كتاب  Bovine mastitis therapy and why it failsكتب الطب

كتاب Bovine mastitis therapy and why it fails

Bovine mastitis therapy and why it fails من كتب طب بيطرى Continuing education — Voortgesette opleiding Bovine mastitis therapy and why it fails J H du Preez a INTRODUCTION Mastitis can occur at any stage of a cow’s productive life. Microbiological investiga - tions of clinical bovine mastitis reveal a causative agent in 75–95% of cases. There is good evidence that microorganisms are involved in almost all cases 36,40,49 . At least 137 infectious causes of bovine mastitis are known, but the majority of cases are caused by only a few common bacterial pathogens, namely staphylococci, strep- tococci, coliforms and Arcanobacterium pyogenes. For antibacterial mastitis therapy to be successful, the active drug must attain and maintain concentrations exceeding the minimum inhibitory concentration (MIC) at the focus of infection for long enough to break the production and toxin-producing cycle of the causative pathogen 3 . This may be prevented by a number of factors that include udder pa - thology and poor selection of anti - microbials, and is also influenced by the route of administration. Therapy may have poor results owing to tissue damage and introduction of new infections dur - ing treatment, and/or failure to eliminate the management factors that predispose to mastitis. Although there is an underly - ing assumption that the primary goal of antibacterial mastitis therapy is to kill bac - teria and that the normal udder is sterile, usually the best that can be achieved is temporary reduction or suppression of the bacterial population to allow the host to overcome the infection. The mecha - nisms to cleanse the udder are evidently poorly developed in some cows, as re - lapses and re-infections commonly follow antimicrobial therapy. Udder infections tend to be dynamic, and stress may con- tribute to udder infections becoming clin- ically apparent 48,49 . The purpose of this article is to provide an update on bovine mastitis therapy and reasons for its failure. PRINCIPLES OF MASTITIS THERAPY The success of mastitis therapy depends on correct diagnosis, appropriateness of the route of administration and the drug selected, stage at which treatment is initi - ated, severity of udder pathology, sup - portive treatment, and elimination of predisposing factors. There is no standard treatment for mastitis, but it is advocated that the clinical forms should be treated according to the severity of the udder in - flammation 12 . Bovine mastitis is most commonly treated by intramammary infusion of drugs 29,64 . This is the route of choice in subclinical, mild or moderately severe mastitis, and is used as an adjunct to parenteral administration in severe mas - titis. Some clinicians prefer intra - mammary administration, without systemic administration, even in severe disease 40 . For effective intramammary treatment, drugs should distribute throughout the udder and be rapidly ab - sorbed into the general blood circulation (Table 1). Significantly better results can be obtained when the drug is adminis - tered intracisternally in 1 of 0.5 % glu - cose solution, rather than in 50 m saline 23 . The disadvantage of local application of antimicrobials is the slow and uneven dis - tribution of certain drugs in the infected udder (Table 1). In acute, severe disease, distribution through the udder may be impaired by inflammation or blockage of milk ducts by debris. Parenteral adminis - tration may overcome these problems, al - though it is usual to administer agents concurrently by the intramammary route 17 . Severely inflamed udders should be milked out frequently, with the aid of oxytocin if necessary. In peracute or acute clinical mastitis cases with systemic signs, combined systemic and intramammary treatment with compatible antibiotics, supplemented with supportive therapy, is recommended 64 . It is always desirable to treat infectious mastitis according to the antimicrobial drug sensitivity pattern of the pathogens and clinical experience 40 . The basic rule in selecting the drug is to opt for one with as narrow a spectrum as possible, to focus treatment on a specific pathogen and minimise side-effects. Because it takes time to do sensitivity determinations, broad-spectrum antibiotics must be given initially for practical reasons, based on knowledge of the pharmacokinetic prop- erties of the drugs and the formula- tion 9,29,32,65,66,67 . In general, narrow-spec- trum antibiotics are bacteriocidal and those with a broad spectrum are bacterio - static 58 . Response to treatment increases with persistence of the antibiotic in the udder. The concentration of the drug used must at least exceed the MIC-value for the pathogen, but preferably also the MBC- value (minimum bacteriocidal concentra - tion) in the udder. If bacteriostatic drugs are used, the need to maintain high con - centrations in the target organ is in - creased. Successful intravenous or intramuscu - lar mastitis therapy depends on effective passage of the drug from blood into milk to reach foci of infection, which is largely governed by lipid solubility, degree of ionisation (dependent on the dissocia - tion constant (pKa)), and the extent of protein-binding of the drug with plasma 44,45,53 , since drugs cross the blood–milk barrier by passive diffusion 30 . Only the unbound or free drug can dif - fuse through the blood–milk barrier and exert pharmacological or antimicrobial 0038-2809 Jl S.Afr.vet.Ass. (2000) 71(3): 201–208 201 a Technology Transfer Division, ARC - Onderstepoort Veterinary Institute, Private Bag X05, Onderstepoort, 0110 South Africa Treatment of bovine mastitis depends on the cause, the clinical manifestation and the antibiotic susceptibility of the agent. Mastitis therapy is commonly unsuccessful owing to pathological changes that occur in the udder parenchyma as a result of the inflammatory reaction to mastitogenic bacteria, pharmacokinetic properties of antimicrobial mastitis drugs, mastitogenic bacterial and related factors, and poor animal husbandry and veterinary interventions.
-
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وصف الكتاب : Bovine mastitis therapy and why it fails من كتب طب بيطرى

