Compliance with recommended drug withdrawal requirements for dairy cows sent to market in Michigan

By examination of computerized individual cow records from January 1981 through June 1985, compliance with premarketing drug withdrawal times was investigated in 23 dairy herds. During this period, 877 cows were culled from 23 herds; 33 cows from 12 herds were in violation of premarketing drug withdrawal times. Six herds had 1 violation, 2 herds had 2 violations, 2 herds had 3 and 4 violations, and 2 herds had 7 and 9 violations. Fifty drugs had been used; 15 drugs were used in violation of drug withdrawal times before cows were sent to market. The most commonly used drugs in violation were oxytetracycline, gentamicin, chloramphenicol, and a combination of lincomycin/spectinomycin. Significant differences between cows in violation and cows not in violation were not observed for age, lactation number, milk production, herd size, or month of culling. However, the 12 herds in violation of premarket drug withdrawal times had significantly (P less than 0.05) more cows culled within 30 days for retained placenta and milk fever, and more cows culled within 30 and 100 days for mastitis, metritis, and displaced abomasum. Although not significant, the 2 herds with 7 and 9 violations had more hired vs family labor than did the other herds with violations.     

Intramammary antibiotics in dairy goats: effect of stage of lactation, parity and milk volume on withdrawal periods, and the effect of treatment on milk compositional quality

The length of the antibiotic withdrawal period after intramammary treatment was influenced by the milk yield of dairy goats during this trial. Shorter withdrawal periods were seen in relatively high yielding dairy goats (production above 1.5 l per day) compared to low producers (less than 1.3 l per day). High yielding goats treated with Curaclox LC (Norbrook [Pharmacia AH]) had a withdrawal period of 42 h, while low yielding goats, treated with the same product, had a withdrawal period of 74 h. The recommended withdrawal period for Curaclox LC for use in cattle is 72 h. Relatively high yielding goats treated with Rilexine 200 LC (Logos Agvet [Virbac]) had a significantly shorter withdrawal period (37 h) than that recommended for use in cattle (96 h). Low yielding goats treated with Spectrazol Milking Cow (Schering-Plough Animal Health) had a significantly longer (95 h) withdrawal period than that recommended for use in cattle (60 h). Withdrawal periods were also influenced by stage of lactation and parity. There was a moderate positive correlation between lactation number and withdrawal period, as measured by TRIS (R2 = 0.621), and a moderate negative correlation between stage of lactation and withdrawal period (R2 = -0.669). In Trials 1, 2 and 3 combined there was a moderate negative correlation between withdrawal period and volume (R2 = -0.511) and a strong positive correlation between withdrawal period and lactation number (R2 = 0.720). The differences in percentage milk fat, protein and lactose before, during and after treatment were not statistically significant except in Trial 3 (Curaclox LC and Rilexine 200 LC) where protein and lactose differed significantly. In Trial 2 (Spectrazol Milking Cow) milk fat percentages differed significantly between treatment and control groups as did protein percentages in Trial 3. These differences are however, not biologically meaningful.     

Withdrawal periods and tissue tolerance after intramammary antibiotic treatment of dairy goats with clinical mastitis

The aim of this study was to determine withdrawal periods (WP) and tissue irritation after administration of three intramammary antibiotics [Curaclox LC (Norbrook (ARK AH)], Spectrazol Milking Cow (Schering-Plough AH) and Rilexine 200 LC [Logos Agvet (Virbac)] in goats with clinical mastitis. Withdrawal periods in goats with clinical mastitis treated with Curaclox LC, were not significantly different from those recommended for use in cows (72 h) with (67 h) or without (48 h) the 24 h mandatory safety margin while Spectrazol caused a significantly longer withdrawal period (122 h) than that recommended for use in cattle with (60 h) and without (36 h) the 24h safety margin. The withdrawal period of clinical mastitis cases treated with Rilexine 200 LC was 48 h compared to the 96 h recommended for use in cows. A linear model of regression with factors influencing the WP in goats with clinical mastitis was as follows: WP = 30.21 + 4.692 (sampling time) + 22.11 (udder pathology) - 13.6 (floccules) - 0.00649 (milk yield). Somatic Cell Counts (SCC) of milk from udder halves with clinical mastitis ranged from 7,053 x 10(3) to 7,948 x 10(3) cells per ml without isolations of bacteria and between 6,476 x 10(3) and 8,479 x 10(3) cells per ml with isolations of bacteria. Most of the variation in SCC could not be explained and the California Milk Cell Test (CMCT) and SCC on their own were not reliable methods for mastitis diagnosis. However, CMCT and SCC were indicators of udder irritation. In goats without clinical mastitis, Spectrazol Milking Cow caused the least tissue irritation followed by Rilexine 200 LC and Curaclox LC. For goats with clinical mastitis, Rilexine 200 LC caused the least irritation, followed by Curaclox LC while Spectrazol Milking Cow caused the most irritation.     

