cefquinome and Mastitis--Bovine

Cefquinome is the first 4th generation cephalosporin antibiotic developed for use in veterinary medicine. A European multicentre study established a high in vitro activity for this modern antimicrobial drug against a wide spectrum of bovine pathogens. Gram-positive and gram-negative mastitis agents were inactivated even at very low active ingredient concentrations, including Enterobacteriaceae which are often resistant to other drugs. The results of clinical trials using experimental E. coli mastitis as an example demonstrate the efficacy of cefquinome in vivo. Parenteral administration at a dose rate of 1 mg/kg body weight when compared with conventional therapy using a control drug with equally good in vitro activity, produced significantly better therapeutic results.

Topics: Animals; Cattle; Cephalosporins; Clinical Trials as Topic; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Mastitis, Bovine; Multicenter Studies as Topic

A randomized clinical trial was conducted to assess efficacy of intramammary cloxacillin and ampicillin (CLOXIMM), intramammary cefquinome (CEFIMM), and intramuscular cefquinome (CEFIM) to treat Streptococcus agalactiae intramammary infections (Trial 1). Subsequently, two treatment groups were extended to assess whether CLOXIMM was not inferior to CEFIMM (Trial 2). Nine farms were included in the study. Milk samples were collected from all quarters of all lactating cows for microbiological identification of S. agalactiae. Positive cows were randomly allocated into four groups: CLOXIMM, CEFIMM, CEFIM, or negative control (CONTROL). Study outcomes were bacteriological cure at 14 (CURE14), 21 (CURE21), and 14 and 21 (CURE1421) days after treatment onset, and somatic cell count. Logistic regression was used to estimate the odds of cure between each treatment and CONTROL. Non-inferiority analysis was performed considering a one-sided 95% confidence interval (CI) and non-inferiority margins (Δ) of 0.10, 0.15, 0.20, and 0.25. Adjusted S. agalactiae bacteriological cure for CLOXIMM, CEFIMM, CEFIM, and CONTROL was 86, 98, 55, and 25% at day 14; 82, 93, 52, and 0% at day 21; and 82, 92, 40, and 0% at days 14 and 21, respectively. Treatment with CLOXIMM and CEFIMM resulted in greater bacteriological cure rates, as compared with CEFIM or CONTROL, which does not justify the use of CEFIM in S. agalactiae eradication programs. The CURE14 difference between CEFIMM and CLOXIMM was of 12.1 percentage points (95% CI: 0.056-0.184). CLOXIMM was considered not inferior to CEFIMM for Δ = 0.20 or 0.25 and inconclusive for Δ = 0.10 or 0.15. Thus, it should be pondered by veterinarians whether an expected 12.1 (5.6-18.4) percentage points increase in cure rate would justify the use of a fourth-generation cephalosporin, as opposed to a combination of traditional IMM drugs (cloxacillin and ampicillin) to treat S. agalactiae subclinical mastitis.

Topics: Ampicillin; Animals; Cattle; Cell Count; Cephalosporins; Cloxacillin; Dairying; Drug Therapy, Combination; Female; Mastitis, Bovine; Risk Factors; Streptococcus agalactiae; Treatment Outcome

Extended duration of clinical mastitis (CM) treatment has been advocated, although results showing its higher efficacy compared with standard treatment are difficult to compare and seem conflicting. In a non-blinded, positively controlled clinical trial with systematic allocation, the efficacy of a standard, 1·5-d cefquinome treatment (ST), and an extended, 5-d intramammary cefquinome treatment (ET) were evaluated. The latter is frequently performed in cows with persistent high somatic cell count (SCC), expecting a better cure. Therefore, cows with CM immediately preceded by at least two consecutive monthly elevated SCC >200 000 cells/ml, were studied. The primary efficacy criteria were bacteriological cure (BC) and clinical cure (CC), while SCC cure was considered a secondary criterion of cure. Least square means of overall BC were not different after ET (79%, n=206) compared with ST (72%, n=203). ET, as compared with ST, improved BC of CM when caused by streptococci, specifically Streptococcus uberis. At day 1·5, only 13% of quarters showed CC, increasing significantly towards 60% at day 5, and 99% at day 14 and at day 21. No significant difference in CC was present between treatment groups. Overall SCC cure was low (22%) and not significantly different between treatment groups, but significantly higher for cases due to enterobacteriacae compared with staphylococci. In conclusion, ET with cefquinome of CM in cows with a persistent high SCC seems to be only indicated when caused by streptococci, mainly Str. uberis but shows no advantage when no information on bacteriological causes of mastitis is available. In our data, absence of CC directly after ST was not related to eventual BC.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Drug Administration Schedule; Female; Mastitis, Bovine; Milk

