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Nuria García-Fernández

Introduction

According to “Dairy 2014 Report 3: Health and Management Practices on U.S. Dairy Operations, 2014”9, the percentage of cows treated with antibiotics for mastitis, respiratory diseases, diarrhea or other digestive problems, reproductive disorders, lameness, or other disease was 22.0, 2.6, 1.1, 7.7, 3.6, and 0.5%, respectively. The Dairy 2014 study was conducted in 17 of the nation’s major dairy states, representing 80.5% of U.S. dairy operations and 81.3% of U.S. dairy cows. Data from this report were collected during 2014 by state and federal veterinary medical officers and animal health technicians from 265 operations with 30 or more dairy cows. Mastitis was the disease that affected the highest percentage of cows (25.7%). Not surprisingly, the highest percentage of cows were treated for mastitis (22.0%).

The percentage of cows treated with antibiotics for mastitis increased significantly from the two previous surveys. In 20026, the percentage of cows treated with antibiotics for mastitis, respiratory diseases, diarrhea or other digestive problems, reproductive disorders, lameness, or other disease was 15.0, 2.2, 2.0, 4.9, 7.0, and 0.2%, respectively. Similarly, in 20077, 2.8% of cows were treated with antibiotics for respiratory diseases, 16.4% for mastitis, 1.9% for diarrhea or other digestive problems, 7.4% for reproductive disorders, 7.1% for lameness, and 0.5% for other diseases.

Antibiotics approved for mastitis treatments

In the United States, no antimicrobials are approved for systemic treatment of mastitis, and only a few antimicrobial drugs are labeled for intramammary treatment of mastitis11. Table 1 shows the antibiotics that the FDA has approved for treatment of mastitis in lactating dairy cows. While several products have been withdrawn from the U.S. market, no new antimicrobials have been approved for mastitis therapy since 200612. Various types of drug use are permitted on dairy farms:

  • Over-the-counter (OTC) drugs may be used only under the exact label specifications and doses.
  • Prescription products (Rx) cannot be purchased without a veterinary prescription. This type of use requires that the product be used exactly as the label specifies. If the product is used outside the label specification, a veterinary label for extralabel use is required. Extralabel use refers to any use of a drug that is not specifically listed on the drug label and that is legal only under the guidance of a local veterinarian who meets the criteria defined for a valid veterinary-client-patient relationship. 

 

Table 1. Antibiotics approved by the FDA for treatment of mastitis in lactating dairy cows
Trade Name Active Ingredient Antibiotic Class Species Route Spectrum Withhold RX
Albacillin suspension special formula 17900-Forte Suspension Novobiocin sodium, penicillin G (procaine) Penicillin G-related penicillins (B-lactams) Dairy, all classes IMM S. aureus, S. agalactiae, S. dysgalactiae, and S. uberis 72h/15d OTC
Albamast Suspension Novobiocin sodium Penicillin G-related penicillins (B-lactams) Dairy, all classes IMM S. aureus 72h/15d RX
Amoxi-mast Amoxicillin trihydrate Penicillins (B-Lactams), amino derivatives Dairy, all classes IMM Penicillin sensitive S. aureus, 60h/12d RX
Cefa-Lak, Today Cephapirin sodium Cephalosporin, 1st generation Dairy, all classes IMM S. agalactiae and S. aureus including strains resistant to penicillin 96h/4d OTC
Dariclox Cloxacillin sodium Penicillinase-resistant penicillins (B-lactams) Dairy, all classes IMM S. agalactiae and S. aureus 48h/10d RX
Erythromast 36 Erythromycin Macrolides Dairy, all classes IMM S. aureus, S. agalactiae, S. dysgalactiae, and S. uberis 36h/0d OTC
Formula A-34 Uni-biotic 4 dose Penicillin G procaine Penicillin G-related penicillins (B-lactams) Dairy, all classes IMM S. agalactiae,S. dysgalactiae, S. uberis 60h/3d OTC
Gallimycin-36 sterile Erythromycin Macrolides Dairy, all classes IMM S. aureus, S. agalactiae, S. dysgalactiae, and S. uberis 36h/14d OTC
Hetacin K Hetacillin Potassium Penicillins (B-Lactams), amino derivatives Dairy, all classes IMM S. agalactiae, S. dysgalactiae, S. aureus, and E. coli 72h/10d RX
Masti-clear Penicillin G procaine Penicillin G-related penicillins (B-lactams) Dairy, all classes IMM S. agalactiae, Dependent on dose/4d OTC
Pirsue Sterile Solution Pirlimycin hydrochloride Macrolides Dairy, all classes IMM Staph spp. and Strep spp. 36h/9d/21d RX
Spectramast LC Ceftiofur hydrochloride Cephalosporin, 3rd generation Dairy, all classes IMM CNS Staph, S. dysgalactiae, E.coli 72h/2d RX
Abbreviations: IMM: intramammary, OTC: over the counter, RX: prescription drug.

