AN OVERVIEW OF CEPHALOSPORINS

IN VETERINARY MEDICINE

Cephalosporins are wide-spectrum β-lactum bactericidal antibiotics, relatively non-

toxic, with the chemical properties being similar to penicillins, but are comparatively
more stable to pH,temperature changes and β-lactamases. They were first introduced for
clinical use in the 1960s.

Cephalosporins are weak acidic drugs produced from Cephalosporium acremonium.

Structurewise, they contain a dihydrothiazine ring and a β-lactam ring having the common
7-aminocephalosporanic acid nucleus.Modifications of this acid nucleus and semisynthetic
sidechain substitutions produce differences in antibacterial spectra, β-lactamase
sensitivities and pharmacokinetic properties. Cephamycins are derived from Streptomyces
species or are synthetic derivatives produced by substituting oxygen for sulfur (methoxy
group) in the cephalosporin nucleus. (John F Prescott, 2006).

The mode of action of cephalosporins being bacterial cell wall synthesis inhibition is
similar to that of the penicillins. The site of action of beta-lactam antibiotics is the
penicillin-binding proteins (PBPs) on the inner surface of the bacterial cell membrane that
are involved in synthesis of the cell wall. In actively growing cells, the cephalosporins bind
to the PBPs within the cell wall and lead to interference in production of cell wall
peptidoglycans resulting in subsequent lysis of the cell in an isoosmotic environment. The
differences in affinity for the types of PBPs by different beta-lactam antibiotics and the
bacterial defense mechanisms explain the variations in bactericidal activity among
cephalosporins. (Donowitz GR and Mandell GL, 1988). Major adverse reactions to
cephalosporins are also similar to those experienced with penicillin. The free base acid
stable forms of cephalosporins are used for oral administration and sodium salt derivatives
are used for parenteral administration. Cephalosporins are well distributed in to most of the
body fluids and tissues such as the kidneys, lungs, joints, bone and biliary tract. However,
with the exception of some of the third generation agents, they penetrate poorly in to the
CSF.
Classification: Cephalosporins have been originally classified into three generations based
primarily on their spectrum of antibacterial activity (Caprile KA, 1988). An expanded
classification has been developed on the basis of antimicrobial activity, including β-lactamase
stability and pharmacological properties (Wise, 1997).
Generationwise, from first to fourth, the spectrum of activity against gram negative
organisms and the stability against β-lactamase increase commonly together with the same
or reduced spectrum of activity against gram positive organisms ,with the exception of fourth
generation agents, which have enhanced activity against gram positive ones. Some of the more
recently developed cephalosporins which may not easily fit into anyone of the generations are
usually included in the generation to which their antibacterial properties most closely
resemble. Most of the cephalosporins are usually active against beta haemolytic streptococci
and against beta lactamse producing staphylococci. Methicillin resistant Staphylococcus,
Mycobacteria and Enterococci spp are resistant to all cephalosporins.
Genera Spectrum of β- Examples
tion activity lactamase Oral Parenteral
Gram Gram stability
+ ve -ve
First + ++ + + Cephalexin Cefazolin
Cefadroxil Cephapirin
Cefadrine
Cephradine Cefalonium
Cephaloglycin Cephalothin
Cefacetrile
Cefatrizine
Cephaloridine
Second ++ ++ ++ Cefamandole Cefaclor
Cefotiam Cefuroxime
Ceforanide axetil
Cefonicid
Cefmetazole Cefprozil
Cefranide Cefuroxime
Loracarbef
Cefoxitin*
Cefotetan*
* Cephamycins
Third + / ++ +++ +++ Cefsulodin Ceftiofur
Ceforanide Cefotaxime
 Cefpodoxime Cefmenoxime
proxetil Ceftriaxone
Cefixime
Ceftibuten Ceftizoxime
Cefdinir Ceftazidime
Cefmenoxime
Cefditren pivoxil Cefovecin
Cefodizime Cefoperazone
Cefetamet Latamoxef
(moxalactam)
Fourth + + / +++ ++++ ++++ Cefmetazole Cefepime
Cefditoren Cefpirome
Cefquinome