Continuing education — Voortgesette opleiding
Bovine mastitis therapy and why it fails
J H du Preez
a
INTRODUCTION
Mastitis can occur at any stage of a cow’s
productive life. Microbiological investiga
-
tions of clinical bovine mastitis reveal a
causative agent in 75–95% of cases. There
is good evidence that microorganisms are
involved in almost all cases
36,40,49
. At least
137 infectious causes of bovine mastitis
are known, but the majority of cases are
caused by only a few common bacterial
pathogens, namely staphylococci, strep-
tococci, coliforms and
Arcanobacterium
pyogenes.
For antibacterial mastitis therapy to be
successful, the active drug must attain
and maintain concentrations exceeding
the minimum inhibitory concentration
(MIC) at the focus of infection for long
enough to break the production and
toxin-producing cycle of the causative
pathogen
3
. This may be prevented by a
number of factors that include udder pa
-
thology and poor selection of anti
-
microbials, and is also influenced by the
route of administration. Therapy may
have poor results owing to tissue damage
and introduction of new infections dur
-
ing treatment, and/or failure to eliminate
the management factors that predispose
to mastitis. Although there is an underly
-
ing assumption that the primary goal of
antibacterial mastitis therapy is to kill bac
-
teria and that the normal udder is sterile,
usually the best that can be achieved is
temporary reduction or suppression of
the bacterial population to allow the host
to overcome the infection. The mecha
-
nisms to cleanse the udder are evidently
poorly developed in some cows, as re
-
lapses and re-infections commonly follow
antimicrobial therapy. Udder infections
tend to be dynamic, and stress may con-
tribute to udder infections becoming clin-
ically apparent
48,49
.
The purpose of this article is to provide
an update on bovine mastitis therapy and
reasons for its failure.
PRINCIPLES OF MASTITIS THERAPY
The success of mastitis therapy depends
on correct diagnosis, appropriateness of
the route of administration and the drug
selected, stage at which treatment is initi
-
ated, severity of udder pathology, sup
-
portive treatment, and elimination of
predisposing factors. There is no standard
treatment for mastitis, but it is advocated
that the clinical forms should be treated
according to the severity of the udder in
-
flammation
12
.
Bovine mastitis is most commonly
treated by intramammary infusion of
drugs
29,64
. This is the route of choice in
subclinical, mild or moderately severe
mastitis, and is used as an adjunct to
parenteral administration in severe mas
-
titis. Some clinicians prefer intra
-
mammary administration, without
systemic administration, even in severe
disease
40
. For effective intramammary
treatment, drugs should distribute
throughout the udder and be rapidly ab
-
sorbed into the general blood circulation
(Table 1). Significantly better results can
be obtained when the drug is adminis
-
tered intracisternally in 1
of 0.5 % glu
-
cose solution, rather than in 50 m
saline
23
.
The disadvantage of local application of
antimicrobials is the slow and uneven dis
-
tribution of certain drugs in the infected
udder (Table 1). In acute, severe disease,
distribution through the udder may be
impaired by inflammation or blockage of
milk ducts by debris. Parenteral adminis
-
tration may overcome these problems, al
-
though it is usual to administer agents
concurrently by the intramammary
route
17
. Severely inflamed udders should
be milked out frequently, with the aid of
oxytocin if necessary. In peracute or acute
clinical mastitis cases with systemic signs,
combined systemic and intramammary
treatment with compatible antibiotics,
supplemented with supportive therapy,
is recommended
64
.
It is always desirable to treat infectious
mastitis according to the antimicrobial
drug sensitivity pattern of the pathogens
and clinical experience
40
. The basic rule in
selecting the drug is to opt for one with as
narrow a spectrum as possible, to focus
treatment on a specific pathogen and
minimise side-effects. Because it takes
time to do sensitivity determinations,
broad-spectrum antibiotics must be given
initially for practical reasons, based on
knowledge of the pharmacokinetic prop-
erties of the drugs and the formula-
tion
9,29,32,65,66,67
. In general, narrow-spec-
trum antibiotics are bacteriocidal and
those with a broad spectrum are bacterio
-
static
58
.
Response to treatment increases with
persistence of the antibiotic in the udder.
The concentration of the drug used must
at least exceed the MIC-value for the
pathogen, but preferably also the MBC-
value (minimum bacteriocidal concentra
-
tion) in the udder. If bacteriostatic drugs
are used, the need to maintain high con
-
centrations in the target organ is in
-
creased.
Successful intravenous or intramuscu
-
lar mastitis therapy depends on effective
passage of the drug from blood into milk
to reach foci of infection, which is largely
governed by lipid solubility, degree of
ionisation (dependent on the dissocia
-
tion constant (pKa)), and the extent of
protein-binding of the drug with
plasma
44,45,53
, since drugs cross the
blood–milk barrier by passive diffusion
30
.
Only the unbound or free drug can dif
-
fuse through the blood–milk barrier and
exert pharmacological or antimicrobial
0038-2809 Jl S.Afr.vet.Ass. (2000) 71(3): 201–208
201
a
Technology Transfer Division, ARC - Onderstepoort
Veterinary Institute, Private Bag X05, Onderstepoort,
0110 South Africa

