Controversies in treating coliform mastitis (Proceedings)

Coliform mastitis is a common and serious disease of housed dairy cattle. Causative bacteria are derived from the family Enterobacteriaceae and are lactose-fermenting, gram negative bacteria. Coliform bacteria are regarded as environmental mastitis pathogens, and a large number of strains can cause mastitis within a herd. Major sources of bacteria are bedding material, manure covered walkways, heavily contaminated water and poorly sanitized teat cup lines. These bacteria (most commonly Escherichia coli and Klebsiella species; Enterobacter, Citrobacter, Pseudomonas and Serratia species have been isolated less frequently) enter the mammary gland via the streak canal, and multiply to high concentrations in the milk. Polymorphonuclear cells ingest and degrade the coliform bacteria, resulting in endotoxin liberation. Endotoxin is believed to cause the clinical signs observed in affected cattle.

There is no accurate clinical method for differentiating coliform mastitis from gram positive mastitis. Clinical judgement is inferior to algorithms, but the latter are not sufficiently accurate for routine use in a clinical situation. It is therefore inappropriate to institute different treatment regimens for gram positive and negative mastitis, unless you have milk culture results. Culturing every cow is expensive, delays institution of appropriate treatment, and approximately 40% of clinical mastitis episodes are culture negative.

Based on the pathophysiology, a rationale treatment can be formulated for cattle with bacteriologically confirmed peracute or acute coliform mastitis. The first goal is to eliminate bacteria and endotoxin from the udder and blood. It is important to realize that the clinical signs of coliform mastitis are directly correlated with glandular bacterial concentration and endotoxin concentration. Antibiotic therapy is therefore indicated in severe clinical cases of mastitis. Based on published efficacy data, likely bacterial antimicrobial susceptibility (if valid as an indicator, cost, pharmacokinetics, and meat residue concerns, if antibiotic therapy is indicated (systemic signs of illness), appropriate treatments would include oxytetracycline (16.5 mg/kg IV q 24 h, for 3-5 days, or 10 mg/g IV q 12 h - extralabel use) and intramammary ceftiofur hydrochloride (125 mg - infuse 1 syringe into each affected quarter, repeat treatment in 24 hours. For extended duration therapy, once daily treatment may be repeated for up to eight consecutive days. An alternative intramammary treatment is cephapirin (200 mg, extralabel use) after the last quarter stripping for the day. The proposed antibiotic treatment regimen also has good efficacy against severe gram-positive mastitis. An alternative systemic antibiotic is ceftiofur (1 mg/lb, IM, daily for 5 days, extralabel use), particularly to prevent or control bacteremia. This treatment protocol caused a significant reduction in the death/cull rate following severe mastitis.

Polymixin B sulfate (50,000 to 2 million units per quarter) dissolved in sterile saline may be used intramammary in nonrefractory cases in valuable cows. Theoretically of great benefit since it complexes endotoxin and therefore prevents the deleterious effect of endotoxin absorption. Practically of minimal value as endotoxin is rapidly absorbed form mammary gland (lipophilic) and polymixin has difficulty reaching endotoxin from the site of administration. Milk withhold at least 9 milkings, extralabel usage. Gentamicin (500 mg) into the quarter of lactating, healthy, mammary gland produced sustained high milk concentrations (29 ug/ml, well above most MIC) at 12 hours. This is because the drug is relatively poorly absorbed from the mammary gland. When administered to cows with experimentally induced coliform mastitis, 500 mg gentamicin did NOT alter the severity or duration of infection, but produced systemic blood levels equivalent to a 14 to 19 month withdrawal for slaughter. This study has minimal relevance to severe clinical disease, as it was conducted in late lactation cows with only mild mastitis. Nevertheless, because of extended slaughter withdrawals, intramammary gentamicin should NOT be administered.

Frequent stripping of the affected quarter Oxytocin (10-20 IU, IM) has been proposed by some to facilitate milk and endotoxin removal. Stripping can be painful to the cow, is often non productive or minimally productive, and takes time and labor so therefore has an associated cost. Stripping also contaminates environment with a proven pathogen, strips out intramammary antibiotic. "Augmented" stripping using isotonic or hypertonic saline infusions (500 ml per quarter) to "flush out" endotoxin. No controlled experimental studies, only testimonials. Difficult to analyze success rate. Our preliminary data suggests that this treatment may increase endotoxin absorption. Certainly, no great improvement following intramammary hypertonic saline administration.

