Cefotaxime

Cefotaxime

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
Pharmacokinetic data
Bioavailability	n/a
Metabolism	Hepatic
Half-life	0.8–1.4 hours
Excretion	50–85% renal
Identifiers
CAS number	63527-52-6 Y
ATC code	J01DD01
PubChem	CID 5479527
DrugBank	DB00493
ChemSpider	4586392 Y
UNII	N2GI8B1GK7 Y
KEGG	D07647 Y
ChEMBL	CHEMBL102 Y
Chemical data
Formula	C16H17N5O7S2
Mol. mass	455.47 g/mol
SMILES O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC(=O)C(=N\OC)\c3nc(sc3)N)COC(=O)C)C(=O)O
InChI InChI=1S/C16H17N5O7S2/c1-6(22)28-3-7-4-29-14-10(13(24)21(14)11(7)15(25)26)19-12(23)9(20-27-2)8-5-30-16(17)18-8/h5,10,14H,3-4H2,1-2H3,(H2,17,18)(H,19,23)(H,25,26)/b20-9+/t10-,14-/m1/s1 Y Key:GPRBEKHLDVQUJE-VINNURBNSA-N Y
Y (what is this?)  (verify)

Cefotaxime (INN) /ˌsɛfɵˈtæksiːm/ is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram positive and Gram negative bacteria. In most cases, it is considered to be equivalent to ceftriaxone in terms of safety and efficacy.

Mechanism of action

Cefotaxime inhibits 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) while cell wall assembly is arrested.^[1]

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.^[2]

Spectrum of bacterial susceptibility

Cefotaxime has been used to treat a wide range of bacteria responsible for causing bone, CNS, skin, and lower respiratory tract infections. Notable species include Streptococcus, Staphylococcus, Enterococcus, and Escherichia. 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

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Clinical use

Cefotaxime is used for infections of the respiratory tract, skin, bones, joints, urogenital system, meninges, and bloodstream. It generally has good coverage against most Gram-negative bacteria, with the notable exception of Pseudomonas. It is also effective against most Gram-positive cocci except for Enterococcus.^[1] It has modest activity against the anaerobic Bacteroides fragilis. In meningitis, cefotaxime crosses the blood–brain barrier better than cefuroxime.

Vial of cefotaxime

Use in plant tissue culture

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,^[5] while vancomycin is used to treat the plant tissue infections with Gram positive bacteria.^[6]

Chemistry

The syn-configuration of the methoxyimino moiety confers stability to β-lactamase enzymes produced by many Gram-negative bacteria. Such stability to β-lactamases increases the activity of cefotaxime against otherwise resistant Gram-negative organisms.

References