First generation cephalosporins

They exhibit higher activity against gram positive bacteria including β-lactamase producing
S.aureus and moderate activity against certain nontransferable β-lactamase producing gram
negative Enterobacteriaceae and fastidious gram negatives. (Frank LA et al, 1993)
• Most effective against aerobic gram-positive cocci, such as Corynebacteria,
Streptococci, and Staphylococci, except methicillin-resistant Staphylococcus aureus and
are effective against several gram-negatives, such as E coli,
Actinobacillus,Proteus,Klebsiella,Salmonella,Shigella,Enterobacter,Haemophilus
influenzae, Pasteurella, and Proteus mirabilis
• Actinobacter, Citrobacter, indole-positive Proteus, and Pseudomonas are resistant.
• The agents under this group are generally susceptible to β-lactamases and are not as
effective as penicillins against anaerobes. Some anaerobic bacteria such as Peptococcus
and peptostreptococcus are susceptible, with the exception of betalactamase producing
Bacteroides and Clostridium difficile.
• Rapid absorption, with high bioavailibility, unaffected by the presence of food especially
in monogastric animals, whereas the absorption is poor and highly erratic in ruminants;
thus being used only in preruminant calves
• Wide distribution in extracellular fluid, but exhibit poor penetration across biological
membranes (including udder) and physiological barriers ( such as blood brain barrier)
 • They are apidly eliminated in urine, with the half life less than one hour except for
cefadroxil which has a longer half life in dogs
• Oral cephalexin, cefadroxil and parenteral cefazolin are the most commonly used first
generation cephalosporins, primarily for skin and soft tissue infections such as pyoderma
caused by streptococci and Staph. aureus, and bacterial endocarditis caused by
Streptococcus viridans and S .aureus. Cephalexin, the earlier drug of choice for
K.pneumoniae urinary tract infections (Ling and Ruby, 1983), has beeen used longterm
(30days) in the treatment of chronic S.intermedius pyoderma, is associated with increased
resistane.
• Higher doses of cefazolin and cephalexin have been commonly used to treat bone and
joint infections in the treatment of open fractures pre or postoperatively and infectious
conditions of the soft tissue like lymphadenitis, abscesses, pharyngitis etc respectively.
Cefazolin may be used subconjuctivally to treat bacterial corneal ulcers in combination
with an aminoglycoside or fluoroquiniolones such as ciprofloxacin. (Thomas.J.Kern,
2004).
• Due to the potent nephrotoxic effect, cephaloridine is no longer used clinically.
Second generation cephalosporins
Use of these antimicrobials is generally reserved for infections that are resistant to first-
generation cephalosporins. Intrarmuscular (IM) Injections are painful, and may cause
thrombophlebitis when administerd intravenously.The broader spectrum of antibacterial
activity may lead to gastrointestinal disturbances and superinfection by resistant
microorganisms including yeasts

• They are as efficacious as or slightly less efficacious than first-generation

cephalosporins against gram-positive pathogens; however, this lack of efficacy is
primarily against S. aureus and S. intermedius

• Greater spectrum of activity than first generation cephalosporins against gram-

negative organisms such as H.influenze, Enterobacter aerogenes and Neisseria species
(Donowitz GR and Mandell GL, 1988).

• Generally these generation agents are ineffective against P. aeruginosa,

Enterococcus Actinobacter species and anaerobes, except cefoxitin and cefotetan,
 which are technically cephamycins, are effective against anaerobic gram negative
organisms, including Bacteroides fragilis, but not active against Pseudomonas.

• They are relatively resistant to β-lactamases, with poor blood-brain barrier

penetrating ability. They exhibit pharmacokinetic properties similar to those of the first
generation cephalosporins.

• Cefuroxime axetil, the only second generation cephalosporin known to adequately

penetrate into cerebrospinal fluid, is an ester of cefuroxime which is hydrolysed in the
intestinal mucosa and liver to yield active drug producing good bioavailability.

• Cefoxitin, valued particularly for its broad activity against anaerobes and
enterobacteriaceae, is used in the treatment of severe mixed infections with anaerobes in
conditions like aspiration pneumonia, bite infections, ruptured intestine gangrene,
peritonitis and pleuritis. ( Petersen SW and Rosin E., 1993)

• Cefuroxime is effective for short lasting dry cow therapy and clinical mastitis, has
been also used to treat otitis media and upper respiratory tract infections in humans.

