PHARMACOLOGICAL CONSIDERATIONS

IN ANTIMICROBIAL THERAPY OF
MASTITIS
 INTRODUCTION
The Aim
 Best antimicrobial treatment regimen for
mastitis
Administering the drug at proper dose
and route
Low MIC for mastitis pathogens.
Preferably bactericidal action
The activity should not be reduced by the
presence of milk
 Good pharmacokinetic characterestics
 Pharmacokinetic (PK) properties:
 Lipid solubility,
 Degree of ionization
 Extent of binding to serum and udder proteins.
 Weak organic bases: macrolides, aminoglycosides,
sulfonamides, polymixin tend to accumulate in milk in the
ionized form after parenteral administration, and attain
concentrations higher than those in blood.
 Weak acids :penicillins and cephalosporins in milk are
much less than those in blood.
 Concentration-dependent group of antimicrobials
(e.g. aminoglycosides and fluoroquinolones)
 Time dependent group
(e.g. penicillins, cephalosporins and macrolides)
 CHOICE OF ROUTE OF ADMINISTRATION

 Type of infection
 streptococci : stay in the milk
compartment, -IMM
 Staphylococcus aureus penetrate into
udder tissue and cause a deep infection
–Systemic and IMM
 Coliforms eliminated spontaneously
from the udder, risk for bacteriaemia =-
the use of systemic administration of
antibiotic;Efficacy of questionable
 Intramammary route

Advantages

 High concentrations of antibiotics

Low consumption of the antimicrobial substances

as the drug is administered straight to the
infection site.
Disadvantages
 Uneven distribution of many substances
Risk for contamination
Some may disturb phagocytosis
Combinations of two or three antibiotics were
introduced to mastitis therapy due to suggested
synergistic action and to cover all pathogens,
Gram-negative bacteria included. The idea of fixed
combination tubes have shown no superiority over
single components in controlled clinical trials.
 Broad-spectrum intramammaries may enhance
emergence of wide-spectrum beta-lactamase
production among bacteria as they are less
efficient than narrow spectrum preparations against
Gram-positive mastitis pathogens, as they are
more targeted towards Gram-negative bacteria .
Parenteral route
 Ruminants eliminate xenobiotics very fast and half-lives
of many antibiotics are short
 Intravenous administration would in general produce
higher concentrations in milk
 The slowly absorbed antibiotic preparations for
intramuscular use are the worst choice in mastitis, because
they do not generally produce therapeutic concentrations in
milk or tissues.
 Dosage recommendations of many antibiotic preparations
for adult cattle are too low with regard to the MIC of the
target bacteria.
 Repeated intramuscular injections of large volumes of
antibiotics are not ideal from the animal welfare point of
view
Interpretation
 IMM : preferred in subclinical,
chronic and mild clinical mastitis

 Parenteral together with IMM

route: in acute clinical mastitis
with swollen parenchyma and
inflamed, blocked milk duct
system,
Approved antimicrobials for bovine mastitis
treatment
 Pirlimycin
 Hetacillin
 Cloxacillin
 Nafcillin
 Amoxicillin
 Novobiocin
 Penicillin G
 Dihydrostreptomycin
 Cephapirin
 Erythromycin
 Sulfamethazine (nonlactating dairy cows only)
Extralabel use: fluoroquinolones, aminopenicillins,
cephalosporins, chloramphenicol tetracyclines,
aminoglycosides and other macrolides.
Macrolides, florfenicol, oxytetracycline,
some fluoroquinolones and rifampin
Good distribution to the udder
following systemic administration.
Sulfa drugs, penicillin G, ampicillin,
ticarcillin and cephalosporins
Intermediate or limited
distribution following systemic
administration
Ceftiofur, aminoglycosides,
spectinomycin, colistin and polymixin B
Poor distribution to the udder
on systemic
Cephapirin , Ceftiofur Cefquinome : BS
Tilmicosin
Macrolide closely related to tylosin, is a narrow
spectrum (gram positive) antibiotic
Pirlimycin
Lincosamide antibiotic, active only against gram
positive bacteria, is effective in eliminating
prepartum infections
Erythromycin
primarily against gram positive bacteria, such as
Staphylococcus and Streptococcus species,
including penicillin resistant ones. indicated only in
the treatment of subacute or subclinical mastitis
manifested by mild changes in the milk or udder.
 Therapy strategies
The mastitic cows :
• Concentrations of antioxidants : vitamin E,
selenium, vitamin A, vitamin C and the minerals:
zinc and copper, which are essential for
maintaining and protecting udder health.
• Anti-oxidant supplementation of dietary rations
improves anti-bacterial function of neutrophils and
decreases incidence and severity of clinical
mastitis.

