cefepime

cefepime
IUPAC name	(6R,7R)-7-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino}-3-[(1-methylpyrrolidin-1-ium-1-yl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
Tradename	Maxipime, others
Drugs.com	Monograph
MedlinePlus	a698037
Pregnancy AU	B1
Routes of administration	Intravenous, Intramuscular
CAS number	88040-23-7
PubChem	5479537
DrugBank	DB01413
ChemSpiderID	4586394
UNII	807PW4VQE3
ChEBI	3508
ChEMBL	1200639
Chemical formula	C19H24N6O5S2
Molecular weight	480.56 g·mol−1

cefepime is a broad-spectrum fourth-generation cephalosporin antibiotic with activity against both Gram-positive and Gram-negative bacteria. It is commonly used in the treatment of moderate to severe infections, including pneumonia, bacteremia, and urinary tract infections, particularly those caused by Pseudomonas aeruginosa. The drug is typically administered via intravenous or intramuscular injection in hospital settings under the supervision of Infectious Diseases Society of America guidelines.

Medical uses

Cefepime is indicated for the treatment of complicated intra-abdominal infections, skin and skin structure infections, and community-acquired pneumonia as recommended by the Food and Drug Administration. It is a first-line agent for febrile neutropenia in patients undergoing chemotherapy at institutions like the Memorial Sloan Kettering Cancer Center. The antibiotic demonstrates efficacy against Enterobacteriaceae such as Escherichia coli and Klebsiella pneumoniae, as well as pathogens like Streptococcus pneumoniae and Staphylococcus aureus. Clinical trials, including those published in the New England Journal of Medicine, support its use for meningitis caused by susceptible organisms in regions following World Health Organization protocols.

Adverse effects

Common adverse effects include rash, diarrhea, and nausea, while more serious reactions can involve Clostridioides difficile infection and anaphylaxis. A notable risk is neurotoxicity, manifesting as encephalopathy or nonconvulsive status epilepticus, particularly in patients with renal impairment or those receiving high doses, as documented in reports from the Centers for Disease Control and Prevention. The European Medicines Agency has issued safety communications regarding potential seizure activity associated with elevated plasma concentrations. Cases of hematologic toxicity such as neutropenia have been observed in patients at the Mayo Clinic receiving prolonged therapy.

Pharmacology

Cefepime exerts its bactericidal effect by inhibiting penicillin-binding proteins, thereby disrupting cell wall synthesis in dividing bacteria. Its pharmacokinetic profile includes low protein binding and a volume of distribution that allows penetration into cerebrospinal fluid, pleural fluid, and bronchial secretions. Metabolism is minimal, with the drug primarily excreted unchanged by the kidneys via glomerular filtration, necessitating dosage adjustment in patients with chronic kidney disease. The half-life is approximately two hours in individuals with normal renal function, as characterized in studies at the National Institutes of Health.

Chemistry

Cefepime is a semi-synthetic derivative of cephamycin with a distinct quaternary ammonium moiety attached at the C-3 position of the cephem nucleus, enhancing its ability to penetrate the outer membrane of Gram-negative bacteria. The oxime group at the C-7 side chain confers stability against hydrolysis by many beta-lactamase enzymes, including those from the TEM-1 and SHV-1 families. Its molecular structure is characterized by an aminothiazole ring, which contributes to its potent activity against Pseudomonas aeruginosa, as analyzed in research from the University of Tokyo.

History

Cefepime was discovered and developed in the late 1980s by the pharmaceutical company Bristol-Myers Squibb as part of efforts to overcome increasing antibiotic resistance mediated by extended-spectrum beta-lactamases. It received approval from the Food and Drug Administration in the United States in 1996, following clinical trials that demonstrated superiority over ceftazidime for certain infections. Subsequent regulatory approvals were granted by Health Canada and the Therapeutic Goods Administration in Australia, solidifying its global use. The drug's introduction was a significant milestone noted in publications by the American Society for Microbiology.

Society and culture

Cefepime is marketed under the brand name Maxipime in many countries and is included on the World Health Organization Model List of Essential Medicines as a critical antimicrobial. Its use is guided by antimicrobial stewardship programs in hospitals like the Johns Hopkins Hospital to combat the rise of multidrug-resistant organisms. Generic versions are manufactured by companies such as Hikma Pharmaceuticals and Fresenius Kabi, following patent expirations. The drug's role in treating infections in critical care medicine is frequently discussed in forums such as the Society of Critical Care Medicine annual meetings.

Category:Cephalosporin antibiotics Category:World Health Organization essential medicines Category:Bristol-Myers Squibb