter infections in the dry period

Quarter milk samples were taken from 150 cows from three dairy farms in south-east Queensland at drying off, two, four and six weeks after drying off, at calving, and one, two and three weeks after calving. In each of the herds, the cows were randomly allocated to three groups of approximately equal size. One group had all the quarters of all the cows treated at drying off with a dry cow antibiotic infusion containing cloxacillin; the second group was given no treatment, and the third group had selected quarters treated on the basis of their high activity of N-acetyl-beta-D-glucosaminidase at drying off. Dry cow treatment resulted in a marked reduction in the number of infected quarters at two and four weeks after drying off, so that the comprehensively treated group had significantly less infected quarters at these times (P<0.02). Twelve dinical cases of mastitis were detected two weeks after drying off in the untreated groups, 10 in the untreated quarters of the selectively treated groups, and no cases in the comprehensively treated groups. These cases were due mainly to Streptococcus uberis and Streptococcus dysgalactiae. The number of infected untreated quarters increased markedly between drying off and two weeks later, but in all three groups there was a marked decrease in the number of infected quarters between six weeks after drying off and calving, suggesting that the mammary glands were more able to overcome infections at this time.