Merck Consumer Preferred Template Version April 2011

Report
Metricure®
Dr. Sayed Fathy , PhD, Livestock Technical Manager
Intervet Middle East, Ltd.
Date 29/02/2012
Positioning statement - Give the new life a clear start
Uterine infections cause
decreased fertility in cattle:
● disruption of ovarian function
● interference during fertilization
process
● impaired embryonic
development and greater
embryonic losses
A healthy uterus gives the
cow a
better chance to conceive and
maintain pregnancy to term.
Metricure® is a tailor made
intrauterine antibiotic formulation
developed especially to meet the
requirements of endometritis
therapy in cows.
Treatment with Metricure brings
improved fertility giving the
treated cows higher chances to
conceive and carry pregnancy to
term.
2
New clinical classification of uterine infections
Sheldon et al., Theriogenology 65 (2006) 1516–1530
Definition
Clinical signs
Puerperal metritis
acute systemic illness due to infection
of the uterus with bacteria, usually
within 10 days after parturition
fetid red-brown watery uterine discharge and,
usually, pyrexia; in severe cases, reduced milk
yield, dullness, inappetance or anorexia, elevated
heart rate, and apparent dehydration
Clinical endometritis
infection of the uterus within 21 days
or more post partum, not
accompanied by systemic signs
presence of purulent
mucopurulent
uterine exudate.
(>50% pus) or
(approx. 50% pus, 50% mucus)
No signs of clinical illness.
Subclinical endometritis
endometrial inflammation of the uterus
usually determined by cytology, in the
absence of purulent material in the
vagina
presence of >18% neutrophils in uterine cytology
samples collected 20–33 days post partum
or
>10% neutrophils at 34–47 days post partum
Usually the main symptom is repeat breeding
Pyometra
accumulation of purulent or mucopurulent material within the uterine lumen and distension of the uterus, in
the presence of an active CL
3
General considerations in the treatment of uterine
infections
• Type of uterine condition and morphology
Metritis in early pp.
Inflammation process involves
practically all layers of uterine wall
Endometritis in later pp. period
Inflammation process usually
involves only endometrium
The blood-endometrium barrier is
not yet orphologically/functionally
restored
The blood/endometrium barrier
function is restored
- It is necessary to
reach with AIF and
AINFL to all layers
Antibiotics administered
parenterally will cross the
B/E barrier and reach
endometrium and uterine
lumen
4
Antibiotics given
parenterally have very
limited chance to cross
the barrier and reach
endometrium &lumen
Main directions in the treatment of uterine infections
Puerperal metritis
- elimination of bacterial
contamination
- improvement of uterine tonicity
- improvement of the function
of endometrial defence
Antibiotics: iu,
E.coli (+), no
irritation
Optional: PGF*
Antibiotics:
i.m, E.coli (+),
pass B/E
barrier
NSAIDs
- limitation of the damage caused
by the bacterial toxins and
inflammatory process
IV therapy
* Data from recent studies support the idea that exogenous PGF2a may have a direct effects
on uterine immune defences: effects that are independent of luteal function and progesterone
concentrations. (Lewis 2004)
5
Main directions in the treatment of uterine infections =
endometritis
Clinical/Subclinical endometritis
- elimination of bacterial
contamination
Prostaglandins
if CL present
- elimination of immunosuppressive
influence of progesterone
Antibiotics: iu,
A.pyogenes (+)
anaerobes (+),
penetration, no
irritation
- fast return of reproductive function
Metricure
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Requirements for anti-infective preparations used
in the treatment of endometritis
 low MIC’s for relevant pathogens, also in anaerobic environment
 effective concentration in endometrium
 resistance to penicillinases
 activity in presence of cellular debris
 active at pH 7
 no interference with normal uterine defence
 should be well tolerated and not caustic
 short or no withdrawal period for milk
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Antibiotics – activity at present
Penicillins
– susceptible to penicillinase, increasing resistance of Bacteroides spp.
Tetracyclines
– no inhibition of activity in uterine environment, some increase in bacterial
resistance noted
Aminoglycosides
– broad spectrum of activity, reduced activity in anaerobic environment, resistance
of A.pyogenes and G(-) often found
Macrolides & lincosamides
- mainly effective against G(+) bacteria, suitable mainly for the treatment
of infections with clear prevalence of G(+) bacteria
Cephalosporines
– active against G(+) (including penicillinase+), very efficient against A.pyogenes
and other G(-) anaerobes. Maintained activity in the presence of pus and in anaerobic
conditions
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Why Metricure?
