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Pharmacokinetic profile of erythromycin after intramammary administration in lactating dairy cows with specific mastitis.

The pharmacokinetics of erythromycin was studied in five lactating dairy cows following single intramammary infusion of 300 mg erythromycin in each of two quarters per cow with specific mastitis. Levels of erythromycin in plasma and quarter milk samples were measured by agar plate diffusion assay using Micrococcus luteus (ATCC 9341) as the test organism. Erythromycin level in plasma reached a peak concentration value (C(max)) of 0.07 +/- 0.01 microg/ml at 30 min; thereafter, levels declined gradually to reach 0.05 +/- 0.00 microg/ml 12 h post drug administration. The pharmacokinetic profile of the drug revealed mean absorption half life (t(1/2 ka)) as 0.26 +/- 0.05 h. The drug was eliminated slowly with elimination half-life (t(1/2 beta)) of 13.75 +/- 0.35 h and elimination rate constant (k(el)) of 0.04 +/- 0.00 h(-1). The volume of distribution based on the zero-time plasma concentration intercept of the least-squares regression line of the elimination phase (V(d(B))) was 0.032 L/kg. The drug crossed to untreated quarters also; mean drug levels of 0.20 +/- 0.07, 0.23 +/- 0.07, 0.17 +/- 0.04, and 0.17 +/- 0.04 microg/ml were found at 3, 6, 8 and 12 h, respectively. The mean drug concentration for treated quarters was measured as 22.97 +/- 2.31 microg/ml milk at first milking (12 h) following drug infusion. No apparent adverse reaction was seen in cows administered erythromycin. It is concluded that following intramammary infusion erythromycin diffuses readily and extensively in various body fluids and tissues and adequate concentration is maintained in udder tissues for at least 12 h post intramammary administration. Thus, erythromycin may be recommended for local therapy of acute mastitis caused by Gram-positive bacteria in lactating dairy cows.

Animals↗

Leukocyte counts and microbiologic cultivation in the diagnosis of puerperal mastitis.

In order to study the value of leukocyte counts and quantitative microbiologic cultivation of milk in the diagnosis of puerperal mastitis, 491 milk samples from nursing women were examined. In milk samples from mammary glands without inflammatory symptoms, leukocyte counts were less than 10(6)/ml of milk, and the milk was sterile or harbored less than 10(3) bacteria/ml. Samples from mammary glands with inflammatory symptoms could be divided into three groups. In one group, leukocyte counts were less than 10(6)/ml of milk, and cultivation results were similar to those of mammary glands without symptoms. The symptoms persisted for an average of 2.1 days. These cases were considered as milk stasis. In another group, the leukocyte counts were greater than 10(6)/ml of milk, but the milk was sterile or contaminated by skin flora bacteria. Average duration of symptoms was 5.3 days. These cases were considered as noninfectious inflammation of the breast. In the third group, leukocyte counts were greater than 10(6)/ml of milk and bacteria occurred in numbers of greater than 10(3)/ml, which suggests the presence of infectious mastitis. In these cases only antibiotic treatment should be recommended.

Animals↗

Non-clinical intramammary infection in lactating ewes and its association with clinical mastitis.

A bacteriological survey for the study of non-clinical intramammary infection in the sheep udder was carried out in 88 Assaf ewes. A mean infection prevalence in the first few weeks of lactation was 55%. The most common bacterial isolates were Micrococcus spp. followed by coagulase negative staphylococcus, together accounting for 93% of the total number of isolates. An infection prevalence of 54% was found in ewelambs 2 days after their first lambing, indicating a marked new infection rate around lambing. Generally, the course of lactation was characterized by dynamic changes of new infection and spontaneous resolution. About 5% of half udders examined developed clinical mastitis. The comparison of bacteriological data from mastitic milk samples and from samples taken from the same half udders before the appearance of the clinical disease could not support the theory that in sheep, mastitis is a clinical exacerbation of a non-clinical intramammary infection.

