Cefotaxime

ADMINISTRATION ROUTES: IV or IM

ALTERNATIVE NAMES: Cefotaxime, Claforan

ICU INDICATIONS:

  1. Treatment of infections caused by susceptible organisms

PRESENTATION AND ADMINISTRATION:

  • IV: 500mg, 1gm and 2gm vials of powder Add at least 2ml of water for injection to a 500mg vial, at least 4ml of water for injection to a 1gm vial or 10ml of water for injection to a 2gm vial then shake well until all powder is dissolved.
  • Inject slowly over 3-5 minutes Store at room temperature
  • Compatible with: Normal saline Glucose and sodium chloride, glucose 5 % and Hartmanns
  • For doses not equalling vial size, prepare the solutions as follows:
Vial size 500mg 1gm 2gm
Volume of diluent 10ml 10ml 10ml
Volume of final solution 10.2ml 10.4ml 11ml
Approximate concentration 50mg/ml 95mg/ml 180mg/ml
  • IM: Reconstitute with 0.5% lignocaine adding 2ml to a 500mg vial, 3ml to a 1gm vial, and 5ml to a 2gm vial. Inject no more than 4ml of solution into either buttock. If the daily dose exceeds 2gm this route is not recommended

DOSAGE:

  • IV: 2gm 8 hourly (may increase to maximum of 12gm daily in severe infections) Note: – During postmarketing surveillance, a potentially life-threatening arrhythmia was reported in each of 6 patients who received a rapid (less than 60 seconds) bolus injection of cefotaxime through a central venous catheter. Therefore, cefotaxime should only be administered as instructed in PRESENTATION AND ADMINISTRATION.

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

  • Dose in renal impairment [GFR (ml/min)]
    • <10           0.5-1gm 8-12 hourly
    • 10-20       dose as in normal renal function
    • >20-50   dose as in normal renal function
  • Dose in renal replacement therapy
    • CAPD         0.5-1gm 8-12 hourly
    • HD             0.5-1gm 8-12 hourly
    • CVVHDF     1gm 12 hourly

DOSAGE IN PAEDIATRICS:

25-50mg/kg/day 6-12hrly; for bacterial meningitis load 100 mg/kg then give 50 mg/kg/ dose (max. 2000 mg/dose) 6 hourly

CLINICAL PHARMACOLOGY:

  • Cefotaxime is a 3rd generation cephalosporin.
  • It has a bactericidal action resulting from inhibition of cell wall synthesis.
  • Cefotaxime sodium has a high degree of stability in the presence of beta-lactamases, both penicillinases and cephalosporinases, of gram- negative and gram-positive bacteria. Cefotaxime has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections:
  • Aerobes, Gram-Positive:
    • Enterococcus spp., Staphylococcus aureus,* including beta-lactamase-positive and negative strains, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes (Group A beta-hemolytic streptococci), Streptococcus spp. *Staphylococci which are resistant to methicillin/oxacillin must be considered resistant to cefotaxime sodium.
  • Aerobes, Gram-Negative:
    • Acinetobacter spp., Citrobacter spp., Enterobacter spp., Escherichia coli, Haemophilus influenzae (including ampicillin-resistant strains), Haemophilus parainfluenzae, Klebsiella spp. (including Klebsiella pneumoniae), Morganella morganii, Neisseria gonorrhoeae (including beta-lactamase-positive and negative strains), Neisseria meningitidis, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia marcescens.
  • NOTE: Many strains of the above organisms that are multiply resistant to other antibiotics, e.g., penicillins, cephalosporins, and aminoglycosides, are susceptible to cefotaxime sodium. Cefotaxime sodium is active against some strains of Pseudomonas aeruginosa.
  • Anaerobes:
    • Bacteroides spp., including some strains of Bacteroides fragilis, Clostridium spp. (Note: Most strains of Clostridium difficile are resistant.) Fusobacterium spp. (Including Fusobacterium nucleatum). Peptococcus spp., Peptostreptococcus spp.

CONTRAINDICATIONS:

  1. Hypersensivity to cephalosporins

WARNINGS

  • Anaphylaxis: Cephalosporins are a common cause of anaphylactic reactions and cross reactivity with penicillins may occur Pseudomembranous colitis Pseudomembranous colitis has been reported with nearly all antibacterial agents, including cefotaxime, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea subsequent to the administration of antibacterial agents.
  • Agranulocytosis: As with other beta-lactam antibiotics, granulocytopenia and, more rarely, agranulocytosis may develop during treatment with cefotaxime sodium, particularly if given over long periods.

PRECAUTIONS

  • General: Prescribing cefotaxime in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Positive direct Coombs’ tests have been reported during treatment with the cephalosporin antibiotics. It should be recognized that a positive Coombs’ test may be due to the drug.
  • Laboratory Tests: No tests additional to usual ICU tests are required
  • Drug/Laboratory Test Interactions: None of note

IMPORTANT DRUG INTERACTIONS FOR THE ICU

  • None of note.

ADVERSE REACTIONS

  • Cardiovascular System: Potentially life-threatening arrhymias following rapid (less than 60 seconds) bolus administration via central venous catheter have been observed. Haematologic System: Neutropenia, transient leukopenia, eosinophilia, thrombocytopenia and agranulocytosis have been reported. Some individuals have developed positive direct Coombs Tests during treatment with cefotaxime sodium and other cephalosporin antibiotics. Rare cases of hemolytic anemia have been reported.
  • Genitourinary System: Moniliasis, vaginitis.
  • Central Nervous System: Headache.
  • Liver: Transient elevations in AST, ALT, serum LDH, and serum ALP levels have been reported. Kidney: As with some other cephalosporins, interstitial nephritis and transient elevations of creatinine have been occasionally observed with cefotaxime sodium.
  • Cutaneous: As with other cephalosporins, isolated cases of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported.

Cephalosporin-Class Adverse Reactions

In addition to the adverse reactions listed above that have been observed in patients treated with cefaclor, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibiotics: fever, abdominal pain, superinfection, renal dysfunction, toxic nephropathy, haemorrhage, false positive test for urinary glucose, elevated bilirubin, elevated LDH, and pancytopenia. Several cephalosporins have been implicated in triggering seizures, paticularly in patients with renal impairment when the dosage was not reduced. If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated

Critical Care Drug Manual

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