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The Efficacy of Intramammary Tilmicosin at Drying-off, and other Risk Factors for the Prevention of New Intramammary Infections during the Dry Period

R. T. Dingwell^*, T. F. Duffield^*, K. E. Leslie^*, G. P. Keefe, L. DesCoteaux, D. F. Kelton^*, K. D. Lissemore^*, Y. H. Schukken, P. Dick^|| and R. Bagg^||

^* University of Guelph, Guelph, Ontario N1G 2W1, Canada
University of Prince Edward Island, Charlottetown, P.E.I. C1A 4P3, Canada
University of Montreal, St. Hyacinthe, Quebec J2S 7C6, Canada
Quality Milk Promotion Services, Cornell University, Ithaca New York 14850-1263, USA
^|| Provel, Division of Eli Lilly Canada Inc., Research Park Centre, Guelph, Ontario N1G 4T2 Canada

Corresponding author:
R. T. Dingwell; e-mail:
rdingwell{at}vet.k-state.edu.

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS ACKNOWLEDGEMENTS REFERENCES

 
The objective of this study was to compare the efficacy of an intramammary infusion, containing tilmicosin phosphate, to an infusion of a negative control intramammary placebo for preventing new intramammary infections (IMI) during the dry period. Cows were enrolled from 24 dairy herds from three geographical regions of Canada. Data from 248 cows and 938 bacteriologically negative quarters at drying-off are summarized. Overall, the rate of new IMI during the dry period was 16.7% of quarters. The new infection rates for quarters that received intramammary tilmicosin compared with the intramammary placebo were 14.4 and 19.4%, respectively. The majority of new IMI was caused by coagulase-negative staphylococci (49%) and environmental streptococcal organisms (26.8%). The probability for quarters to develop new IMI in the dry period was significantly increased when cows had higher milk production before drying-off (P = 0.04), when cows had longer dry periods (P = 0.02), and when dry cows were housed in tie-stall barns (P = 0.002). Higher parity cows and those that had a linear score somatic cell count (SCC) above 4 on the last DHI test were also at increased risk for new IMI (P < 0.10). Administration of intramammary tilmicosin appears to be an efficacious therapy for prevention of new IMI; however, there is currently no approved intramammary formulation of this product available. Use of blanket dry cow antibiotic therapy compared to selective dry cow therapy, as well as the importance of identifying risk factors and managing the environment of dry cows are discussed.

Abbreviation key: CFU = colony forming units, CNS = coagulase-negative staphylococci, DCT = dry cow antibiotic therapy, LS = linear score, OR = odds ratio

Key Words: dry period • mastitis • risk factor • tilmicosin

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS ACKNOWLEDGEMENTS REFERENCES

 
The importance of the dry period with respect to udder health management programs has been well documented (Cousins et al., 1980; Funk et al.,1982; Eberhart, 1986; Oliver and Sordillo, 1988). The epidemiology of new IMI that occur during the dry period has been studied (Neave et al., 1950; Smith et al., 1985), and the importance of IMI that persist into the next lactation has been recognized (Enevoldsen et al., 1992; Osteras and Sandvik, 1996). From an udder health perspective, the goal of the dry period is to have as few infected quarters as possible at the next calving (Eberhart, 1986; Leslie, 1994). One of the key aspects to achieving this goal is to prevent new infections from occurring in quarters that are bacteriologically negative at the time of drying-off. Presently, administration of dry cow antibiotic treatment (DCT) at the time of drying-off is one of the most effective means of achieving this goal. The incidence of new infections in quarters that do not receive DCT may be as high as 10 to 12% (Eberhart, 1986). The reduction in this rate achieved by DCT has been estimated to be 50 to 75% (Smith et al., 1985; Schukken et al., 1993).

