Bacterial infections can range from mild to life-threatening, and selecting the right antibiotic is key to effective treatment. Cefepime is a cephalosporin antibiotic that is often prescribed to help manage serious bacterial infections.
Approved by the FDA in 1996, cefepime is known for its ability to fight a wide range of bacteria, including some resistant strains.
This article provides a detailed overview of cefepime, from how it works to its clinical uses, dosage, safety considerations, and more.
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What is Cefepime?
Cefepime is a fourth generation cephalosporin antibiotic. Cephalosporins are a group of antibiotics derived from the fungus Acremonium spp. and are used to treat bacterial infections.
Cefepime, approved by the FDA in 1996, has a broad spectrum of activity, meaning it may work against a wide range of bacteria, including some that other antibiotics may not effectively treat.
As a fourth-generation cephalosporin, it may havean increased ability to combat both Gram-positive and Gram-negative bacteria than previous generations, including strains resistant to earlier cephalosporins. It is effective against certain resistant gram-negative bacteria, such as Pseudomonas aeruginosa, and gram-positive bacteria, including Streptococcus pneumoniae, based on susceptibility testing.
Compared to older cephalosporins, cefepime is more stable against beta-lactamases, which makes it effective for treating serious infections like pneumonia, febrile neutropenia, and complicated urinary tract infections.
Brand Names
Cefepime is also available under the brand name Maxipime.
Mechanism of Action
Cefepime is an antibiotic in the cephalosporin family. It works by stopping bacteria from building their cell walls, which are essential for their survival.
Cefepime attaches to special proteins called penicillin-binding proteins (PBPs) that bacteria use to create their protective outer layer. Without this layer, the bacteria become weak and eventually die.
Compared to older antibiotics, cefepime is less susceptible to destruction by beta-lactamase enzymes (some bacteria use these to resist treatment). It can pass through tough outer barriers of certain bacteria, making it effective against a wide range of infections, including those caused by resistant germs.
Additionally, cefepime spreads well throughout the body, reaching places like the fluid around the lungs, joints, bones, spinal fluid, and even breast milk. Its ability to cross the blood-brain barrier makes it especially useful for treating infections like meningitis.
This wide reach helps cefepime treat hard-to-access areas, making it an important option for serious infections. Cefepime is not effective against all resistant bacteria; susceptibility testing is recommended before use.
What are Cephalosporin Antibiotics?
Cephalosporins are a versatile family of antibiotics derived from the fungus Acremonium (formerly known as Cephalosporium). They belong to the beta-lactam class of antimicrobials, known for their broad-spectrum activity against both gram-positive and gram-negative bacteria.
Cephalosporins are grouped into five generations, with each generation improving its ability to fight tougher, more resistant bacteria. They work by stopping bacteria from building their protective cell walls, which causes the bacteria to die.
Over time, changes in their structure have made cephalosporins better at resisting bacterial enzymes like beta-lactamases that try to destroy them and have improved their ability to reach different parts of the body, including the brain.
Clinical Uses of Cefepime
Cefepime has important clinical applications.
Indications
Cefepime is used to treat various serious bacterial infections. Commonly treated conditions include:
- Pneumonia: cefepime treats both hospital-acquired and community-acquired types, particularly moderate-to-severe pneumonia, pneumonia alongside bacteremia (bacteria in the blood), or those cases caused by resistant bacteria.
- Febrile Neutropenia: this is a potentially life-threatening fever in patients with low white blood cell counts, often due to chemotherapy.
- Urinary Tract Infections (UTIs): complicated infections (infections linked to structural or medical complications) as well as uncomplicated infections (infections in healthy people with normal urinary anatomy) caused by bacteria like Escherichia coli and Klebsiella pneumoniae, and Proteus mirabilis.
- Skin and Soft Tissue Infections: such as cellulitis and wound infections due to Staphylococcus aureus (non methicillin-resistant, or non-MRSA, strains only) or Streptococcus pyogenes.
