Cefepime

Cefepime

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)
Routes of administration	Intravenous, intramuscular
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	100% (IM)
Metabolism	Hepatic 15%
Biological half-life	2 hours
Excretion	Renal 70–99%
Identifiers
CAS Number	88040-23-7
ATC code	J01DE01 (WHO)
PubChem	CID 5479537
DrugBank	DB01413
ChemSpider	4586395
UNII	807PW4VQE3
KEGG	D02376
ChEBI	CHEBI:478164
ChEMBL	CHEMBL186
Chemical data
Formula	C19H24N6O5S2
Molar 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
InChI 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 Key:HVFLCNVBZFFHBT-ZKDACBOMSA-N
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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.

References

1. 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.
2. "Information for Healthcare Professionals: Cefepime (marketed as Maxipime)". Retrieved 2009-08-02.
3. 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.
4. "www.accessdata.fda.gov" (PDF).
5. 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.
6. http://www.toku-e.com/Assets/MIC/Cefepime.pdf