uberis is one of the most common pathogens isolated from clinical and
subclinical cases of mastitis in cows in VI centres in the UK1 and penicillin is still widely regarded as the first choice treatment of these infections2.
Strep. uberis gives rise to clinical and subclinical infections in
lactating cows where it accounts for high cell counts and poor milk
quality. It may also cause subclinical mastitis in dry cows and heifers
prior to calving3.
Although less common, Strep. agalactiae and Strep. dysgalactiae are
still occasional causes of herd outbreaks of clinical and subclinical
Staph. aureus is a cause of severe and often life threatening mastitis
in dairy cows. Mamyzin Injection contains penethamate hydriodide, a
prodrug of penicillin G which accumulates in high levels in both
mastitic and normal milk due to its unique pharmacokinetic profile. It
is licensed for the treatment of mastitis caused by penicillin
Good clinical practice in the treatment of bovine mastitis
The species of organism isolated from a case of mastitis is central to
the choice of antibiotic for treatment and to determining the likely
prognosis. The severity of the disease, however, although also an
indicator of prognosis, is more likely to dictate whether the systemic
or intramammary, or indeed both, are selected as a route of
antibacterial administration or indeed whether supplementary therapy
e.g. non-steroidal anti-inflammatory drugs such as meloxicam
(Metacam®), are required. It will also determine the likelihood of the
animal being seen by a veterinary surgeon or whether it is treated on
farm using prescribed treatment protocols. A recent survey carried out
amongst specialist cattle vets from the UK15
revealed that almost 80% of cows treated for mastitis are treated on
farm without veterinary surgeon intervention. Of these cases, 30% are
likely to receive parenteral therapy, either alone or concurrently with
intramammary therapy. Of those seen by a vet, 85% receive parenteral
As is quoted in the literature2
and dictated by good clinical practice, this survey also revealed that
in cases where the species of pathogen is known, a narrow spectrum
antibiotic would be the treatment of choice of almost 90% of veterinary
surgeon responding. Despite intensive veterinary use of penicillin in
recent years, most gram+ve organisms responsible for mastitis in cattle
have shown little increase in resistance to it and the whole group of
related antibacterial substances. This is explained by the fact that
penicillins do not induce the formation of R plasmids in streptococci
necessary for the transmission of the bacterial resistance16.
In the case of mastitis causing streptococci (Strep. uberis, Strep.
dysgalactiae, Strep. agalactiae), in vitro resistance towards
penicillin G appears extremely rare.
Today, in the UK, most streptococci isolated from cases of mastitis are considered to be fully3 susceptible to penicillin G yet current therapeutic options result in only a 60% perceived response rate15. In other countries, the MIC levels are generally low for these organisms confirming high levels of susceptibility17,18.
Although beta-lactamase (penicillinase) does not inactivate
penethamate, it does of course inactivate penicillin G, the active
product of penethamate. Beta-lactamase producing staphylococci are
therefore unlikely to respond to treatment with Mamyzin. According to
the literature, there is no evidence that coagulase negative
staphylococci isolated from cases of clinical mastitis are resistant to
penicillin G. The efficacy of the antibacterial therapy in the
treatment of mastitis due to gram-ve bacteria is uncertain20.
Bacterial self-cure is common with clinical effects being the result of
the bacterial endotoxins produced. Non-steroidal anti-inflammatory
drugs such as Metacam® are usually indicated. Mamyzin is not indicated
for the treatment of Escherichia coli induced mastitis.
Whilst clinical mastitis is important both in terms of animal welfare
and farm economics, sub-clinical mastitis is a major source of economic
loss on many dairy farms. Losses are due to elevated somatic cell
counts (SCC) of infected cows and the associated loss in milk yield20, 21.
In addition, when the number of infected cows in a herd is high, bulk
milk SCC (BMSCC) may be elevated. This may result in further economic
loss because milk quality is monitored by regulatory agencies to
determine its suitability for human consumption and penalties on bulk
milk with high SCC have been imposed by commercial bottling and
Treatment of cows with sub-clinical mastitis is a way to reduce the
duration and number of infections, but treatment itself is also a cause
of financial loss and is generally considered to be unsatisfactory in
of cases treated. The majority of these losses are due to lost
production as a result of withholding periods and discarded milk
following antibiotic therapy21.To
be economically viable, the gains of treatment, i.e. the gains
resulting from the cure of sub-clinical mastitis, must offset the
losses. Conclusion In order to eliminate an infectious agent from a
case of mastitis in cattle, it is important that:
- The pathogen concerned is susceptible to the antibiotic chosen
- The distribution of the active ingredient has to be excellent in the targeted tissue i.e. udder and milk
- The concentration of the active ingredient in the udder and/or the
milk must be above the MIC 90 value (NB: it is unimportant how much
above the MIC the concentration reaches)
- The duration of treatment must be long enough to achieve both a clinical and bacteriological cure24
The treatment of mastitis in cattle - a desirable outcome
Whilst a positive response of clinical mastitis to treatment can be
defined as the disappearance of clinical symptoms such as abnormalities
of milk, swelling of the udder, anorexia, reduced milk production,
fever etc. it is well recognised that assessment of other non-clinical
indicators of disease are also important in determining recovery.
Bacterial cure is defined as the disappearance of the causal organism - identified by culture -which was present at the start of treatment.
Usually, two milk samples are collected after the full duration of
effect of the antibiotic, taken at 7-10 day intervals. These should be
free of the pathogen which was isolated prior to treatment. Since the
recurrence of clinical mastitis in individual cows is high, it is
likely that this occurs as a result of failure to achieve
bacteriological cure despite the disappearance of clinical signs. This
poor response in terms of bacterial cure can be attributed to a poor or
irregular distribution of the active ingredient throughout the mammary
tissue as a result of compression or obstruction of the lactiferous
canals by inflammatory swelling. This may also explain why many
organisms susceptible to antibiotics in vitro do not respond in the
field and why prolonged therapy, often given as pulses of treatment so
as to remain within the licensed recommendations, is increasingly
becoming a treatment option.
Given that mastitis is an inflammatory response to infection or injury,
it is valuable to measure other parameters in the laboratory so as to
assess the presence of or recovery from disease. The concentration of
somatic cells (SSC) measured in milk correlates with the cellular
response to infection in the udder and can be used to define the
severity of the inflammatory response and to measure 'cytological'
recovery. By definition, since it is a non-clinical parameter, it is
valuable in the assessment of both clinical and sub-clinical disease. A
high SSC can be present for a long time even after elimination of the
causal infectious agent and whether causing clinical or sub-clinical
disease. Full recovery of the udder cannot be assumed in the presence
of a persisting high SCC despite the elimination of clinical symptoms.
In acute inflammation of the udder, the cellular junctions of the
tissue are destroyed so allowing chloride ions to leak out and
accumulate in the milk. This augments the conductivity of the milk and
this can be used as a simple, and often automated, indicator of
inflammation and as an indicator of recovery.