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ROLE OF ANTIMICROBIAL THERAPY IN SMALL RUMINANT PRACTICE

Antimicrobial drugs are used in animals, humans, and plants to treat and prevent
bacterial infections and to improve production efficiency in food-producing animals.
Variability in susceptibility to different antimicrobial drugs has become a major factor
affecting the successful treatment of bacterial diseases. The primary goal of antimicrobial
drug use for treatment and prevention of bacterial infections should be to control bacterial
growth to enable host responses to contain or eliminate bacteria responsible for disease.
Although antimicrobial drugs can help the host contain and eliminate infections, these drugs
should not be considered solely responsible for eliminating infections in the host as both
innate and developed immune responses are critical and optimizing immune status can
minimize the effect of infections without use of antimicrobial drugs. A brief overview of the
role of the commonly used antimicrobials classes in small ruminants is discussed in this
article.

FLUOROQUINOLONES: They are broad spectrum rapidly acting bactericidal agents,


exhibiting concentration dependent killing and post antibiotic effect. Spectrum of activity is
against gram positive, gram negative organisms; some of the agents showing extended
spectrum against mycoplasma, Chlamydia,anaerobes .Better ocular tolerability with less
toxicity to corneal epithelium makes FQs as good ocular antiinfectives, with ofloxacin
achieving the highest aqueous concentration. They are active in presence of abscess in spite
of often unfavorable environmental conditions. Of the currently available fluoroquinolones,
all have a similar spectrum of activity, but they may vary in potency. Against some gram-
negative bacilli, especially Pseudomonas aeruginosa, ciprofloxacin is more active than
veterinary quinolones. Levofloxacin possesses excellent activity against gram positive, gram-
negative and anaerobes compared to ofloxacin and ciprofloxacin..Well distributed in to
tissues : kidney, lung, prostate, genital tract, bones, phagocytes and inflammatory fluid. They
are distributed into cytosol where they can reach intracellular pathogens.(Brucella,
Mycoplasma, Mycobacterias).They are synergestic with beta-lactams,aminoglycosides. and
antagonistic with macrolides,tetracyclines, chloramphenicol.
Arthropathy: (Noninflammatory erosive arthropathies) in young growing animals, retinal
degeneration (in cats) CNS-excitability and seizure (Rapid IV administration).Phototoxicity
are the adverse effects .Concurrent administration of drugs that contain divalent or trivalent
cations, such as aluminum, calcium, iron, magnesium, or zinc cations (antacids, sucralfate,
laxatives iron supplements, and molasses. multivitamins) will significantly inhibit oral
absorption and NSAIDs may increase the risk of CNS stimulation and convulsions.The
hepatic clearance of methylxanthines, like theophylline and caffeine gets reduced on
concurrent administration with FQs , resulting in CNS related toxicity signs
Doses:sheep,goats:enrofloxacin(2.5to5,PO,IM,SC,q24h),marbofloxacin(2,IM,IV,SC,q24h),

danofloxacin(6,IMq48h).

CEPHALOSPORINS: They are wide-spectrum β-lactum bactericidal antibiotics exhibiting


time-dependent efficacy. They are classified into four generations, based primarily on their
spectrum of antibacterial activity and resistance to β-lactamases. Generationwise, the
spectrum of activity against gram negative organisms and the stability against β-lactamase
increase from first to fourth, along with same or reduced spectrum of activity against gram
positive organisms, except for 4th generation agents, which have enhanced activity aginst
gram positive pathogens. Oral cephalexin, cefadroxil and parenteral cefazolin are the most
commonly used first generation cephalosporins, primarily for skin and soft tissue infections
such as pyoderma The oral absorption is poor and highly erratic in ruminants, thus used
only in preruminant young ones.