Third generation cephalosporins

They are not the first choice antimicrobial agents in animals and their use should be
reserved for situations, where other alternatives are not available. They are used to treat bone
and joint infections, pneumonia, enteritis, endocarditis, rhinosinusitis as well as cystitis;

• High antibacterial activity and broad resistance to β-lactamases, though, are less
effective than 1st and 2nd generation cephaosporins against gram positive bacteria
(Mark.G.Papich , 1984).

• They are the most effective of the cephalosporins against antibiotic-resistant

gram-negative aerobes, effective against Proteus vulgaris, Enterobacter,Citrobacter,
Haemophilus,Neisseria and Moraxella species (Caprile KA., 1988; Papich MG,
1984)

• Moderate activity against gram positive bacteria and are inferior in activity against
staphylococci, although they are generally effective against penicillin resistant
Streptococcus pneumoniae.
• Ceftriaxone ceftizoxime, cefotaxime and ceftazidime are the only cephalosporins
that consistently reach effective concentration in the central nervous system due to
their ability to cross the blood-brain barrier and are effective in therapy for susceptible
pathogens in bacterial meningitis.

• Ceftriaxone is extensively protein bound, with the half life of 8 hours needing
once daily dosing. The biliary elimination occurring with ceftriaxone and latamoxef
makes them to be avoided or used cautiously in species with expanded large intestines (
adult horse)

• Cefpodoxime is stable in the presence of many beta-lactamase enzymes, and is

effective against many beta-lactamase producing bacteria; however, it is not active
against most obligate anaerobes. It has been approved for use in skin infections in dogs.

• Ceftazidime and Cefoperazone, are highly active against Pseudomonas

aeruginosa among all cephalosporins, (Moore KW et al, 2000) compared to
Ceftriaxone and Ceftizoxime, which also have antipseudomonal activity to some
extent. Ceftazidime may be reconstituted with1% lignocaine for IM injection to reduce
pain. In the treatment of endopthalmitis, ceftazidime has been suggested as an
alternative for intravitreal amikacin to cover gram negative organisms including
P.aeruginosa, because of high therapeutic index with a lower risk of retinal toxicity
than amikacin. (Thomas.J.Kern, 2004). Cefoperazone is contraindicated in the
herbivore species with an expanded bowel. (horses). It has been used by intramammary
route for treating coliform mastitis.

• Cefovecin differs from other similar cephalosporin antibiotics as it stays in the

dog’s or cat’s body for a very long time after it has been injected. It is generally given
as a single injection, and the effect of the injection lasts for up to14 days. Depending on
the infection concerned, the injection can be repeated if necessary , upto three
times( EPAR Report, 2006)

Cefovecin is rapidly and completely absorbed, reaching peak plasma

concentration within hours and is fully available following parenteral
administration.The elimination half life of 5.5days in canine plasma makes the
molecule suitable for a long interval between administrations. (Stegemann MR et
 al, 2006). The invitro activity of cefovecin sodium is similar to that of
cefpodoxime proxetil. (Stegemann MR et al, 2006) It has been effectively
used in dogs and cats to treat skin and soft tissue infections; such as wounds,
abscesses and pyoderma and also urinary tract infections.

Cefovecin should not be used in dogs or cats of less than 8 weeks old, or in dogs
or cats with severe kidney problems (renal dysfunction). As no studies have been
made in breeding animals and it has an exceptionally long duration in the body, it
should not be used in pregnant or lactating dogs or cats and treated animals should
not be used for breeding for 12 weeks after the last injection.