A lack of persistency of therapeutic levels of antibiotic late into the dry period and the ineffectiveness of commercially available DCT products against gram-negative organisms, has prompted recent research efforts to address alternatives to DCT (Bradley and Green, 2001). Furthermore, with increased concern over the routine practice of DCT due to the possible development of antibiotic resistance, there is reason to consider selective use of DCT. A major reason for minimal adoption of selective DCT is the lack of an appropriate, cheap, sensitive, and specific cow-side test that would accurately determine which cows are infected at the time of drying-off and require DCT (Eberhart, 1986; Leslie, 1994). Furthermore, risk factors for the development of new IMI during the dry period are not well understood. Also, with the adoption of a selective DCT program, the ability to prevent new infections during the dry period would be greatly decreased.

Over a period of 1 yr beginning in the summer of 1999, a large field trial was conducted to evaluate the efficacy of a novel intramammary DCT, containing a sterile solution of tilmicosin phosphate, administered at drying-off for preventing new infections during the dry period. A negative control placebo treatment was used as the comparison group. The objectives of this study were to document the rate of new IMI that developed under natural conditions in quarters that were bacteriologically negative entering the dry period and to determine the efficacy of intramammary tilmicosin administered at drying-off for preventing new infections compared with placebo-treated control cows. In addition, the risk factors associated with the development of new IMI during the dry period were described.

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS ACKNOWLEDGEMENTS REFERENCES

 
Sample Size Requirements and Herd Selection
Prior to the start of this study, calculation of a sample size was performed to be able to detect a 50% decrease in the rate of new IMI between the two treatment groups. From the published literature (Eberhart, 1986), we expected that 10% of untreated quarters would develop a new IMI. With a 95% confidence level and a power of 80%, sample size calculations determined that approximately 900 cows (450 in each of the two treatment groups) would be required to detect a significant difference between the two treatments. To achieve these numbers, cows in 24 dairy herds located in three eastern Canadian provinces participated in the field trial [Ontario (n = 17), Quebec (n = 3), Prince Edward Island (n = 4)]. Herds were selected based on proximity to the investigator in each region, to allow for weekly visits by a trained technician. Herd size ranged from 32 to 168 cows with an average of 80 cows. Cows that had not received antibiotic treatment in the last 3 wk and that were a minimum of 1 mo from the time of scheduled drying-off were eligible for enrollment.

Sampling Time Line and Treatment Randomization
A study technician aseptically collected aseptic mammary quarter milk samples from all eligible cows starting at 21 d (sample 1) before scheduled drying-off and again at 14 d (sample 2) before drying-off. Drying-off date was calculated to ensure cows would have a minimum 60-d dry period for antibiotic residue clearance. Cows that had all four quarters culture negative on both initial samples were defined as culture negative and appropriate for assignment to a treatment group. These cows were sampled for a third time at drying-off (d 0; sample 3) and randomized to receive treatment. As this sample was taken on the day of drying-off, laboratory culture results of these samples were not available in time to be able to use this information to influence randomization of treatments. This sample was used to increase the confidence that quarters defined as uninfected in samples 1 and 2 were still uninfected on the day of drying-off. No cow was used in the analysis if the data from the third sample did not agree with previous results. Each cow was randomly assigned to receive an intramammary formulation of 1500 mg of tilmicosin phosphate (supplied by Provel, Division of Eli Lilly Canada, Inc., Guelph, Ontario, Canada) or an intramammary placebo. The placebo contained a sterile solution of propyl gallate and EDTA in water, which was identical to the tilmicosin formulation except that the tilmicosin was replaced with water. The intramammary infusions were performed by the study technicians, as soon as possible after the last milking, using the partial insertion technique. Following the subsequent calving, all cows were sampled at 3 to 9 d (DIM; sample 4). The definition of an uninfected quarter in this study is a quarter that was bacteriologically negative on all three samples prior to and including the day of drying-off. A new infection was defined as presence of a pathogen in the sample collected postcalving.