Cefoxitin and cefotetan (cephamycins) are second generation ones, effective against
anaerobic gram negative organisms, are used in the treatment of anaerobic infectious
conditions like aspiration pneumonia, bite infections, ruptured intestine gangrene, peritonitis
and pleuritis.Ceftriaxone, ceftizoxime, cefotaxime and ceftazidime are the third generation
ones, have the ability to cross blood-brain barrier, effective in therapy for bacterial
meningitis. Ceftazidime and Cefoperazone, are highly active against Pseudomonas
aeruginosa among all cephalosporins, compared to Ceftriaxone and Ceftizoxime, which
also have antipseudomonal activity to some extent. Ceftiofur has broader activity against
gram-positive and beta-lactamase–producing strains as well as anaerobes. Ceftiofur
presentation is in three formulations: ceftiofur crystalline freee acid, ceftiofur hydrochloride
and ceftiofur sodium salt.; is indicated for treatment of bronchopneumonia in sheep, caused
by Pasteurella hemolytica or P.aeruginosa. Ceftiofur sodium (50mg/ml powder vials for inj)
and ceftiofur hydrochloride (50mg/ml sterile suspension) are the formulations approved for
use in dogs, horses, catlle,sheep, goats and swines. Ceftiofur sodium has been used for
treating coliform mastitis to reduce toxaemia. .Cefquinome, an extended spectrum beta-
lactam, is used for treating bovine respiratory disease and mastitis.

Adverse Effects: Gastrointestinal disturbances ,Hypersensitivity reaction Bleeding


disorders: as all cephalosporins can inhibit vitamin K synthesis by suppressing gut flora.
Prophylactic vitamin K therapy is recommended when any of these medications is used for
prolonged periods in malnourished or seriously ill patients. Hepatic dysfunction, Renal
insufficiency , Abscesses or other severe local tissue reactions ( with IM injections) and
thrombophlebitis(IV). Most of the cephalosporins are synergistic with aminoglycosides and
nephrotoxic risk when used with other nephrotoxic medications: loop diuretics, NSAIDS.

Dosages (mg/kg) of approved cephalosporins in sheep and goats: Ceftiofur sodium -


1.1-2.2, IM ,SC,q24h; Cefazolin-10 ,IM, q8h; Cephapirin - 200mg TD, I/mammary, q12h;
Cefoperazone- 250 mg Total dose(TD), I/mammary,,q12h; Cefuroxime- 250 mg TD,
I/mammary,q12h;Cephacetrile - 1.1-2.2, IM ,SC,q24h Ceftriaxone- 25-50, IM ,IV,q12h;
Cefadroxil - 25 mg,PO, q12h; Cephradine - 7, PO,q12h ; Cefetamet – 10,PO, q12h;
Ceftazidime- 20-40, IM,,q24h
MACROLIDES: are bacteriostatic antibiotics,(bactericidal at high concentrations.) The
spectrum is similar to that of penicillins and are often used as penicillin substitutes In
addition,they are active against Mycoplasmae, Chlamydiae, Legionellae, gram positive
anaerobes etc. The newer agents like clarithromycin (Not indicated in goats and horses),
azithromycin, dirithromycin are found to be effective against opportunistic pathogens
:toxoplasma, cryptosporidia, H.pylori etc. They should not be used with chloramphenicol or
lincosamides.

Erythromycin: The spectrum is narrow- mostly gram positive organisms and a few gram
negative organisms. It the drug of choice in corynebacterial infections , respiratory , neonatal
ocular inflammation, or genital chlamydial infections . Erythromycin is not recommended in
adult horses (oral and systemic) and ruminants (oral). Erythromycin estolate, can produce
acute cholestatic hepatitis (fever, jaundice, impaired liver function), probably as a
hypersensitivity reaction. Dose: cattle: 8-15mg/kg,IM,bid; Foals: 25mg/kg,PO or IM, tid;
Sheep and swine: 2-6mg/kg, IM,sid

Tilmicosin recommended for treatment of pneumonia in cattle, sheep and pigs, associated
with Pasteurella, Actinobacillus, mycoplasma species. It is as effective or more effective than
other established treatments: ceftiofur, oxytetracycline, or florfenicol for treating: .bovine
respiratory disease. Injections to horses, goats, swine, or nonhuman primates can be fatal;
heart,the target of toxicity via depletion of cardiac intracellular calcium and thus
contraindicated in goats,. Dose: Cattle ,sheep: 10mg/kg, SC, q 72 h.

