Cefotaxime

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[edit] BRAND NAMES

[edit] STRUCTURE

Cefotaxime.jpg

[edit] MECHANISM OF ACTION

Cefotaxime is a third-generation broad spectrum bactericidal cephalosporin antibiotic. Cephalosporins are Beta-Lactam drugs that are bactericidal agents that inhibit bacterial cell wall synthesis by binding to one or more of the pencillin-binding proteins (PBPs) which in turn inhibit the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis.

Cefotaxime is exceptionally active in vitro against Gram-negative organisms sensitive or resistant to first or second generation Cephalosporins. It is similar to other cephalosporins in activity against Gram-positive bacteria.

Cefotaxime is considered to be equivalent to ceftriaxone in terms of safety and efficacy.

[edit] INDICATIONS

Cefotaxime is indicated in the treatment of the following infections either before the infecting organism has been identified or when caused by bacterial organisms sensitive to cefotaxime:

  • Septicaemias.
  • Respiratory tract infections such as acute and chronic bronchitis, bacterial pneumonia, infected bronchiectasis, lung abscess and post-operative chest infections.
  • Urinary tract infections such as acute and chronic pyelonephritis, cystitis and asymptomatic bacteriuria.
  • Skin and soft tissue infections such as cellulites, peritonitis and wound infections.
  • Bone and joint infections such as osteomyelitis, septic arthritis.
  • Obstetric and gynaecological infections such as pelvic inflammatory disease.
  • Gonorrhoea particularly when penicillin has failed or is unsuitable.
  • Other Bacterial infections meningitis and other sensitive infections suitable for parenteral antibiotic therapy.

PROPHYLAXIS: The administration of Cefotaxime prophylactically may reduce the incidence of certain post-operative infections in patients undergoing surgical procedures that are classified as contaminated or potentially contaminated or in clean operations where infection would have serious effects. Protection is best ensured by achieving adequate local tissue concentrations at the time contamination is likely to occur. Administration should usually be stopped within 24 hours since continuing use of any antibiotic in the majority of surgical procedures does not reduce the incidence of subsequent infection. The following organisms have shown in vitro sensitivity to Cefotaxime:

  • GRAM POSITIVE: Staphylococci, including coagulase-positive, coagulasenegative and penicillinase-producing strains. Beta-haemolytic and other streptococci such as Streptococcus mitis (viridans)(many strains of enterococci, e.g. Streptococcus faecalis, are relatively resistant). Streptococcus (Diplococcus) pneumonia Clostridium spp.
  • GRAM NEGATIVE: Escherichia coli, Haemophilus influenzae including ampicillin resistant strains. Klebsiella spp., Proteus spp. (both indole positive and indole negative). Enterobacter spp., Neisseria

spp. (including B-lactamase producind strains of N. gonorrhoeae). Salmonella spp. (including Sal. typhi). Shigella spp. Providencia spp. Serratia spp: Citrobacter spp. Cefotaxime has frequently exhibited useful in vitro activity against Pseudomonas and Bacteroides species although some strains of Bacteroides fragilis are resistant. There is in vitro evidence of synergy between Cefotaxime and aminoglycosides antibiotics such as gentamycin against some species of gram-negative bacteria including some strains of Pseudomonas. No in vitro antagonism has been noted. In severe infections caused by Pseudomonas spp. The addition of an aminoglucoside antibiotic may be indicated.

[edit] DOSAGE

The dosage, route and frequency of administration should be determined by the severity of infection, the sensitivity of the causative organisms and condition of the patient. Therapy may be initiated before the results of sensitivity tests are known.

Adults: The recommended dosage for mild to moderate infections is 1g 12 hourly. However, dosage may be varied according to the severity of the infection, sensitivity of the causative organisms and condition of the patient. Therapy may be initiated before the results of sensitivity tests are known. In severe infections dosage may be increased up to 12g daily given in 3 or 4 divided doses. For infections caused by sensitive Pseudomonas spp. Daily doses of greater than 6g will usually be required.

Children: The usual dosage range is 100-150mg/kg/day in 2 to 4 divided doses. However, in very severe infections doses of up to 200mg/kg/day may be required.