Herd Management and Other Data Collection
During one of the scheduled visits to each farm, the technician at each site administered a comprehensive herd survey. Data collected included housing style, milking hygiene practices, management of the environment for both lactating and dry cows, as well as routine drying-off procedures used by each individual farm. Management factors used to determine appropriate drying-off time, such as expected calving date and milk production, and specific practices such as abrupt versus intermittent cessation of milking, gram-negative core-antigen vaccination, and teat-end protection were also collected. Individual cow DHI data for the last three DHI test dates, prior to and including the month of drying-off, were obtained. The DHI data consisted of dry period length, SCC, linear score somatic cell count (LS), 305-d milk production estimate, and 24-h test day yields of milk, fat, and protein.

Bacteriological Procedures
Teats were aseptically prepared prior to collection of all samples according to NMC sample collection and handling guidelines (NMC, 1999). Samples were frozen and shipped to the Mastitis Research Laboratory at the University of Guelph. All laboratory procedures were performed by the same individuals, and in accordance with NMC recommendations (NMC, 1999). The laboratory staff were blinded to treatment. Briefly, depending on the day of arrival at the lab, samples were either thawed at room temperature or stored at –20°C for a period of not longer than 5 d, and then thawed the first day of the following week. An inoculum of 0.01 ml of milk was plated onto a Columbia base agar containing 5% sheep blood. Plates were incubated at 37°C and examined for bacterial growth at 24 and 48 h. Colonies were tentatively identified as staphylococci, streptococci, coliform, or other pathogens based on colony growth, morphology and appearance, pattern of hemolysis, catalase reaction, and Gram staining. Staphylococcal isolates were tested for coagulase production with the tube coagulase test. Streptococcal isolates were further subcultured with agar containing esculin. Gram-negative bacteria were plated on MacConkey agar to facilitate identification. Gross appearance and reaction to citrate were used to differentiate Escherichia coli and Klebsiella sp. For each positive quarter, the number of colony forming units (CFU) per 0.01 ml milk was reported in one of four categories: 1 to 5, 6 to 10, 11 to 50, or 50 cfu. Quarters were considered to be infected if they were culture positive for any major mastitis pathogen, or if they had greater than 10 cfu of coagulase-negative staphylococci (CNS) in 0.01 ml of milk. A sample was considered contaminated if three or more colony types were present on a plate. Since all samples were frozen, quarter SCC determination was not performed.

Statistical Analyses
Data generated from the quarter-milk cultures, herd management surveys, and individual cow DHI records were stored in a Microsoft Access database. Records for 1163 quarters from 294 cows on 24 farms, identified as culture negative prior to drying-off, were extracted from the database and imported into SAS version 8.01 (SAS, 1999). Descriptive statistics were generated using the univariate and frequency procedure in SAS (PROC UNIVARIATE, PROC FREQ, SAS v.8.01). Differences in infection rates were tested with a chi-square (²) analysis. Logistic regression for the probability of a quarter developing a new infection during the dry period was modeled by fitting a generalized linear model using the GENMOD procedure, with the logit link function, and a binomial error distribution (PROC GENMOD, SAS v.8.01). Since quarters within a cow are not independent, correlation within cow was accounted for using generalized estimation equations (Liang and Zeger, 1986; Zeger et al., 1988; Barkema, 1997). Data were analyzed by quarter, cow, and herd levels, acknowledging that there was clustering of quarters within a cow, as well as of cows within a herd. The variance components at both the herd and cow level were evaluated (PROC VARCOMP, SAS v.8.01) to decide whether cow and herd effects would be considered as either random or fixed effects in the final model. Since herds had a very low variance component, the most appropriate and best fitting model included herd as a fixed effect and cows within herds as a clustering variable. A compound symmetry correlation structure (equal correlation between quarters within a cow) was used. In fitting herds as a fixed effect, a herd size variable was created to identify each herd that had more than 100 cows. This allowed comparison between these herds, as well as to those that were smaller in size. This distinction was necessary as the model did not converge when a parameter was estimated for each individual herd. The choice of herd size was based on inherent differences in management strategies and housing styles associated with larger herds. The linearized logistic regression model can be expressed as:

where: = intercept, COV_k = effect of kth covariate (such as breed, treatment, lactation number, dry period length), and e_k = random error term.