Source: Food Animal Residue Avoidance Databank (2018)

According to the results of the Dairy 2014 Report 39, the primary antibiotics used to treat mastitis were third-generation cephalosporins, lincosamide, and first-generation cephalosporins (50.5, 24.6, and 15.1% of treated cows, respectively; Table 2). 

Table 2. Percentage of cows by primary antibiotic used formastitis treatment
Primary Antibiotic Used % Treated Cows
Third-Generation Cephalosporins 50.5
Lincosamide 24.6
First-Generation Cephalosporins 15.1
Penicilins 8.7
Tetracycline 0.2
Sulfonamide 0.2
Other 0.7
Source: National Animal Health Monitoring System, 2018. Dairy 2014 Report 3:

“Health and Management Practices on U.S. Dairy Operations, 2014”.

The treatment of clinical mastitis occurring in 51 large dairy herds in Wisconsin was recently evaluated12. The distributed clinical mastitis treatments in 589 cows were:

  • Ceftiofur (Intramammary, 74.9%)
  • Hetacillin (Intramammary, 19.7%)
  • Cephapirin (Intramammary, 13.7%)
  • Amoxicillin (Intramammary, 4.8%)
  • Sulfadimethoxine (Systemic, 3.7%)
  • Pirlimycin (Intramammary, 2.7%)

The use of intramammary antibiotics at dry-off is common in U.S. dairy herds. Administering intramammary antibiotics at the time of dry-off cures many existing infections and reduces the incidence of new infections. Table 3 shows the antibiotics that the FDA has approved for the treatment of dry cows. “Dairy 2014 Report 2: Milk Quality, Milking Procedures, and Mastitis on U.S. Dairies, 2014”8 indicated that almost 1 of 10 operations (9.2%) did not use a dry-cow treatment; a percentage of these were organic operations in which the use of antibiotics is not allowed. These results align with those of another study conducted in 51 large dairy herds in Wisconsin, in which only 8% of farms did not use any form of dry cow therapy17.

