No

Antibiotic, Cephalosporin (Third Generation)

Treatment of susceptible infection in respiratory tract, skin and skin structure, bone and joint, urinary tract, gynecologic as well as septicemia, and documented or suspected meningitis. Active against most gram-negative bacilli (not Pseudomonas) and gram-positive cocci (not enterococcus). Active against many penicillin-resistant pneumococci.

B

Hypersensitivity to cefotaxime, any component, or cephalosporins

Modify dosage in patients with severe renal impairment; prolonged use may result in superinfection; a potentially life-threatening arrhythmia has been reported in patients who received a rapid bolus injection via central line. Use caution in patients with colitis; minimize tissue inflammation by changing infusion sites when needed. Use with caution in patients with a history of penicillin allergy especially IgE-mediated reactions (eg, anaphylaxis, urticaria); may cause antibiotic-associated colitis or colitis secondary to C. difficile.

1% to 10%:

Dermatologic: Rash, pruritus

Gastrointestinal: Diarrhea, nausea, vomiting, colitis

Local: Pain at injection site

<1%: Anaphylaxis, urticaria, arrhythmias (after rapid IV injection via central catheter), pseudomembranous colitis, neutropenia, thrombocytopenia, eosinophilia, headache, fever, transaminase elevations, interstitial nephritis, increased BUN, increased creatinine, increased transaminases, phlebitis, candidiasis, vaginitis,

Other reactions with cephalosporins include seizures, Stevens-Johnson syndrome, toxic epidermal necrolysis, renal dysfunction, toxic nephropathy, cholestasis, aplastic anemia, hemolytic anemia, hemorrhage, pancytopenia, agranulocytosis, colitis, superinfection

Usually well tolerated even in overdose, convulsions possible; many beta-lactam antibiotics have the potential to cause neuromuscular hyperirritability or seizures

Hemodialysis may be helpful to aid in the removal of the drug from the blood, otherwise most treatment is supportive or symptom directed

Increased effect: Probenecid may decrease cephalosporin elimination

Increased toxicity: Furosemide, aminoglycosides may be a possible additive to nephrotoxicity

Reconstituted solution is stable for 12-24 hours at room temperature and 7-10 days when refrigerate and for 13 weeks when frozen; for I.V. infusion in NS or D₅W, solution is stable for 24 hours at room temperature, 5 days when refrigerated, or 13 weeks when frozen in Viaflex® plastic containers; thawed solutions previously of frozen premixed bags are stable for 24 hours at room temperature or 10 days when refrigerated

Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.

Distribution: Widely distributed to body tissues and fluids including aqueous humor, ascitic and prostatic fluids, and bone; penetrates CSF best when meninges are inflamed; crosses the placenta and appears in breast milk

Metabolism: Partially in the liver to active metabolite, desacetylcefotaxime

Half-life:

Cefotaxime: Premature neonates <1 week: 5-6 hours; Full-term neonates <1 week: 2-3.4 hours; Adults: 1-1.5 hours (prolonged with renal and/or hepatic impairment)

Desacetylcefotaxime: 1.5-1.9 hours (prolonged with renal impairment)

Time to peak serum concentration: I.M.: Within 30 minutes

Elimination: Renal excretion of parent drug and metabolites

Neonates: I.V.:

0-1 week: 50 mg/kg every 12 hours

1-4 weeks: 50 mg/kg every 8 hours

Infants and Children 1 month to 12 years: I.M., I.V.: <50 kg: 50-180 mg/kg/day in divided doses every 4-6 hours

Meningitis: 200 mg/kg/day in divided doses every 6 hours

Children >12 years and Adults:

Gonorrhea: I.M.: 1 g as a single dose

Uncomplicated infections: I.M., I.V.: 1 g every 12 hours

Moderate/severe infections: I.M., I.V.: 1-2 g every 8 hours

Infections commonly needing higher doses (eg, septicemia): I.V.: 2 g every 6-8 hours

Life-threatening infections: I.V.: 2 g every 4 hours

Preop: I.M., I.V.: 1 g 30-90 minutes before surgery

C-section: 1 g as soon as the umbilical cord is clamped, then 1 g I.M., I.V. at 6- and 12-hours intervals

Dosing interval in renal impairment:

Cl_cr 10-50 mL/minute: Administer every 8-12 hours

Cl_cr <10 mL/minute: Administer every 24 hours

Hemodialysis: Moderately dialyzable

Dosing adjustment in hepatic impairment: Moderate dosage reduction is recommended in severe liver disease

Continuous arteriovenous or venovenous hemodiafiltration (CAVH) effects: Administer 1 g every 12 hour

Observe for signs and symptoms of anaphylaxis during first dose; CBC with differential (especially with long courses)

Positive direct Coombs', false-positive urinary glucose test using cupric sulfate (Benedict's solution, Clinitest®, Fehling's solution), false-positive serum or urine creatinine with Jaffé reaction

May cause nervousness; case reports of euphoria, delusion, illusions, and depersonalization with cephalosporins

May rarely cause neutropenia; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This medication is administered I.M. or I.V. Drink 2-3 L fluid/day. If diarrhea occurs, yogurt or buttermilk may help. May cause false-positive test with Clinitest®; use another form of testing. May interfere with oral contraceptives; additional contraceptive measures are necessary. Report severe, unresolved diarrhea; vaginal itching or drainage; sores in mouth; blood, pus, or mucus in stool or urine; easy bleeding or bruising; unusual fever or chills; rash; or respiratory difficulty. Breast-feeding precautions: Consult prescriber if breast-feeding.

Cefotaxime can be administered IVP over 3-5 minutes or I.V. retrograde or I.V. intermittent infusion over 15-30 minutes; do not admix with aminoglycosides in same bottle/bag; observe for signs and symptoms of anaphylaxis during first dose

Infusion, as sodium, premixed, in D₅W (frozen): 1 g (50 mL); 2 g (50 mL)

Powder for injection, as sodium: 500 mg, 1 g, 2 g, 10 g

Brogden RN and Spencer CM, "Cefotaxime. A Reappraisal of Its Antibacterial Activity and Pharmacokinetic Properties, and a Review of Its Therapeutic Efficacy When Administered Twice Daily for the Treatment of Mild to Moderate Infections," Drugs, 1997, 53(3):483-510.

Deeter RG, Weinstein MP, Swanson KA, et al,"Crossover Assessment of Serum Bactericidal Activity and Pharmacokinetics of Five Broad-Spectrum Cephalosporins in the Elderly," Antimicrob Agents Chemother, 1990, 34(6):1007-13.

Donowitz GR and Mandell GL, "Beta-Lactam Antibiotics," N Engl J Med, 1988, 318(7):419-26 and 318(8):490-500.

Klein NC and Cunha BA, "Third-Generation Cephalosporins," Med Clin North Am, 1995, 79(4):705-19.

Ludwig E, Székely É, Csiba A, et al,"Pharmacokinetics of Cefotaxime and Desacetylcefotaxime in Elderly Patients," Drugs, 1988, 35(Suppl 2):51-6.

Marshall WF and Blair JE, "The Cephalosporins," Mayo Clin Proc, 1999, 74(2):187-95.

Spritzer R, Kamp HJ, Dzoljic G, et al, "Five Years of Cefotaxime Use in a Neonatal Intensive Care Unit," Pediatr Infect Dis J, 1990, 9(2):92-6.