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.

Generation

Spectrum of activityGram Gram + ve -ve

β-lactamase stability

Examples

Oral Parenteral

First + + + + + CephalexinCefadroxilCefadrineCephradineCephaloglycin

Cefazolin

Cephapirin

Cefalonium

Cephalothin

Cefacetrile

Cefatrizine

Cephaloridine

Second + + + + + + Cefamandole Cefotiam Ceforanide Cefonicid Cefmetazole Cefranide Loracarbef Cefoxitin* Cefotetan*

* Cephamycins

Cefaclor

Cefuroxime axetil

Cefprozil

Cefuroxime

Third + / ++ + + + + + + Cefsulodin Ceforanide

Ceftiofur

Cefotaxime

Cefpodoxime proxetilCefixime Ceftibuten Cefdinir CefmenoximeCefditren pivoxil CefodizimeCefetamet

Cefmenoxime

Ceftriaxone

Ceftizoxime

Ceftazidime

Cefovecin

Cefoperazone Latamoxef (moxalactam)

Fourth + + / +++ + + + + + + + + CefmetazoleCefditoren

Cefepime

CefpiromeCefquinome

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

All cephalosporins

Anemia;,Hyperprothrombinemia, Thrombocytopenia, Platelet dysfunction

Anorexia, diarrhoea , vomiting (oral)

Thrombophlebitis

Abscess

Reversible on discontinuation

Administration with food

Careful aseptic administration

Horses cefpodoxime proxetil,cefotaxime

cefoxitin

cefazolin

Colic, diarrhea

Laminitis

Hypersensitivity

Seen with high doses

Cattle Ceftiofur SC route Local ear swelling, may develop a transciently drooping ear, medication leakage or bleeding from the site just after injection

Strict SC, Hygiene,Aseptic administration

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 cephalosporin

Dose (mg per kg)

Route Interval (Hour)

Major indications

Ceftiofur sodium,

Ceftiofur

HCL, 50mg/ml

Ceftiofur crystalline free acid suspension

1.1-2.2

6.6

15-20

IM ,SC

SC

IV,IM,SC

24

24

12

Acute metritis , Retained fetal membranes,

Bacterial pneumonia, bovine respiratory disease complex (shipping fever), Pododermatitis, acute bovine interdigital necrobacillosis , Severe coliform mastitis

Cefazolin

Cephapirin

Cefoperazone

Cefuroxime

Cephacetrile

Cephalothin

Ceftriaxone

Cefadroxil

Cephradine

Cefetamet

( calves)

Ceftazidime

10

200mg totaldose

250 mg Total dose

250 mg Total dose

250 mgTD

55

25-50

25

7

10

20-40

IM

Intramammary

Intramammary

Intramammary

Intramammary

SC

IM,IV

PO

PO

PO

IM

8

12

Single dose

Single dose

SD

6

24

12

12

24

12-24

bone, joint, respiratory, skin, soft tissue infections

Mastitis

Mastitis

Mastitis

Mastitis

skin, soft tissue infections

Serious complicated respiratory, CNS, Genitourinary tract infections

In preruminant calves only , for wound infections

Upper respiratory tract and urinary tract infections

Antipseudomonal

2. HORSES

Approved cephalosporin

Dose (mg per kg)

Route Interval (Hour)

Major indications

Ceftiofur sodium

Cefotaxime

2.2-5.5

20-30

IM,IV

IM,IV

24

8

Bone, joint, respiratory, skin, soft tissue, and urinary tract infections.

Neonatal sepsis and secondary bacterial

Cephradine

(foals)

Cefadroxil

(foals)

