Antimicrobial therapies in reproduction

USE OF ANTIMICROBIALS FOR THE
TREATMENT OF REPRODUCTIVE
DISEASES IN DOMESTIC ANIMALS
Dr. Ishwor Dhakal
MVSc Surgery
Agriculture and Forestry University, Nepal

Introduction
 Antimicrobials are widely used to prevent and
treat the infectious agent that cause different
indication related to reproduction.
 Indications related to reproduction
 Mastitis
 Metritis
 Endometritis
 Placentitis
 Retained Placenta
 Cervicitis
 Veginitis
Be aware of antimicrobial resistance

Antimicrobial therapies
Parenteral
IM / IV
Locally
IMM / IU

INTRAUTERINE ANTIBIOTIC
THERAPY
 Intrauterine infusions need to be administered
with sterile equipment and proper aseptic
preparation of the dam.
Objectives: Use sufficient volume to achieve
uniform distribution
Intrauterine therapy has been preferred over
systemic treatment.
Complication: secondary bacterial or fungal
infections, exhibit severe endometrial irritation
or may fail to resolve an infection.

Table 1. Guidelines for administration of intrauterine antibiotics in mare
Drug Dose per infusion Comments
Amikacin 2gm a
Buffer with bicarbonate or large volume of
saline (200 ml); Excellent gram
negative coverage
Ampicillin 2gmb
Use only the soluble product; Susceptible Gram-
positive & E coli
Ceftiofur sodium 1 gm Broad spectrum; save for resistant organisms
Gentamicin 1-2 gma
Buffer with bicarbonate or large volume of
saline (200 ml); Some S. zooepidemicus;
Enterobacter spp., E.coli, Klebsiella spp.,
Proteus spp., Serratia spp, P. aeruginosa, S.
aureus
Penicillin
(potassium)
5 million U S. zooepidemicus
Neomycin 4 gm
Gram-negative organisms; Some E.coli & some
Klebsiella spp.)
Ticarcillin clavulanic acid 3-6 gm
Beta-lactamase inhibitor confers greater activity
against Enterobacter; S. aureus, B. fragilis;
Infuse with a minimum of 200 ml of saline
a Buffered with equal volume of 7.5% bicarbonate and diluted in saline
b Use at high dilutions because it can be irritating

Antimicrobials
 Macrolides, trimethoprim or fluoroquinolones
are lipophilic antimicrobials - highest volumes
of distributation - high concentration in
peripheral parts of the body.
 Sulphonamides and oxytetracycline (OTC)
are moderate lipid solubility - therapeutic
concentrations in the reproductive organs.
 Penicillins and cephalosporins are mostly
ionized in the plasma and their distribution is
limited

Withdrawal times of some drugs used in theriogenology.*
Active substance Dose
Withdrawl time (days)
Cattle
Sheep
meat
Swine
meatMeat Milk
Ceftiofur hydrochloride
injection
2.2mg/kg per day*5
(50 mg/mL) SQ/ IM
3 0 N/A N/A
Oxytetracycline injection
3-5mg/lb per day*2
(50 mg/mL) IM/ IV
22
(15-
28)
Not for use in lactating
dairy animals
(Maximum amounts of
OTC residues were
found 72)
N/A N/A
Sulfabromemethazine
sodium
90mg/lb repeat after 48h
if necessary
(15 g/bolus) PO
18 4 (96 h; 8 milkings) N/A N/A
Tylosin
8mg/lb per day (50-
200mg/ml) IM
21
Not to be used in
lactating dairy cows
N/A N/A
Sulfamethazine sustained
release
- 16
Not to be used in
lactating dairy cows
N/A N/A

 Aminoglycosides (amikacin and gentamicin
sulfate), sulfonamides (sulfamethazine), and
carboxypenicillin (ticarcillin) are not allowed
for use in animal intended for human food.

Use of Antimicrobial in
reproduction
Bovine mastitis
 Treatment of mastitis is done based on
bacteriological diagnosis and antibiotic sensitivity.
 Most commonly used antimicrobials for treatment is
ceftriaxazone, ciprofloxacin, benzyl penicillin etc.
 Intramammary administration is recommended for
clinical mastitis caused by streptococcal species
 Coliform mastitis: No IMM, Parenteral, supportive
therapy NSAID.

Bovine Uterine infections
 The most common bacterial species present
during the first 2 weeks PP are E. coli,
Trueperella pyogenes, Pseudomonas spp.,
Streptococcus spp., Staphylococcus spp.,
Clostridium spp., Fusobacterium spp. and
Bacteroides spp.
 Uterine infections depends on
 pre-disposing factors - RP
 the efficacy of host defence mechanisms and
 the pathogenicity of the bacteria involved

Uterine diseases manifestations
 puerperal metritis (puerperal metritis and
clinical metritis)
 clinical endometritis,
 subclinical endometritis and
 pyometra

Retained Placenta
 No treatment until there are signs of systemic
illness. Spontaneous decay and expulsion with
lochia is possible. PG can be given to keep
open the cervix and treatment for endometritis
can be given. Conventional manual removal is
not indicated.
 Application of antimicrobial boluses -
inconclusive

Puerperal metritis
 The treatment of choice was either IU
infusion of antimicrobials or parenteral
antimicrobials.
 Recommended antimicrobials are
benzylpenicillin, OTC and ceftiofur.