Clinical Staphylococcus aureus mastitis is difficult to cure. Extended antimicrobial treatment is often advocated as a practical approach to improve cure rates; however, scientific evidence of this hypothesis is lacking. A multi-centered, nonblinded, randomized, positive-controlled clinical trial was conducted in 5 European countries-France, Hungary, Italy, the Netherlands, and the United Kingdom-to study the efficacy of an extended intramammary cefquinome treatment (5 d) compared with a standard intramammary cefquinome treatment (1.5 d) of Staph. aureus clinical mastitis. Least squares means estimates of bacteriological cure during lactation were 34% [standard error (SE)=9.9%] for the standard treatment group and 27% (SE=8.4%) for the extended treatment group. In the final model, extended therapy was not significantly better. The only factor predicting bacteriological cure was pretreatment cow somatic cell count (SCC). Cows with >250,000 cells/mL in milk before treatment were less likely to cure. Least squares means of clinical cure during lactation was 60% (SE=19%) for the standard treatment group and 82% (SE=12%) for the extended treatment group. In the final model, clinical cure after extended treatment was significantly better. Pretreatment cow udder firmness predicted clinical cure. Firm udders were less likely to cure clinically. Irrespective of treatment regimen, new infection rates with pathogens other than Staph. aureus were higher (42%) after bacteriological cure than after nonbacteriological cure (22%) and cured cows had a significantly lower SCC. In conclusion, independent of the treatment protocol, cows with an SCC <250,000 cells/mL before treatment showed a higher probability of bacteriological cure. It appears that successful treatment of clinical Staph. aureus mastitis with cefquinome is associated with an increased number of new infections with coagulase-negative staphylococci. Extended treatment improved clinical, but not bacteriological, cure rates compared with the standard treatment. These results indicate that extending treatment of clinical Staph. aureus mastitis with cefquinome should not be recommended.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cell Count; Cephalosporins; Female; Mammary Glands, Animal; Mastitis, Bovine; Milk; Staphylococcal Infections; Treatment Outcome

The objectives of the present study were to evaluate the efficacy of intra-mammary-administered cefquinome for the treatment of sub-clinical mastitis in lactating dairy cows and to determine if extended therapy would enhance treatment efficacy. Seventy-three Holstein dairy cows from a single farm with 150 infected quarters were enrolled in the study. Infected cows were allocated randomly to one of three treatment regimens: (1) conventional (standard) regimen: 75 mg of cefquinome administered three times at 16-h intervals (25 infected cows, 52 intra-mammary infections (IMI)), (2) extended regimen: 75 mg of cefquinome administered six times at 16-h intervals (26 infected cows, 58 IMI) and (3) negative untreated control group (22 cows, 40 IMI). Most IMI were caused by coagulase-negative staphylococci, streptococci other than Streptococcus agalactiae and coliforms. The overall bacteriological cure (BC) rates for sub-clinical IMI were 84.61%, 91.37% and 20% for the conventional, extended and the control groups, respectively, indicating a higher BC rate for the treated groups than the control group (P < 0.001). Significant differences in somatic cell count (SCC) were detected between the treated versus the control group (P < 0.001). No differences, concerning the BC rate or SCC, were observed between the extended and the conventional groups. Although fat and protein percentages increased in the treated groups, there were no significant differences in post-treatment milk production between the groups. Results of this study indicate that cefquinome therapy was effective in reducing SCC and eliminating sub-clinical IMI in lactating dairy cows, but extended therapy did not enhance treatment efficacy.