Animals↗

Comparative in vitro activity of three cephalosporins against Staphylococcus aureus isolated from bovine mastitis.

This report compares the in vitro activity of three cephalosporins (cephalothin, cefoxitin and ceftriaxone) against 57 Staphylococcus aureus strains isolated from cows with clinical mastitis on the basis of the minimal inhibitory (MIC) and minimal bactericidal concentrations (MBC). The majority of the S aureus strains showed resistance to cefoxitin and ceftriaxone and sensitivity to cephalothin. The highest MICs and MBCs were found for cefoxitin and ceftriaxone. Antimicrobial tolerance (MBC/MIC greater than or equal to 32:1) was observed in relation to cephalothin and ceftriaxone. The data suggest that these cephalosporins may not be effective for the treatment of staphylococcal bovine mastitis. The precise definition of their antimicrobial efficacies requires more detailed in vitro and in vivo studies.

Animals↗

Anti-inflammatory ketoprofen in the treatment of field cases of bovine mastitis.

The efficacy of ketoprofen in the treatment of acute clinical mastitis was evaluated in a clinical trial comprising a non-blind controlled study and a blind, placebo-controlled study. All the cows were treated with 20 g sulphadiazine and 4 g trimethoprim intramuscularly upon diagnosis, and half the dosage was given once daily thereafter. In addition, the ketoprofen treatment groups received 2 g ketoprofen intramuscularly once daily for the duration of the antimicrobial therapy. Recovery rates for the non-blind contemporary controls and the blind placebo-controls were 83.7 per cent and 70.7 per cent, respectively. In the non-blind controlled ketoprofen and the placebo-controlled ketoprofen treatment groups, recovery rates were 94.7 per cent and 92.3 per cent, respectively. The odds ratio (OR) of recovery was significantly (P < or = 0.01) high in the placebo-controlled study (OR = 6.75, confidence interval [CI] = 1.45 to 31.4), and high but not significant in the non-blind controlled study (OR = 2.64, CI = 0.53 to 13.10). It was concluded that ketoprofen significantly improved recovery in clinical mastitis in dairy cows.

Animals↗

Granulomatous mastitis caused by histoplasma and mimicking inflammatory breast carcinoma.

Two cases of a lobular, necrotizing granulomatous process causing a unilateral painful breast mass mimicking carcinoma are presented for comparison. While the morphologic appearance in each case was that of lobular granulomatous mastitis, the etiologic agent in one case appeared to be Histoplasma capsulatum, based on Grocott methenamine silver staining, and represents the second reported case of histoplasmosis involving only breast parenchyma. Awareness of the rare entity, granulomatous mastitis, is important for the pathologist because the definitive diagnosis is made microscopically. Thorough evaluation of the breast tissue is essential for its management and should eventually contribute to the clarification of its etiology.

Adult↗

Dietary selenium effects on milk eicosanoid concentration in dairy cows during coliform mastitis.

The effect of selenium deficiency on the product profile of arachidonic acid oxidation by enzymatic pathways in Holstein cows with experimentally-induced coliform mastitis was investigated. The animals were fed dairy rations containing 0.05 mg Se/kg dry matter, with the supplemented group receiving additional Se to increase the dietary concentration to approximately 0.35 mg Se/kg dry matter. Cows were inoculated intracisternally with 30 colony-forming-units of Escherichia coli at 14-16 weeks of lactation. Eicosanoids and bacteria numbers were recorded at various intervals of time for 60 h postinoculation. Milk from cows fed the Se-depleted diet had significantly higher (p less than 0.05) concentrations of TXB2 between 24 and 48 h and 6-keto-PGF1 alpha between 24 and 60 h postinoculation. Milk PGE2 concentration was significantly higher in the Se-deficient group at 24 h, whereas LTB4 was higher between 36 and 60 h postinoculation in the Se-deficient cows (p less than 0.05). Milk bacteria numbers were significantly higher between 16 and 24 h postinoculation in the Se-deficient group and three of the four cows in this group required euthanasia, whereas all four cows in the Se-supplemented group recovered without therapeutic intervention. These data indicate marked effects of dietary Se on milk eicosanoid concentrations in response to an E. coli infection. The changes in eicosanoid concentrations may be associated with the altered pathogenesis and outcome of mastitis in a Se-deficient state.

