Cefotaxime

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Cefotaxime
Cefotaxime.svg
Cefotaxime ball-and-stick.png
Systematic (IUPAC) name
(6R,7R,Z)-3-(Acetoxymethyl)-7-(2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Clinical data
Trade names Claforan ; Cefatam (LGls)
AHFS/Drugs.com monograph
MedlinePlus a682765
Pregnancy cat. B1 (AU) B (US)
Legal status Prescription Only (S4) (AU)
Routes Intravenous and Intramuscular
Pharmacokinetic data
Bioavailability n/a
Metabolism Hepatic
Half-life 0.8–1.4 hours
Excretion 50–85% renal
Identifiers
CAS number 63527-52-6 YesY
ATC code J01DD01
PubChem CID 5479527
DrugBank DB00493
ChemSpider 4586392 YesY
UNII N2GI8B1GK7 YesY
KEGG D07647 YesY
ChEMBL CHEMBL102 YesY
Chemical data
Formula C16H17N5O7S2 
Mol. mass 455.47 g/mol
 YesY (what is this?)  (verify)

Cefotaxime (INN) /ˌsɛfɵˈtæksm/ is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, cefotaxime is a broad spectrum antibiotic with activity against numerous Gram positive and Gram negative bacteria.

Mechanism of action[edit]

Cefotaxime is a β-lactam antibiotic (which refers to the structural components of the drug molecule itself). As a class, β-lactams inhibit bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs). This 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) in the absence of cell wall assembly.[1]. Due to the mechanism of its attack on bacterial cell wall synthesis, β-lactams are considered to be bactericidal[2].

Unlike β-lactams such as penicillin and amoxicillin--which are highly susceptible to degradation by β-lactamase enzymes (produced, for example, nearly universally by Staphylococcus aureus)--cefotaxime boasts the additional benefit of resistance to β-lactamase degradation. This characteristic is due to the structural configuration of the cefotaxime molecule. The syn-configuration of the methoxyimino moiety confers stability against β-lactamase enzymes.[3] Consequently, the spectrum of activity is broadened to include several β-lactamse producing organisms (which would otherwise be resistant to β-lactam antibiotics), as outlined below.

Cefotaxime, like other β-lactam antibiotics, does not only block the division of bacteria, including cyanobacteria, but also the division of cyanelles, the photosynthetic organelles of the Glaucophytes, and the division of chloroplasts of bryophytes. In contrast, it has no effect on the plastids of the highly developed vascular plants. This supports the endosymbiotic theory and indicates an evolution of plastid division in land plants.[4]

Spectrum of bacterial susceptibility[edit]

As a β-lactam antibiotic in the third-generation class of cephalosporins, cefotaxime is active against numerous gram-positive and gram-negative bacteria, including several with resistance to classic β-lactams such as penicillin. These bacteria often manifest as infections of the lower respiratory tract, skin, central nervous system (CNS), bone, and intra-abdominal cavity. While regional susceptibilities must always be considered, cefotaxime typically is effective against the following organisms (in addition to many others)[2]:

  • Staphylococcus aureus (not including MRSA) and S. epidermidis
  • Streptococcus pneumoniae and S. pyogenes
  • Escherichia coli
  • Haemophilus influenzae
  • Neisseria gonorrhoeae and N. meningitidis
  • Klebsiella spp
  • Proteus mirabilis and P. vulgaris
  • Enterobacter spp.
  • Bacteroides spp.
  • Fusobacterium spp.

Notable organisms against which cefotaxime is not active include Pseudomonas and Enterococcus.[1] As listed, it has modest activity against the anaerobic Bacteroides fragilis.

The following represents MIC susceptibility data for a few medically significant microorganisms.

  • Haemophilus influenzae: ≤0.007 µg/mL - 0.5 µg/mL
  • Staphylococcus aureus: 0.781 µg/mL - 172 µg/mL
  • Streptococcus pneumoniae: ≤0.007 µg/mL - 8 µg/mL

[5] [6]

Historically, cefotaxime has been considered to be comparable to ceftriaxone (another third-generation cephalosporin) in safety and efficacy for the treatment of bacterial meningitis, lower respiratory tract infections, skin and soft tissue infections, genitourinary tract infections, bloodstream infections, as well as prophylaxis for abdominal surgery.[7][8][9]The majority of these infections are caused by organisms traditionally sensitive to both cephalosporins. However, ceftriaxone has the advantage of once daily dosing, whereas the shorter half-life of cefotaxime necessitates two or three daily doses for efficacy. Changing patterns in microbial resistance suggest that cefotaxime may be suffering greater resistance than ceftriaxone, whereas the two were previously considered comparable.[10] It is also important to consider regional microbial sensitivities when choosing any antimicrobial agent for the treatment of infection.

