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Mamyzin in the treatment of mastitis
Clinical mastitis
In an open, positive controlled, multi-centre, randomised field study carried out in the East of France23, 24
the effects of intramuscular administration of penethamate (three
consecutive days) were compared with intramammary treatment, using a
cloxacillin/ampicillin combination, in clinical mastitis in lactating
cows. The inclusion criteria allowed selection of cases of acute
clinical mastitis characterised by abnormal milk, oedema or swelling of
the affected quarter and hyperthermia. The cows in the penethamate
group received an intramuscular injection of 10g of penethamate
hydriodide on day 1 followed by 5g on the two following days without
concurrent intramammary infusion. In the control group, the affected
quarters were treated daily for three days with the intramammary
infusion containing 200mg of cloxacillin and 75mg of ampicillin without
associated parenteral treatment. Clinical recovery was defined as a
return to normal of clinical parameters identified as being abnormal on
day 1 and was evaluated on days 2, 3, 8, 17 and 22. Bacteriological
recovery was defined as an absence of the pathogen isolated on day 1
(before all treatment) on milk samples taken on day 17 and 22. In
animals infected with Streptococcus uberis, the rate of bacteriological
cure was equivalent in both groups: 74% after penethamate treatment and
71% in the control group. The rates of recovery with regards to other
bacterial species which were isolated (Staphylococcus aureus, E. coli
and CNS) were also equivalent. Overall, the rate of bacteriological
cure was shown to be statistically equivalent in both treatment groups
(p >0.05), although numerically slightly higher in those in the
penethamate group (67% vs. 57%). In cases caused by streptococci, the
bacteriological cure rate reached 73% in the Mamyzin treated group.
(table 2)
The SCC of the affected quarters decreased in both groups following
treatment although there was a higher % of Mamyzin treated cows with
QSCC <250,000 on day 17 compared to the control group (p ≤0.05).
Furthermore, there was a more marked reduction in the SCC in all the
quarters - whether affected or not by clinical mastitis - after
treatment in the penethamate group compared with the animals treated by
the intramammary route. A greater proportion of quarters which had a
SSC >250,000 cells/ml prior to treatment reduced their count
to<250,000 cells/ml on day 17 and 22 (p <0.01). (fig 5) These
results show that not only is penethamate useful in treating clinical
mastitis, but it gives additional value by treating the sub-clinical
infections which may occur concurrently in adjacent quarters.
A recent New-Zealand study compared the rate of clinical and
bacteriological cure as well as the effect on SCC of two different
protocols used to treat clinical and sub-clinical mastitis25. Animals
were treated with an intramammary infusion of a proprietary preparation
containing 1g of procaine benzyl penicillin and 0.5g of
dihydrostreptomycin three times at 24 hour intervals or with two
subcutaneous injections of penethamate (10g then 5g) at 24 hour
intervals. 798 cases of clinical mastitis were assessed and
Streptococcus uberis was the most frequently isolated pathogen. Milk
samples were taken 14 and 21 days after treatment for bacteriology and
SSC. The rate of clinical recovery, SSC and the rate of bacteriological
cure were comparable between the treatment groups. It was concluded
that in the presence of a low incidence of penicillin resistant
organisms, penicillin based mastitis therapies are of use in the
routine treatment of clinical mastitis.
Mamyzin in the treatment of clinical mastitis
In the presence of clinical mastitis caused by Strep. uberis or
penicillin sensitive staphylococci, penicillin is still considered to
be treatment of choice. Pharmacokinetic data show that penethamate
provides a favourable means of delivering penicillin to treat
intramammary infections. Mamyzin provides advantages over intramammary
therapy alone in that it effectively controls sub-clinical disease which
may be present on currently in adjacent quarters. Although no data are
currently available which support the concurrent use of Mamyzin and
intramammary therapy, there is good rationale for this regime in
circumstances where Strep. uberis is considered to be the primary or
most likely pathogen but when other non-penicillin sensitive pathogens
may also be present.
Sub-clinical mastitis
A randomised, controlled field trial was performed in 70 milking cows
in The Netherlands to determine the therapeutic efficacy of penethamate
hydriodide (Mamyzin) against chronic, sub-clinical streptococcal
mastitis during lactation26. Quarter milk samples were collected from
sub-clinical cases of Streptococcus uberis or Streptococcus dysgalactiae
mastitis to determine the effect of treatment on bacteriological cure
and decrease of somatic cell count at individual quarter level.
Longitudinal data analysis was performed to determine the effect of
antibiotic therapy on cow milk SCC, and cow milk yield. Quarters were
eligible for inclusion following two consecutive SCCs >500,000
cells/ml and two positive bacteriological analyses carried out at 4 day
intervals prior to treatment. The results in cows receiving penethamate
were compared to those in an untreated control group. Bacteriological
cure (negative bacteriological analysis 10 and 20 days after treatment)
occurred in 59% of affected quarters in the treated group compared with
0% in the non treated control group. Treatment resulted in a
significant decrease in SCC at cow and quarter level in comparison to
untreated controls.
A SCC cure (2 affected quarter SCC <250,000 cells/ml 10 and 20 days
after treatment) occurred in 20% of cows in the treated group and 0% in
the control group. (fig 5) Almost 17% of non treated quarters evolved
to become clinical while none in the penethamate group evolved into
clinical mastitis (p <0.05). Furthermore, none of the untreated
quarters recovered spontaneously. The authors commented that
antibacterial treatment of sub-clinical infections during lactation
contributes to prevention of the spread of mastitis in the dairy herds
and to the reduction of bulk milk somatic cell counts. In the
New-Zealand study cited earlier 25 595 cows presenting with clinical
mastitis in several quarters were the subject of investigation of
adjacent quarters affected with sub-clinical disease. The cows with
clinically affected quarters were treated with penethamate or with an
intramammary infusion containing 1g of procaine benzyl penicillin and
0.5g of dihydrostreptomycin, three times at 24 hour intervals; the
adjacent quarters affected by sub-clinical mastitis in the penethamate
group (111 quarters) were defined as receiving treatment whereas those
in the control group did not (123 quarters).
