Cefepime (INN, AAN, BAN, USAN)
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| Systematic (IUPAC) name |
(6 R,7 R, 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 |
or |
| Trade names |
Maxipime |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a698021 |
Pregnancy
category |
- AU: B1
- US: B (No risk in non-human studies)
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| Legal status |
- AU: S4 (Prescription only)
- CA: ℞-only
- UK: POM (Prescription only)
- US: ℞-only
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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 Y |
| ATC code |
J01DE01 |
| PubChem |
CID: 5479537 |
| DrugBank |
DB01413 Y |
| ChemSpider |
4586395 Y |
| UNII |
807PW4VQE3 Y |
| KEGG |
D02376 Y |
| ChEBI |
CHEBI:478164 Y |
| ChEMBL |
CHEMBL186 Y |
| Chemical data |
| Formula |
C19H24N6O5S2 |
| Molecular mass |
480.56 g/mol |
SMILES
-
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
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InChI
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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 Y
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Key:HVFLCNVBZFFHBT-ZKDACBOMSA-N Y
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| Y (what is this?) (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.
Contents
- 1 Medical use
- 1.1 Spectrum of bacterial susceptibility
- 2 Chemistry
- 3 Trade names
- 4 Synthesis
- 5 References
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
- ^ Yahav D, Paul M, Fraser A, Sarid N, Leibovici L (2007). "Efficacy and safety of cefepime: a systematic review and meta-analysis". Lancet Infect Dis 7 (5): 338–48. doi:10.1016/S1473-3099(07)70109-3. PMID 17448937.
- ^ "Information for Healthcare Professionals: Cefepime (marketed as Maxipime)". Retrieved 2009-08-02.
- ^ Barbhaiya RH, Forgue ST, Gleason CR, Knupp CA, Pittman KA, Weidler DJ, Martin RR (1990). "Safety, tolerance, and pharmacokinetic evaluation of cefepime after administration of single intravenous doses". Antimicrob. Agents Chemother. 34 (6): 1118–22. doi:10.1128/aac.34.6.1118. PMC 171768. PMID 2203303.
- ^ "www.accessdata.fda.gov" (PDF).
- ^ Chapman TM, Perry CM (2003). "Cefepime: a review of its use in the management of hospitalized patients with pneumonia". Am J Respir Med 2 (1): 75–107. doi:10.1007/bf03256641. PMID 14720024.
- ^ http://www.toku-e.com/Assets/MIC/Cefepime.pdf
- ^ S. Aburaki et al., DE 3307550 ; eidem, U.S. Patent 4,406,899 (both 1983 to Bristol-Myers).
- ^ Naito, T; Aburaki, S; Kamachi, H; Narita, Y; Okumura, J; Kawaguchi, H (1986). "Synthesis and structure-activity relationships of a new series of cephalosporins, BMY-28142 and related compounds". The Journal of antibiotics 39 (8): 1092–107. PMID 3759661.
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Antibacterials: cell envelope antibiotics (J01C-J01D)
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| Intracellular |
- Inhibit peptidoglycan subunit synthesis and transport: NAM synthesis inhibition (Fosfomycin)
- DADAL/AR inhibitors (Cycloserine)
- bactoprenol inhibitors (Bacitracin)
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| Glycopeptide |
- Inhibit PG chain elongation: Vancomycin# (Oritavancin
- Telavancin)
- Teicoplanin (Dalbavancin)
- Ramoplanin
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β-lactams/
(Inhibit PBP
cross-links) |
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| Other |
- polymyxins/detergent
- depolarizing
- Hydrolyze NAM-NAG
- Gramicidin
- Isoniazid
- Teixobactin
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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Index of bacterial disease
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| Description |
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| Disease |
- Gram-positive firmicutes
- Gram-positive actinobacteria
- Gram-negative proteobacteria
- Gram-negative non-proteobacteria
- Cholera
- Tuberculosis
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| Treatment |
- Antibiotics
- cell wall
- nucleic acid
- mycobacteria
- protein synthesis
- other
- Antibodies
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