Cefazolin

Cephalexin

Ceftriaxone

Cefamandole

Cefoperazone

Cefoxitin

Cephalothin

Cephapirin

Cefpodoxime proxetil

Cefepime

10-20

10-20

10-20

25-33

25-50

10-30

30-50

20

10-30

20-30

50

5-10

2.2

IV

PO

IV

PO

IM,IV

IV,IM

IM.IV

IV,IM

IM,IV

IM,IV

PO

PO

IM

8

8-12

6-8

6

12-24

4-8

6-8

8

6

8-12

8-12

6-12

8

meningitis

bone, joint, respiratory, skin, soft tissue, and urinary tract infections

skin and soft tissue infections and urinary tract infections

prophylaxis of Perioperative infections

skin and soft tissue infections

bone, joint, respiratory, skin, soft tissue,CNS and urinary tract infections

General indications of respective generation cephalosporins

Gram negative or polymicrobial anaerobic infections

Susceptible bacterial infections

Serious respiratory infections, skin, soft tissue

Cefpirome

Ceftazidime

11

25-50

IM

IV,IM

8

8-12

Nosocomial and urinary tract infections

Antipseudomonal cephalosporin

3. DOGS

Approved cephalosporin

Dose (mg per kg)

Route Interval (Hour)

Major indications

Cefazolin

Cefaclor

Cefixime

Cefoxitin

Cefotetan

Ceftazidime

Cefpodoxime proxetil

10-30

15-30

5-10

10-20

15-30

30

25-50

5-10

IV,IM,SC

IV,IM,

PO

PO

IV,IM,SC

IM,IV

IM,IV,SC

PO

6-8

6-8

12-24

8-12

6-8

8

8-12

12

prophylaxis of Perioperative infections- including bone surgery

susceptible bacterial skin, and soft tissue infections

bone, bladder, respiratory ,skin and soft tissue e infections.

Gram negative polymicrobial anaerobeinfections

Gram negative or polymicrobial anaerobic infections

Major gram negative including Pseudomonal infections

Skin and soft tissue infections

Susceptible bacterial

Cephalothin

Cephradine

Cephalexin

Cefadroxil

Cefovecin

Cephaloglycin

Cephapirin

Cefamandole

Ceftriaxone

Cefoperazone

Cefotaxime

Ceftiofur sodium

Ceftizoxime

10-30

15-30

10-25

10-20

8

10-20

10-2010-30

15-50

20

20-40

2.2

25-40

IM,IV

PO

PO

PO

SC

IM,IV

8-12IM

IM,IV

IM

IV,IM

IM

IV,IM

4-8

12

8-12

12

14 Days

6-8

6-88

24

6-8

8-12

24

8-12

infections

skin and soft tissue infections

skin ,soft tissue nfections

skin ,soft tissue nfections

skin inf. (pyoderma),urinary tract infections

pyoderma

Staphylococcal infections

bone, joint, respiratory, skin, soft tissue,CNS and urinary tract infections

Antipseudomonal,

Multidrug resistant bacterial strains of Enterobacteiaceae family

Respiratory, skin, soft tissue, and urinary tract infections

Respiratory, skin, soft tissue, and urinary tract infections

Respiratory, skin, soft tissue, and urinary tract infections

Cefuroxime

Cefetamet

10-15

4-8

IV

PO

8-12

12-24

4. CATS

Approved cephalosporin

Dose (mg per kg)

Route Interval (Hour)

Major indications

Cephalexin

Cefotaxime

Cefadroxil

Ceftriaxone

10-30

20-40

10-20

15-50

IV,IM, SC

IV,IM

PO

IM, IV

6-8

8-12

12

24

Respiratory, skin, soft tissue, and urinary tract infections

Bone,respiratory, skin, soft tissue, and urinary tract infections

Skin and soft tissue and urinary tract infections

Respiratory, skin, soft tissue,CNS and urinary tract infections

5. PIGS

Approved cephalosporin

Dose (mg per kg)

Route Interval (Hour)

Major indications

Ceftiofur

(Free acid)

Ceftiofur crystalline oil suspension

(100mg/ml)

3-5

5

IM

IM

24

5days

Respiratory tract infections

6. POULTRY

Approved cephalosporin

Dose (mg per kg)

Route Interval (Hour)

Major indications

Cephalexin

Ceftiofur

(Free acid)

Cephalothin

25-50

1.3-2.6

100

PO

IM

IM

8-12

24

8-12

susceptible bacterial infections in cranes, ducks, emu, pigeons, and quails

Escherichia coli infections

susceptible bacterial infections in cranes, ducks, emu, pigeons, and quails

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