Cefotaxime
Cefotaxime is a **third-generation parenteral cephalosporin** antibiotic with a broad spectrum of activity against both gram-positive and gram-negative bacteria. Key clinical features include: * **Extended Gram-Negative Coverage**: Highly effective against *Enterobacteriaceae* (e.g., *Klebsiella*, *E. coli*, *Salmonella*, *Proteus*). * **Anaerobic Activity**: Effective against many anaerobes including *Bacteroides fragilis* and *Clostridium* spp. * **CNS Penetration**: Unlike first- and most second-generation cephalosporins, cefotaxime achieves therapeutic concentrations in the **cerebrospinal fluid (CSF)** when the meninges are inflamed, making it a valuable option for bacterial meningitis and spinal cord infections. * **Administration**: Must be given parenterally (IV, IM, SC) as it is not appreciably absorbed orally. IV administration should be slow (over 3-5 minutes) to minimize adverse reactions. > **Clinical Pearl**: While it has excellent activity against many gram-negative aerobes, its efficacy against *Pseudomonas aeruginosa* is variable and often clinically disappointing. A 30-microgram cefotaxime disk should be used for Kirby-Bauer susceptibility testing.
Mechanism: Cefotaxime is a **time-dependent, bactericidal** antibiotic. * **Mechanism**: It binds to specific **penicillin-binding proteins (PBPs)** located inside the bacterial cell wall โ inhibits the third and final stage of bacterial cell wall peptidoglycan synthesis โ leads to cell lysis and death mediated by bacterial cell wall autolytic enzymes (autolysins). * **Metabolism**: It is partially metabolized in the liver to **desacetylcefotaxime**, an active metabolite that works synergistically with the parent compound to enhance antibacterial activity.
Dosing by species
- Soft tissue infections ยท 22 mg/kg IV, IM or SC q8h for 7 days or less or 50 mg/kg IV or IM q12h for 7 days or less ยท IV, IM, SC ยท q8h or q12h ยท 7 days or less
- Orthopedic infections ยท 20-40 mg/kg IV, IM or SC q6-8h for 7 days or less ยท IV, IM, SC ยท q6-8h ยท 7 days or less
- Severe bacteremia ยท 20-80 mg/kg IV q6h or 10-50 mg/kg IV q4-6h for as long as necessary ยท IV ยท q4-6h ยท As long as necessary
- Susceptible infections ยท 25-50 mg/kg IV, IM or SC q8h ยท IV, IM, SC ยท q8h
- Sepsis ยท 20-80 mg/kg IV, IM q8h ยท IV, IM ยท q8h
- CNS infections (spinal cord) ยท 25 mg-50 mg/kg IV, IM q8h ยท IV, IM ยท q8h
- Acute sepsis or serious susceptible infections ยท 40-50 mg/kg ยท IV/IM/SC ยท q8h ยท Until clinical resolution ยท Standard recommended dose.
- Susceptible infections ยท 10-20 mg/kg ยท IV/IM/SC ยท q12h ยท Until clinical resolution ยท Lower dose suggested by some authors to have good clinical efficacy.
- Susceptible infections (most birds) ยท 50-100 mg/kg IM three times a day ยท IM ยท TID ยท May be used with aminoglycosides, but nephrotoxicity may occur. Reconstituted vial good for 13 weeks if frozen.
- Bacterial infections, bacterial hepatitis ยท 75-100 mg/kg IM or IV q4-8h ยท IM, IV ยท q4-8h
Routes of administration
Contraindications
- Patients with a documented history of hypersensitivity to cephalosporins
Adverse effects
- Pain at the IM injection site
- Thrombophlebitis (after IV administration)
- Hypersensitivity reactions (rashes, fever, eosinophilia, anaphylaxis)
- Antibiotic-associated diarrhea (alteration of gut flora)
- Sterile abscesses or local tissue reactions
- Rarely: Nephrotoxicity, neurotoxicity (at high doses), neutropenia, agranulocytosis, thrombocytopenia, hepatitis
Drug interactions
- Aminoglycosides / Nephrotoxic drugs (e.g., amphotericin B) ยท Potential for additive nephrotoxicity. In vitro studies show synergistic antibacterial activity, but they must NOT be mixed in the same syringe or fluid bag.
- Probenecid ยท Competitively blocks the renal tubular secretion of cefotaxime, significantly increasing its serum levels and prolonging its elimination half-life.
- Oxytetracycline ยท Bacteriostatic agents may antagonize the bactericidal activity of cephalosporins. ยท moderate
- Erythromycin ยท Bacteriostatic agents may antagonize the bactericidal activity of cephalosporins. ยท moderate
- Aminoglycosides ยท Synergistic antibacterial effect, but do not mix in the same syringe due to chemical incompatibility. ยท minor
- Amphotericin B ยท Increased risk of nephrotoxicity. ยท major
- Furosemide ยท Loop diuretics may increase the risk of nephrotoxicity when used with cephalosporins. ยท major
Monitoring
- Clinical efficacy (resolution of infection signs)
- Renal function parameters (BUN, creatinine, urinalysis) in compromised patients or those on concurrent nephrotoxic drugs
Overdose
Acute cephalosporin overdoses are unlikely to cause significant life-threatening problems. However, massive overdoses may exacerbate adverse effects, potentially leading to **neurotoxicity** (seizures, encephalopathy), **nephrotoxicity**, or severe gastrointestinal upset. Treatment should consist of standard supportive care and monitoring.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.