Table 3. Antibiotics approved by the FDA for treatment of mastitis in dry cows
Trade Name Active Ingredient Antibiotic Class Species Route Spectrum Withhold RX
Quartermaster Dihydrostreptomycin sulfate/ penicillin G procaine Aminoglycosides/ Penicillin G-related Dairy, dry IMM S. aureus 96h postcalving/60 days RX
Dry Clox Cloxacillin benzathiene Penicillinase-resistant penicillins (B-lactams) Dairy, dry IMM S. aureus and Strep agalactiae 30 days RX
Boviclox Cloxacillin benzathiene Penicillinase-resistant penicillins (B-lactams) Dairy, dry IMM S. aureus and S. agalactiae 72h post calving, 30d RX
Orbenin DC Cloxacillin benzathine Penicillinase-resistant penicillins (B-lactams) Dairy, dry IMM S. agalactiae and S. aureus 28d RX
Dry-mast Dihydrostreptomycin sulfate, penicillin G (procaine) Aminoglycosides/ Penicillin G-related Dairy, dry IMM S. aureus and S. agalactiae 24h postcalving/ OTC
Albadry Plus Novobiocin sodium, penicillin G procaine Antibacterial (other)/penicillin G-related Dairy, dry IMM S. aureus and S. agalactiae 72h postcalving/ 30d OTC
Go-dry Penicillin G procaine Penicillin G-related penicillins (B-lactams) Dairy, dry IMM S. agalactiae, S. dysgalactiae, S. uberis 72h post-calving/14d OTC
Formula A-34 Uni-biotic 4 dose Penicillin G procaine Penicillin G-related penicillins (B-lactams) Dairy, dry IMM S. agalactiae, S. dysgalactiae, S. uberis 72h/14d OTC
Biodry Suspension, Drygard suspension Novobiocin sodium Penicillin G-related penicillins (B-lactams) Dairy, dry IMM S. aureus and S. agalactiae 30 days OTC
Cefa-dri, Tomorrow Cephapirin benzathine Cephalosporin, 1st generation Dairy, dry IMM S. agalactiae and S. aureus including penicillin-resistant strains 72h postcalving/42D OTC
Spectramast DC Ceftiofur hydrochloride Cephalosporin, 3rd generation Dairy, dry IMM S. aureus, S. dysgalactiae, and S. uberis 16d RX
Erythro-36 Dry, Gallimycin-36 Dry Erythromycin Macrolides Dairy, dry IMM S. aureus, S. agalactiae, S. dysgalactiae, and S. uberis 36h/14d OTC
Abbreviations: IMM: intramammary, OTC: over the counter, RX: prescription drug.

Source: Food Animal Residue Avoidance Databank (2016)

“Dairy 2014 Report 2”8 indicated that almost all cows (93.0%) were treated with dry-cow intramammary antimicrobials at dry-off. A higher percentage of cows in large operations (96.4%) were treated at dry-off compared to the percentage of cows in small or medium operations (81.9 and 82.6%, respectively). The most commonly used dry-cow antibiotics were penicillin G (procaine)/dihydrostreptomycin (36.9% of cows) and cephapirin (31.0% of cows; Table 4).

Table 4: For cows treated with dry-cow intramammary antibiotics,percentage of cows treated, by type of antibiotic
Antibiotic Percent of cows*
Cephapirin benzathine 31.5
Penicillin G procaine/Dihydrostreptomycin 23.8
Ceftiofur hydrochloride 22.3
Penicillin G (procaine)/Novobiocin 11.6
Doxacillin benzathine 9.1
Penicillin G procaine 0.7
Other 0.9
* As a percentage of cows dry treated. Some cows were treated with more

than one antibiotic.

– Source: NAHMS 2014

 

On-farm culture

On-farm culture can help reduce the administration of antibiotics, which may have several benefits, including preventing the unnecessary discarding of milk while waiting for laboratory results, decreasing the potential for drug residue in milk, and improving treatment outcomes as a result of targeted treatments10. It has been stated that, in between 10 and 40% of cases, cultures from clinical mastitis yield no bacterial growth and therefore do not require antimicrobial therapy16. In a recent study of 20 dairies in Wisconsin, 80% of all antimicrobials used were for the treatment or prevention of mastitis, and 50% for clinical mastitis15. Taking into account the mentioned study, with 50% of all antimicrobial drugs used in dairy farms dedicated to clinical mastitis treatment, the selective treatment of clinical mastitis based on on-farm culture results can potentially reduce the total antimicrobial use on dairy farms by 25%. Lago et al.4 conducted a multi-state, multi-herd clinical trial on 422 cows from Minnesota, Wisconsin, and Ontario, Canada, and observed that the treatment of clinical mastitis with intramammary antibiotics could be reduced by half without significant differences in days to clinical cure by using on-farm culture systems to guide strategic treatment decisions in cows with clinical mastitis. In addition, a recent study conducted by University of Minnesota researchers reduced antibiotic use in dry cows by 48% through the use of a selective dry cow therapy at the quarter level based on culture results13.