Topics: Animals; Anti-Bacterial Agents; Asymptomatic Infections; Cattle; Cell Count; Cephalosporins; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Injections, Intradermal; Iran; Mammary Glands, Animal; Mastitis, Bovine; Staphylococcal Infections; Staphylococcus; Streptococcal Infections; Streptococcus; Time Factors

This field study focused on the possible effects of increased milking frequency (milking four times a day in comparison with milking twice a day) on clinical and bacteriological cure rates of clinical, antibiotically treated mastitis cases. Parameters tested were clinical, microbiological and full (cytomicrobiological) cure as well as the development of milk yield after the clinical mastitis episode. Cows from a large dairy herd meeting the study criteria (n=93) were assigned to two treatment groups by a systematic randomization scheme (blocked by body temperature <=or >39.5 degrees C). Both groups were randomly divided by experimental treatments: a) antibiotic intramammary treatment and milking 2-times a day; b) antibiotic intramammary treatment and milking 4-times a day. Treatments were initiated before the culture results were known. Cows were surveyed and evaluated on days 1-6, 24 and 31. No significant differences between treatment and control groups regarding clinical cure, microbiological cure, full cure and milk production could be established. Applying a 4-times a day milking regime did not lead to any significant effect, either positive or negative. Therefore, the results suggest that milking 4-times a day as a supporting therapy for mild, moderate and severe antimicrobially treated mastitis cases cannot be recommended.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cell Count; Cephalosporins; Dairying; Female; Lactation; Logistic Models; Mastitis, Bovine; Milk; Time Factors

The objective of this clinical control trial was to examine the effectiveness of the classical homeopathic treatment strategy in cases of mild and moderate bovine clinical mastitis in comparison with antibiotic and placebo treatments. Owing to characteristics of the selected herds, only cases of clinical mastitis caused by environmental pathogens and clinical cases with negative bacteriological result in the pre-treatment milk sample were included in the trial. A total of 136 lactating dairy cows with 147 affected quarters from four herds in Germany were randomly allocated to three treatment groups. The cows were examined on days 0, 1, 2 and on days 7, 14, 28 and 56 post initial infection to assess clinical signs. Simultaneously, with the exception of days 1 and 2, quarter milk samples for laboratory examinations (bacteriology, somatic cell count) were collected to assess bacteriological and cytological cure rates. On days 28 and 56, treatment strategies did not differ significantly with respect to the clinical outcomes and the total cure rate in cases of bacteriological negative mastitis (n=56). In cases of pathogen-positive mastitis (n=91), the cure rate after 4 and 8 weeks was similar between the two treatment strategies, homeopathy and antibiotic treatment, but the difference between the homeopathic and the placebo treatment at day 56 was significant (P<0·05). The results indicate a therapeutic effect of homeopathic treatment in cases of mild and moderate clinical mastitis. However, independent of treatment strategy and bacteriological status, the total cure rate was on a low level, revealing limitations in the effectiveness of both antibiotic and homeopathic treatment strategies.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Cloxacillin; Female; Mastitis, Bovine; Materia Medica

We performed a survey aimed at analyzing milk samples collected from cows with mastitis for the presence of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. Single-quarter mastitic milk samples obtained from 400 cows in 23 Greek dairy herds with a history of E. coli mastitis were processed for the selective isolation of ESBL-producing E. coli. The antimicrobial susceptibility of the ESBL-producing isolates was analyzed using agar disk diffusion, and minimum inhibitory concentrations of colistin were determined by broth microdilution. We used PCR followed by DNA sequencing to characterize the β-lactamases and mcr-1 (colistin resistance) genes, and for phylotyping and multilocus sequence typing. We found a total of 89/400 (22.25%) E. coli isolates from 12/23 (52%) farms. Six isolates originating from 6 cows on a single farm were ESBL producers and were resistant to cefquinome, amoxicillin-clavulanic acid, aztreonam, ampicillin, and colistin. Five of these isolates were resistant to trimethoprim-sulfamethoxazole, and 5 to streptomycin. The 6 ESBL producers were mcr-1-positive and carried bla