• Ceftiofur is a cephalosporin that does not clearly fit into the third generation
cephalosporin, has been called as a new generation cephalosporin

It has broader gram-positive activity, including good activity against

Streptococci, and less activity against Pseudomonas than other third-generation
cephalosporins. It is active against beta-lactamase–producing strains as well as
anaerobes, such as Fusobacterium necrophorum and Bacteroides
melaninogenicus

The tissue distribution of ceftiofur has shown it to be unique, although the way
in which this affects efficacy in the extra-label treatment of infections is not
known. It is found in endometrial tissue within four to eight hours of
subcutaneous administration to postpartum cows. The highest concentration of
ceftiofur are found in kidneys after intramuscular administration to pigs and
sheep, followed in pigs by the injection sites, lungs, liver, and muscle (Beconi
Barker MG et al, 1995) .

Rapidly metabolized by the plasma esterases in to active metabolite

desfuroylceftiofur; both the parent compound and the active metabolite being
highly protein bound, resulting in long elimination half life; thus allowing once
daily dosing.

It is available in three formulations: ceftiofur crystalline freee acid, ceftiofur

hydrochloride and ceftiofur sodium salts. The crystalline free acid form is an
injectable suspension for cattle and pigs at 200mg/ml and 100mg/ml ceftiofur
 equivalent concentration respectively, which can be administered IM and
subcutaneously. The withdrawl period is zero and three days for milk and meat
respectively.

The injectable crystalline oil suspension formulation of ceftiofur is

administered subcutaneously in cattle, in the middle third of the posterior aspect of
the ear or in the posterior aspect of the ear where it attaches to the head (base of
the ear), avoiding all the blood vessels. This gives plasma concentrations above
MIC of common respiratory tract pathogens for about six days. In swine, this is
administered to the post auricular region of the neck intramuscularly; the volume
of injection at each site being a maximum of 2ml.

Ceftiofur is indicated for treatment of bronchopneumonia in cattle, especially

when 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 administered intramammarily for treating coliform

mastitis as an extralabel use and approved for treatment of urinary tract infections
in dogs. (Mark G Papich, 2007). Cutaneous drug reaction to ceftiofur,
characterised by hair loss and pruritus has been described in cows. (John F
Prescott., 2006). Toxicity studies have shown that horses tolerate doses up to 11
mg/kg q 24 h IM, with pain at the injection site and decreased feed consumption
being the most commonly observed adverse effect at the highest dose (Mark G.
Papich, 2001).

• Because of the broad antibacterial activity of these cephalosporins,

gastrointestinal disturbances snd superinfection by the resistant organisms, including
yeasts, can occur.

• The excretion of these generation agents is largely through urine, though

ceftriaxone and latamoxef are excreted in bile, making them to be avoided or used
cautiously if at all in horses.
Fourth generation cephalosporins
They exhibit extended spectrum of activity than third generation agents, against both
gram positive and gram negative organism and increased stability against hydrolysis by beta-
lactamases
• High activity against Enterobacteriaceae, moderate activity against P.aeruginosa and
enhancedactivity against staphylococci
• Generally indicated in various infections where resistance to β-lactum antibiotics is
expected. They exhibit excellent penetration ability in to CSF and possess chemical
characteristics that may lead to reduced development of resistance by gram negative
organisms. However, they are not indicated for enteric pathogens causing food-borne
disease
• Cefepime and cefpirome are used presently only in humans (Bryskier et al, 1994).
• Cefquinome, an extended spectrum beta-lactam, is used presently only in veterinary
medicine. It is safe, well tolerated and used parenterally for the treatment of bovine
respiratory disease (BRD and also used intrmammarily for mastitis.
Pharmacokinetics
The pharmacokinetic characteresics of cephalosporins are typical of beta lactams, with an
elimination half life of 1-2 hrs for majority of the drugs.

Absorption: The absorption is good after oral administration especially in monogastric

animals, which may be enhanced by formulatrion as prodrugs which are metabolized to the
active compound in the body. The absorption of most of the cephalosporins is unaffected by
the presence of food, except for cephradine for which it may be delayed. The poor oral
absorption in horses makes the amount of active drug in the intestine that could potentially
disturb the intestinal bacteria. Foals absorb these drugs better the adults. Ceftiofur sodium, the
only registered injectable cephalosporin for horses, is well tolerated with the only adverse
effect being decreased food consumption attributed to changes in the gastrointestinal bacterial
flora. (Mark.G.Papich, 2003).

