cephalosporin
The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus '' Acremonium'', which was previously known as ''Cephalosporium''.
Together with cephamycins, they constitute a subgroup of β-lactam antibio ...
antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
. Cefepime has an extended spectrum of activity against
Gram-positive
In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall.
The Gram stain is ...
and
Gram-negative
Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists ...
bacteria
Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
, with greater activity against both types of organism than third-generation agents. A 2007
meta-analysis
Meta-analysis is a method of synthesis of quantitative data from multiple independent studies addressing a common research question. An important part of this method involves computing a combined effect size across all of the studies. As such, th ...
suggested when data of trials were combined, mortality was increased in people treated with cefepime compared with other β-lactam antibiotics. In response, the U.S.
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
(FDA) performed their own meta-analysis which found no mortality difference.
Cefepime was patented in 1982 by
Bristol-Myers Squibb
The Bristol-Myers Squibb Company, doing business as Bristol Myers Squibb (BMS), is an American multinational pharmaceutical company. Headquartered in Princeton, New Jersey, BMS is one of the world's largest pharmaceutical companies and consist ...
and approved for medical use in 1994. It is available as a
generic drug
A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...
and sold under a variety of trade names worldwide.
It was removed from the
World Health Organization's List of Essential Medicines
The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...
in 2019.
Medical use
Cefepime is usually reserved to treat moderate to severe
nosocomial
A hospital-acquired infection, also known as a nosocomial infection (from the Greek , meaning "hospital"), is an infection that is acquired in a hospital or other healthcare facility. To emphasize both hospital and nonhospital settings, it is s ...
pneumonia
Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...
, infections caused by multiple drug-resistant microorganisms (e.g. ''
Pseudomonas aeruginosa
''Pseudomonas aeruginosa'' is a common Bacterial capsule, encapsulated, Gram-negative bacteria, Gram-negative, Aerobic organism, aerobic–facultative anaerobe, facultatively anaerobic, Bacillus (shape), rod-shaped bacteria, bacterium that can c ...
'') and
empirical
Empirical evidence is evidence obtained through sense experience or experimental procedure. It is of central importance to the sciences and plays a role in various other fields, like epistemology and law.
There is no general agreement on how t ...
treatment of
febrile
Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with body temperature exceeding the normal range caused by an increase in the body's temperature set point in the hypothalamus. There is no single agre ...
neutropenia
Neutropenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria ...
.
Cefepime has good activity against important pathogens including ''Pseudomonas aeruginosa'', ''
Staphylococcus aureus
''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posi ...
'', and multiple drug-resistant ''
Streptococcus pneumoniae
''Streptococcus pneumoniae'', or pneumococcus, is a Gram-positive, spherical bacteria, hemolysis (microbiology), alpha-hemolytic member of the genus ''Streptococcus''. ''S. pneumoniae'' cells are usually found in pairs (diplococci) and do not f ...
''. A particular strength is its activity against
Enterobacteriaceae
Enterobacteriaceae is a large family (biology), family of Gram-negative bacteria. It includes over 30 genera and more than 100 species. Its classification above the level of Family (taxonomy), family is still a subject of debate, but one class ...
. Whereas other cephalosporins are degraded by many
plasmid
A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria and ...
- and
chromosome
A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...
-mediated
beta-lactamase
Beta-lactamases (β-lactamases) are enzymes () produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems ( ertapenem), although carbapene ...
s, 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
Cefepime Induced Neurotoxicity
Cefepime crosses the
blood brain barrier
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells.
Blood is compo ...
antagonist
An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain. Up to 15% of ICU patients treated with cefepime will experience cefepime induced neurotoxicity. Symptoms typically begin within 2-6 days of cefepime administration and include diminished level of consciousness, disorientation,
aphasia
Aphasia, also known as dysphasia, is an impairment in a person's ability to comprehend or formulate language because of dysfunction in specific brain regions. The major causes are stroke and head trauma; prevalence is hard to determine, but aph ...
,
myoclonus
Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle, a joint, or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus ( myo- "muscle", clonus "spasm") describes a medical sign and, ...
,
seizures
A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...
The combination of the ''syn''-configuration of the
methoxy
In organic chemistry, a methoxy group is the functional group consisting of a methyl group bound to oxygen. This alkoxy group has the formula .
On a benzene ring, the Hammett equation classifies a methoxy substituent at the ''para'' position a ...
moiety
Moiety may refer to:
__NOTOC__ Anthropology
* Moiety (kinship), either of two groups into which a society is divided
** A division of society in the Iroquois societal structure in North America
** An Australian Aboriginal kinship group
** Native Ha ...
and the aminothiazole moiety confers extra stability to
β-lactamase
Beta-lactamases (β-lactamases) are enzymes () produced by bacteria that provide Multiple drug resistance, multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems (ertapenem ...
enzymes produced by many bacteria. The ''N''-
methyl
In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated as ...
pyrrolidine
Pyrrolidine, also known as tetrahydropyrrole, is an organic compound with the molecular formula (CH2)4NH. It is a cyclic secondary amine, also classified as a saturated heterocycle. It is a colourless liquid that is miscible with water and most ...
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.