 Combination of multiple intramuscular injections

with intramammary infusions over a three-day
period result in highest tissue antibiotic
concentrations.
 Subacute clinical mastitis
• Intramammary infusion for a minimum of three
days, accompanied by frequent hand stripping
to remove secretion and debris
• Treatments should be continued until at least
24 hours after the disappearance of clinical
symptoms.
• A true cure, whereby all infecting
microorganisms are eliminated from the
affected quarter, occurs in only 10 to 50% of
cases.
• The cure rate is dependent on how long the
infection has been present, age of the cow,
type of organism involved, and other factors
Acute mastitis
• Acute, or systemic, mastitis is most often
caused by coliform and other Gram-
negative organisms
• Numerous other pathogens including
Gram-positive cocci and mycotic organisms
can all result in severe mastitis.
• IMM therapy to inhibit Gram-positive
growth in addition to parenteral (systemic)
antimicrobials that have broad spectrums of
activity are administered.
 Macrolides: Not effective against coliform bacteria.
 Penicillin, oxytetracycline(IV), ceftiofur, cephapirin and
florfenicol offer some choices, although penicillin and
ceftiofur do not penetrate udder tissue well.
 The efficacy of systemic ceftiofur as a treatment of
clinical mastitis remains unproven and caution should
be exercised in continuing antimicrobial therapy
 Milking out the affected quarter every 2 -3 hours.
Oxytocin may be used to facilitate milk evacuation and
remove toxic materials and debris. However the
oxytocin treated cows had more relapses and
additional infections due to environmental streptococci.
 Corticosteroids only in peracute toxic cases, but should
never be used in other mastitis cases. Aqueous
dexamethasone sodium sulfate, a single dose one time
treatment : aid in reducing swelling and pain and enhance
the removal of toxic secretions as well as promote better
diffusion of intramammary infusions
 NSAIDS: flunixin meglumine, aspirin, phenylbutazone, and
ketoprofen
 Fluid replacement: Large volumes of BES; 20 litres in the
first one to two hours, and up to 60 liters over a 12-hour
period.
 Commercial distilled water can be bought in large
economical quantities and mixed with pre-weighed amounts
of salt to provide the fluids needed.
 Hypertonic(7.5%) saline solution (4ml/kg,IV): immediate
expansion of ECF and temporarily counter some of the
effects associated with endotoxemia.
 Followed by 5 to 10 gallons of water orally
 Administering 150 to 250 grams of sodium
bicarbonate with the first three to 5 liters of
electrolyte solution and adding 500 mL of 50%
glucose to the first few liters of electrolyte restores
vital body fluids, dilutes toxins, and counteracts
acidosis .

 Calcium BG and Potassium chloride

 Dietary vitamin E and selenium reduce the

severity and frequency of coliform mastitis .
Chronic mastitis
 Long duration, frequently recur with mild clinical mastitis
despite previous therapy, and can add substantial costs and
risks associated with treatment.
 Identification of the pathogen should be performed before
any extensive therapy is instituted.
 Drug distribution, although theoretically available in the
mammary gland, may not be efficacious because of
extensive fibrosis and micro-abscess formation in the gland.
 In herds with a high prevalence of S. aureus infections, the
emphasis on teat dipping, culling, milking machine
maintenance, milking hygiene, and segregation of infected
cows to gradually reduce prevalence of infection.
 Antibiotics : reduce shedding of bacteria by clinical cows,
and thus help reduce the spread, but may not reduce
overall prevalence in the herd.
 Heifers calving with mastitis: Dry treated 50 to 60 days with
approved dry cow therapy. and treated 7 to 14 days prior to
calving
Reasons for treatment failure
 Lack of contact between bacteria and
antibiotics due to scar tissue formation
 Protection within leukocytes
 Poor drug diffusion
 Inactivation by milk and tissue proteins
 Microbial resistance to antibiotics;
development of bacterial L-forms;
metabolically inactive organisms
 Improper treatment procedures like
stopping the therapy too soon.
Nonantibiotic approaches for alleviating clinical signs
 Hypertonic saline (7.5%; 2 mL/ 45 kg BW,IV or 500 to
1000 mL, intramammarily) has been used in some
cases(50-60% success rate), once after each milking for
two to three days to alleviate clinical symptoms
 Lactobacillus (probiotic) intramammary infusions have
been tried with poor success rates (21%).
 Clay mixed with water or oil (pine or thyme oil), made in
to a paste adhering to the udder, has proved efficient as
poultice to treat inflammation caused by mastitis
 Many herbal medicines have been also considered to be
quite effective in treatment of mastitis.. The formulated
herbal products with antibacterial, anti inflammatory ,
analgesic and immunostimulatory properties and plants
which boost the mammary gland health have been tried
as mastitis therapeutic agents
 Homeopathy
 Cytokines
 Bacteriocins
PLANTS BOOSTING MAMMARY HEALTH
Tinospora cordifolia
(Amruta Balli, Madhu parni)
Cuminum cyminum
(Jeerige)
Cyamopsis tetragonoloba
( gori kai)
Cymbopogon martinii
( kashi hullu)
Limnophila aromatica
Nigella sativa
Ocimum basilicum
Anethum graveolens
(Sabbakki soppu)
Amaranthus spinosus
( mullu harive soppu )
Syzygium aromaticum
( clove, lavanga)