Intramammary application of ozone therapy to acute clinical mastitis in dairy cows

The infusion of ozone into the inflamed quarter of cows with clinical mastitis was performed and the efficacy of ozone therapy was evaluated. Ozone was infused into the inflamed quarter via a teat canal using ozone gas generating equipment. Nineteen Holstein cows with acute clinical mastitis were divided into two groups: 15 cows treated with ozone therapy, and 4 cows treated with antibiotic therapy. Systemic and local clinical signs, California Mastitis Test scores, the mastitis causing pathogens, electronic conductivity of milk, and somatic cell counts in milk from ozone- and antibiotic-treated quarters, were compared between the groups. Sixty percent (9/15) of cows with acute clinical mastitis treated with ozone therapy, did not require any antibiotics for recovery. This newly developed ozone therapy method was proven to be effective, safe, and cost effective, and carries no risk of drug residues in milk.     

Host-response patterns of intramammary infections in dairy cows

Many different bacterial species have the ability to cause an infection of the bovine mammary gland and the host response to these infections is what we recognize as mastitis. In this review we evaluate the pathogen specific response to the three main bacterial species causing bovine mastitis: Escherichia coli, Streptococcus uberis and Staphylococcus aureus. In this paper we will review the bacterial growth patterns, host immune response and clinical response that results from the intramammary infections. Clear differences in bacterial growth pattern are shown between bacterial species. The dominant pattern in E. coli infections is a short duration high bacteria count infection, in S. aureus this is more commonly a persistent infection with relative low bacteria counts and in S. uberis a long duration high bacteria count infection is often observed. The host immune response differs significantly depending on the invading bacterial species. The underlying reasons for the differences and the resulting host response are described. Finally we discuss the clinical response pattern for each of the three bacterial species. The largest contrast is between E. coli and S. aureus where a larger proportion of E. coli infections cause potentially severe clinical symptoms, whereas the majority of S. aureus infections go clinically unnoticed. The relevance of fully understanding the bovine host response to intramammary infection is discussed, some major gaps in our knowledge are highlighted and directions for future research are indicated.     

Pre-slaughter withdrawal times for drugs in dairy cows

Using a pharmacokinetic model based on drug concentrations in tissue fluids of normal animals, calculated withdrawal times were compared with the observations made in emergency-slaughtered diseased animals. After multiplying the calculated withdrawal times for muscle and kidney cortex tissues by a factor of 2 to 3, and 4 to 5, respectively, a good estimate was obtained for predicting drug withdrawal times for diseased animals treated with beta-lactam antibiotics, oxytetracycline, and aminoglycoside antibiotics. Criteria for determining three different drug tolerance levels of edible tissues were presented and discussed.     

Prevalence and incidence of intramammary infections in lactating dairy goats

AIM: To determine the prevalence of intramammary infection (IMI) of lactating dairy goats between 0 and 4 days postpartum, the prevalence and incidence rate of new IMI at Weeks 2, 14 and 27 of lactation, and the relationship between herd-level prevalence of IMI and bulk tank somatic cell count (BTSCC).

METHODS: Milk samples were collected from 8% of a herd (total 624 does) from 18 dairy goat herds in the Waikato region of New Zealand, for bacteriology and somatic cell count (SCC) determination, from both glands within 4 days of kidding (Week 0) and again at Weeks 2, 14 and 27. Prevalence of IMI was determined at each time point and incidence rate calculated for Weeks 0–2, 2–14, and 14–27. Greenwood and Reed-Frost models were compared for estimation of the transmission parameter for all pathogens, and for Staphylococcus aureus, coagulase negative staphylococci (CNS) and Corynebacterium spp. separately.

RESULTS: Bacteria were isolated from 1,122/4,814 (23.3%) glands, with CNS (13.4%) and Corynebacterium spp. (7.3%) being the most common isolates. Prevalence of any IMI increased with stage of lactation, varied among herds, and increased with age (all p<0.05). Incidence rate was 80, 24 and 7 new IMI/10,000 gland days for Weeks 0–2, 2–14 and 14–27, respectively. Incidence rate for any IMI increased with age and with the presence of an IMI in the contralateral gland, and varied among herds (p<0.001). The transmission of each pathogen was better modelled assuming contagiousness (Reed-Frost models), than not (Greenwood models).

At gland level, IMI increased SCC at all stages of lactation (p<0.001). The gland prevalence of IMI within herds was positively associated with ln BTSCC at Week 2 (p=0.02), but not Weeks 14 or 27 (p>0.05).

