ADMINISTRATION ROUTES:
IV, IM
ALTERNATIVE NAMES:
Cefotaxime, Claforan
ICU INDICATIONS:
- Treatment of infections caused by susceptible organisms
PRESENTATION AND ADMINISTRATION:
IV:
500 mg, 1 gm and 2 gm vials of powder
Add at least 2 mL of water for injection to a 500 mg vial, at least 4 mL of water for injection to a 1 gm vial or 10 mL of water for injection to a 2 gm vial then shake well until all powder is dissolved.
For doses not equalling vial size, prepare the solutions as follows:
| Vial size | 500 mg | 1 gm | 2 gm |
|---|---|---|---|
| Volume of diluent | 10 mL | 10 mL | 10 mL |
| Volume of final solution | 10.2 mL | 10.4 mL | 11 mL |
| Approximate concentration | 50 mg/mL | 95 mg/mL | 180 mg/mL |
Inject slowly over 3-5 minutes
Store at room temperature
Compatible with:
Normal saline, glucose and sodium chloride, 5% dextrose, Hartmanns
IM:
Reconstitute with 0.5% lignocaine adding 2 mL to a 500 mg vial, 3 mL to a 1 gm vial, and 5 mL to a 2 gm vial. Inject no more than 4 mL of solution into either buttock. If the daily dose exceeds 2 gm this route is not recommended
DOSAGE:
IV:
2 gm TDS. May increase to maximum of 12 gm daily in severe infections
Note: during post-marketing 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) | DOSE |
|---|---|
| <10 | 0.5 - 1 gm q8-12hrly |
| 10-20 | dose as in normal renal function |
| >20-50 | dose as in normal renal function |
Dose in renal replacement therapy
| MODALITY | DOSE |
|---|---|
| CAPD | 0.5-1 gm q8-12hrly |
| HD | 0.5-1 gm q8-12hrly |
| CVVHDF | 1 gm BD |
DOSAGE IN PAEDIATRICS:
25-50 mg/kg/day q6-12hrly. For bacterial meningitis load 100 mg/kg then give 50 mg/kg dose QID (with maximum of 2 gm per dose)
CLINICAL PHARMACOLOGY:
Cefotaxime is a 3rd generation cephalosporin. It has 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-haemolytic 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 (such as 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:
- 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, granulocytopaenia 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 recognised 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 IN ICU:
None of note
ADVERSE REACTIONS:
Cardiovascular System:
Potentially life-threatening arrhythmias following rapid (less than 60 seconds) bolus administration via central venous catheter have been observed.
Haematologic System:
Neutropaenia, transient leukopaenia, eosinophilia, thrombocytopaenia 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 haemolytic anaemia 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 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 pancytopaenia.
Several cephalosporins have been implicated in triggering seizures, particularly 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