Antibiotic persistence and tolerance in the lactating goat following intramammary therapy

Due to the impact of the dairy quota system, the commercial use of goats for the production of milk and associated products is attractive to farmers diversifying their dairy interest. Intensification of milking and the expansion of herds will inevitably increase the incidence of caprine mastitis. The pharmaceutical industry and the veterinary surgeon will be required to provide data and advice upon the performance of currently available bovine intramammary products when used in the goat. This study produced evidence that one available bovine intramammary product, when infused into the glands of milking goats, produced a withholding time approximately double that defined for the cow. Following a course of infusions after three successive milkings, milk was not available for human consumption or for the production of cheese and yoghurt until 112 hours after the final infusion. This situation is likely to be representative of that which will occur for other currently available bovine intramammaries when prescribed in the goat.     

Residue persistence in sheep milk following antibiotic therapy

Drug residues in milk supplies may have public health implications and can interfere in the manufacture of dairy products, such as cheese. In Spain, most ewe milk production is destined for cheese making, often using raw milk. This study analyses the main factors influencing antibiotic depletion time in lactating dairy sheep. 42, Manchega ewes were distributed into three groups, each receiving a different treatment (cephalexin intramammary infusion, penicillin G intramuscular, and oxytetracycline intravenous injections). During and after the recommended withdrawal period, milk samples were taken at each milking. A microbiological inhibition test (Brilliant Black Reduction, BRT) was used to screen all samples and antibiotic withholding times were established using a logistic regression model. The response to the BRT method in milk from individual ewes treated showed that the effect of the milking order was significant (P<0.001) with the three antibiotics. However the only influence on milk yield was with the intramammary treatment (P<0.005). The BRT method was found to be very sensitive, particularly to the two beta-lactamic antibiotics.     

Modelling the concentration-time relationship in milk from cattle administered an intramammary drug

Whittem, T., Whittem, J. H., Constable, P. D. Modelling the concentration–time relationship in milk from cattle administered an intramammary drug. J. vet. Pharmacol. Therap.  35 , 460–471. Antimicrobial drugs are often infused directly through the streak canal into the bovine udder for the treatment or prevention of mastitis. These infusions have two major problems: drug residues in milk and variable antimicrobial efficacy. Both problems are influenced by the pharmacokinetics of intramammary delivery and elimination of drugs. This pharmacokinetics does not conform to the assumptions of traditional first‐order mamillary pharmacokinetic models. To help understand drug delivery into and elimination from the udder, a new approach to pharmacokinetic modelling of the udder is proposed. This new model was used to predict the movement of drug within the udder and the concentrations of drug achieved within physiological compartments of the udder. These predictions were examined using computer modelling. The model was evaluated using data from in vivo intramammary infusion of cefuroxime. The model predicts that changes in milking efficiency (residual volume), milk productivity and milking frequency can impact both the drug residue persistence and the time that milk drug concentrations exceed the minimum inhibitory concentrations for pathogens. The model provides a new tool for future evaluation of intramammary dosing studies.     

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 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.     

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。     

Effect of milk fraction on concentrations of cephapirin and desacetylcephapirin in bovine milk after intramammary infusion of cephapirin sodium

Clinical mastitis in dairy cows is commonly treated with intramammary (IMM) antimicrobial agents. Pharmacokinetic data are used to design treatment regimens and determine withholding times. In some pharmacokinetic studies, investigators measure antimicrobial concentrations in foremilk, whereas in others, they use bucket milk or do not specify the milk fraction sampled. Our objective was to compare antimicrobial concentrations in foremilk, bucket milk, and strippings after IMM treatment of six healthy Holsteins. One mammary gland/cow was infused with 200 mg of cephapirin (CEPH) after each of the two milkings, using different milking frequencies and treatment intervals in a randomized crossover design. Treated glands were sampled at the first milking following each infusion. Antimicrobial concentrations in milk were measured using HPLC/MS/MS. CEPH concentration was higher in foremilk (geometric mean 44.2 μg/mL) than in bucket milk (15.7 μg/mL) or strippings (18.5 μg/mL), as it was true for desacetylcephapirin (DAC) (59.5, 23.0, and 30.2 μg/mL, respectively). This finding, which was based on milk samples collected at the first milking after IMM infusion, suggests that pharmacokinetic data based on drug concentrations in foremilk may be misleading. Strippings were more representative of bucket milk than foremilk. The relationship between milk fraction and antimicrobial concentration should be investigated for other IMM antimicrobial agents. Meanwhile, it is essential that pharmacokinetic and residue studies report the fraction of milk that was analyzed.     

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.     