Distribution: Cephalosporins distribute very well into most of the body tissues and fluids
including bone, pleural fluid, pericardial fluid and synovial fluid. Higher levels are found in
inflamed than in normal bone. Very high levels are found in the urine, but they penetrate poorly
into prostatic tissue and aqueous humor Cephalosporins can be found in bile fluid if no biliary
obstruction is present. The passage across biological or physiological membranes is generally
poor. Most of the cephalosporins have poor penetration of the blood-brain barrier, (Abdel-
Rahman SM et al, 2000) except for some of the third-generation antibiotics like cefotaxime,
ceftriaxone ceftizoxime and ceftazidime have been shown to adequately penetrate in to
cerebrospinal fluid in normal meninges. Therapeutic concentration of cefotaxime, moxalactam,
cefuroxime, ceftizoxime, ceftazidime and ceftriaxone can be found in the CSF after parenteral
dosing in patients with inflamed meninges. Protein binding of the drugs is widely variable and
species specific. Cephalosporins tend to bind to equine and canine plasma proteins less than
human plasma proteins. Also, Cephalosporins enter milk in low concentrations. All
cephalosporins cross the placenta with no adverse teratogenic or fetotoxic effects, except a
slight decrease in fetal weight which is noticed in laboratory animals. The high level of
protein binding by ceftiofur in adult animals causes its distribution to differ
from that of other cephalosporins. Also, the primary metabolite of ceftiofur,
desfuroylceftiofur, has a reactive sulfhydryl group that forms reversible
covalent bonds with plasma and tissue proteins. (Jaglan PS et al, 1994) .
Free concentrations of ceftiofur and its active metabolites tend to be lower
than expected when dosages shown to be effective in the treatment of a
disease are administered, possibly because of their unique protein binding
abilities.

The distribution of ceftiofur into other tissues has also shown it to be

unique, Ceftiofur is found in endometrial tissue within four to eight hours of
subcutaneous administration in postpartum cows.(Okker H et al, 2002).
The highest concentration of ceftiofur is found in kidneys, followed by the
injection sites, lungs, liver, and muscle after intramuscular administration to
pigs and sheep. (Beconi Barker MG et al, 1995). The distribution of ceftiofur
into milk is insufficient to produce therapeutic concentrations when the
medication is administered at recommended dosages. (Owens WE, et al,
1990). However, the survival rate of cattle with severe coliform mastitis can
be increased with systemic ceftiofur administration, a result attributed to
controlling the effects of bacteremia. (Erskine RJ et al, 2002).
Biotransformation: Biotransformation of cephalosporins is not clinically significant from the
patient’s point of view. Cefotaxime, cephalothin, and cephapirin undergo biotransformation in
the liver to desacetyl derivatives. Cefpodoxime proxetil is a prodrug that is converted by de-
esterization in the gastrointestinal tract to an active metabolite, cefpodoxime. The metabolites
of many cephalosporins may retain some of the antibacterial activity.

Elimination: For most of the cephalosporins, elimination is by renal tubular secretion and/or
glomerular filtration.Thus dose must be adjusted in case of severe renal failure/insufficiency to
guard against accumulation and toxicity. Cefoperazone, Cefamandole and Ceftriaxone are
eliminated through bile into the feces; and are frequently used in patients with renal
insufficiency

Adverse Effects: Adverse effects with the cephalosporins are usually not serious and
relatively have a low frequency of occurrence.

• Gastrointestinal disturbances: Anorexia, vomiting and diarrhoea are the

common signs. Administering the drug with a small meal/food may help alleviate these
symptoms. Because the cephalosporins may also alter gut flora, antibiotic-associated
diarrhoea can occur as well as the selection out of resistant bacteria residing in the colon
of the animal.

• Hypersensitivity reaction: Hypersensitivity reactions unrelated to dose can occur

with these agents and can be manifested as urticarial rashes, fever, eosinophilia,
angioedema, lymphadenopathy serum sickness, or acute anaphylaxis which may be
exhibited as allergic response. The incidence of allergic reactions is one to two percent
in patients without a history of allergy to penicillins. Cephalosporins should be
avoided or used with caution in individuals who are allergic to penicillins, as 5 to 15%.
of penicllin sensitive individuals show cross sensitivity with cephalosporins. The
incidence of cross-reactivity in veterinary patients is unknown. Cephalosporins are
contraindicated in patients with a history of hypersensitivity to them. They should be
used cautiously in patients with documented hypersensitivity to other beta-lactam
antibiotics viz: penicillins, penems, monobactams.