Treatment of bovine mastitis depends on the cause, the clinical manifestation and the antibiotic susceptibility of the agent. Mastitis therapy is commonly unsuccessful owing to pathological changes that occur in the udder parenchyma as a result of the inflammatory reaction to mastitogenic bacteria, pharmacokinetic properties of antimicrobial mastitis drugs, mastitogenic bacterial and related factors, and poor animal husbandry and veterinary interventions.


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La thérapie de la mammite bovine et pourquoi elle échoue من كتب طب بيطرى

Formation continue - Voortgesette opleiding
La mastite bovine et pourquoi elle échoue
J H du Preez
a
INTRODUCTION
La mammite peut survenir à n'importe quel stade de la
vie productive d'une vache . Microbiological Investiga
-
tions de la mammite bovine clinique révèlent un
agent causal dans 75-95% des cas. Il
existe de bonnes preuves que les micro-organismes sont
impliqués dans presque tous les cas
36,40,49
. Au moins
137 causes infectieuses de la mammite bovine
sont connues, mais la majorité des cas sont
causés par seulement quelques bactéries
pathogènes communes , à savoir les staphylocoques, les
streptocoques, les coliformes et les
Arcanobacterium
pyogenes.
Pour que la mastite antibactérienne
réussisse, le médicament actif doit atteindre
et maintenir des concentrations dépassant
la concentration minimale inhibitrice
(CMI) au foyer de l'infection pendant
assez longtemps pour rompre le
cycle de production et de production de toxines du
pathogène responsable
3
. Ceci peut être évité par un
certain nombre de facteurs qui incluent pa mamelle
-
thology et une mauvaise sélection des anti
-
microbiens, et est également influencée par la
voie d'administration. La thérapie peut
avoir de mauvais résultats en raison de lésions tissulaires
et l' introduction de nouvelles infections dur
-
traitement, et / ou l'échec à éliminer
les facteurs de gestion qui prédisposent
à la mammite. Bien qu'il y ait une sous - tendre
-
hypothèse ing que l'objectif principal de la
thérapie de mammites antibactérienne est de tuer bac
-
tères et que la mamelle normale est stérile,
généralement le meilleur qui peut être réalisé est la
réduction temporaire ou la suppression de
la population bactérienne pour permettre à l'hôte
surmonter l'infection. Le mecha
-
nismes pour nettoyer les mamelles sont évidemment
peu développée chez certaines vaches, tel qu'il est
-
devient caduque et réinfections souvent suite à une
antibiothérapie. Infections mammaires
ont tendance à être dynamiques et le stress peut contribuer
à ce que les infections de la mamelle deviennent cliniquement
apparentes
48,49
.
Le but de cet article est de fournir
une mise à jour sur la thérapie de la mammite bovine et les
raisons de son échec.
PRINCIPES DE MASTITE THÉRAPIE
Le succès de la thérapie mastite dépend
du diagnostic correct, la pertinence de
la voie d'administration et le médicament
choisi, stade auquel le traitement est initi
-
ATED, la gravité de la pathologie de la mamelle, sup
-
traitement plices, et l' élimination des
facteurs prédisposants. Il n'y a pas de
traitement standard pour la mammite, mais il est préconisé
que les formes cliniques doivent être traitées en
fonction de la gravité de l
'
inflammation de la mamelle
12
.
La mastite bovine est le plus souvent
traitée par perfusion intramammaire de
médicaments
29,64
. Ceci est la voie de choix dans
subclinique, doux ou modérément sévère
mammites et est utilisé comme adjuvant à l'
administration parentérale dans mastite