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 specific egg yolk immunoglobulin (IgY) to bovine mastitis caused by Staphylococcus aureus

The objective of this study was to estimate the efficacy of specific egg yolk immunoglobulin (IgY) to bovine mastitis caused by Staphylococcus aureus. Eighteen lactating cows with clinical mastitis and 18 lactating cows with experimental mastitis (1 quarter per cow) were randomly assigned to three treatments: IgY (20mg/ml) infusion, penicillin (100mg/ml) infusion and no infusion. Treatments for clinical mastitis and experimental mastitis were performed by a 6-day course of intramammary infusion with a dosage of 10ml at an interval of 12h. Milk samples were collected at morning milking time for testing color, clot, somatic cell counts (SCC) and bacterial count. For most of the cows treated with IgY and penicillin, the milk color and clot recovered to normal form during the therapy course. The milk SCCs and bacterial counts of treated cows decreased compared to those of untreated cows (p<0.05). The cure rates by IgY for experimental and clinical mastitis were 83.3% and 50%, respectively, and those by penicillin were 66.7% and 33.3%, respectively. These results showed the potential of specific IgY to be an alternative therapy for mastitis caused by S. aureus.     

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.     

Bovine Mastitis due to Prototheca zopfii: Clinical,Epidemiological and Pathological Aspects in a Brazilian Dairy Herd

The clinical, epidemiological and pathological aspects of protothecal mastitis in a Brazilian dairy herd are described. Prototheca zopfii infection was diagnosed in 11 of 121 milking cows. Clinical mastitis refractory to usual therapy was observed in 7 cows. Several environmental conditions conducive to the growth of Prototheca spp., such as wetness, muddiness and the presence of organic material, were present in the dairy. Improper milking practices and insanitary infusion of the intramammary antibiotics were also observed. Six cows with protothecal mastitis were slaughtered and the affected quarters of each cow were examined by histology and immunohistochemical staining for bovine keratin and P. zopfii. The histological lesions were characterized by interstitial infiltrates of macrophages, plasma cells and lymphocytes; algae were seen in the alveolar lumen and interstitium. The lack of a positive reaction with an antiserum against bovine keratin in the mammary alveolar epithelial layer in some affected areas suggests destruction of milk-producing tissues, which may be related to the low milk production observed. The algal organisms stained positively with a polyclonal antibody against P. zopfii.     

Interleukin-1β infusion in bovine mammary glands prior to challenge with <Emphasis Type="Italic">Streptococcus uberis</Emphasis> reduces bacterial growth but causes sterile mastitis

Dairy cows are especially vulnerable to intramammary infection by the bacterial pathogen Streptococcus uberis in the dry period. Use of immunotherapeutic agents at drying off could increase cellular defences in the gland and prevent establishment of new S. uberis infections. This study investigated the potential of infusing recombinant bovine interleukin-1 beta (rbIL-1beta) in the mammary glands as a prophylactic agent against subsequent intramammary challenge with S. uberis in the early dry period. Immediately after the last milking at commencement of the dry period, one cow from each of 10 monozygous twinsets was infused with 10 microg of rbIL-1beta in two quarters and the other twin was infused with the carrier agent, sterile phosphate buffered saline. Twenty-four hours later, the quarters were infused with 10(3) colony-forming units (CFU) of S. uberis. Bacteriology, somatic cell count (SCC), concentrations of specific cytokines and antibody responses were monitored in mammary gland secretions and sera for the next 21 days. Infusion of rbIL-1beta into mammary glands at commencement of the dry period was associated with less new S. uberis intramammary infections, as determined by the number of quarters with bacterial growth. However, high SCC in quarters following infusion of rbIL-1beta masked the full beneficial effect of this procedure.     

Effects of intramammary infusions of interleukin-8 on milk protein composition and induction of acute-phase protein in cows during mammary involution

The effects of interleukin-8 (IL-8) on bovine mammary functions such as milk protein secretion and the blood-milk barrier during mammary involution were evaluated. Following the final milking, recombinant bovine (rb) IL-8 (5 or 25 microg) and a saline placebo were individually infused into the left- and right-front teat cisterns of 6 cows, respectively. Three cows without treatment at the final milking were also used as controls. Mammary secretions and blood were collected at -24, 0, 10, 24, 72, 168, 336, and 720 h after infusion. In the mammary glands infused with 25 microg of rbIL-8, the increases in somatic cell counts and in the concentrations of serum albumin, IgG1 and IgG2, and the decreases in the concentrations of alpha- and beta-casein and beta-lactoglobulin were greater than in the control glands. In the mammary glands infused with 5 microg of rbIL-8, compared to the glands infused with 25 microg of rbIL-8, these changes were moderate. These results indicate that rbIL-8 impairs the integrity of the blood-milk barrier and suppresses milk-specific protein secretions. In the cows infused with 25 microg of rbIL-8, the rectal temperature and serum haptoglobin level were transiently elevated after the infusion, showing that intramammary infusion of rbIL-8 could elicit systemic inflammation.     