Antisera directed against the lipid A core of endotoxin are presently available from a few sources: Re mutant of Salmonella typhimurium (ENDOSERUM, Cross protective Salmonella typhimurium antiserum, Immvac Inc, Columbia MO, HiGamm-Equi, Lake Immunogenetics, Inc, Ontario NY) and Rc mutant of Escherichia coli (J5). These products have had variable success in treatment of endotoxemia in horses and calves. Designed to be administered IV, anecdotal reports of intramammary administration. Unknown efficacy at present, very expensive, unlikely to be cost effective even if efficacy is proven.

Intravenous fluids are required to preload the cow and treat the "distributive shock" associated with endotoxemia. Ideally this should consist of at least 20 L of a balanced, isotonic, polyionic solution such as Ringers solution. Additional dextrose has been demonstrated in other endotoxic animal species to have additional beneficial effects in endotoxic shock, however, these studies have limited relevance to clinical coliform mastitis in cattle. If prolonged IV fluid therapy is not practical, a one time administration of 2 L of hypertonic saline (2400 mOsm/L NaCl, at 4-5 ml/kg IV, over 5 minutes) in conjunction with at least 16 L of water intraruminally will probably be better than no fluid therapy.

Ketoprofen 2 g, IM, q 24h for duration of clinical mastitis significantly improved recovery in field cases of clinical mastitis (placebo controlled, masked study). This is the only study to demonstrate field efficacy, suggesting that ketoprofen should be the NSAID of choice when treating coliform mastitis. The half life of ketoprofen is short (30 minutes), suggesting that it should be administered more frequently than at 24h intervals (the recommended dose in horses is 2.2 mg/kg, IM, q 24h. Extrapolating this to the 500 kg cow produces a dose of 1.1 g, IM, q 24h).

Flunixin meglumine, 2.2 mg/kg (1 mg/lb) IV once is the label claim for bovine mastitis and this is an appropriate initial dose rate. A 36 hour milk withhold is required. Flunixin meglumine significantly reduces rectal temperature and quarter signs following experimental induction of coliform mastitis. No effect on heart and respiratory rates, milk production, rumen activity, and appetite. Beneficial effect attributed to antipyretic, analgesic, and anti-inflammatory action. Flunixin meglumine treatment was instituted at very early stage of clinical disease (2 hours post inoculation). Flunixin meglumine in conjunction with a progesterone implant is potentially indicated for the prevention of endotoxin induced-PGF2α mediated luteolysis in pregnant cattle. This is a very real and probably common cause of early embryonic loss in dairy cattle. A study that compared the efficacy of flunixin meglumine, aspirin, and phenylbutazone in endotoxic cows indicated that flunixin meglumine was superior to the other two agents. Flunixin meglumine has the advantage of a label claim in cattle (ketoprofen does not have a label claim for treating any type of cattle).

References

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Constable PD, Schmall LM, Muir WW, Hoffsis GF: Respiratory, renal, hematologic, and serum biochemical effects of hypertonic saline in endotoxemic calves. Am J Vet Res 1991, 52(7):990-998.

Constable PD. Acute endotoxemia increases left ventricular contractility and diastolic stiffness in calves. Shock, 1999;12(5):391-401.

MF Haddad, DE Morin, PD Constable, JB Messick, WL Hurley. Effects of intramammary hypertonic saline infusion in cows with experimentally induced coliform mastitis. J Vet Intern Med, 2001;15:325 (Abstract #214).

Haddad MF, Morin DE, Smith GW, Constable PD. Comparison of clinical, hematologic, and serum biochemical values in cows with naturally-occurring or experimentally-induced coliform mastitis. National Mastitis Council International Mastitis and Milk Quality Symposium, 2001 meeting.

Morin DE, Constable PD. Characteristics of dairy cows during episodes of bacteriologically negative clinical mastitis or mastitis caused by Corynebacterium spp. J Am Vet Med Assoc, 1998;213(6):855-861.

Morin, D.E., P.D. Constable, and G.C. McCoy. 1998. Use of clinical parameters for differentiation of gram-positive and gram-negative mastitis in dairy cows vaccinated against lipopolysaccharide core antigens. J Am Vet Med Assoc. 212:1423.

Smith GW, Constable PD, Morin DE. Ability of hematologic and serum biochemical variables to differentiate Gram-negative and Gram-positive mastitis in dairy cows. J Vet Intern Med 2001;15:394-400.