Chemistry:Cefepime
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 (FDA) performed their own meta-analysis which found no mortality difference.[2]
Cefepime was patented in 1982 by Bristol-Myers Squibb and approved for medical use in 1994.[3] It is available as a generic drug and sold under a variety of trade names worldwide. [4]
It was removed from the World Health Organization's List of Essential Medicines in 2019.[5]
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.[6]
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:[7]
- Escherichia coli: ≤0.007 – 128 μg/ml
- Pseudomonas aeruginosa: 0.06 – >256 μg/ml
- Streptococcus pneumoniae: ≤0.007 – >8 μg/ml
Cefepime induced neurotoxicity
Cefepime crosses the blood brain barrier and exhibits a concentration-dependent ϒ-aminobutyric acid (GABA) antagonist effect, which can cause neurological symptoms in susceptible individuals, particularly those with renal dysfunction.[8][9] Up to 15% of ICU patients treated with cefepime will experience cefepime induced neurotoxicity.[9] Symptoms typically begin within 2-6 days[10] of cefepime administration and include diminished level of consciousness, disorientation, aphasia, myoclonus, seizures, and nonconvulsive status epilepticus.[11] Symptoms typically resolve within 1-3 days of discontinuing cefepime.[10]
Chemistry
The combination of the syn-configuration of the methoxy imino moiety and the aminothiazole moiety confers extra stability to β-lactamase enzymes produced by many bacteria. The N-methyl pyrrolidine 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,[when?] cefepime became available as a generic and is now[when?] marketed by numerous companies worldwide under tradenames including Neopime (Neomed), Maxipime, Cepimax, Cepimex, and Axepim.
References
- ↑ "Efficacy and safety of cefepime: a systematic review and meta-analysis". The Lancet. Infectious Diseases 7 (5): 338–348. May 2007. doi:10.1016/S1473-3099(07)70109-3. PMID 17448937.
- ↑ "FDA Alert: Cefepime (marketed as Maxipime)". Information for Healthcare Professionals. Food and Drug Administration. https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm167254.htm.
- ↑ Analogue-based Drug Discovery. John Wiley & Sons. 2006. p. 496. ISBN 978-3-527-60749-5. https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA496. Retrieved 19 September 2020.
- ↑ "Cefepime (maxipime), large spectrum 4th generation cephalosporin, resistant to beta-lactamases].".
- ↑ Executive summary: the selection and use of essential medicines 2019: report of the 22nd WHO Expert Committee on the selection and use of essential medicines. Geneva: World Health Organization. 2019. WHO/MVP/EMP/IAU/2019.05. License: CC BY-NC-SA 3.0 IGO.
- ↑ "Cefepime: a review of its use in the management of hospitalized patients with pneumonia". American Journal of Respiratory Medicine 2 (1): 75–107. 2003. doi:10.1007/bf03256641. PMID 14720024.
- ↑ "Cefepime Susceptibility and Concentration Range (μg/ml) Minimum Inhibitory Concentration (MIC) Data". The Antimicrobial Index. toku-e.com. http://www.toku-e.com/Assets/MIC/Cefepime.pdf.
- ↑ "Characterizing Cefepime Neurotoxicity: A Systematic Review". Open Forum Infectious Diseases 4 (4). 2017. doi:10.1093/ofid/ofx170. PMID 29071284.
- ↑ 9.0 9.1 "Cefepime-induced neurotoxicity: a systematic review". Critical Care 21 (1): 276. November 2017. doi:10.1186/s13054-017-1856-1. PMID 29137682.
- ↑ 10.0 10.1 "Cefepime-induced neurotoxicity" (in English). Journal of Neurocritical Care 12 (2): 74–84. 2019-12-24. doi:10.18700/jnc.190109. ISSN 2005-0348. https://www.e-jnc.org/journal/view.php?doi=10.18700/jnc.190109.
- ↑ "Cefepime-induced neurotoxicity". https://acphospitalist.acponline.org/archives/2023/07/12/free/cefepime-induced-neurotoxicity.htm.
External links
- "Cefepime". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/name/cefepime.
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