There is increased awareness of treatment-related costs and the economic costs of extensive antibacterial therapy for mastitis. Treatment of only Gram-positive infections after the use of on-farm culture can result in significant cost reductions. A study that enrolled 189 cases of mild to moderate mastitis estimated that a net income of about $3,342 per month or about $18 per case can be obtained15. Lago et al.4 published a review of antibiotic usage on dairy farms that included a collection of studies on the economic consequences of mastitis treatments, including milk production losses due to clinical and subclinical mastitis, mastitis-related infertility, the culling of costs, and the transmission of infection to other cows. This review presented a collection of recent studies conducted in the United States showing that the average treatment cost of a case of clinical mastitis ranges from between $50 to $2121,14,17. The direct costs associated with antibiotic treatment include extra labor (19%), the cost of antibiotics or other therapeutics (21%), and discarded milk (60%)17. Bar et al.1 estimated that the average treatment cost of a case was $50, distributed as follows: discarded milk (40%), drugs (40%), and labor (20%). The number of days during which milk is discarded depends mainly on the treatment protocol and the withhold time of the product used for treatment. Pinzón-Sánchez et al.14 estimated that the expected monetary value per case of mild or moderate clinical mastitis ranged from $25 (no intramammary antimicrobial) to $212 (eight-day extended treatment) per case, depending on the treatment strategy implemented. By using an on-farm culture system to strategically identify and treat clinical mastitis, Iowa State University researchers reduced the direct cost of clinical mastitis by 65%.

Furthermore, the typical milk discard period after a case of clinical mastitis (including treatment and withdrawal time) is about six days. If a 1,000-cow dairy herd experienced a 6% mastitis treatment rate per month, that herd would discard approximately 360 cow-days’ worth of milk every month (60 cases at six days milk discard). At a 36/cow/day milk yield and $330/tn milk, the discarded milk would be valued at $4,320 per month or about $52,000 per year. In this scenario, each additional day of milk discard will create another $8,500 per year in discarded milk costs18.

Application

The successful treatment of mastitis depends on early detection and proper diagnosis. On-farm culture methods are generally used to attain rapid access to results in situ that allow for an early mastitis diagnosis and facilitate the decision-making process with respect to mastitis treatment. On-farm culturing enables producers to obtain bacteriological results in just 24 hours. Because antibiotics do not cure many mastitis cases, withholding antibiotic treatment for 24 hours does not really affect treatment success rates. Cows that need treatment (those with Gram-positive infections) can be treated once the results are obtained. Cows with cases that will not respond to antibiotics (those with Gram-negative infections) may be monitored to ensure that they are systemically treated if the immune system is unable to fight the infection and the mastitis becomes toxic. However, cows that successfully fight off Gram-negative infections will not have been treated with antibiotics, meaning no treatment costs and no milk discard. In conclusion, selective treatment of clinical mastitis based on on-farm culture results can potentially reduce total antimicrobial use on dairy farms.

About the author

Nuria García-Fernández is the Research Manager at the Dairy Knowledge Center, LLC. She holds a DVM and a PhD in Biological Sciences (specialization in Dairy Manufacturing) and has extensive experience with veterinary diagnostics and antimicrobial susceptibility testing. She has conducted research studies on molecular diagnostics, antimicrobial resistance genes, and the use of enzymes in cleaning biofilms on dairy separation membranes. nuria@dairykc.com