6-Ketoprostaglandin F1 alpha↗

Enhanced killing of penicillin-treated S. aureus by host defences: effects of amoxycillin, cloxacillin and nafcillin in vitro and in experimental mastitis.

The effects of pretreatment of Staphylococcus aureus with subMIC or 10 x MIC amoxycillin, cloxacillin and nafcillin on subsequent killing by bovine neutrophils or sensitivity to lysostaphin were examined in vitro, using penicillinase positive and negative strains. All penicillins increased the susceptibility of S. aureus to bovine neutrophils; with amoxycillin this was most marked with the penicillinase negative strain. Cloxacillin pretreatment was significantly more effective than nafcillin or amoxycillin in some tests and equally effective in others. The sensitivity of S. aureus to lysostaphin was increased following cloxacillin or nafcillin exposure. In a mouse model of mastitis, more cloxacillin and nafcillin-treated S. aureus (at 1/4 MIC) were killed than untreated bacteria 1 hr after infection but by 4 hr no differences were found. No differences were seen after intramammary infection with 10 x MIC penicillin-treated S. aureus. In glands with established chronic mastitis both cloxacillin and nafcillin at high doses failed to kill staphylococci. These findings indicate that prior exposure to penicillins increases staphylococcal susceptibility to killing by neutrophils but following phagocytosis, intracellular bacteria are protected from the lethal action of penicillins.

Amoxicillin↗

Effects of in vitro supplementation with alpha-tocopherol and selenium on bovine neutrophil functions: implications for resistance to mastitis.

A low vitamin E/selenium status has been associated with increased vulnerability of dairy cattle to mastitis. Since polymorphonuclear leucocytes (PMN) provide the major cellular defence mechanism within the mammary gland, the effect of in vitro supplementation with vitamin E and selenium on the function of these cells was investigated. Both vitamin E and selenium enhanced the chemotactic and random migration of PMN and increased the production of superoxide following stimulation with phorbol myristate acetate. Vitamin E, but not sodium selenite, was also found to enhance the phagocytosis of opsonised Staphylococcus aureus by PMN. No synergistic effects of the two nutrients were observed. These results obtained in vitro may indicate the potential benefits of in vivo supplementation of dairy cows with vitamin E and selenium in terms of enhancing their natural resistance to mastitis.

Animals↗

Modulation of resistance to mastitis pathogens by pretreatment of mice with T-2 toxin.

T-2 toxin, a secondary metabolite of Fusarium species, is a mycotoxin with immunomodulatory activity. In the present investigation the effects of T-2 toxin on host resistance was studied. The virulence of Escherichia coli and Staphylococcus aureus in the mammary glands of mice treated with T-2 toxin was compared with their virulence in control mice. Virulence was estimated from the ability to induce various types of lesions and bacterial growth in the mammary gland. Pretreatment of mice with a single dose (3 mg/kg body weight) of T-2 toxin by gavage reduced the virulence of both E. coli (P less than 0.05) and S. aureus (P less than 0.01). Microscopic lesions in the infected glands varied in character, from consistently non-reactive necrosis of the entire mammary gland to limited inflammatory reactions. The former were more abundant in control mice than in mice treated with T-2 toxin. Although treatment by gavage with T-2 toxin (0.75 mg/kg body weight/day) for 14 days prior to inoculation had no significant effect on the course of the mastitis infection, virulence was slightly lower in the T-2 toxin treated mice. Both single-dose and successive treatment with T-2 toxin enhanced the respiratory burst activity of macrophages. Pre-inoculation treatment with T-2 toxin also caused a significant increase in the number of peritoneal cells, T-2 toxin did not show bacterial effects on the E. coli or S. aureus strains used for the inoculations. The data indicate that T-2 toxin has modulatory effects on the cell-mediated immune system, and that enhancement of resistance to common mastitis pathogens in mice pretreated with a single dose of T-2 toxin is associated with migration and activation of macrophages.