CONCLUSIONS: Prevalence of IMI increased with stage of lactation, but the highest incidence rate of new IMI occurred in early lactation. Models accounting for the contagious nature of infection fitted better than those not accounting for contagiousness. BTSCC was only associated with prevalence of IMI in early lactation.

CLINICAL RELEVANCE: Reduction of BTSCC in dairy goats may be best achieved by minimising the prevalence and incidence of new IMI in early lactation. Further studies are required to define management factors associated with the between herd, and stage of lactation, effects on prevalence and incidence rate in order to reduce BTSCC throughout lactation.     

Determination of cloxacillin residues in dairy cows after intramammary administration

The aim of this study was to perform a comparative analysis of the characteristics of cloxacillin (CLO) (MRL of withdrawal in bovine milk is 30 ng/g) after a single intramammary (IMM) dose in the dry period (DP) and lactation (LP), and to establish a high‐performance liquid chromatography (HPLC) analytical method for CLO detection in milk. The research was conducted on a group of 10 cows in DP and 10 in LP. A single dose of 600 mg of CLO was administrated by the IMM route for a single quarter in DP and 500 mg for a single quarter in LP. CLO concentration was analyzed by HPLC. CLO was monitored at a wavelength of 206 nm. Pharmacokinetic calculations were performed using Phoenix^® WinNonlin^® 6.4 software. The calibration curve was linear over the range of 13.03–28 019.00 ng/g with the coefficient of determination R² > 0.999. CLO withdrawal in both the LP and DP group had a biphasic nature. The total CLO elimination in the DP and LP group was reached after 36 and 6.5 days, respectively. A quantitative and confirmatory method for the determination of CLO in fresh milk has been established. We have confirmed that the withdrawal of CLO in the DP group is not a linear process and has a stepwise character.     

Study of intramammary infections in dairy goats from mountainous regions in Italy

Extract

The manufacture of dairy products from the milk of small ruminants presents an opportunity to improve the economics of farming in remote areas such as the mountainous regions in northern Italy. Mastitis, particularly subclinical and chronic, is the most persistent and widespread problem affecting milk quality. Currently, there is a lack of information concerning the most common causal agents of mastitis in dairy goat herds in Italy. This study was undertaken to determine the aetiology and prevalence of intramammary infections (IMI), and to measure somatic cell counts (SCC) of dairy goats in mountainous regions of northern Italy.     

Treatment of persistent intramammary infections with Streptococcus uberis in dairy cows

A survey was conducted of the prevalence of environmental pathogens, especially Streptococcus uberis, as causes of clinical mastitis in dairy cows. The response of intramammary infections with S uberis to conventional treatment was monitored by taking milk samples for bacteriology and somatic cell counting seven, 14 and 21 days after the treatment. The results showed that 51 per cent of the infections failed to respond, and the odds of cases failing to respond was significantly increased when the individual quarter somatic cell count seven days after the treatment was greater than 201,000 cells/ml. Ninety-six per cent of the suspected S uberis isolates identified by culture were confirmed as S uberis by using the api 20 Strep system. Restriction endonuclease fingerprinting was used to type the strains of S uberis isolated from 75 milk samples from 32 cows. Analysis showed that 96 per cent of the cases of S uberis that failed to respond to conventional treatment were persistent infections with one strain rather than reinfections with different strains. The persistent cases of S uberis were treated further with an extended course of intramammary preparations containing either procaine penicillin with dihydrostreptomycin or cefquinome. There was no significant difference between the cure rates achieved by the two preparations, and 55 per cent of the cases that had failed to respond to conventional treatment responded to the additional treatment.     

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。     

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.     

Risk factors for intramammary infections and relationship with somatic-cell counts in Italian dairy goats

Routine examination of milk was performed on five herds of lactating goats in northern Italy as part of a milk quality-monitoring program in the year 2000. As part of the study, aseptic samples of foremilk were collected monthly from both half udders during the entire lactation for 305 goats, resulting in a total of 4571 samples. The samples were tested with cytological and bacteriological analyses to evaluate the relationship between mammary infections and somatic-cell count (SCC; Fossomatic (TM) method). Prevalence of intramammary infection (IMI) was 40.2% (n = 1837) of all udder-half samples examined. The most-prevalent mastitis agents were coagulase-negative Staphylococci (CNS), 80% (n = 1474 udder-half samples); within this group, Staphylococcus epidermidis was the most-prevalent species (38%). Other prevalence were Staphylococcus aureus 6% (n = 112 udder-half samples) and environmental pathogens 14% of infected udder-half samples (n = 251) with a diverse mixture of species, none of which had a frequency of >4%. Enterococcus faecalis was the most-frequently isolated among this group. Neither Salmonella spp. nor Listeria monocytogenes were detected. The risk (sample level) of infection differed across herds, parities, and stage of lactation according to results from logistic multiple regression. Infection was more common among goats in third and fourth parities and during the later stages of lactation. Of the 2734 samples from uninfected udder halves, the mean log₂ SCC was 3.9 cell/ml; of the 1837 bacteriological positive samples, the mean log₂ SCC was 5.6 cell/ml. According to results from a linear mixed model, concentrations of somatic cells tended to increase with increasing age and days in milk and with the presence of bacteria. Infection with S. aureus was associated with the highest SCS.     

