Comparative and Veterinary Pharmacology

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S. aureusin 1964. The percentage declined to 16% in 2000, whilstS. agalactiaehas
long been eradicated from the herd (Table 4 ).
The overall incidence of mastitis had also decreased by 70% by 1988 (Booth
1988 ), and the average somatic cell count (SCC) (number of leucocytes) of milk
sold from farms declined from 550,000 cells/mL in 1972 to a national level below
200,000 cells/mL in 2004 (Hillerton and Berry 2005 ). Milk quality in the EU is
subject to the standards set in the EC Milk Hygiene Directive (92/46), which
stipulates that producers should not sell milk if the SCC exceeds 400,000 cells/
mL. This standard is based on the average SCC over a 3-month period. The
European farmer has a financial incentive to keep the milk SCC below this level.
The control gained over contagious pathogens causing intramammary infections
over the last four decades has been accompanied by a change in the aetiology of
mastitis. There has been an increase in the incidence of infections caused by
environmental pathogens such asS. uberisand coliforms, notablyE. coli(Table 4 ).
Thus, despite significant overall progress, clinical and sub-clinical mastitis remain
amongst the costliest diseases affecting the animal health sector, with an estimated
financial burden of £300 million in the UK (Hillerton and Berry 2005 ).
Transition from the dry period to lactation is a vulnerable and high risk phase for
the modern dairy cow (Pyo ̈ra ̈la ̈ 2008 ); the biggest disease challenge at that time is
mastitis, as most clinical cases occur soon after calving and in early lactation. It is
not surprising, therefore, that the most common indication for antimicrobial usage
in the lactating dairy cow was found to be clinical mastitis in a recent Finnish
survey (Thomson et al. 2008 ). The use of either intramammary or systemic route
(usually subcutaneous or intramuscular injection) or both to administer antimicro-
bial drugs for the treatment of clinical mastitis continues to be a subject of debate. It
is evident that some compounds, due to their physico-chemical properties, notably
low lipid solubility, have very limited distribution into the udder, i.e. there is poor
penetration of the blood milk barrier (Ziv 1980 ), and the most efficient delivery
system for such drugs is infusion into the gland via the teat canal. Such compounds
include the penicillins, early-generation cephalosporins and aminoglycosides. On
the other hand, macrolides, tetracyclines and fluoroquinolones distribute well into
the mammary gland after systemic administration. The penetration of macrolides,
which are weak organic bases, is particularly favoured by diffusion (ion) trapping
in milk, which has a lower pH than plasma; it is a classic illustration of the
Henderson–Hasselbalch principle of unequal distribution of drugs across biological


Table 4Causes of clinical mastitis (% positive identifications) over time in a
British dairy herd (from Hillerton and Berry 2005 )
1964 1985–1990 2000
Streptococcus agalactiae 1.9 0 0
Steptococcus dysgalactiae 22 8.3 0
Streptococcus uberis 20 43 33
Staphylococcus aureus 43 20.3 16
Coliforms 2.4 22.8 43
Arcanobacterium pyogenes 4.5 5.4 1.2

Population Medicine and Control of Epidemics 125

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