- Intra-abdominal Infections: including peritonitis and infections following surgery, caused by Escherichia coli, viridans group streptococci, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter species, or Bacteroides fragilis.
Cefepime is also effective against infections caused by multi-drug-resistant bacteria, such as Pseudomonas aeruginosa. In some cases, it is used in combination with other antibiotics for synergistic effects.
Cefepime is FDA-approved for treating pneumonia, febrile neutropenia, urinary tract infections, and intra-abdominal infections. Off-label uses may be considered under the guidance of a healthcare provider.
Cefepime and Concerns About Antibiotic Resistance
Antibiotic resistance, particularly in gram-negative bacteria, poses challenges to cefepime’s effectiveness in some cases.
Bacteria can resist cefepime by producing specialized enzymes like ESBLs, AmpC, and carbapenemases or using efflux pumps to get rid of the drug (efflux pumps are a large part of the increasing cefepime resistance of Pseudomonas aeruginosa).
While cefepime works well against Serratia marcescens, Proteus mirabilis, methicillin-susceptible Staphylococcus aureus, and Streptococcus pneumoniae, it doesn’t work on methicillin-resistant staphylococci, enterococci, or multidrug-resistant Acinetobacter baumannii.
Certain factors make resistance more likely, like previous use of other antibiotics (e.g., cephalosporins, penicillins, or quinolones) and patients being transferred from long-term care facilities. This resistance can lead to serious outcomes, including higher death rates in patients with bloodstream infections caused by resistant Pseudomonas aeruginosa.
To fight resistance, experts suggest stricter testing guidelines, like EUCAST standards (MIC ≤ 1 mg/L), which are better at showing cefepime’s limitations. Using higher doses or longer infusions can help but often isn’t enough for highly resistant bacteria.
Emerging treatments, such as cefepime-zidebactam combinations, show potential but require further research to confirm their effectiveness and safety. Reducing or pausing cefepime use in hospitals, especially ICUs, has been shown to lower resistance and help keep it effective for treating infections.
Healthcare providers should conduct susceptibility testing to ensure the appropriate use of cefepime.
Dosage and Administration
The appropriate dosage and administration route are always determined by a medical professional. Dosage adjustments should always be guided by a healthcare provider based on individual patient factors.
Standard Dosage Guidelines
Cefepime dosage varies depending on the patient’s age, weight, infection type, and kidney function. Typical guidelines include:
Adults: 1 to 2 grams administered every 8 to 12 hours via intravenous (IV) or intramuscular (IM) routes.
Pediatric Patients: 50 mg per kilogram of body weight every 8 to 12 hours, depending on the severity of the infection.
Renal Impairment: Dosage adjustments may be necessary for patients with reduced kidney function, based on creatinine clearance, to minimize the risk of drug accumulation and potential toxicity.
Routes of Administration
Cefepime is primarily administered through:
Intravenous (IV) Injection: this method delivers the medication directly into the bloodstream for rapid action. It is infused over 30 minutes to an hour.
Intramuscular (IM) Injection: cefepime is injected intramuscularly for patients who cannot receive IV therapy.
Side Effects and Safety Profile
As with any medication, understanding the risks and side effects of cefepime is essential. Patients experiencing severe side effects should contact their healthcare provider immediately and may need to discontinue use under medical supervision.