Clinical metritis
 The self-cure rate for clinical metritis is high.
 Metritis is treat with systemic antibiotics are
indicated because they more easily penetrate
the myometrium.

Clinical endometritis
 Incidence of clinical endometritis is very less than
puerperal metritis.
 Administration of PGF is the treatment of choice
for CE, at least when a corpus luteum (CL) is
present.
 IU infusions: tetracycline, penicillin, cephapirin,
chloramphenicol, diluted Lugol’s iodine,
gentamycin, spectinomycin, sulphonamides,
nitrofurazone, iodine and chlorhexidine, but many
of them are no longer approved for this use.

Endometritis
 Treatment:
1. Irrigation with a physiological NS (40-42oC, 24 liters) to
remove secretion or debris.
2. IU infusion of 50 ml of 0.2% of povidine iodine, or,
antibiotics (30 to 50 ml) such as ampicillin, penicillin,
kanamycin, tetracycline (1:1 dilution in DW) or according to
the sensitivity test.
3. Similar drugs can be given parentally if needed.
4. Self cleaning by inducing estrus with a PG inj during luteal
phase.
5. If present a cystic ovarian condition, treat it.

FUNGAL ENDOMETRITIS
 Irrigation of uterus with disinfectant solutions
used for fungal infections include 3% (v/v)
hydrogen peroxide solution (30 ml hydrogen
peroxide in 1 L of 0.9% saline), 2% (v/v)
acetic acid (white vinegar-20 ml of vinegar in
1 L of 0.9% saline), 0.1-0.2% (v/v) povidone-
iodine solution, or 20% DMSO for 5-7 days
for 2-3 estrous.
 Duration can be shorten by using PG.Be aware of antimicrobial resistance

Table . Usual dosages of systemic and topical antifungal agents for use in equine reproduction
Drug Dosage Route Interval (h) Spectrum
Systemic
Amphotericin B 0.3 to 0.9 mg/kg IV* 24-48 Broad spectrum
Ketoconazole 20 mg/kg (in 0.2 N
HCL)
NGTa 12 Yeastc
Fluconazole Loading dose 14
mg/kg
5 mg/kg
PO, IV 24 Yeast
Itraconazole 5 mg/kg POb, IV 12-24 Broad spectrumd
Topical
Clotrimazole 400 – 700 mg IU 24h x 7d Broad spectrum
Miconazole 500 – 700 mg IU 24h x 7d Broad spectrum
Nystatin 0.5 – 2.5 million
unitse
IU 24h x 7d Yeast
Amphotericin B 100 -200 mg IU 24h x 7d Broad spectrum
Amphotericin B 100 mg IU 24h x 7d Yeast
a Nasogastric intubation is require to avoid the irritant effect of HCL on the oral cavity and throat
b The bioavailability of the oral suspension is superior to that of the capsules
c Yeasts: Candida spp
d Broad spectrum: yeasts, Aspergillus, dimorphic fungi
* Diluted to 1 mg/ml in 5% dextrose and administered over 1-2 h
e Must be diluted in sterile water (100 to 200 ml) as it precipitates in saline

Vaginitis:
 Inflammation due to bacterial
infection (staph, strept, E coli, A. pyogenes
etc).
 Treatment: Vaginal irrigation with a
nonirritating antiseptic solution or with a
antibiotic solution.

Cervicitis:
 Inflammation of the cervical canal (acutely or chronically),
often accompanies endometritis and results from the bacterial
infection at the time of abortion, dystocia and ROP. Also
results from injuries while inappropriately using equipments
during insemination, and diagnosis and treatment of uterine
diseases.
 Treatment: Vaginal irrigation with a non-irritating
antiseptic solution, luke warm physiological saline, 1%
povidine solution or an antibiotic solution can be infused into
the cervical canal. Repeated estrus cyclicity may heal the
condition naturally, so maintaining normal ovarian function is
important. Also treat for vaginitis and endometritis if mixed
inflammation is noticed.

Valid veterinarian-client-patient
relationship exists only when:
 medical judgments of veterinarian
 sufficient knowledge of the medical condition
of the animals.
 readily available for follow-up in case
something goes wrong.

 Diseased animals should be treated both from an
animal welfare point of view and to restore their
production capacity.
 Proper use of antimicrobial does not have any
known negative effect on animal welfare or public
health; the consumers’ concerns have to be taken
into account in livestock production.
 The antibiotics in livestock production are probably
used as growth promoters.

Antibiotics considered safe during
pregnancy:
 Amoxicillin
 Ampicillin
 Clindamycin
 Erythromycin
 Penicillin
 Nitrofurantoin

Conclusion
 Drug selection should be based, whenever possible,
on microbiologic culture and sensitivity tests.
 In food animals, proper withholding times must be
observed for meat and milk after antibiotic use
 Animal health and fertility should be enhanced by
selection and good management rather than by
widespread use of antibiotics.
 Antibiotics should be used judiciously as
inappropriate course and dose are often the major
instigating factor for antibiotic resistance.Be aware of antimicrobial resistance

Thank
You

Antimicrobial therapies in reproduction

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