To assess the effect of month of drying-off on the new IMI rate, a season variable was created using 3-mo intervals. Spring was designated as March to May, summer as June to August, fall as September to November, and winter included December to February. A univariate model with each independent variable of interest was evaluated first, with all significant variables at P < 0.20 allowed to enter the multivariable model. A backwards stepwise procedure was used to determine the final model. The effects of treatment and herd were forced into the model. Statistical significance was declared at P < 0.10. All biologically plausible two-way interactions were tested. The estimated regression parameters were converted to odds ratios.

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS ACKNOWLEDGEMENTS REFERENCES

 
The total number of cows that were defined as culture negative and randomized to treatment was 294. Cases where protocol was not followed, or cows did not have mammary quarter samples taken at 3 to 9 DIM (due to cows having received other antibiotic treatment, aborting in the dry period, dry period length exceeding 90 d, or having been sold), were excluded. Overall, 46 cows were excluded for these reasons. Furthermore, 41 quarters with contaminated samples were excluded, yielding an overall quarter sample contamination rate of 4.2%. In the case where a cow experienced clinical mastitis prior to 3 to 9 DIM and a sample was collected, this sample was considered as the postcalving sample and representative of a new infection. In total, 248 individual cow records, representing 938 uninfected quarters, were available for analysis of risk factors for developing new IMI, and efficacy of intramammary tilmicosin for preventing new IMI, in the dry period.

Descriptive data pertaining to the herds and cows are presented in Tables 1 and 2. The majority of herds (67%) housed their cows in tie-stall facilities and 23/24 herds milked Holstein cows. The management survey of specific management practices pertaining to the dry period revealed that 67% of herds routinely ended lactation by abrupt cessation of milking, and 25% of producers indicated that they routinely administered a gram-negative core antigen vaccine. Furthermore, 29% indicated that they attempted to protect the teat-ends of cows during the dry period, either with commercially available products or with their postmilk teat disinfectant. In the majority of herds (79%), dry cows were separated into two different management groups, and the average number of maternity pens used on these farms was two, with a range of zero to eight.

The bacteriological results from mammary quarter samples and new infection rates are shown in Table 3. Overall, the rate of new IMI in quarters during the dry period was 16.7%. The most common bacterial pathogens isolated at 3 to 9 DIM from cows with new infections were the CNS (49%). Infections caused by environmental streptococci spp. were the most prevalent among the major mastitis pathogens. Streptococcus uberis were responsible for 15.9% of new infections, with other Streptococcus spp. contributing 9.6% and Streptococcus dysgalactiae at 1.3%. New IMI caused by coliform bacteria were primarily E. coli (5.7%) and Klebsiella spp. (3.2%). Staphylococcus aureus was isolated in 10.8% of the total new infections that occurred during the dry period.

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS ACKNOWLEDGEMENTS REFERENCES

 
As outlined in the materials and methods section, sample size requirements were calculated before this study. It was determined that a total of 900 cows would be needed to detect a significant difference, of at least 50% in the rate of new IMI, between the two treatment formulations administered at drying-off. For reasons beyond our control, a decision was made based on economic and other considerations to cease enrollment of cows into this study 6 mo before the expected termination date. Thus, data from only 294 cows were available for analysis when the trial ended. Due to the decreased sample size and subsequent lack of power to the study, which may lead to a type-two epidemiological error, a decision was made to relax the P-value at which significance was declared. A type-two error occurs when it is declared on the basis of trial results that no true effect exists, when in fact a variable may produce a worthwhile effect (Martin, 1987). Consequently, the results previously reported and the following discussion are based on significance having been declared at a P < 0.10 level.