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Cattle; Cephalosporins; Colistin; Dairying; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Farms; Female; Greece; Mastitis, Bovine; Microbial Sensitivity Tests; Milk; Multilocus Sequence Typing

This Research Communication describes the residue concentration of a dry cow antibiotic in two different milk fractions and describes effects of milk fraction and milk composition on the test performance of a rapid screening and a microbial inhibitor test. Thirteen dry cows were treated with an intramammary dry cow antibiotic containing 150 mg cefquinome. Quarter foremilk and stripping samples were collected on the first 10 d postpartum. All milk samples were analyzed for milk composition by the local Dairy Herd Improvement Association and were tested for antibiotic residues using the rapid screening test Milchtest BL and the microbial inhibitor test Delvotest BR Brilliant Plates. The residue concentration of cefquinome was determined in foremilk and stripping samples from milkings 1, 2, 3, 5, and 7 after calving using high performance liquid chromatography - tandem mass spectrometry. The logarithm of cefquinome concentration (logCef) was higher in foremilk than in stripping samples and higher in milk samples with lower lactose content. Furthermore, logCef decreased with the number of milkings (P < 0.001). The Milchtest BL was more likely to be not evaluated (i.e. no test and control line or no control line appeared) in stripping samples and milk samples with higher protein content. In the Delvotest BR Brilliant Plates milk samples with higher protein content were more likely to have a false positive result (i.e. the screening test result was positive, but the HPLC-MS/MS result was below the detection limit of the screening test). These results indicate that foremilk is the recommended milk fraction to be tested for residues of cefquinome and that a high protein content can be a cause of test failure and false positive results when milk during the first 10 d postpartum is tested for antibiotic residues using screening tests.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Chromatography, High Pressure Liquid; Colostrum; Drug Residues; False Positive Reactions; Female; Mastitis, Bovine; Milk; Postpartum Period; Tandem Mass Spectrometry

The main objectives of this study were to quantify the consumption of antimicrobials on a convenience sample of dairy herds and to determine the association between herd-level antimicrobial consumption and inhibition zone diameters (IZD) of non-aureus staphylococci and Staphylococcus aureus isolates from subclinical mastitis cases. Also, the association between the IZD of non-aureus staphylococci and Staph. aureus isolates within a herd was studied. Antimicrobial consumption data on 56 Flemish dairy farms were obtained between 2013 and 2014 by so-called garbage can audits and expressed as antimicrobial treatment incidence (ATI), with the unit of ATI being the number of defined daily doses animal (DDDA) used per 1,000 cow-days. The average total ATI in adult dairy cattle for all active substances was 18.73 DDDA per 1,000 cow-days and ranged from 6.28 to 42.13 DDDA between herds. The ATI of critically important (for human health) antimicrobials was 6.91 DDDA per 1,000 cow-days; that is, 37% of total antimicrobial consumption. The average ATI for intramammary therapy of (sub)clinical mastitis, intramammary dry-cow therapy, and systemically administered therapy was 5.20, 6.70, and 6.73 DDDA, respectively. The IZD of 239 non-aureus staphylococci and 88 Staph. aureus isolates originating from milk samples from cows with subclinical mastitis collected on selected dairy herds were determined using Kirby-Bauer disk diffusion and ranged between 6 and 42 mm. Because only a limited number of clinical breakpoints (Clinical and Laboratory Standards Institute) and epidemiological cut-off values (European Committee on Antimicrobial Susceptibility Testing) are available for mastitis-causing bacteria in bovine, IZD were used as a proxy for antimicrobial resistance. Inhibition zone diameters of non-aureus staphylococci for cefquinome, a critically important β-lactam antibiotic, were negatively associated with the ATI of critically important β-lactam for systemically administered therapy and positively with the ATI for intramammary therapy of (sub)clinical mastitis of critically important β-lactam antimicrobials. Only for neomycin was a positive association between the IZD of non-aureus staphylococci and Staph. aureus isolates within the same herd observed.

