There are dozens of different cephalosporin drugs available for either human or veterinary use and more are added every year. The cephalosporin class of antibiotics is beta-lactams and so is distantly related to the penicillins. They are usually divided into three classifications referred to as generations. The spectrum of activity is different for each of these generations and the third generation generally have the widest spectrum of activity. There is one-third generation cephalosporin that is approved for use in the horse, Naxcel. However the generally excellent spectrum of activity and lower toxicity of this group of drugs has led to the experimentation of other third generation cephalosporins usually replacing the aminoglycosides in the treatment of mixed and gram negative infections. This article discusses the characteristics of this group of antibiotics including dosage information on Cephalosporin, Cefadroxil (Cefa-Tabs), Cefazolin (Ancef, Kefzol), Cefepime, (Maxipime), Cefoxitin (Mefoxin), Cefotaxime (Claforan), Ceftiofur, (Naxcel), Cephapirin (generic and Cefadyl).

Cephalosporins are bactericidal antibiotics and act by inhibiting mucopeptide synthesis in the cell wall. Like other beta-lactam antibiotics, cephalosporins are generally considered to be more effective against actively growing bacteria. The spectrum of activity is different for each of the generations with first most active against gram positives, the second has increased efficacy against gram negatives, and the third generation generally have the widest spectrum of activity. Since many common infections of the horse (Strangles, wounds, etc.) involve gram positive organisms, the third generation cephalosporin like Naxcel may not be a first choice for many of these type infections.