Depletion of florfenicol in lactating dairy cows after intramammary and subcutaneous administration

Eighteen Holstein dairy cows ranging in body weight from 500–700 kg and with an average milk yield of 37 ± 6 kg/day were used to investigate the depletion of florfenicol (FFL) in milk and plasma of dairy cows. Three groups of six were administered FFL: Group A, intramammary (IMM) infusion of ~2.5 mg FFL/kg BW at three consecutive milking intervals (total amount of ~7.5 mg/kg BW); Group B, one IMM infusion (20 mg/kg BW) into one quarter and Group C, one subcutaneous (SC) treatment (40 mg/kg BW). IMM infusions were into the right front quarter. Cows were milked daily at 06:00 and 18:00 h. The highest concentrations (C_max) and time to C_max (T_max) were: 1.6 ± 2.2 μg·FFL/mL milk at 22 h (Group A), 5.5 ± 3.6 μg·FFL/mL milk at 12 h (Group B), and 1.7 ± 0.4 μg·FFL/mL milk at 12 h (Group C). The half‐lives (t_1/2) were ~19, 5.5, and 60 h, for Groups A, B, and C, respectively. FFL was below the limit of detection (LOD) by 60 h in three Group B cows, but above the LOD at 72, 84, and 120 h in three cows. FFL was above the LOD in milk from Group C's cows for 432–588 h. Plasma values followed the same trends as milk. The results demonstrate that IMM‐infused FFL is bioavailable and below the LOD within 72–120 h. The concentration of FFL was detectable in both plasma and milk over the course of 2–3 weeks after SC administration. The absence of residue depletion data presents problems in determining safe levels of FFL residues in milk and edible tissues. The data presented here must not be construed as approval for extra‐label use in food animals.     

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.     

A comparison of two dose levels of antibiotics for intramammary treatment of clinical mastitis in cows

A clinical trial was conducted in Nordre Valdres, Norway, to examine the effect of a low-level vs. a high-level intramammary antibiotic treatment of clinical mastitis. It was also of interest to identify significant risk factors and to estimate the probability of no recovery for given defined levels of risk factors. Quarter milk samples from 166 cows with clinical mastitis were examined before and after treatment, at 3 weeks interval. The two treatment levels did not differ significantly with respect to recovery rate. The probability of no recovery could be estimated by using information on the severity of general clinical signs, lactation number, bacteriological findings, and quarter location.     

Patterns of mycoplasma shedding in the milk of dairy cows with intramammary mycoplasma infection

OBJECTIVE: To determine patterns of mycoplasma shedding in the milk of dairy cows with intramammary mycoplasma infection. DESIGN: Prospective clinical trial. ANIMALS: 10 Holstein cows with intramammary mycoplasma infection. PROCEDURE: Milk samples were collected from each cow daily for 28 days and plated on mycoplasma agar to evaluate shedding patterns. To determine whether enrichment improved recovery of organisms, some samples were also inoculated in mycoplasma enrichment medium and incubated for 4 days prior to plating. Somatic cell count (SCC) was determined in samples collected weekly. RESULTS: Mycoplasma organisms were not isolated from 81 of 280 (29%) composite milk samples, but > 10(6) colonies/mL were obtained from 151 (54%). Similarly, mycoplasma organisms were not isolated from 433 of 1,008 (43%) quarter milk samples, but > 10(6) colonies/mL were obtained from 392 (39%). For 71 of 104 (68%) samples, mycoplasma organisms were isolated both following direct plating and following enrichment; for 24 of 104 (23%), mycoplasma organisms were isolated only following enrichment; and for 9 of 104 (9%), mycoplasma organisms were isolated only after direct plating. There was a linear correlation between logarithm of the SCC and logarithm of the number of colony-forming units of mycoplasma per milliliter of milk for composite and quarter milk samples. CONCLUSIONS AND CLINICAL RELEVANCE: Shedding of organisms was inconsistent in dairy cows with intramammary mycoplasma infection, increasing the risk of misdiagnosis if multiple milk samples are not tested.