Animals↗

The detection of obligate anaerobic bacteria in udder secretions of dry cattle with mastitis during summer: a comparison between gas-liquid chromatography and bacteriological culturing methods.

Udder secretions sampled during the summer in 1984 and 1985 from mastitic quarters of 51 non-lactating cattle, mainly heifers less than 2 years of age, were examined bacteriologically for the presence of (facultative) aerobic and obligate anaerobic bacteria (OAB) and by gas-liquid chromatography (GLC) in order to detect volatile fatty acids (VFA), metabolic end-products of OAB. Forty-nine samples yielded positive cultures and in 20 cases these were mixtures of (facultative) aerobes and OAB. Only two specimens appeared to be sterile and from one specimen only were OAB cultured. Corynebacterium pyogenes was isolated from 35% of the cases and Peptococcus indolicus and Fusobacterium necrophorum from 31 and 22%, respectively. In most specimens (19/21) which yielded OAB after culturing, VFA (C3-C6) could be detected by GLC. Detection of VFA in summer mastitis secretions appeared to be a useful technique to evaluate the importance and association of OAB with summer mastitis. Because samples can be easily collected and stored at -20 degrees C, this is especially advantageous in situations where adequate facilities for the isolation of OAB are not readily available.

Acute Disease↗

Bacterial growth in mastitic whey in relation to bacterial association with mastitis.

The growth of mastitis pathogens (eight strains) and non-pathogenic bacteria (eight strains) was studied using microturbidometry. All bacteria grew well in whey originating from uninflamed quarters. However, the growth of bacteria which are not considered to be mastitis pathogens (Lactobacillus plantarum, Bacillus subtilis, Streptococcus lactis and Pseudomonas fluorescens) became suppressed by whey from mastitic quarters. On the contrary, the growth of Staphylococcus aureus and Escherichia coli was generally better in mastitic samples. Streptococcus agalactiae showed inconsistent results.

Animals↗

Serum resistance and the traT gene in bovine mastitis-causing Escherichia coli.

Ninety-five Escherichia coli isolates from bovine mastitis, 47 isolates from milking machine filters, 36 enterotoxigenic (ETEC) and 43 verocytotoxigenic (VTEC) isolates from cows were examined for the ability to resist the bactericidal effects of 90% gnotobiotic calf serum. There was no significant difference in the percentage of isolates in each group which demonstrated resistance. Two potential virulence traits, the traT gene and the K1 capsular antigen, previously shown to be related to serum resistance, in human E. coli pathogens, were also examined. Using colony blot hybridization there was no significant difference in the percentage of isolates in each group carrying the traT gene. A significant relationship between the presence of the traT gene and serum resistance was not found in any of the four groups of E. coli isolates tested. Only 3.2% of the bovine mastitis, 2.1% of the milk filter and 4.6% of the VTEC isolates were positive for the K1 capsular antigen. Again, no correlation between either the K1 antigen and serum resistance or between the K1 antigen and the presence of the traT gene was found in any of the four groups. None of the antimicrobial resistance patterns of the isolates were the same as those demonstrated by R plasmids known to carry the traT gene. Thus, it appears that the traT gene may not be related to serum resistance in bovine E. coli isolates.

Animals↗

Enhanced virulence of Staphylococcus aureus from bovine mastitis induced by growth in milk whey.

