Cefepime

Cefepime is a fourth-generation broad-spectrum cephalosporin antibiotic commonly used to treat various bacterial infections caused by Gram-positive and Gram-negative bacteria.

Chemical Structure and Classification

Cefepime belongs to the earlier generation of cephalosporin class of antibiotics, beta-lactam drugs. It has enhanced stability against beta-lactamase enzymes and increased activity against Gram-negative organisms.

Mechanism of Action

Like other beta-lactam antibiotics, Cefepime works by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs), which are critical for the final stages of cell wall formation. The disruption of cell wall synthesis leads to bacterial cell lysis and death.

Spectrum of Activity

Cefepime has a broader spectrum as compared to third-generation cephalosporins, with increased activity against both Gram-negative organisms (like Pseudomonas aeruginosa) and Gram-positive organisms (like Streptococcus pneumoniae).

Pharmacokinetics of Cefepime

Absorption and Distribution

Cefepime administration is through parenteral route (usually intravenously or intramuscularly). It is not absorbed orally. It distributes widely throughout the body after administration, including the lungs, kidneys, and cerebrospinal fluid (CSF).

Metabolism and Elimination

Most of the Cefepime is not metabolized in the liver. It is excreted unchanged by the kidneys. Therefore, dosage adjustments are necessary in patients with renal impairment.

Half-Life

The half-life of cefepime is approximately 2 hours in healthy individuals but may vary in individuals with renal dysfunction.

Protein Binding

Cefepime is approximately 16-20% protein-bound; thus, a larger proportion of the drug is active and available for antibacterial action.

Indications for Cefepime Use

Cefepime is indicated for various serious bacterial infections due to its broad-spectrum activity.

Common Indications

Pneumonia (both community-acquired and hospital-acquired)
Urinary Tract Infections (UTIs)
Skin and Soft Tissue Infections
Intra-abdominal Infections (often in combination with other antibiotics)
Febrile Neutropenia (in immunocompromised patients)

Empiric Therapy

It is often used as part of empiric therapy for febrile neutropenia or severe infections, especially in hospitalized patients who may have multidrug-resistant bacteria.

Dosage and Administration

The dosage depends on the following factors

severity of the infection,
the patient’s renal function,
the specific pathogen being treated.

Adult Dosing

Mild to Moderate Infections: 1-2 g every 12 hours
Severe Infections: 2 g every 8 hours
Febrile Neutropenia: 2 g every 8 hours

Pediatric Dosing

Pediatric doses depend on age and weight, ranging from 50 mg/kg to 100 mg/kg per day.

Renal Dosing Adjustments

Dose adjustments are needed in patients with renal insufficiency because it is excreted through the kidneys. For patients with creatinine clearance of less than 60 mL/min, the dose should be reduced accordingly.

Side Effects of Cefepime and Adverse Reactions

Like all antibiotics, it has some side effects.

Common Side Effects

Nausea,
Vomiting
diarrhea
Pain, redness, and swelling at the injection site

Serious Side Effects

Neurotoxicity
Confusion,
Seizures
encephalopathy (especially in patients with renal impairment)
Allergic Reactions such as Rash, fever, and anaphylaxis
Hematologic Effects such as Leukopenia, thrombocytopenia, and eosinophilia

Risk of Superinfections such as Clostridium difficile-associated diarrhea.

Contraindications

Hypersensitivity to Cefepime
History of Severe Allergic Reactions to beta-lactam antibiotics

Drug Interactions

It can interact with various other medications, which can alter its effectiveness or increase the risk of side effects.

Renal Toxicity

Concomitant use of cefepime with nephrotoxic agents (e.g., aminoglycosides, vancomycin) can lead to renal toxicity. Thus, monitor its concentration carefully.

Probenecid

Probenecid decreases renal clearance of cefepime. It increases drug concentration and prolongs half-life.

Popular Brand Names of Cefepime

Brand Name	Manufacturer	Formulation
Maxipime	Bristol-Myers Squibb	Injection (IV/IM)
Cefepime Teva	Teva Pharmaceuticals	Injection (IV/IM)
Eprime	Eris Life Sciences	Injection (IV/IM)
Cepim	Hetero Drugs Ltd	Injection (IV/IM)
Mexum	High Noon	Injection (IV/IM)

Conclusion

Cefepime is a potent and versatile antibiotic that plays a crucial role in managing serious infections, particularly those caused by multidrug-resistant bacteria. Its broad spectrum of activity, along with its pharmacokinetic properties, makes it a valuable tool in modern medicine.