Cefotaxime is a semi-synthetic antibiotic that is considered as the prototype of the third-generation cephalosporins. It has relatively wide spectrum of activity. It generally has good coverage against most Gram-negative bacteria. It is also effective against most Gram-positive cocci except for Entercoccus. It is active against penicillin-resistant strains of streptococcus pneumonia. However, it is not so active on anaerobes particularly Bacteriodes fragilis, Pseudomonas aeruginosa and Staphylococcus aureus. It is highly resistant to many, but not all, bacteria β-lactamases.

Pharmacokinetics

Cefotaxime sodium is not appreciably absorbed after oral administration and must be given parenterally. After IM OR SC injection, cefotaxime is well absorbed(>90%) and distributed into body fluids and tissues. It is partially metabolized in vivo to desacetylcefotaxime, which is less active than the parent compound. The desacetylcefotaxime may act synergistically with parent compound against some susceptible bacteria. The desacetylcefotaxime is further metabolized to inactive metabolites which along with unmetabolised cefotaxime are excreted in the urine. The plasma half-life of cefotaxime is about 45-60 minutes in dogs and cats, but the deacetylated metabolite may permit longer dosing intervals in some cases.

Mechanism of Action

All cephalosporins are bactericidal. They inhibit bacterial cell wall synthesis in a manner similar to that of penicillins. However, they bind to different proteins than those required by penicillins and are less susceptible to penicillinases. Like other beta-lactam antibiotic, cephalosporins are generally considered to be more effective against actively growing bacteria.

Clinical Uses

Cefotaxime is used for infections of the respiratory tract, skin, bones, joints, urogenital system, meningitis and septicemia. In Veterinary medicine, cefotaxime sodium is primarly used in the treatment of gram-negative meningitis in small animals. It is also used in other veterinary species when an injectable third-generation cephalosporin is indicated.

Adverse effects

The cephalosporins are relatively non-toxic antibiotics with relatively low frequency of allergic reactions. Hypersensitivity reaction, if occurs, is similar to that produced by penicillins with manifestations of rashes, fever, esinophilia, lymphadenopathy, or full-blown anaphylaxis. About 10% of the penicillin sensitive individuals show some cross-reactivity to cephalosporins. Other adverse reactions associated with cephalosporins in animals may include GI disturbances (nausea, vomiting and diarrhoea), superinfection, pain at IM injection site and lethargy. Prolonged treatment with cephalosporins in man has been associated with interstitial nephritis, hepatitis, thrombocytopenia and neutropenia.

Contraindications and Precautions

Like Penicillins, cephalosporins are contraindicated in patients those are hypersensitive to them or penicillins. Prolonged administration of cephalosporins should be avoided in animals, particularly cats, as they may lead to anaemia or superinfection. Cephalosporins should be used with caution in pregnant animals as they cross placenta and reach foetal tissues. Dosage adjustment may be required in patients with renal insufficiency.

Drug Interactions

Drug interaction of cephalosporins are generally similar to those of penicillins. Concomitant use aminoglycosides and loop diuretics (e.g. furosemide) appears to potentiate the nephrotoxic effect of cephalosporins. Bacteriostatic agents (e.g. chloramphenicol) interfere with bactericidal action of cephalosporins, thus their concurrent administration should be avoided. Probenecid administered concurrently with cephalosporins increases and prolongs plasma level by competitively inhibiting renal tubular secretion.

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