Tylosin is used to treat: swine dysentery, pleuropneumonia due to Haemophilus


parahemolyticus, colitis in dog, Mycoplasma canis and Mycoplasma haemocanis infection in
dog,cattle. It is used against gram positive bacteria for shipping stress, pink eye,footrot in
goats. Dosage:Kids: 1-2ml SC; Adults: 5ml per 100lb SC every 24 hours for 5 days.
Use a larger (18ga or 20ga) needle for this thickish medication.
Dose:Cattle: 10-20mg/kg,IM,bid; Pig: 10mg/kg, IM, bid

LINCOSAMIDES: bacteriostatic drug (particularly active against grampositive bacteria,


and mycoplasma, and good activity against anaerobic bacteria . Lincomycin has efficacy
against Erysipelothrix,, Leptospira pomona, Mycoplasma, (activity similar to that of
erythromycin,but less than that of other macrolides).Staphylococcu, and Streptococcus
species. Clindamycin has a spectrum of activity-Mycoplasam, anaerobes such as
Actinomyces,Bacteroides sp, Clostridium perfringens ..They are widely distributed in to
respiratory tissue, soft tissue and, bones; indicated for streptococci ,staphylococci and
anaerobic infections. In horses,rabbits, chinchillas, guinea pigs, neonates and hamsters:
lincosamides are contraindicated due to the risk of gastrointestinal adverse effects like
serious fatal enterocolitis and diarrhoea. Oral lincomycin in ruminants results in : anorexia,
ketosis, and severe diarrhoea. Antidiarrheals, adsorbent (kaolin/astringent)with oral
lincomycin significantly decrease absorption. Dose: Lincomycin: 10 mg/kg, IM, bid- Cattle,
sheep.

TETRACYCLINES: are broad-spectrum with activity against gram-positive and gram-


negative bacteria, including some anaerobes. They are also active against chlamydia,
mycoplasmas, some protozoa, and several rickettsiae, including Anaplasma, Ehrlichia, and
Haemobartonella. Oxytetracycline for medicated feed and soluble powder and tetracycline
soluble powderare indicated in the treatment of enteritis , pneumonia. Long-acting
oxytetracycline injection is indicated in the treatment of pododermatitis (‘foot rot’) caused by
susceptible Fusobacterium necrophorum. Oxytetracycline HCl injection s indicated in uterine
infections, skin, soft tissue infections, septic arthritis(joint ill). Antacids,Calcium supplements,
such as calcium carbonate, Iron supplements, Magnesium-containing laxatives, Sodium
bicarbonate;concurrent use with tetracyclines may result in formation of nonabsorbable
complexes; also, concurrent use within 1 to 3 hours of antacid or sodium bicarbonate
administration may result in decreased absorption of oral tetracyclines because of increased
intragastric pH.
AMINOGLYCOSIDES: Amikacin’s spectrum of activity include coverage against many
aerobic gram negative and some aerobic gram positive bacteria, including most species of E.
coli, Klebsiella, Proteus, Pseudomonas, Mycoplasma, and Staphylococcus. Several strains of
Pseudomonas aeruginosa, Proteus, and Serratia that are resistant to gentamicin will still be
killed by Amikacin (10mg/kg.IM,q24h ).

Amikacin is used clinically to treat serious gram negative infections in most species. Because
Neomycin is more nephrotoxic and less effective against several bacterial species than either
Gentamicin or Amikacin, its use is generally limited to the oral treatment of enteral infections
-colibacillosis (bacterial enteritis) caused by Escherichia coli . (20mg/kg.PO.q12h).
Gentamicin (1-2mg/kg,IV,IMq8h ) is effective against gastro-intestinal and respiratory
infections of cattle, calves, sheep, goats and swine, caused by bacteria such as E. coli,
Klebsiella, Pasteurella and Salmonella spp. These agents can cause:
nephrotoxicity,ototoxicity,neuromuscular blockade, facial edema, pain/inflammation at
injection site, peripheral neuropathy and hypersensitivity reactions

PENEMS (CARBAPENEMS): Carbepenems are a new class of beta-lactam antibiotics that