Common Side Effects
The following are common side effects seen with cefepime:
- Diarrhea
- Skin rash or itching (pruritus)
- Nausea
- Vomiting
- Headache
- Stomach pain
- Irritation at the injection site
- Mouth infections (oral thrush)
- Vaginal infections (vaginitis)
- Fever (especially in children)
Serious or Severe Side Effects
The following severe side effects have been noted with cefepime:
Nervous System Problems
- Confusion or trouble thinking
- Brain swelling (encephalopathy)
- Seizures
- Jerking movements (myoclonus)
- Seeing or hearing things that aren’t real (hallucinations)
- Falling into a coma
- Stroke-like symptoms
Digestive System Problems
- Severe diarrhea or inflammation in the colon, including pseudomembranous colitis
- Liver damage
Skin Problems
- Hives (urticaria)
- Severe skin reactions like Stevens-Johnson syndrome
- Red, swollen spots on the skin (erythema multiforme)
Blood Problems
- Positive Coombs test (used to check for blood issues) without signs of blood cell damage
- Low blood cell counts (pancytopenia)
- Serious anemia (anaplastic anemia)
Allergic Reactions
- Severe allergic reactions, even in some people allergic to penicillin (rare)
- Delayed allergic reactions caused by the immune system
Other Serious Issues
- Kidney damage
- Severe infections caused by C. difficile (a potentially dangerous bacteria that can grow in the gut after antibiotics and is common in hospital settings)
Important Notes About Cefepime Use
- Older adults, people with kidney problems, or critically ill patients have a higher chance of getting serious brain or nerve issues like confusion or seizures.
- Prolonged cefepime use may increase the risk of infections, such as Clostridioides difficile, which can be challenging to manage.
Precautions and Contraindications
Key safety considerations around cefepime use include:
Pregnancy and Breastfeeding
Cefepime, a category B drug, is generally considered safe, but consultation with a healthcare provider is essential because cefepime should only be used if necessary.
Cefepime is excreted in human breast milk at low concentrations, so caution is recommended when administering it to breastfeeding women. Monitor infants for potential side effects like diarrhea or thrush.
Cefepime should only be used during pregnancy or breastfeeding under direct guidance from a healthcare provider.
Allergies
Patients with a history of allergies to penicillin or other beta-lactam antibiotics should inform their healthcare provider before taking cefepime.
Drug and Other Interactions
Avoid combining cefepime with medications that affect kidney function, such as aminoglycosides or diuretics.
Patients most likely to experience severe neurological side effects are those with kidney problems, older adults, and critically ill patients if dosages are not adjusted.
Warning Regarding Prolonged Use
Prolonged use may lead to overgrowth of resistant or nonsusceptible microorganisms, such as C. difficile or fungal infections.
Monitoring and Red Flags
It’s important to monitor for the following “red flag” symptoms:
Neurological Adverse Effects
Symptoms such as confusion, seizures, hallucinations, encephalopathy, or coma require immediate evaluation and may necessitate dose adjustment or discontinuation under medical supervision.
Hypersensitivity Reactions
Monitor for signs of allergic reactions, particularly in patients with a history of beta-lactam allergy.
Superinfections
Watch for signs of Clostridioides difficile infections, including diarrhea or colitis, as cefepime can disrupt normal gut flora.
Drug Interactions
It’s important to be aware of the following significant drug interactions:
- With Aminoglycosides: higher chance of kidney damage and hearing problems.
- With Diuretics (like furosemide): higher risk of kidney damage.
- With Vaccines: cholera and typhoid vaccines may not work as well.
- Urinary Glucose Tests: some tests may give false positive results; glucose oxidase-based tests are better to use.
Pharmacokinetic Alterations
Sepsis or severe illness may alter drug levels, necessitating careful monitoring of drug concentrations.
Overdose Symptoms
Overdose symptoms may present as neurotoxicity. Dialysis is recommended in severe cases to reduce drug levels.
Regular monitoring by a healthcare provider is essential to prevent or address adverse effects promptly.
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Key Takeaways
- Purpose: Cefepime is a fourth-generation cephalosporin antibiotic commonly used to treat serious bacterial infections, including pneumonia, febrile neutropenia, and complicated urinary tract infections.
- Mechanism of Action: Cefepime inhibits bacterial cell wall synthesis, making it effective against a broad range of bacteria, including some resistant strains.
- Usage: Proper use requires susceptibility testing and medical guidance to ensure effectiveness and reduce the risk of resistance.
- Side Effects: Common side effects include nausea, diarrhea, and skin rash, while serious risks like neurotoxicity or severe allergic reactions require immediate medical attention.
- Precautions: Patients with kidney impairment, allergies to beta-lactams, or prolonged use should be closely monitored to prevent complications.
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