• Bleeding disorders: Some of the second and third generation cephalosporins

(Cefotetan, Ceftazidime, Cefamandole and Cefoperazone) have been associated with an
increased risk of bleeding due to a decrease in prothrombin activity and anti- vitamin K
effects. Critical illness, poor nutritional status, and the presence of liver disease may be
more important risk factors for hypoprothrombinemia and bleeding; because 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.

• Renal insufficiency : Nephrotoxicity may occur in patients with renal

insufficiency, receiving the full dosage of cephalosporins; and thus dosage needs to
be adjusted

• Pain at the injection site: Although this effect is less so with cefazolin than other
agents. sterile abscesses or other severe local tissue reactions with IM injections are also
possible but are much less common. Thrombophlebitis is also possible after IV
administration of these drugs.

• A Disulfiram-like Effect: When cefamandole, cefotetan, moxalactam,

cefoperazone are ingested with alcohol or alcohol containing medications, this effect if
seen. These cephalosporins contain the N methylthiotetrazole side chain [NMTT],
which blocks the second step in alcohol oxidation resulting in acetaldehyde
accumulation and toxicity

• Other effects: Some other adverse effects noticed in humans include eosinophilia,
hearing loss (cefuroxime) seizures, especially with high doses and in patients with renal
function impairment. The adverse effects of some of the cephalosporins noticed in
animals are given in the table below. (John F Prescott, 2006)

Species Agent Adverse effect Remarks

Dogs Ceftiofur Anemia;,Hyperprothrombinemia, Reversible on
Thrombocytopenia, Platelet discontinuation
dysfunction
All cephalosporins
Anorexia, diarrhoea , vomiting Administration
(oral) with food
Thrombophlebitis Careful aseptic
Abscess administration
Horses cefpodoxime Colic, diarrhea
 proxetil,cefotaxime Seen with high
doses
cefoxitin Laminitis
cefazolin Hypersensitivity
Cattle Ceftiofur SC route Local ear swelling, may develop Strict SC,
a transciently drooping ear, Hygiene,Aseptic
medication leakage or bleeding administration
from the site just after injection

Incompatibilities: The admixture of any cephalosporin with other medications in the

same syrienge is not recommended. The admixture of beta-lactam antibacterials (penicillins
and cephalosporins) and aminoglycosides may result in substantial mutual inactivation and
therefore should not be mixed in the same syrienge, intravenous bag or bottle.
Laboratory value alterations : There may be alteration in the laboratory values of

the patient receiving cephalosporin therapy. Some of the laboratory values affected were 1.
False-positive or false negative glucosuria (cephalexin) .2.Increased urine ketone values 3.
Elevated serum and urine creatinine levels 4. False-positive Proteinuria (cefamandole) .5.
Prolonged clotting time

Interactions

• Food: Administration of oral cephalosporins, such as cefadroxil, with food decrease the
nausea in those animals prone to the side effect; administration of cefixime with food can
decrease the bioavailability by one half; the absorption of cephalexin is not affected by
food. However, due to the adverse effects like diarrhoea and vomiting associated with
most of the orally administered cephalosporins, it may be desirable to administer them
along with food.

• Aminoglycosides: Although cephalothin has been associated with an increased risk of

nephrotoxicity when administered with an aminoglycoside, this interaction may not apply
to other cephalosporins. It has been shown that most of the cephalosporins demonstrate
synergistic activity when combined with an aminoglycoside, and often combined in the
treatment of febrile illness in neutropenioc patients. Combination of cefepime with
aztreonam is synergestic against P.aeruginosa.
• Probenecid : Probenecid, administered concurrently with a cephalosporin will inhibit
renal tubular secretion and in some cases increase the serum concentrations and prolong
the serum half-life of the cephalosporins, including cefadroxil, cefoxitin, cephalothin, and
cephapirin; probenecid has not been shown to alter the renal tubular secretion of ceftiofur
in dairy cattle or of cefazolin in mares

• Antacids and H2-receptor antagonists: They decrease the absorption and peak plasma
levels of cephalosporins and thus should not be taken within 1 hour of taking these
antacids.