Results of this study have described the rate of new IMI in treated and untreated control quarters, risk factors for developing new IMI during the dry period, and the efficacy of intramammary tilmicosin administered at drying-off. Overall, the rate of new IMI was higher than what was estimated from the scientific literature, as the expected rate in untreated quarters has been reported to be 10 to 12% (Eberhart, 1986), 12.3% (Williamson et al., 1995), and 9% (Natzke et al., 1975).

Three considerations must be addressed in discussing this rate of new IMI in comparison to other reported rates. The first consideration is the criterion that defined a new IMI. Common differences exist between published reports include the sampling schedule and the interpretation of laboratory results that constitute an IMI (Eberhart, 1986). In this study, we decided to consider quarters infected with greater than 10 cfu of CNS in 0.01 ml of milk, as having an infection based on NMC guidelines (NMC, 1987). Almost half (49%) of new infections in this study were caused by CNS. Therefore, if these CNS-positive cultures were not considered infections in the analysis, the new IMI rate would be decreased almost by half, to 8.7%.

A second consideration is the treatment of quarters at drying-off. Although a cohort of negative quarters received no antibiotic, all quarters were aseptically prepared by research technicians on the day of drying-off and infused with an intramammary preparation. The question arises whether these placebo treated quarters are truly "untreated" as compared with quarters that receive no preparation by infusion at the time of drying-off. One could hypothesize that the process of preparing teats and actually infusing them with a sterile placebo, could decrease the rate of new IMI. Administration of such a placebo may act as physical barrier to prevent penetration of bacterial organisms, as has been achieved by administering internal teat sealers at drying-off (Meaney, 1977; Woolford et al., 1998; Huxley et al., 2002). The results of this study show that the rate of new IMI was 19.4% in quarters receiving the placebo. If the rate in untreated quarters is expected to be 8 to 12%, either the bacterial challenge was higher in this population of herds, the process of infusing the placebo contributed to new infections, or the rate is higher due to our definition of new infections. A study done by Osteras and Sandvik (1996), studying the effect of selective dry cow therapy on various outcomes, included four treatment groups at drying-off, one of which was an intramammary placebo. There was no significant difference in the incidence rate of clinical mastitis postintramammary infusion between the placebo and DCT. In the current study, the possibility of introducing infections via intramammary infusion was minimized by having trained research technicians perform these duties.

The third issue pertaining to the observed rate of IMI is the relatively high proportion of new infections (10.8%) that were caused by Staphylococcus aureus. In studies conducted in regions such as in New Zealand, with a very low prevalence of contagious pathogens, the new infection rate is usually equal to or less than the expected 10% quarter new IMI rate during the dry period (Browning et al., 1990). All of the herds in this study had known S. aureus cows present. One potential explanation for this observed rate of S. aureus is that these were not new infections occurring in the dry period but rather existing infections that were not identified prior to drying-off. Although plausible, this should have been minimized by having three quarter samples negative prior to and including the day of drying-off. The sensitivity of bacteriological culture to identify existing S. aureus IMI is highest when three or more consecutive cultures are used (Sears et al., 1990).

The second main objective of this study was to identify significant risk factors for the probability of a quarter to become infected during the dry period. From the final logistic regression model, the lactation number of the cow, the LS, and milk production recorded for the cow on the last DHI test, the dry period length, as well as the type of housing facility and regional location of the herd, all had an impact on the rate of new IMI during the dry period.

