Cefepime

From Infogalactic: the planetary knowledge core
Jump to: navigation, search
Cefepime (INN, AAN, BAN, USAN)
Cefepime2DCSD.svg
Cefepime ball-and-stick.png
Systematic (IUPAC) name
(6R,7R,Z)-
7-(2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido)-
3-((1-methylpyrrolidinium-1-yl)methyl)-8-oxo-5-thia-
1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylate
Clinical data
Pronunciation /ˈsɛfᵻpiːm/ or /ˈkɛfᵻpiːm/
Trade names Maxipime, Voco
AHFS/Drugs.com monograph
MedlinePlus a698021
Pregnancy
category
  • AU: B1
  • US: B (No risk in non-human studies)
Legal status
Routes of
administration		 Intravenous, intramuscular
Pharmacokinetic data
Bioavailability 100% (IM)
Metabolism Hepatic 15%
Biological half-life 2 hours
Excretion Renal 70–99%
Identifiers
CAS Number 88040-23-7 YesY
ATC code J01DE01 (WHO)
PubChem CID: 5479537
DrugBank DB01413 YesY
ChemSpider 4586395 YesY
UNII 807PW4VQE3 YesY
KEGG D02376 YesY
ChEBI CHEBI:478164 YesY
ChEMBL CHEMBL186 YesY
Chemical data
Formula C19H24N6O5S2
Molecular mass 480.56 g/mol
  • O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC(=O)C(=N\OC)/c3nc(sc3)N)C[N+]4(C)CCCC4)C([O-])=O
  • InChI=1S/C19H24N6O5S2/c1-25(5-3-4-6-25)7-10-8-31-17-13(16(27)24(17)14(10)18(28)29)22-15(26)12(23-30-2)11-9-32-19(20)21-11/h9,13,17H,3-8H2,1-2H3,(H3-,20,21,22,26,28,29)/b23-12-/t13-,17-/m1/s1 YesY
  • Key:HVFLCNVBZFFHBT-ZKDACBOMSA-N YesY
  (verify)

Cefepime is a fourth-generation cephalosporin antibiotic. Cefepime has an extended spectrum of activity against Gram-positive and Gram-negative bacteria, with greater activity against both types of organism than third-generation agents.

A 2007 meta-analysis suggested when data of trials were combined, mortality was increased in people treated with cefepime compared with other β-lactam antibiotics.[1] In response, the U.S. Food and Drug Administration performed their own meta-analysis which found no mortality difference.[2]

Cefepime was developed by Bristol-Myers Squibb[3][4] and marketed beginning in 1994. It is now available as a generic drug and sold under a variety of trade names worldwide.

Medical use

Cefepime is usually reserved to treat moderate to severe nosocomial pneumonia, infections caused by multiple drug-resistant microorganisms (e.g. Pseudomonas aeruginosa) and empirical treatment of febrile neutropenia.[5]

Cefepime has good activity against important pathogens including Pseudomonas aeruginosa, Staphylococcus aureus, and multiple drug-resistant Streptococcus pneumoniae. A particular strength is its activity against Enterobacteriaceae. Whereas other cephalosporins are degraded by many plasmid- and chromosome-mediated beta-lactamases, cefepime is stable and is a front-line agent when infection with Enterobacteriaceae is known or suspected.

Spectrum of bacterial susceptibility

Cefepime is a broad-spectrum cephalosporin antibiotic and has been used to treat bacteria responsible for causing pneumonia and infections of the skin and urinary tract. Some of these bacteria include Pseudomonas, Escherichia, and Streptococcus species. The following represents MIC susceptibility data for a few medically significant microorganisms.

  • Escherichia coli: ≤0.007 - 128 μg/ml
  • Pseudomonas aeruginosa: 0.06 - >256 μg/ml
  • Streptococcus pneumoniae: ≤0.007 - >8 μg/ml

[6]

Chemistry

The combination of the syn-configuration of the methoxyimino moiety and the aminothiazolyl moiety confers extra stability to β-lactamase enzymes produced by many bacteria. The N-methylpyrrolidine moiety increases penetration into Gram-negative bacteria. These factors increase the activity of cefepime against otherwise resistant organisms including Pseudomonas aeruginosa and Staphylococcus aureus.

Trade names

Following expiration of the Bristol-Myers Squibb patent, cefepime became available as a generic and is now marketed by numerous companies worldwide under tradenames including Neopime (Neomed), Maxipime. Cepimax, Cepimex, and Axepim.

Synthesis

Cefepime synthesis:[7] and antibacterial activity:.[8]

The starting material (1) for cefepime can be prepared in a few steps from the readily available 7-aminocephalosporanic acid (7-ACA). The primnary amino group in 1 is then protected as its Schiff base (2) by condensation with benzaldehyde. The allylic chloride is converted to the more reactive iodide by Finkelstein reaction with sodium iodide. Treatment of the reactive iodide with N-methylpyrrolidine leads to the quaternary salt (3). Reaction with formic acid cleaves both the protecting groups; ion-exchange chromatography of the crude product then affords the betaine (4). The primary amine is coupled with the 1-benzotriazole derivative (5) of one of the traditional cephalosporin side chains. There is thus obtained the antibiotic cefepime (6).

References

  1. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ http://www.toku-e.com/Assets/MIC/Cefepime.pdf
  7. ↑ S. Aburaki et al., DE 3307550 ; eidem, U.S. Patent 4,406,899 (both 1983 to Bristol-Myers).
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
Retrieved from "https://infogalactic.com/w/index.php?title=Cefepime&oldid=1657628"