References

  1. Bar, D., L.W. Tauer, G. Bennett, R.N. Gonzalez, J.A. Hertl, Y.H. Schukken, H.F. Schulte, F.L. Welcome, and Y.T. Grohn. 2008. The cost of generic clinical mastitis in dairy cows as estimated using dynamic programming. J. Dairy Sci. 91:2205–2214.
  2. Ball, A. and L. L. Timms. 2006. Use of the California mastitis test and an on-farm culture system for strategic identification and treatment of fresh cow subclinical intramammary infections and treatment of clinical mastitis. Iowa State University Animal Industry Report: AS 652, ASL R2102. Available at: http://lib.dr.iastate.edu/ans_air/vol652/iss1/35
  3. Food Animal Residue Avoidance Databank. 2018. A component of the Food Animal Residue Avoidance & Depletion ProgramK. KH L . http://www.farad.org/vetgram/search.asp
  4. Lago, A. Godden, S.M., Bey, R., Ruegg, P.L., and K. Leslie. 2011. The selective treatment of clinical mastitis based on on-farm culture results: I. Effects on antibiotic use, milk withholding time, and short-term clinical and bacteriological outcomes. J. Dairy Sci. 94:4441-4456.
  5. Lago, L., S. M. Godden, and P. L. Ruegg. 2014. Treat or not treat? etiology-based treatment decisions for clinical mastitis. Proceeding National Mastitis Council. Pp: 43 – 63.
  6. National Animal Health Monitoring System. 2005. National Animal Health Monitoring System. Dairy 2002 Part IV: “Antimicrobial Use on U.S. Dairy Operations, 2002”. https://www.aphis.usda.gov/animal_health/nahms/dairy/downloads/dairy02/Dairy02_dr_PartIV.pdf
  7. National Animal Health Monitoring System. 2008. National Animal Health Monitoring System. Dairy 2007 Part III: “Reference of Dairy Cattle Health and Management Practices in the United States”. https://www.aphis.usda.gov/animal_health/nahms/dairy/downloads/dairy07/Dairy07_dr_PartIII_rev.pdf
  8. National Animal Health Monitoring System. 2016. Dairy 2014 Report 2: “Milk Quality, Milking Procedures, and Mastitis on U.S. Dairies, 2014. https://www.aphis.usda.gov/animal_health/nahms/dairy/downloads/dairy14/Dairy14_dr_Mastitis.pdf
  9. National Animal Health Monitoring System. 2018. Dairy 2014 Report 3: “Health and Management Practices on U.S. Dairy Operations, 2014”. https://www.aphis.usda.gov/animal_health/nahms/dairy/downloads/dairy14/Dairy14_dr_PartIII.pdf
  10. Neeser, N.L., Hueston W. D., Godden, S.M., and F. B. Russell. 2006. Evaluation of the use of an on-farm system for bacteriologic culture of milk from cows with low-grade mastitis. J Am Vet Med Assoc. 228:254-260.
  11. Oliveira, L. 2012. Characteristics of clinical mastitis occurring in cows on large dairy herds in Wisconsin. Dept. of Dairy Science. PhD Diss. University of Wisconsin, Madison.
  12. Oliveira, L. and P. L. Ruegg. 2013. Treatments of clinical mastitis occurring in cows on 51 large dairy herds in Wisconsin. J. Dairy Sci. 97 :1–11.
  13. Patel, K., S. Godden, E. Royster, J. Timmerman, B. Crooker., and N. McDonald. 2016. Pilot Study: Evaluation of the effect of selective dry cow therapy on udder health. Proceeding of the Minnesota Dairy Health Conference.
  14. Pinzón-Sánchez, C., V. E. Cabrera, and P. L. Ruegg. Decision tree analysis of treatment strategies for mild and moderate cases of clinical mastitis occurring in early lactation. J. Dairy Sci. 94:1873–1892.
  15. Pol, M, Bearzi, C., Maito, J., and Chaves, J.   On-Farm Culture: Characteristics of the test.  Proc. 48th Ann., Meeting NMC., Charlotte, NC, Jan, 25-28.
  16. Roberson, J. R. 2003. Establishing treatment protocols for clinical mastitis. Vet. Clin. North Am. Food Anim. Pract. 19:223-234.
  17. Rodrigues, A. C. O., D. Z. Caraviello, and P. L. Ruegg. Management of Wisconsin dairy herds enrolled in milk quality teams. J. Dairy Sci. 88:2660–2671.
  18. Ruegg, P., Godden, S., Lago A., Bey R., Leslie K. 2009. On Farm Culturing for Better Milk Quality. Western Dairy Management Conference, Reno, Nevada, USA.
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