Higher parity cows were more likely to develop new infections during the dry period than were younger cows (P = 0.08). An association between the rate of dry period IMI and parity has been previously documented (Ward and Schultz, 1973; Smith et al., 1985). A suggested reason for an increased rate of IMI with increasing parity is that this association may be related to a decrease in the integrity of the streak canal, allowing for bacterial penetration (Cousins et al., 1980). Factors affecting timely closure of the teat streak canal are not well understood. However, research has estimated that 5 to 20% of teats may indeed still be open 6 wk into the dry period (Williamson et al., 1995; Dingwell et al., 2001b). The impact of milk production on the rate of teat streak canal closure, and the rate of new IMI has been investigated (Oliver et al., 1956; Natzke et al., 1975; Oliver et al., 1990). An observed difference in milk production across parity levels, directly resulting in the difference in IMI rate, has not been confirmed. Due to the difference in management systems and production levels between the time of previous studies and today, 24-h yield of milk on the last DHI test was specifically obtained for cows enrolled in our study. Interestingly, there was a significant relationship between new IMI during the dry period and milk production (P = 0.04). Interpreting the coefficient in the logistic scale, the log odds of developing a new IMI during the dry period increases by 0.291 per kg of milk production on the last DHI test. Thus, as milk production on the last DHI test increased, the odds of developing a new IMI increased 1.3 times. This finding is consistent with a previous report based on the analysis of Ontario DHI records for over 30,000 lactations (Dingwell et al., 2001a). There was a significant relationship with cows producing higher levels of milk being more likely to have a higher LS after the dry period (Dingwell et al., 2001a). The shortcomings of the analysis of that data were that it was retrospective, did not look at individual herds, and also did not contain any bacteriological information. However, in combination, the results of these two studies demonstrate an association with milk production at drying-off and the rate of new IMI. This should warrant more attention to management strategies that decrease milk production before drying-off, and further research in this area is warranted.

There was an interaction between milk production before drying-off and dry period length (P = 0.06). When both dry period length and milk production increase, the rate of new IMI tends to decrease (OR = 0.99). This finding may suggest that there is a negative effect of the combinations of either a short dry period and increased milk production, or a decreased milk production and a long dry period. Thus, if cows are dried off at a high level of production, they should not be subjected to a short dry period. Milk leaking and the rate of new IMI have been shown to be associated with cows that leaked milked being at a 1.8 times higher risk to develop IMI in the dry period (Enevoldsen and Sorensen, 1992).

The length of the dry period has been documented as an important factor in the development of new IMI (Enevoldsen and Sorensen, 1992). The primary source of bacterial challenge during the dry period is from the environment (Eberhart, 1986). Therefore, attention should be paid to minimizing the exposure of teat-ends to environmental organisms by maintaining dry cows in a clean and dry area. There is a need to develop strategies to protect the cow and bacteriologically negative quarters from this environmental challenge in the known periods of greatest susceptibility. Even by minimizing the dry period length, efforts to prevent bacterial penetration, particularly in the periparturient cow, are necessary.

For cows that were culture negative entering the dry period, LS at the last DHI test was a significant factor in predicting the probability of new IMI to occur. Cows with an LS > 4 (raw SCC of 200,000 cells/ml of milk) on the last DHI test prior to drying off, were 1.9 times more likely to develop a new dry period infection in a quarter, compared with cows that were equal to or below this LS value (P = 0.06). There are several plausible explanations for this finding. First, the possibility that an elevated LS on the last DHI test was due to a subclinical infection that was not detected, and that was erroneously defined as a new infection after calving, cannot be ruled out. Another possible explanation is that the association between the LS and new IMI rate is exaggerated by the definition of CNS as a new infection. Cows with CNS infections have significantly higher quarter SCC (Timms and Schultz, 1987; Lam et al., 1997). Therefore, one explanation might be that cows had an elevated LS prior to drying off due to the presence of CNS, at a level that was not considered to be an infection based on our definition. Following the dry period, which is characterized by a lack of teat-end hygiene associated with milking, the CNS organisms proliferated to a level whereby they were defined as a new IMI from the dry period. Finally, research has also shown that infection with CNS may increase the susceptibility of quarters to infections with major pathogens (Hogan et al., 1988; Lam et al., 1997). Thus, another explanation may be that an elevated LS prior to drying-off due to a CNS infection, resulted in a higher rate of new infections during the dry period by major pathogens. Contrary to this finding are reports whereby CNS infections are preventive for IMI, especially for those caused by S. aureus (Nickerson and Boddie, 1994; Schukken et al., 1999). Regardless of the explanation, care must be taken in interpreting this finding as the days between last DHI test and the date of drying-off were not constant.