. Certains cliniciens préfèrent l' administration intra
-
mammaire, sans
administration systémique, même en cas de
maladie sévère
40
. Pour un
traitement intramammaire efficace , les médicaments devraient distribuer
tout au long de la mamelle et être rapidement ab
-
sorbée dans la circulation sanguine générale
(tableau 1). Peuvent significativement meilleurs résultats
sont obtenus lorsque le médicament est adminis
-
tered intracisternale en 1
de 0,5% glu
-
solution de cose, plutôt que dans 50 m
saline
23
.
L'inconvénient de l' application locale d'
antibiotiques est la dis lente et inégale
-
tribution de certains médicaments dans les personnes infectées
mamelle (tableau 1). Dans les cas de maladie aiguë sévère, la
distribution à travers la mamelle peut être
altérée par l'inflammation ou le blocage des
canaux galactophores par des débris. Administration parentérale
-
tration peut surmonter ces problèmes, al
-
mais il est habituel d'administrer des agents en
même temps que par la intramammaire
voie
17
. Les mamelles gravement enflammées doivent
être traites fréquemment, à l'aide d'
ocytocine si nécessaire. Dans
les cas de mammite clinique aiguë ou aiguë avec signes systémiques,
un
traitement systémique et intramammaire combiné avec des antibiotiques compatibles,
complété par un traitement de soutien,
est recommandé
64
.
Il est toujours souhaitable de traiter la
mammite infectieuse en fonction du
profil de sensibilité aux médicaments antimicrobiens des pathogènes
et de l'expérience clinique
.
. La règle de base dans la
sélection du médicament est d'opter pour
un spectre aussi étroit que possible, de concentrer le
traitement sur un pathogène spécifique et de
minimiser les effets secondaires. Parce qu'il prend le
temps de faire des déterminations de sensibilité, des
antibiotiques à large spectre doit être donné d'
abord pour des raisons pratiques, basée sur la
connaissance des priétés pharmacocinétiques
proprié- des médicaments et la formulation
tion
9,29,32,65,66,67
. En général, à
spectre étroit des antibiotiques sont bactéricides et
ceux qui ont un large spectre sont bactério
-
statique
58
.
La réponse au traitement augmente avec
persistance de l'antibiotique dans la mamelle.
La concentration du médicament utilisé doit
au moins dépasser la valeur MIC pour le
pathogène, mais de préférence aussi le MBC-
valeur (concentration

) dans le pis. Si les médicaments bactériostatiques
sont utilisés, la nécessité de maintenir une haute con
-
centration dans l'organe cible est en
-
froissé.
La réussite intraveineuse ou intramuscu
- le
traitement des mammites lar dépend efficace
passage du médicament du sang dans le lait
pour atteindre les foyers d'infection, qui est en grande partie
régie par la solubilité des lipides, le degré d'
ionisation (dépendant de la dissocia
-
constante constante (pKa)), et l'étendue de
la liaison des protéines du médicament avec le
plasma
44,45,53
, puisque les médicaments traversent la
barrière du lait sanguin par diffusion passive
30
.
Seul le médicament non lié ou libre peut dif
-
fuse à travers la barrière sang et le lait
exercer pharmacologique ou antimicrobien
0038-2809 Jl S.Afr.vet.Ass. (2000) 71 (3): 201-208
201
a
Division du transfert de technologie, ARC -
Institut vétérinaire Onderstepoort , Private Bag X05, Onderstepoort,
0110 Afrique du Sud

Treatment of bovine mastitis depends on the cause, the clinical manifestation and the antibiotic susceptibility of the agent. Mastitis therapy is commonly unsuccessful owing to pathological changes that occur in the udder parenchyma as a result of the inflammatory reaction to mastitogenic bacteria, pharmacokinetic properties of antimicrobial mastitis drugs, mastitogenic bacterial and related factors, and poor animal husbandry and veterinary interventions.
 



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