Topics: Animals; Anti-Infective Agents; Cattle; Cephalosporins; Female; Humans; Mastitis, Bovine; Milk; Staphylococcal Infections; Staphylococcus; Staphylococcus aureus

Waste milk samples from 103 farms in England and Wales were examined for the presence of β-lactam antibiotics and ESBL-producing Enterobacteriaceae. Approximately 10 months after the initial sampling, further waste milk, environmental and faecal samples from farms shown to be positive for CTX-M Escherichia coli were investigated further. Isolates with an ESBL phenotype were tested by PCR for the presence of blaCTX-M, blaOXA, blaSHV and blaTEM genes. Isolates positive for blaCTX-M were sequenced to determine CTX-M type. Representative isolates were further examined by PFGE, plasmid replicon typing and serotyping. Of particular interest, 21.4% of waste milk samples contained residues of the cephalosporin cefquinome, which was significantly associated with CTX-M bacteria. Such bacteria occurred in 5.8% of the waste milk samples (including 3.9% CTX-M E. coli). CTX-M types identified were 1, 14, 14b and 15, but none of the E. coli were serotype O25, the serotype of the human pandemic strain.

Topics: Animals; beta-Lactamases; Cattle; Cephalosporins; DNA, Bacterial; England; Escherichia coli; Escherichia coli Infections; Feces; Female; Mastitis, Bovine; Microbial Sensitivity Tests; Milk; Polymerase Chain Reaction; Serotyping; Statistics, Nonparametric; Surveys and Questionnaires; Wales

The effectiveness of antibiotic treatment of clinical mastitis (CM) is classically evaluated using bacteriological cure, which provides a concise and objective way of assessing efficacy but does not reflect the situation in the field where persistence or recurrence of clinical signs lead to perceived treatment failure. If clinical signs persist or recur, intramammary (IMM) treatment is often extended or supplemented with parenteral therapy in the expectation of a more efficient elimination of clinical signs or a lower probability of recurrence. The objective of this study was to evaluate the efficacy against clinical persistence or recurrence of three cefquinome treatment regimes, standard 1.5-day intramammary (SIMM), 5-day extended intramammary (EIMM) and combination of EIMM plus 5-day extended parenteral (ECOMBO) treatment. The study was conducted on three dairy farms with a high recurrence rate of environmental mastitis. Efficacy was evaluated using a multi-level model at the quarter and at the cow level, based on the persistence or recurrence of clinical signs at any time during a 105-day period following the end of the initial treatment, independent of pathogen. The most prevalent pathogens were E. coli (16.9%) and S. uberis (11.97%). EIMM and ECOMBO significantly decreased the persistence or recurrence of CM by 8% and 6% at the quarter level and by 9% and 8% at the cow level, respectively. ECOMBO may not reduce the persistence or recurrence of CM beyond EIMM. Whilst extended treatment regimens offered an improved outcome in this study, the producer and practitioner need to carefully consider such regimens from the perspective of prudent antibiotic use.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Drug Administration Schedule; Female; Mastitis, Bovine; Recurrence

The aim of this study was to develop and evaluate an enzyme immunoassay (EIA) for the cephalosporin antibiotic in milk, in combination with a new microbiological test system (brilliant black reduction test, BRT-P). Polyclonal antibodies against cefquinome were produced in rabbits, using cefquinome-keyhole limpet hemocyanine as the immunogen. These antibodies and a cefquinome-glucose oxidase conjugate were used in a competitive indirect EIA. The detection limit for cefquinome in milk was 1.5 ng ml(-1), recoveries were 80-128% at 4-40 ng ml(-1). Cross-reactivities with other cephalosporins/penicillins were all <1%. The EIA was used to determine cefquinome in incurred raw milk, the BRT-P (detection limit ≈ 20 ng ml(-1)) and a receptor assay (ßeta-s.t.a.r., detection limit ≈ 15 ng ml(-1)) were used in parallel. Five lactating cows, suffering from clinical mastitis, were treated with cefquinome by simultaneous intramammary and intramuscular injection. Cefquinome residues (maximum 10-27 μg ml(-1)) were most exclusively found in the udder quarter which was treated intramammary, residue levels in the other three quarters were low (<20 ng ml(-1)). Even in milk from intramammary-dosed quarters, residue levels fell below European Union maximum residue level (MRL, 20 μg kg(-1)) 2 days before the end of the withdrawal period. EIA, BRT-P, and ßeta-s.t.a.r. results showed acceptable agreement for milk samples, but the newly developed EIA is superior in aspects of sensitivity. In conclusion, this is the first one description of immunoassay and microbiological tests capable to determine cefquinome in milk at the MRL in incurred sample material.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Female; Glucose Oxidase; Hemocyanins; Immunoenzyme Techniques; Mastitis, Bovine; Milk; Molecular Structure; Stereoisomerism