The type of housing facility was observed to significantly influence the rate of new IMI during the dry period. The probability for new IMI was significantly lower (P = 0.002) when cows were housed in a free-stall barn. Although no causal effect for this finding is readily apparent, we hypothesize that any relationship between type of facility and overall udder health, including new dry period infections, may be a function of general management practices associated with different herd sizes usually accommodated by tie stalls compared with free stalls. Such practices may include milking system, milking hygiene, cleanliness of environment and maternity pens, and postmilking teat disinfection, as well as cows having access to outdoor areas during the dry period.

A major objective of this research was to compare the efficacy of a new intramammary product containing tilmicosin phosphate to a negative control placebo infusion for the prevention of new infections during the dry period. In the final regression model, quarters that received intramammary tilmicosin at drying-off were 1.5 times less likely (OR = 0.65) to develop a new IMI during the dry period, compared to quarters that received a negative control placebo (P = 0.08). Given that the difference between tilmicosin and placebo infusion in the new infection rate was significant at P < 0.05 in the univariate analysis (14.4 and 19.4%, respectively), and the previous discussion on the dramatic decrease in sample size leading to a potential type-two error if a level of P < 0.05 is strictly adhered to, this finding was considered significant. Intramammary tilmicosin administered at drying-off appears to be an effective DCT for prevention of new IMI. This finding would have to be repeated and comparisons to a positive control performed as well, before recommendations are made to use this antibiotic. Furthermore, no DCT containing tilmicosin is commercially available.

	CONCLUSIONS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS ACKNOWLEDGEMENTS REFERENCES

 
The overall new infection rate during the dry period, of bacteriologically negative quarters, was observed to be 16.7% of quarters in this study. The infection rate for quarters that received tilmicosin at drying-off was 14.4%, compared with a 19.4% rate in the placebo-treated control group. Intramammary tilmicosin appears to be an efficacious DCT for prevention of new IMI over the dry period. No approved intramammary formulation containing tilmicosin is currently available for this use.

The importance of identifying significant risk factors for the development of new IMI in the dry period is a growing concern as a result of increased scrutiny of the practice of treating all quarters of all cows with DCT at the end of lactation. Our results indicate that the risk of new IMI is significantly higher in cows that were producing more milk as recorded on the last DHI test, that had a longer dry period, and that were older. Until such time that there is a rapid method available which incorporates identified risk factors and current udder health status information that would allow for individual cow decisions at the end of lactation to promote selective DCT, the recommendation remains to administer DCT to all quarters of all cows.

	ACKNOWLEDGEMENTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS ACKNOWLEDGEMENTS REFERENCES

 
The authors gratefully acknowledge the work of the research technicians at each site: Jeromy TenHag, Theresa Rogers, Isabelle Dutil, Angela Fairfield, and Alana McNicholl. Thanks to the producers who participated in the study. Drs. Guy Archambault, Jamie Hobson, and Jean Moreau contributed herds from their veterinary practices. A special thanks to Gord Vessie for his organization of trial supplies and monitoring and to Anna Bashiri and the staff at the Mastitis Research Laboratory. This study was supported financially by Provel (Division of Eli Lilly Inc., Canada), the Dairy Farmers of Ontario, and the Ontario Ministry of Agriculture, Food, and Rural Affairs.

Received for publication February 25, 2002. Accepted for publication May 21, 2002.

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS ACKNOWLEDGEMENTS REFERENCES

 


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