Appropriate antibacterial spectrum = proven high
activity against A. pyogenes, F. necrophorum
and other G(-) anaerobes
Maintained activity in anaerobic conditions
Ability to reach sufficient levels in endometrium and
uterine lumen (proven with biopsy studies)
No negative effect on endometrial defence
mechanisms
No irritation to endometrium
No withdrawal time for milk
Easy to administer, hygienic packaging
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20 ml injector with uterus pipette
each syringe contains 500 mg cephapirin
Bacterial dynamics in (endo)metritis
Bacteria
A. pyogenes
Gram neg. anaerobes
E. coli
Peptostreptococci
remaining
Acute
Subacute
33-83%
49-67%
67-85%
60-80%
23-52%
33-85%
17-70%
0-17%
<5%
7-39%
Bacteriology in uteri infected or non-infected with A. pyogenes
100
Bact spp
Fusobact
E. coli
80
60
40
20
0
A. pyo +
A. pyo -
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Bacteriological efficacy of Metricure
Values of MIC90 of cephapirin (mcg/ml) for the major pathogens involved in clinical
endometritis in cattle
Bacteria
MIC90 in mcg/ml
0.12 – 0.25
A. pyogenes
Black pigmented
G(-) anaerobes
0.25
F. necrophorum
0.12
Streptococcus spp.
0.12
Staphylococcus spp.
0.25
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Levels of cephapirin in endometrium
% of biopsies
100
80
60
40
20
0
0.10 mcg/g
0.25 mcg/g
concentration above
What really counts is that the effective concentrations of cephapirin
were shown in endometrium through biopsy – the active not only is
present in the uterine lumen but well inside the endometrium
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Concentrations of cephapirin in endometrium and plasma at 4, 8, 24 and 72 hours after
administration of Metricure
Hours after administration of Metricure
Concentration of cephapirin in
endometrium (mcg/g)
Concentration of cephapirin in plasma
(mcg/g)
4h
8h
9.62
24h
72h
4.9
0.8
(>38MIC)
23.08
(>92 MIC)
(>19 MIC)
(>3MIC)
0.06
0.02
< 0.01
< 0.01
MIC90 = 0.25 mcg/ml
Detection limit – 0.01mcg/ml
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High concentrations in endometrium –
from features to benefits
Bacteria are eliminated not
only from the uterine lumen but
also from endometrial crypts
High concentrations of active are
reached and maintained for at
least 24h in endometrium
High cure rate and limited
chance for relapses (no
surviving “hidden” bacteria)
Higher pregnancy rates and
reduced days open = improved
profitability of the herd
14
Why does fast elimination of A.pyogenes brings
such important benefits?
Effect of elimination of contamination with A.pyogenes on
subsequent fertility of dairy cows
15
Selective efficacy against A.pyogenes –
from features to benefits
Fast return of treated cows to full
reproductive potential
Effective elimination of
A.pyogenes contamination
Higher pregnancy rates and
reduced days open = improved
profitability of the herd
16
Efficacy of Metricure –
results of the independent field trials
Scott McDougall. Effect of intrauterine antibiotic treatment on reproductive performance of dairy cows
following periparturient disease.
Results:
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Efficacy of Metricure –
results of the independent field trials
Kanismanickam et al. The effect of a single administration of cephapirin or
cloprostenol on the reproductive performance of dairy cows with subclinical
endometritis. Theriogenology 63 (2005) 818-830
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The basic direction for the use of Metricure in
the treatment of uterine disorders in cattle
Metricure has been specially developed for treatment of clinical and
subclinical endometritis in later post partum period.
Its features match exactly the needs:
- bacteriological activity focusing on A.pyogenes
- excellent penetration into endometrium
- zero withdrawal time for milk
- proven prompt return to fertility
Metricure should not be used to treat acute puerperal metritis (product
focusing on E.coli should be selected)
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Proposed decision tree for the treatment of
endometritis in cows
Day > 21 pp - Check for size consistence and contents of the uterus
and presence of vaginal/cervical discharge/add lab methods if in
doubt
Endometritis confirmed
No CL on the ovary
Presence of CL on the ovary
PGF2a i.m. (e.g. Estrumate; 2ml)
72h later – intrauterine antibiotic
(e.g. Metricure)
Intrauterine antibiotic
(e.g. Metricure)
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Thank
you
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