In this study, Streptococcus uberis was the predominant pathogen and
the bacteriological cure rate was significantly greater in the
penethamate group compared with the control group (p <0.05). This
emphasises the value of systemic treatment of clinical mastitis, which
permits the treatment of both clinically and sub-clinically affected,
and thereby often unrecognised, quarters. It should be recalled that in
the French study described above 23, 24 which examined the effect of
Mamyzin on clinical mastitis, adjacent non-clinically affected quarters
showing SSCs>250,000 prior to treatment also showed a significant
reduction in SSC following treatment. Treatment of clinically affected
quarters therefore brought about a significant benefit in adjacent
sub-clinically, concurrently affected, quarters.
A New Zealand case report27
describes a milk quality investigation and the use of Mamyzin on a 550
cow farm where a high number of clinical cases and a rapidly elevating
bulk milk cell count was encountered and where Streptococcus agalactiae
was the causal pathogen. Various milking defects were identified and
remedied after which all cows were treated with either intramammary dry
cow therapy (Orbenin Enduro® n=400) if dry or with Mamyzin (n=150) if
lactating. The bulk milk cell count fell from the peak of over 800,000
cells per ml over an eight week period to remain below 250,000 cells
per ml following the treatment phase. The relationship of antibiotic
concentration in the milk to antibacterial efficacy in cows with
sub-clinical mastitis caused by Staphylococcus aureus was the subject of
a specific study in 198528. A comparison of penicillin G (procaine
salt) and different esters of penicillin G including penethamate was
made following the intramuscular administration of each presentation.
The protocol for the administration of penethamate was two or four
injections given at 24 hour intervals, each injection corresponding to
5x106 IU of penicillin G/cow/day. 62.7% of quarters affected by
sub-clinical mastitis caused by susceptible Staphylococcus aureus
recovered after two days of treatment compared with 68.8% of affected
areas which recovered after four days of treatment. First lactation
cows, or cows with a history of SCCs below 250,000 cells/ml were
selected from five dairy herds on the basis of a high SCC (>250,000
cells/ml) at their first herd test. Cows were divided into control and
treatment groups based on ear tag number. Cows in
the control group received no treatment, whilst those in the treatment
group received Mamyzin daily for three days. SCC records were assessed
for the remainder of the lactation. Across all cows, treatment with
Mamyzin led to a significant increase in the number of animals whose
SCC remained below 250,000 cells/ml for the remainder of the lactation
(58% vs 25% p <0.05). For first and second lactation animals,
treatment with a single course of Mamyzin led to an increase in the
number of animals whose SCC remained below 250,000 cells/ml for the
remainder of the lactation from 11% in controls to 72% in the treatment
group.
Mamyzin in the treatment of sub-clinical mastitis
In a number of studies, Mamyzin has been shown to be highly effective
in the treatment of sub-clinical mastitis. This has, in most cases, been
demonstrated by the positive effects of treatment on somatic cell
counts and improvement in milk quality. 6.3 Dry cows and heifers The
effective control of mastitis occurring in heifers is essential if the
likelihood of clinical or sub-clinical infections during the following
lactation is to be reduced.
In the spring of 2002 a prospective cohort study was carried out on the
parenteral use of Mamyzin on heifers pre-calving within a commercial
dairy herd in Central Southland, New Zealand29. In the face of an
increasing incidence of mastitis in heifers at calving, a treatment
protocol involving the use of Mamyzin was initiated for the ensuing
season. As a result 35 were untreated (controls) and 54 were treated
with 10g of Mamyzin 7 days before expected calving date. If heifers did
not calve within 7 days, they received a second treatment (n=3).
There was a significant difference between treatment and control groups
in the incidence of mastitis at calving. Heifers treated with Mamyzin
had almost half the risk of mastitis as control heifers (RR = 0.49, p =
0.0197). There was no significant difference between groups in mastitis
incidence at 7 days post calving. There was a significant difference
between groups in culling levels due to mastitis rate in the Mamyzin
treated group. Treatment gave rise to a significant return on
investment.
A case study was carried out on a 350 cow dairy herd in Italy30
with a problem of Staph. aureus infections during the first lactation.
It employed a regime of two injections of Mamyzin given to all heifers
24 hours apart, 2 months before calving followed by strict segregation
of non-infected heifers from the rest of the herd as identified by the
presence of a contaminated milk sample 10 and 20 days post calving. 10%
of tested heifers showed positive bacterial contamination of which 81%
were coagulase negative staphylococci and 9% were Staph. aureus.
Introduction of the strategy gave rise to a decrease in the incidence
of Staph. aureus infections at calving (20.9% to 6.47%). Preliminary
results showed a positive impact on SSC (significant reduction by 45%)
and total milk yield (+8.2%)
Interactions
Traditionally, penicillin has been used concurrently with many other
types of antibiotics to offer a wider spectrum of antibacterial
activity. It should be noted however, that since penicillin is a
bactericidal antibiotic dependent on bacterial multiplication for
effect, it may be neutralised by bacteriostatic antibiotics such as the
macrolides and tetracyclines.
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