Clinical Use[edit]

Given its broad spectrum of activity, cefotaxime is used for a variety of infections, including:

  • Lower respiratory tract infections - e.g. pneumonia (most commonly caused by S. pneumoniae).
  • Genitourinary system infections - urinary tract infections (e.g. E. coli, S. epidermidis, P. mirabilis) and cervical/urethral gonorrhea.
  • Gynecologic infections - e.g. pelvic inflammatory disease, endometritis, and pelvic cellulitis.
  • Bacteremia/Septicemia - secondary to Streptococcus spp, S. aureus, E. coli, and Klebsiella spp.
  • Intra-abdominal infections - e.g. peritonitis
  • Bone and join infections - S. aureus, Streptococcus spp.
  • CNS infections - e.g. meningitis/ventriculitis secondary to N. meningitidis, H. influenzae, S. pneumoniae.[2]

Although cefotaxime has demonstrated efficacy in the preceding infections, this does not imply that it is considered to be the first-line agent. In meningitis, cefotaxime crosses the blood–brain barrier better than cefuroxime.

Vial of cefotaxime

Dosing and Administration[edit]

Cefotaxime is administered by intramuscular (I.M.) injection or intravenous (I.V.) infusion.

While dosing varies according to the targeted infection and individual characteristics of the patient, typical adult doses of cefotaxime range between 1-2g every 4-12 hours.[11] As cefotaxime is metabolized to both active and inactive metabolites by the liver and largely excreted in the urine, dose adjustments may be appropriate in patients with renal or hepatic impairment.[2] [12] [13]

Adverse Reactions[edit]

Cefotaxime is contraindicated in patients with a known hypersensitivity to cefotaxime or other cephalosporins. Caution should be used and risks weighed against potential benefits in patients with an allergy to penicillin, due to cross-reactivity between the classes.

The most common adverse reactions experienced are:

  • Pain and inflammation at the site of injection/infusion (4.3%)
  • Rash, pruritus, or fever (2.4%)
  • Colitis, diarrhea, nausea, vomiting (1.4%)[2]

Use in plant tissue culture[edit]

Cefotaxime is the only cephalosporin which has very low toxicity in plants, even at higher concentration (up to 500 mg/L). It is widely used to treat plant tissue infections with Gram negative bacteria,[14] while vancomycin is used to treat the plant tissue infections with Gram positive bacteria.[15]


References[edit]

  1. ^ a b Cefotaxime drug information
  2. ^ a b c d e U.S. Food and Drug Administration. U.S. Department of Health and Human Services. Claforan Sterile (cefotaxime for injection, USP) and Injection (cefotaxime injection, USP). 19 June 2009. http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050596s035,050547s066lbl.pdf
  3. ^ Adeleke, OE, et al. Asian J. Biol. Life Sci. Sept.-Dec. 2012; 1(3):186-190.
  4. ^ Britta Kasten und Ralf Reski (1997): β-lactam antibiotics inhibit chloroplast division in a moss (Physcomitrella patens) but not in tomato (Lycopersicon esculentum). Journal of Plant Physiology 150, 137-140. [1]
  5. ^ http://antibiotics.toku-e.com/antimicrobial_463_19.html
  6. ^ http://www.toku-e.com/Assets/MIC/Cefotaxime%20sodium%20USP.pdf
  7. ^ Scholz, H. et al. Prospective comparison of ceftriaxone and cefotaxime for the short-term treatment of bacterial meningitis in children. Chemotherapy. 1998 Mar-Apr;44(2):142-7.
  8. ^ Woodfield, JC, et al. A comparison of the prophylactic efficacy of ceftriaxone and cefotaxime in abdominal surgery. Am J Surg. 2003 Jan;185(1):45-9.
  9. ^ Simmons, BP, et al. Cefotaxime twice daily versus ceftriaxone once daily. A randomized controlled study in patients with serious infections. Diagn Microbiol Infect Dis. 1995 May-Jun;22(1-2):155-7.
  10. ^ Gums, JG, et al. Differences between ceftriaxone and cefotaxime: microbiological inconsistencies. Ann Pharmacother. 2008 Jan;42(1):71-9. Epub 2007 Dec 19.
  11. ^ Lexicomp. Cefotaxime (Lexi-Drugs). http://online.lexi.com.proxy1.lib.tju.edu/lco/action/doc/retrieve/docid/patch_f/6555
  12. ^ Bertels, RA, et al. Serum concentrations of cefotaxime and its metabolite desacetyl-cefotaxime in infants and children during continuous infusion. Infection. 2008 Oct;36(5):415-20. doi: 10.1007/s15010-008-7274-1. Epub 2008 Sep 12..
  13. ^ Coombes, JD. Metabolism of cefotaxime in animals and humans. Rev Infect Dis. 1982 Sep-Oct;4 Suppl:S325-32.
  14. ^ cefotaxime for plant tissue culture
  15. ^ vancomycin for plant cell culture