The dry period is a critical time in the lactation cycle, offering the optimum time for cure of existing intramammary infection (IMI), while also encompassing the periods of highest susceptibility to new intramammary infection. Until recent years, intramammary infection in the dry period has been controlled with the use of antibiotic dry cow therapy. The aim of this study was to investigate 3 different dry cow therapy regimens, in low-somatic cell count (SCC; bulk milk SCC<250,000 cells/mL) herds in southwest England. A total of 489 cows was recruited to the study and randomly allocated to receive either the broad-spectrum antibiotic cefquinome, a combination treatment comprising the narrow-spectrum antibiotic cloxacillin and an internal teat sealant, or the narrow-spectrum antibiotic cloxacillin alone. All quarters were sampled for bacteriology at drying off and again in the week immediately postcalving; 2 quarters were also sampled 2 wk before the estimated calving date to allow an assessment of infection dynamics during the dry period. Quarters were subsequently monitored for clinical mastitis for the first 100 d of lactation. Conventional multilevel (random effects) models were constructed to assess the efficacy of products in preventing IMI. Survival analysis was used to examine factors that influenced the risk of clinical mastitis using conventional Cox proportional hazards models. No differences were identified between the treatment groups in terms of cure of IMI caused by the major pathogens. Quarters in both the combination and cefquinome-treated groups were more likely to be free of a major pathogen or enterobacterial pathogen postcalving. With respect to clinical mastitis, the cefquinome-treated group was less likely to develop clinical mastitis than was the cloxacillin treated group.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Cattle; Cell Count; Cephalosporins; Cloxacillin; Drug Therapy, Combination; Female; Lactation; Mammary Glands, Animal; Mastitis, Bovine; Milk; Postpartum Period; Random Allocation

Maintenance of adequate drug concentration at the site of infection is an important problem in mastitis antibiotic therapy, and the efficacy of intramammary β-lactams can be optimized by maintaining the drug concentration at the site of infection above the minimum inhibitory concentration (MIC) as long as possible. The most important pharmacokinetic and pharmacodynamic parameter for efficacy evaluation is time during which drug concentrations exceed the MIC (t>MIC). In this study, we assessed the pharmacokinetic profile of cefquinome (CFQ) after repeated intramammary administration in healthy cows and cows subclinically infected with Staphylococcus aureus as well as the MIC of Staph. aureus field strains. In addition, the degree of drug passage was investigated from udder to bloodstream by measuring systemic drug absorption in healthy and infected animals. Cefquinome concentrations were quantified by HPLC (UV-visible detection) in milk samples collected from quarters and from blood serum samples. The systemic drug absorption was negligible in healthy and subclinically infected animals (maximum concentration 0.09±0.02 and 0.1±0.01 μg/mL in healthy and subclinically infected animals, respectively). The MIC(90) value for CFQ in Staph. aureus field strains (n=20) was 0.24 μg/mL. The pharmacokinetic and pharmacodynamic evaluation, determined by t>MIC, showed an equal persistence of CFQ in all quarters, indicating an equivalent activity of the drug regardless of the pathological status of the udder. Moreover, with literature data regarding CFQ MIC, the t>MIC has been calculated for other bacterial species.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Drug Administration Routes; Female; Lactation; Mammary Glands, Animal; Mastitis, Bovine; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus

Factors affecting bacteriological cure rates (BCR) and new intramammary infections (IMI) during the dry period as well as clinical mastitis (CM) during early lactation were investigated in 414 German Holstein dairy cows receiving dry cow therapy. Cows were treated with either benethamine benzylpenicillin (300,000 IU), penethamate hydriodide (100,000 IU), and framycetin sulphate (100 mg, n = 136), or cefquinome (150 mg, n = 135), or benzathine cloxacillin (1,280 mg, n = 143). Overall BCR, IMI, and CM at parturition were 86.4%, 20.7%, and 4.3%, respectively. The three antibiotic treatments differed only in BCR, with cloxacillin yielding better results than the others. Udder quarters from cows with > 4 lactations had a higher risk of IMI and CM at calving. Chronic changes in udder tissues were linked to a lower BCR and were associated with a higher risk of CM during early lactation. The risk of CM at calving was higher in udder quarters with unspecific or subclinical mastitis before drying off. In conclusion, with antibiotic dry cow therapy, age and health status of the udder appear to be major determinants of IMI and CM during the dry period and early lactation, while BCR was associated with the antibiotic type and udder tissue status.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Cattle; Cephalosporins; Female; Framycetin; Germany; Incidence; Lactation; Mammary Glands, Animal; Mastitis, Bovine; Penicillins; Risk Factors

Mammary glands taken at slaughter from healthy lactating cows were perfused in vitro with warmed and gassed Tyrode solution. Cefquinome (88.8mg cefquinome sulphate per 8mL) was administered by the intramammary route to all quarters and/or "systemically" via the perfusion fluid at concentrations similar to those measured in plasma following intramuscular administration of 1mg cefquinome per kg body weight. Samples of the perfusate were taken over a 6-h period and from the regional lymph nodes after 6h. Using a scalpel, sections of glandular tissue - at different distances from and vertical to the teat right up to the udder base - were gathered from four quarters each per route of administration at 2, 4 and 6h. The cefquinome content of the tissue samples was analysed by high performance liquid chromatography with diode array detection and of the perfusate samples by bioassay. After intramammary administration, the concentration of cefquinome in the glandular tissue decreased exponentially with increasing distance from the teat. The addition of cefquinome to the perfusion fluid produced a mean concentration of 0.2-0.5microg/g at all glandular tissue sites. Combined intramammary and systemic treatment ensured that concentrations exceeded the MIC(90) values of the most common mastitis pathogens in all areas of the udder by 2h post-administration. There was considerable variability in the tissue concentrations of cefquinome, particularly after intramammary administration. These results suggest that for the treatment of acute mastitis a combination of both intramammary and systemic administration is likely to be advantageous in order to rapidly produce maximum cefquinome concentrations in all regions of the udder.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Chromatography, High Pressure Liquid; Female; Infusions, Parenteral; Injections, Intramuscular; Lymph Nodes; Mammary Glands, Animal; Mastitis, Bovine; Perfusion; Tissue Distribution

The efficacy of intramuscularly and intramammarily administered cefquinome was evaluated in experimental Escherichia coli mastitis in dairy cows. Forty-seven multiparous, Israeli Holstein cows in early lactation that produced at least 25 L/d of milk were used, and 400 to 750 cfu of E. coli were infused into two healthy quarters of each cow. Cows were randomly assigned to one of the following treatment groups: 1) 75 mg of cefquinome administered intramammarily three times at 12-h intervals, 2) 75 mg of cefquinome administered intramammarily three times at 12-h intervals and 1 mg/kg of cefquinome administered intramuscularly two times at a 24-h interval, 3) 1 mg/kg of cefquinome administered intramuscularly two times at a 24-h interval, and 4) 75 mg of ampicillin and 200 mg of cloxacillin administered intramammarily three times at 12-h intervals. All cows developed typical signs of acute clinical mastitis by 12 to 16 h postinoculation. Parenteral cefquinome therapy, with or without intramammary cefquinome (groups 2 and 3), significantly improved clinical recovery and return to milk production. The bacteriological cure rates were considerably and significantly higher for cows in the groups treated with cefquinome than for cows in the group treated with ampicillin and cloxacillin. This study supported the efficacy of cefquinome in the treatment of clinical coliform mastitis in dairy cows.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Escherichia coli; Escherichia coli Infections; Female; Injections, Intramuscular; Lactation; Mammary Glands, Animal; Mastitis, Bovine