• Anticoagulants: Coumarin- or indandione-derivative, or Heparin or Thrombolytic agents,

concurrent use of these medications may increase the risk of bleeding/haemorrhage
associated with cephalosporins because of the Nmethylthiotetrazole [NMTT] side chain
on these medications. Dosage adjustments of anticoagulants may be necessary during and
after therapy with cephalosporins having NMTT side chain

• Nephrotoxic medications: Cephalothin has been associated with an increased incidence

of nephrotoxicity when used concurrently with aminoglycosides; this effect has rarely
been seen with other cephalosporins used at appropriate doses. The potential for increased
nephrotoxicity exists when cephalosporins are used with other nephrotoxic medications,
such as loop diuretics, especially in patients with pre-existing renal function impairment;
renal function should be monitored carefully in patients receiving cephalosporins and
aminoglycosides concurrently.

• Platelet aggregation inhibitors: Hypoprothrombinemia induced by large doses of

salicylates and the gastrointestinal ulcerative or hemorrhagic potential of nonsteroidal
anti-inflammatory drugs, salicylates, or sulfinpyrazone may increase the risk of
hemorrhage if used concurrently with cephalosporins

DOSAGES AND INDICATIONS OF THE CEPHALOSPORINS

APPROVED FOR VETERINARY USE
1. CATTLE SHEEP AND GOATS

Approved Dose (mg Route Interval Major indications

cephalosporin per kg) (Hour)
Ceftiofur 1.1-2.2 IM ,SC 24 Acute metritis , Retained
sodium,
Ceftiofur fetal membranes,
HCL, 50mg/ml Bacterial pneumonia, bovine
respiratory disease complex
(shipping fever),
Ceftiofur 6.6 SC 24 Pododermatitis, acute
crystalline free bovine interdigital
acid suspension necrobacillosis , Severe
15-20 IV,IM,SC 12 coliform mastitis
Cefazolin
bone, joint, respiratory, skin,
10 IM 8 soft tissue infections
Cephapirin
200mg Intramammary 12 Mastitis
totaldose Mastitis
250 mg Intramammary Single
Cefoperazone Total dose
dose
Mastitis

Cefuroxime 250 mg Intramammary

Total Single Mastitis
Cephacetrile dose
dose
Intramammary
250 SD
Cephalothin mgTD
SC skin, soft tissue infections
Ceftriaxone 55 6
25-50 IM,IV
24
Serious complicated
respiratory, CNS,
Genitourinary tract
Cefadroxil infections

Cephradine 25 PO In preruminant calves only ,

12 for wound infections
7 PO
12
Cefetamet
( calves) 10 PO
24 Upper respiratory tract and
Ceftazidime urinary tract infections
20-40 IM
12-24 Antipseudomonal
2. HORSES

Approved Dose (mg per Route Interval Major

cephalosporin kg) (Hour) indications
Ceftiofur 2.2-5.5 IM,IV 24 Bone, joint,
sodium respiratory,
 skin, soft
tissue, and
urinary tract
infections.
Cefotaxime Neonatal
20-30 IM,IV 8 sepsis and
secondary
bacterial
Cephradine meningitis
(foals) 10-20 IV 8 bone, joint,
respiratory, skin,
soft tissue, and
urinary tract
infections
Cefadroxil
skin and soft
(foals) 10-20 PO 8-12
tissue infections
and urinary tract
Cefazolin infections

10-20 IV 6-8 prophylaxis of

Perioperative
infections
Cephalexin skin and soft
25-33 PO 6 tissue infections
Ceftriaxone bone, joint,
respiratory, skin,
25-50 IM,IV 12-24 soft tissue,CNS
and urinary tract
infections
Cefamandole
General
10-30 IV,IM 4-8
indications of
Cefoperazone respective
30-50 IM.IV 6-8 generation
cephalosporins
Gram
Cefoxitin negative or
20 IV,IM 8 polymicrobial
anaerobic
infections
Cephalothin
10-30 IM,IV 6