Neonates: The recommended dosage is 50mg/kg/day in 2 to 4 divided doses. In severe infections 150-200mg/kg/day, in divided doses, have been given.

Dosage in Gonorrhoea: A single injection of 1g may be administered intramuscularly or intravenously.

Dosage in Renal Impairment: Because of extra-renal elimination, it is only necessary to reduce the dosage of Cefotaxime in severe renal failure (GFR < 5ml/min = serum creatinine approximately 751 micromol/1). After an initial loading dose of 1g, daily dose should be halved without change in the frequency of dosing, i.e. 1g in 12 hourly becomes 0.5g 12 hourly, 1g 8 hourly becomes 0.5g 8 hourly etc. As in all other patients, dosage may require further adjustment according to the course of the infection and the general condition of the patient.

Cefotaxime may be administered by intramuscular or intravenous infusion.

For intravenous infusion, 1-2g of Cefotaxime is dissolved in 40-100ml of Water for Injection. The prepared infusion may be administered over 20-60 minutes.

[edit] CONTRAINDICATIONS

Known or suspected hypersensitivity to cephalosporins

[edit] PRECAUTIONS

[edit] INTERACTIONS

  • Aminoglycosides and potent diuretics: Cephalosporin antibiotics at high dosage should be given with caution to patients receiving aminoglycoside antibiotics or potent diuretics such as frusemide as these combinations are suspected to adversely affect renal function. However, at the recommended doses, enhancement of nephrotoxicity is unlikely to be a problem with Cefotaxime.
  • Probenecid interferes with the renal tubular transfer of Cefotaxime delaying its excretion and increasing the plasma concentration.

Interference with Laboratory tests: A positive Coombs test may be seen during treatment with Cephalosporins. This phenomenon may occur during treatment with cefotaxime

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category B (US). Cefotaxime should be used during pregnancy only if clearly needed.
  • Nursing Mothers: Cefotaxime is excreted in human milk in low concentrations. Caution should be exercised when Cefotaxime is administered to a nursing woman.

[edit] SIDE EFFECTS

Adverse reactions to Cefotaxime have occurred relatively infrequently and have generally been mild and transient.

Effects reported include candidiasis, nausea, vomiting, abdominal pain, and diarrhea (diarrhea may sometimes be a symptom of Pseudomembranous colitis), transient rises in liver transaminases, alkaline phosphatase and/or bilirubin.

As with other cephalosporins, changes in renal function have been rarely observed with high doses of Cefotaxime , particularly when co-prescribed with aminoglycosides.

Rare cases of interstitial nephritis have been reported in patients treated with Cefotaxime.

Administration of high doses of cephalosporins, particularly in patients with renal insufficiency, may result in encephalopathy (e.g. impairment of consciousness, abnormal movements and convulsions).

Hypersensitivity reactions have been reported. These include skin rashes, pruritus & less frequently urticaria, drug fever and very rarely anaphylaxis (e.g. angioedema, bronchospasm possibly culminating in shock).

As with other Cephalosporins, occasional cases of bullous reactions such as Stevens Johnson syndrome, toxic epidermal necrolysis and erythema multiforme have also been reported.

As with other beta-lactam antibiotics, granulocytopenia and more rarely agranulocytosis may develop during treatment with Cefotaxime, particularly if given over long periods. A few cases of eosinophilia and neutropenia have been observed, reversible when treatment is ceased. Some cases of rapidly reversible eosinophilia and thrombocytopenia on stopping treatment, have been reported. Rare cases of haemolytic anaemia have been reported. For cases of treatment lasting longer than 10 days, blood count should therefore be monitored.

Transient pain may be experienced at the site of injection. This is more likely to occur with higherdoses. Occasionally, phlebitis has been reported in patients receiving intravenous Cefotaxime. However, this has rarely been a cause for discontinuation of treatment. A very small number of cases of arrhythmias have occurred following rapid bolus infusion through a central venous catheter.


The following symptoms have occurred after several weeks of treatment for Lyme's disease (borreliosis):

Skin rash, itching, fever, leucopenia, increases in liver enzymes, difficulty of breathing, joint discomfort. To some extent these manifestations are consistent with the symptoms of the underlying disease, for which the patient is being treated.

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