Management of the dairy herd treated with bovine somatotropin

Cows that produce large quantities of milk require more management and higher quality of management than cows producing smaller quantities of milk. This is true whether improvements in milk production occur through genetic selection, increased milking frequency, or use of bovine somatotropin (bST). The milk response to use of bST is similar (10 to 15%) to that of three times a day (3x) milking and we expect that the management required to maintain the increased production through successive lactations with bST will be similar to that required for the 3x herd. Maximum economic benefit from use of bST will be achieved by dairy managers who (1) feed cows to maximize intake of diets with appropriate nutrient content and balance, (2) maintain proper body condition of their cows, and (3) have health and reproduction management programs that prevent rather than cure problems. Efficient use of record-keeping systems that enable the manager to monitor individual cow status will be advantageous. Economic forces will continue to bring change to the dairy industry. The manager that plans for change and ensures that the dairy's management programs allow for the most economically efficient production will be in position to adapt to these changes. The well-managed dairy will be able to adopt new, efficiency-enhancing technologies, such as bST, to ensure the continued opportunity to compete in the dairy industry.     

Phenotypic characterisation of Australian sheep and cattle isolates of Mannheimia haemolytica,Mannheimia granulomatis and Mannheimia varigena

OBJECTIVE: To perform a comprehensive phenotypic characterisation of 35 isolates of bacteria previously identified as haemolytic Pasteurella-Actinobacillus and obtained from cattle and sheep. DESIGN: The 35 isolates that had been obtained from Australian animals, 30 from cattle and five from sheep, were compared with reference strains of the five recognised species of the genus Mannheimia--M. haemolytica, M. glucosida, M. granulomatis, M. ruminalis and M. varigena. RESULTS: Thirty-four of the isolates could be confidently assigned to three species of the genus Mannheimia. Twenty-nine were M. haemolytica, with 25 being isolated from cattle and four from sheep. All but three of the bovine M. haemolytica were isolated from pneumonic lungs. Of the three remaining bovine M. haemolytica isolates, one was obtained in pure culture from a bovine milk sample and the other two as part of a mixed flora associated with a middle ear infection of a calf suffering mucosal disease. Of the four ovine M. haemolytica isolates, two were isolated in pure culture from milk and two, also in pure culture, from pneumonic lungs. Three bovine isolates were identified as M. granulomatis--one from a tongue abscess, one from a jaw abscess and one from a lung showing suppurative bronchopneumonia. Two bovine isolates were identified as M. varigena--one coming from an udder and the other from a spleen. The available diagnostic records provided no information on whether these isolates were associated with a disease process. The remaining isolate was obtained from an ovine tongue abscess and could not be assigned to a recognised species within the genus Mannheimia. CONCLUSION: The study represents the first time that M. haemolytica, M. granulomatis and M. varigena have been recognised as being present in cattle and sheep in Australia. Veterinary laboratories that encounter Pasteurella-Actinobacillus-like organisms from cattle and sheep should attempt as complete a characterisation as possible to help improve our knowledge of the disease potential of these organsims.     

Dairy sheep production research at the University of Wisconsin-Madison,USA-a review

Commercial milking of sheep is a new agricultural industry in the United States starting approximately 30 yr ago. The industry is still small, but it is growing. The majority of the sheep milk is used in the production of specialty cheeses. The United States is the major importer of sheep milk cheeses with 50 to 60% of annual world exports coming to the United States during the past 20 yr. Therefore, there is considerable growth potential for the industry in the United States. The only dairy sheep research flock in North America is located at the Spooner Agricultural Research Station of the University of Wisconsin-Madison. The research program started in 1993 and has been multifaceted; dealing with several areas important to commercial dairy sheep farmers. The East Friesian and Lacaune dairy breeds were compared and introduced to the industry through the research program. Both dairy breeds produced significantly more milk than traditional meat-wool breeds found in the U.S., but the two breeds differed in their production traits. East Friesian-cross ewes produced more lambs and slightly more milk than Lacaune-cross ewes whereas Lacaune-cross ewes produced milk with a higher percentage of fat and protein than East Friesian-cross ewes. Lactation physiology studies have shown that ewes with active corpora lutea have increased milk yields, oxytocin release during milking is required to obtain normal fat percentages in the milk, large udder cisterns of dairy ewes can allow for increased milking intervals, and short daylengths during late pregnancy results in increased milk yield. In the nutrition area, legume-grass pastures and forages with a higher percentage of legume will result in increased milk production. Grazing ewes respond to additional supplementation with increased milk yield, but it is important to match the supplement to the quality of the grazing. Ewes on high quality legume-grass pastures that are high in rumen degradable protein respond with increased milk production to supplements high in energy and/or     

Antibiotic residues in goats milk following intramammary treatment

Two lactational intramammary antibiotic preparations (cloxacillin and oxytetracycline) were each used to treat eight goats by intramammary infusion in one half. The rate of release of the antibiotics was monitored by a diffusion assay based on the sensitive organism Bacillus stearothermophilus var. calidolactis. Cloxacillin was still detectable 156 hours after the final treatment while oxytetracycline was undetectable 108 hours following treatment. A small but significant amount of antibiotic was translocated between treated and untreated halves of the udder in both cases.