Susceptible
Cephapirin bacterial
 20-30 IM,IV 8-12 infections
50 PO 8-12
Cefpodoxime
proxetil 5-10 PO 6-12 Serious
Cefepime respiratory
infections, skin,
2.2 IM 8 soft tissue
Cefpirome Nosocomial and
urinary tract
11 IM 8 infections
Ceftazidime

25-50 IV,IM 8-12 Antipseudomonal

cephalosporin

3. DOGS

Approved Dose (mg per Route Interval Major indications

cephalosporin kg) (Hour)
Cefazolin 10-30 IV,IM,SC 6-8 prophylaxis of
Perioperative
infections- including
bone surgery
Cefaclor susceptible bacterial
15-30 IV,IM, 6-8 skin, and soft tissue
infections
bone, bladder,
respiratory ,skin and
Cefixime 5-10 PO 12-24 soft tissue e
infections.
Gram negative
polymicrobial
anaerobeinfections
10-20 PO 8-12
Cefoxitin
15-30 IV,IM,SC 6-8 Gram negative or
polymicrobial
30 IM,IV 8 anaerobic
Cefotetan infections

Major gram
negative including
 Pseudomonal
25-50 IM,IV,SC 8-12 infections
Ceftazidime
Skin and soft tissue
infections

5-10 PO 12 Susceptible bacterial

Cefpodoxime infections
proxetil

10-30 IM,IV 4-8 skin and soft tissue

Cephalothin infections

15-30 PO 12 skin ,soft tissue

Cephradine nfections
skin ,soft tissue
nfections
10-25 PO 8-12
skin inf.
Cephalexin (pyoderma),urinary
tract infections
10-20 PO 12
Cefadroxil pyoderma

8 SC 14 Days
Cefovecin Staphylococcal
infections
10-20 IM,IV 6-8
Cephaloglycin
bone, joint,
10-20 8-12 6-8 respiratory, skin, soft
Cephapirin 10-30 IM 8 tissue,CNS and
urinary tract
Cefamandole
infections
15-50 IM,IV 24
Ceftriaxone

Antipseudomonal,
Multidrug resistant
bacterial strains of
Enterobacteiaceae
20 IM 6-8 family
Cefoperazone
Respiratory, skin, soft
tissue, and urinary
tract infections
Respiratory, skin, soft
20-40 IV,IM 8-12 tissue, and urinary
Cefotaxime tract infections
Respiratory, skin, soft
2.2 IM 24 tissue, and urinary
Ceftiofur
tract infections
sodium
25-40 IV,IM 8-12

Ceftizoxime
10-15 IV 8-12
Cefuroxime

4-8 PO 12-24
Cefetamet

4. CATS

Approved Dose (mg per Route Interval Major indications

cephalosporin kg) (Hour)
Cephalexin 10-30 IV,IM, SC 6-8 Respiratory,
skin, soft tissue,
and urinary tract
infections
Cefotaxime Bone,respiratory,
20-40 IV,IM 8-12 skin, soft tissue,
and urinary tract
infections
Cefadroxil 10-20 PO 12 Skin and soft tissue
and urinary tract
infections
Respiratory, skin,
Ceftriaxone 15-50 IM, IV 24 soft tissue,CNS and
urinary tract
infections
5. PIGS

Approved Dose (mg per Route Interval Major indications

cephalosporin kg) (Hour)
Ceftiofur 3-5 IM 24
(Free acid) Respiratory tract
 Ceftiofur 5 IM 5days infections
crystalline oil
suspension
(100mg/ml)

6. POULTRY

Approved Dose (mg Route Interval Major indications

cephalosporin per kg) (Hour)
Cephalexin 25-50 PO 8-12 susceptible bacterial
infections in cranes,
ducks, emu, pigeons, and
quails
Ceftiofur 1.3-2.6 IM 24 Escherichia coli
(Free acid) infections

IM 8-12 susceptible bacterial

infections in cranes, ducks,
Cephalothin 100 emu, pigeons, and quails

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