More Information on NAXCEL® Rx Pharmacia & Upjohn Cephalosporin(s) brand of ceftiofur sodium sterile powder NADA No.: 140-338 Active Ingredient(s): Each mL of the reconstituted drug contains ceftiofur sodium equivalent to 50 mg ceftiofur. The pH was adjusted with sodium hydroxide and monobasic potassium phosphate. Indications: For intramuscular injection in horses. NAXCEL® Sterile Powder is indicated for treatment of respiratory infections in horses associated with Streptococcus zooepidemicus . Pharmacology: NAXCEL® Sterile Powder contains the sodium salt of ceftiofur which is a broad spectrum cephalosporin antibiotic active against gram-positive and gram-negative bacteria including b -lactamase-producing strains. Like other cephalosporins, ceftiofur is bactericidal in vitro , resulting from inhibition of cell wall synthesis. Chemical Name of Ceftiofur Sodium: 5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[[(2-amino-4-thiazolyl)(methoxyimino)-acetyl]amino]-3-[[(2-furanyl-carbonyl)thio] methyl]-8-oxo-, monosodium salt, [6R-[6 a , 7 b (Z)]]- Clinical Microbiology: Ceftiofur has demonstrated in vitro and in vivo activity against Streptococcus zooepidemicus , a major bacterial pathogen associated with equine respiratory infections. The drug also demonstrated in vitro activity against Pasteurella spp., Streptococcus equi, S equisimilis, Actinobacillus spp. and Moraxella spp., bacterial pathogens also associated with equine respiratory disease. The clinical significance of this in vitro activity is not known. Laboratory Microbiology: Ceftiofur has demonstrated in vitro activity against other gram-negative pathogens, such as E coli, P mirabilis, P vulgaris, Klebsiella pneumoniae/oxytoca and Salmonella typhimurium and against gram-positive pathogens such as Streptococcus bovis, Staphylococcus intermedius, S xylosus, S simulans, S epidermidis and beta hemolytic streptococci. Ceftiofur was effective when tested in a variety of mouse disease models involving E coli, Pasteurella haemolytica, Haemophilus somnus, Pasteurella multocida or Salmonella typhimurium . However, the clinical significance of these findings in horses is not known. Dosage and Administration: Administer to horses at a dosage of 1.0 to 2.0 mg ceftiofur per pound of body weight (2-4 mL reconstituted sterile solution per 100 lb body weight). A maximum of 10 mL may be administered per injection site. Treatment should be repeated at 24-hour intervals, continued for 48 hours after clinical signs have disappeared and should not exceed 10 days. Administration: Reconstituted NAXCEL® Sterile Powder is to be administered by intramuscular injection only. Reconstitution of the Sterile Powder: NAXCEL® Sterile Powder should be reconstituted as follows: 1 gram vial - Reconstitute with 20 mL Sterile Water for Injection. Each mL of the resulting solution contains ceftiofur sodium equivalent to 50 mg ceftiofur. 4 gram vial - Reconstitute with 80 mL Sterile Water for Injection. Each mL of the resulting solution contains ceftiofur sodium equivalent to 50 mg ceftiofur. Withdrawal Time: Residue Warnings: Not for use in horses intended for human consumption. Contraindication(s): As with all drugs, the use of NAXCEL® Sterile Powder is contraindicated in animals previously found to be hypersensitive to the drug. Precaution(s): Store unreconstituted product at controlled room temperature 20? to 25?C (68? to 77?F) [see USP]. Store reconstituted product either in a refrigerator 2? to 8?C (36? to 46?F) for up to 7 days or at controlled room temperature 20? to 25?C (68? to 77?F) [see USP] for up to 12 hours. Reconstituted NAXCEL® Sterile Powder can be frozen for up to 8 weeks without loss in potency or other chemical properties. Carefully thaw the frozen material under warm to hot running water, gently swirling the container to accelerate thawing. The frozen material may also be thawed at room temperature. Protect from light. Color of the cake may vary from off-white to a tan color. Color does not affect potency. Caution(s): Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. The safety of ceftiofur has not been determined for horses intended for breeding. The administration of antimicrobials to horses under conditions of stress may be associated with acute diarrhea that could be fatal. If acute diarrhea is observed, discontinue use of this antimicrobial and initiate appropriate therapy. Warning(s): Not for human use. Keep out of reach of children. Penicillins and cephalosporins can cause allergic reactions in sensitized individuals. Topical exposure to such antimicrobials, including ceftiofur, may elicit mild to severe allergic reactions in some individuals. Repeated or prolonged exposure may lead to sensitization. Avoid direct contact of the product with the skin, eyes, mouth, and clothing. Persons with a known hypersensitivity to penicillin or cephalosporins should avoid exposure to this product. In case of accidental eye exposure, flush with water for 15 minutes. In case of accidental skin exposure, wash with soap and water. Remove contaminated clothing. If allergic reaction occurs (e.g., skin rash, hives, difficult breathing), seek medical attention. The material safety data sheet contains more detailed occupational safety information. To report adverse effects in users, to obtain more information or obtain a material safety data sheet, call 1-800-253-8600. Residue Warnings: Not for use in horses intended for human consumption. Toxicology: Animal Safety: In a safety study, horses received a daily intramuscular injection of either 0 mg/lb/day (saline control), 1.0 mg/lb/day (50 mg/mL), 3.0 mg/lb/day (100 mg/mL), or 5.0 mg/lb/day (200 mg/mL) of an aqueous solution of ceftiofur sodium for 30 or 31 days. Ceftiofur sodium was well tolerated when administered intramuscularly to male and female horses at doses up to 5.0 mg/lb/day for 30 or 31 days. No clinical evidence of irritation was noted at any dose. The drug-related changes detected in this study were limited to a transient decrease in food consumption in horses receiving 3.0 or 5.0 mg/lb/day ceftiofur, and general mild skeletal muscle irritation at the injection sites which resolved by regeneration of muscle fibers. In a tolerance study, horses received a single daily intravenous infusion of either 0 (saline), 10.0 or 25.0 mg/lb/day of an aqueous solution (50 mg/mL) of ceftiofur for 10 days. The results indicated that ceftiofur administered intravenously at a dose of 10.0 or 25.0 mg/lb/day apparently can change the bacterial flora of the large intestine thereby leading to inflammation of the large intestine with subsequent diarrhea and other clinical signs (loose feces, eating bedding straw, dehydration, rolling or colic and a dull, inactive demeanor). Decreased food consumption, a loss of body weight, hematologic changes related to acute inflammation and stress, and serum chemistry changes related to decreased food consumption and diarrhea were also associated with treatment at these doses. The adverse effects were most severe a few days after dosing was initiated and tended to become less severe toward the end of the 10-day dosing period. Side Effects: The use of ceftiofur may result in some signs of immediate and transient local pain to the animal. Presentation: NAXCEL® Sterile Powder is available in 1 gram and 4 gram vials. Disclaimer: Every effort has been made to ensure the accuracy of the information published. However, it remains the responsibility of the readers to familiarize themselves with the product information contained on the product label or package insert.