The virulence towards mice of Staphylococcus aureus strains from bovine mastitis was enhanced upon growth in milk whey compared to homologous organisms grown in tryptic soy broth (TSB). In the mouse mastitis model, S. aureus grown in milk whey caused more severe lesions than homologous strains grown in TSB. Staphylococcus aureus strain F1440 grown in milk whey induced 75% mortality and local necrotic reaction in subcutaneously inoculated mice, whereas the homologous strain grown in TSB caused only 5% mortality and slight skin reaction. Extracellular capsule on milk whey-grown, S. aureus could not be demonstrated. However, diffuse type colony morphology could be correlated with an increased virulence of S. aureus towards mice.

Animals↗

Penicillin G and penicillin G-tinidazole treatment of experimentally induced summer mastitis--effect on elimination rates of bacteria and outcome of the disease.

Two udder hind quarters of ten pregnant heifers were inoculated experimentally with a combination of Actinomyces pyogenes, Peptostreptococcus indolicus and Fusobacterium necrophorum at a dose of 9 x 10(8) colony forming units (CFU) of each species of bacteria. The development of aerobic-anaerobic mastitis was followed-up clinically and through analysis of udder secretion samples. All heifers developed acute clinical mastitis. Thick, purulent secretions with foul odour were already present 24 h after infusion. At 32 h post inoculation, 19 of 20 quarters harboured all infused bacteria, the viable counts of bacteria varying from 10(4) to 10(5) CFU/ml. No bacteria were isolated from blood samples taken simultaneously. NAGase values of udder secretions, indicating tissue damage, were high. The heifers were treated systemically with penicillin G alone, or in combination with tinidazole. Treatment started 32 h after inoculation and was continued for three days. The anaerobic bacteria (F. necrophorum and P. indolicus) were usually eliminated within four days, while A. pyogenes infections often persisted in the quarters. Penicillin G with tinidazole was not more effective than penicillin G alone: of the four heifers which recovered from infection, two were treated with penicillin G alone and two with the drug combination. The most important factor affecting the recovery seemed to be the host response of individual heifers. The six heifers which did not recover from the infection were continuously infected after calving, harbouring A. pyogenes in ten quarters, and P. indolicus and F. necrophorum each in three quarters.

Animals↗

Staphylococcus aureus capsule and slime as virulence factors in ruminant mastitis. A review.

Staphylococcus aureus is one of the most prevalent causes of ruminant mastitis. The interaction of this microorganism with the host is strongly dependent on its cell surface properties, specially concerning the presence of the exopolysaccharide-containing outer layers (glycocalyx), which appear to play an important role in virulence. In this article, the definition and recognition of the types of exopolysaccharide layers are described, together with their likely role in the pathogenesis of mastitis.

Animals↗

Imaging of granulomatous mastitis: assessment of three cases.

Granulomatous mastitis is a benign, inflammatory breast disease of unknown aetiology, which can mimic breast carcinoma in its clinical manifestations. Imaging features of three cases of granulomatous mastitis mimicking breast carcinoma on both clinical and radiographic examination are presented, with special emphasis on the role of dynamic contrast-enhanced-magnetic resonance mammography in the differential diagnosis.

Adult↗

Interleukin-8 expression by mammary gland endothelial and epithelial cells following experimental mastitis infection with E. coli.

Epithelial and endothelial cells play a pivotal role in initiating and controlling the movement of leukocytes into tissues during inflammation through the production of cytokines and chemokines such as interleukin-8 (IL-8). In situ hybridization with an IL-8 riboprobe was used to determine IL-8 mRNA expression by mammary gland epithelial and endothelial cells in cows with experimental Escherichia coli mastitis. Epithelial cells of the gland, especially surrounding the alveoli, had increased IL-8 mRNA levels at all time points at which tissue samples were collected (8, 12, and 24h) after E. coli challenge. Levels of IL-8 expression in the epithelial cells decreased at 24h post-infection. IL-8 expression by mammary gland endothelial cells was low, but did increase slightly at 24h post-infection. Both epithelial and endothelial cells of the mammary gland can contribute to the production of IL-8 that is typically seen in coliform mastitis.

Animals↗