include imipenem-cilastatin sodium , meropenem, faropenem and ertapenem; the first two
currently approved for use in dogs only. Imipenem is a broad-spectrum antibiotic with
excellent activity against a variety of gram positive and gram negative organism (both
aerobic and anaerobic), by comparison to third and fourth generation cepahalosporins.. It is
resistant to most forms of beta-lactamase including that produced by staphylococcus. The
carbapenems are more rapidly bactericidal than the cephalosporins and less likely to induce
release of endotoxin in an animal from gram-negative sepsis. Resistance to carbapenems has
been extremely rare in veterinary medicine. The disadvantages of carbapenems include
induction of resistance, inconvenient administration, and high cost. Side effects: Allergy,
gastrointestinal disturbances: nausea and vomiting.,seizures, hypersalivation and
vocalization , indicating pain after IM amd SC administration in dogs was noticed. The
empirical dose in dogs and cats is 5-10mg/kg, IV or deep IM, every 8 hours ,and in horse :
10-20mg/kg, IV, every 6 hours . Meropenem, has antibacterial activity greater than
imipenem, with advantage over imipenem is that it is more soluble and can be administered
in less fluid volume and more rapidly. Dose in dog is 2-5mg/kg, slow IV (with IV fluids) ,
every 6 hours; 5 -10mg/kg, deep IM every 8 hours or 8-12 mg/kg SC, every 8 -12 hours.
Carbapenems are synergistic with aminoglycosides against P.aeruginosa.

METRONIDAZOLE: Nitroimidazoles with activity against trichomonads and amebae


include metronidazole, tinidazole, nimorazole, flunidazole, and ronidazole. Metronidazole and
nimorazole are effective in the treatment of giardiasis, while dimetridazole, ipronidazole, and
ronidazole control histomoniasis in poultry. Several nitroimidazoles have activity against
trypanosomes. The principal clinical indications for metronidazole include the treatment of
specific protozoal infections (amebiasis, trichomoniasis, giardiasis, and balantidiasis) and
anaerobic bacterial infections such as those that may be seen in abdominal abscesses,
peritonitis, empyema, genital tract infections, periodontitis, otitis media, osteitis, arthritis, and
meningitis, and in necrotic tissue; primarily used with other antibiotics to treat mixed bacterial
infections in which anaerobic bacteria are present.It is also used prophylactically after colic or
other abdominal surgery when mixed bacterial infections are a risk. Metronidazole is
generally given orally although it is also absorbed rectally. Rectal administration is
occasionally used in the very sick patient when anorexia and weight loss are a problem.
Dose: 15-25mg/kg, q6h; IV,IM,PO, IR; 20-25mg/kg,q12h; IV,IM,PO,IR ( in horses, dogs)

SUGGESTED EMPIRICAL ANTIBACTERIALS IN SMALL RUMUNANTS


BASED ON INFECTION SITE

Infection site First choice drugs Alternate choice drugs


Skin Amoxicillin-clavulanate Trimethoprim-sulfonamides
Cephalosporins Fluoroquinolones

Urinary Cephalosporins Trimethoprim-sulfonamides


(Genital ) tract Amoxicillin / Ampicillin Fluoroquinolone
Amoxicillin-clavulanate Tetracycline

Respiratory tract Amoxicillin-clavulanate Macrolides


Fluoroquinolones Aminoglycosides (amikacin,
Cephalosporins gentamicin)
Chloramphenicol
Extended-spectrum
cephalosporin (2nd/3rd generation)

Septicemia Amoxicillin-clavulanate Aminoglycoside


Cephalosporin Extended-spectrum
Fluroroquinolone cephalosporins

Bone and joint Cephalosporins Trimethoprim-sulfonamides


Amoxicillin-clavulanate Extended spectrum
cephalosporins
Fluoroquinolones,Clindamycin

CNS Penicillin G,Trimethoprim- Ceftriaxone, cefotaxime, ceftazidime,


sulfamethoxazole, Cefuroxime,Ceftizoxime
Ampicillin,(plus gentamicin) fluoroquinolones

Spectrum of activity of various antibacterial classes

Class Activity against Type of microorganism


Bacteria

Aerobic Anaerobic Myco Rickettsi Chlamydia Protozoa


a
Gram Gram Gram Gram plasma
- ve + ve -ve
+ ve

Aminoglycosides + + -- -- + -- -- --

Penicillins + + -- -- -- -- -- --

Potentiated + + + + -- -- -- --
penicillins
Cephalosporins + + + + -- -- -- --

Chloramphenicol + + + + + + + --

Lincosamides + + + + + -- -- +

Macrolides + -- + + + -- + --

Pleuromutilins + -- + + + -- + --

Tetracyclines + + + + + + + --

Fluorouinolones + + + + + + + --

Sulfonamides + + -- -- + -- + +

Trimethoprim + + -- -- -- -- -- +

Nitroimidazoles -- -- + + -- -- -- +

Polymixin -- + -- -- -- -- -- --

Bacitracin + -- + -- -- -- -- --

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