Cephalosporins are not absorbed as rapidly or to as great an extent compared to administration of these drugs in small animals or humans. This limits the use of the oral route of administration for many drugs in horses. The exception to this rule may be foals which absorb these drugs from the intestines better than adults. For instance Cefadroxil has shown relatively good oral absorption in foals with a mean systemic availability (%F) of 58% and longer terminal half-life compared to IV.

Cephalosporins are widely distributed to most 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. Bile levels can reach therapeutic concentrations with several of the agents as long as biliary obstruction is not present. With the exception of cefuroxime, no first or second generation cephalosporin enters the CSF (even with inflamed meninges) in therapeutically effective levels. Therapeutic concentrations of cefotaxime, moxalactam, cefuroxime, ceftizoxime, ceftazidime and ceftriaxone can be found in the CSF after parenteral dosing in patients with inflamed meninges.

The first generation of cephalosporins include (routes of administration in parentheses):

• cephalothin (IM/IV)
• cefazolin (IM/IV)
• cephapirin (IM/IV/Intramammary)
• cephradine (IM/IV/PO in other species but not the horse)
• cephalexin (PO in other species but not the horse)
• cefadroxil (PO in other species but not the horse)

Their spectrum of activity is quite similar. They possess generally excellent coverage against most gram-positive pathogens and variable to poor coverage against most gram negative pathogens. With the exception of Bacteroides fragilis, most anaerobes are very susceptible to the first generation agents. Rhodococcus equi is usually resistant but corynbacterium is usually sensitive. Strains of Staphylococcus epidermidis may have variable susceptibilities. The following bacteria are regularly resistant to the 1st generation agents: Group D streptococci/enterococci (S. faecalis, S. faecium), Methicillin resistant Staphylococci, indole-positive Proteus sp., Pseudomonas sp., Enterobacter sp., Serratia sp. and Citrobacter sp..

The second generation cephalosporins include:

• cefaclor (PO in other species but not the horse)
• cefamandole (IM/IV)
• cefonicid (IM/IV)
• ceforanide (IM/IV)
• cefuroxime (PO in other species but not the horse/IM/IV).
• cefoxitin (IM/IV) a cephamycin
• cefotetan (IM/IV) a cephamycin that some call a 3rd generation cephalosporin

In addition to the gram positive coverage of the 1st generation agents, these agents have expanded gram negative coverage. However in regard to their spectrums of activity against most species of gram negative bacteria, there is enough variation between these agents that susceptibility testing is generally required to determine sensitivity. The second generation agents have not found widespread use in most veterinary practices, although cefoxitin has been used somewhat.

The third generation cephalosporins retain the gram positive activity, though less so than the first generation, but have much expanded gram negative activity. Included in this group are:

• cefotaxime (IM/IV)
• moxalactam (actually a 1-oxa-beta-lacatam; IM/IV)
• cefoperazone (IM/IV)
• ceftizoxime (IM/IV)
• ceftazidime (IM/IV)
• ceftriaxone (IM/IV)
• ceftiofur (IM)
• cefixime (PO in other species but not the horse).

As with the 2nd generation agents, enough variability exists with individual bacterial sensitivities that susceptibility testing is necessary for most bacteria. Usually only ceftazidime and cefoperazone are active against most strains of Pseudomonas aeruginosa. Because of the excellent gram negative coverage of these agents and when compared to the aminoglycosides, their significantly less toxic potential, they have been used on an increasing basis in veterinary medicine.