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cefotaxime (Claforan)

Tradename: Claforan. 3rd generation cephalosporin. Indications: - treatment of bacterial infections due to susceptible organisms - gram negative rod infection (other than Pseudomonas) - CNS infections - documented or suspected meningitis - lower respiratory tract infections - pneumonia - ventilator-associated pneumonia - intra-abdominal infections - peritonitis - urogenital infections - skin or soft tissue infections - sepsis - proctitis - ophthalmia neonatorum - prophylaxis for perioperative infection - cesarean section - empiric treatment of fever of unknown origin Dosage: 1) 1-2g IV/IM every 6-8 hours. 2) Children: 50-180 mg/kg/day IV divided every 4-6 hours. 3) meningitis: 200 mg/kg/day 4) severe infection (> 50 kg) : 1-2 g every 4-6 hours 5) life-threatening infection 2 g every 4 hours 6) maximum: 12 g/day Dosage adjustment in renal failure: creatinine clearance dosage > 50-90 mL/min 1-2 g every 8-12 hours 10-50 mL/min* 1-2 g every 12-24 hours < 10 mL/min# 1-2 g every 24 hours * same dose for continuous arteriovenous hemofiltration # 1 g IV after hemodialysis Pharmacokinetics: 1) widely distributed to body tissues & fluids, including a) aqueous humor, ascitic fluid, prostatic fluid bone b) penetrates CSF when meninges are inflammed c) crosses placenta d) appears in breast milk 2) protein bindng 31-50% 3) partially metabolized in the liver to an active metabolite, desacetylcefoxatime 4) elimination 1/2life: a) cefotaxime: 1-1.5 hours, prolinged with renal &/or hepatic insufficiency (15-35 hours ESRD) b) desacetylcefoxatime: 1.5-1.9 hours, prolonged with renal impairment c) 60% excreted unchanged in the urine, 23% as metabolites 5) time to peak serum concentration: a) 5 minutes after IV administration b) within 30 minutes after IM administration 6) elimination by hemodialysis 20-50% Antimicrobial activity: Gram positive - Streptococcus - Streptococcus group A - Streptococcus group B - Streptococcus group C - Streptococcus group G - Streptococcus pneumonia - Streptococcus viridans, milleri - Staphylococcus - Staphylococcus aureus (MSSA) - Staphylococcus epidermidis (+/-) Gram negative - Neisseria - Neisseria gonorrhoeae - Neisseria meningitidis - Moraxella catarrhalis - Haemophilus - Haemophilus influenzae - Haemophilus parainfluenzae - Haemophilus ducreyi - Escherichia coli - Klebsiella species - Enterobacter species - Serratia species - Salmonella species - Shigella species - Proteus - Proteus mirabilis - Proteus vulgaris - Providencia species - Morganella species - Morganella morganii [5] - Citrobacter species - Citrobacter diversus - Aeromonas species - Acinetobacter species - Pseudomonas - Pseudomonas aeruginosa (+/-) - Pseudomonas cepacia - Yersinia - Yersinia enterocolitica - Yersinia pseudotuberculosis Anaerobes - Bacteroides melaninogenicus - Clostridium species - Peptostreptococcus species - Fusobacterium [5] Adverse effects: 1) not common (1-10%) - pain at injection site, rash, pruritus, fever, eosinophilia, colitis, diarrhea, nausea/vomiting 2) uncommon (< 1%) - headache, pseudomembranous colitis, transient neutropenia, thrombocytopenia, phlebitis transient elevation of BUN, creatinine, transaminases 3) other - Coomb's test may be positive Drug interactions: -> probenecid decreases renal clearance of cefotaxime by 50% Laboratory: 1) specimen: a) serum b) keep specimen on ice-water c) centrifuge at 4 degrees C d) remove cells as soon as possible e) freeze at -70 degrees C until assayed 2) methods: HPLC, MB 3) interferences: -> desacetyl metabolite may interfere with microbiological assay (MB)

Interactions

drug interactions drug adverse effects of cephalosporins

General

cephalosporin, 3rd generation

Properties

MISC-INFO: elimination route KIDNEY LIVER 1/2life 1.1 +/- 0.2 HOURS protein-binding 36% pregnancy-category B safety in lactation ? elimination by hemodialysis +/-

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Sanford Guide to antimicrobial therapy 1997
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
  5. Deprecated Reference
  6. Department of Veterans Affairs, VA National Formulary